エドガーで原本を確認する
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Date of report (Date of earliest event reported):
October 4, 2025
NEONC TECHNOLOGIES HOLDINGS, INC.
(Exact Name of Registrant as Specified in Its Charter)
Delaware
(State or Other Jurisdiction of Incorporation)
| 001-42567 | 92-1954864 | |
| (Commission File Number) | (IRS Employer Identification No.) |
| 23975 Park Sorrento, Suite 205 Calabasas, CA | 91302 | |
| (Address of Principal Executive Offices) | (Zip Code) |
(818) 570-6844
(Registrant’s Telephone Number, Including Area Code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbols | Name of each exchange on which registered | ||
| Common Stock, par value $0.0001 | NTHI | The Nasdaq Stock Market LLC |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 1.01. | Entry into a Material Definitive Agreement |
On October 4, 2025, NeOnc Technologies Holdings, Inc. (the “Company”) entered into a Master Services Agreement (the “MSA”) with Insights Pharmaceutical Research LLC (“IROS”), a contract research organization based in the United Arab Emirates and an affiliate of Group 42 Holding Ltd. and Mubadala Investment Company PJSC. The MSA establishes the terms and conditions under which IROS will provide clinical research services to in support of the Company’s clinical development programs in the UAE. The MSA will be transferred to the Company’s controlled UAE subsidiary (NuroCure) once its incorporation is complete.
Under the MSA, IROS will serve as the Company’s contract research organization for clinical trials conducted in the UAE and will be responsible for regulatory submissions, site selection and management, clinical monitoring, data management, and trial reporting activities, in accordance with Good Clinical Practice guidelines and applicable UAE and FDA regulations. Each specific project or study will be governed by a separate work order under the MSA.
The first work order to be executed under the MSA covers a multi-site, randomized Phase 2b/3 study titled A Multi-Site, Randomized, Phase 2b/3 Study Evaluating Overall Survival of Intranasal NEO100 in Patients with Progressive or Recurrent Grade III Astrocytomas and Glioblastoma Multiforme (GBM), Stratified by IDH1 Mutation Status, Compared to Best Standard of Care. The initial work order has an estimated budget of approximately $2.4 million in service fees and $0.1 million in pass-through costs, payable in four milestone-based installments through study completion. The Company retains all rights to clinical data, intellectual property, and regulatory filings arising from the studies performed under the MSA.
The MSA sets out the general terms on which all projects will be conducted. In addition to performance commitments and payment terms, it includes customary provisions relating to confidentiality, indemnification and liability, insurance, audit and inspection, data protection, termination rights, compliance with applicable laws and dispute resolution. The agreement is governed by the laws of the Abu Dhabi Global Market.
The foregoing description of the MSA does not purport to be complete and is qualified in its entirety by reference to the full text of the MSA, which is filed as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated herein by reference.
| Item 7.01. | Regulation FD Disclosure. |
On October 9, 2025, the Company issued a press release announcing two major strategic developments that solidify its expansion into the Middle East. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01 and Exhibit 99.1 furnished hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 9.01. | Financial Statements and Exhibits. |
| (d) | Exhibits |
| Exhibit No. | Description | |
| 10.1 | Master Services Agreement, dated October 4, 2025 | |
| 99.1 | Press Release, dated October 9, 2025 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Dated: October 9, 2025 | NeOnc Technologies Holdings, Inc. | ||
| By: | /s/ Amir Heshmatpour | ||
| Name: | Amir Heshmatpour | ||
| Title: | President and Executive Chairman | ||
Exhibit 10.1
E X E C U T I O N V E R S I O N M A S T E R S E R V I C E A G R EE M E N T N E O N C TE C H N O L OG I E S H O L D I N G S , I N C .
A N D I N S I GH T S PH A R M A C E U T I C A L R E S E A R C H LL C 1 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N M A S T E R S E R V I C E S A GR E E M E N T T his M a s t e r S e r v i ce s A gr e e m e nt ( h e r ei n a ft e r Ag r e e m e n t E ff ec t i v e D a te 4 October 2025 , (hereinafter (1) N E O N C T E CH N O L O G I E S HO L D I N G S, I N C . , a c om p a n y r e gi s t e red o n t h e N a s d a q s t o c k e x ch a n g e w it h i t s p ri n c i p al pl a c e o f bu s i n e s s a t 2 3 9 7 5 P a r k S o r r e n t o, Suite 2 0 5 , C a l a b a s a s , C A 9 1 3 0 2 , Un i t ed S t a te s ( h e r e i n a f t e r C LI E N T ; - a n d - (2) I N S I G H T S PH A R M A C E U TI C A L R E S E A R C H L L C , a l imi t ed l i a bi l i ty c om p a n y i n c o r po r a te d i n th e Un i t ed A r a b Emira t e s w it h i t s p r i n c i p a l pl a c e o f b u s in e s s at a t B u i l di ng of M a s d a r M 13 T L i mi t e d, S E 4 5 _ 0 5 , P lot C 16 , Kh ali f a C i t y, A bu D h a bi , U nite d A r a b E m ir a t e s I R O S . I R OS a n d C L I EN T P a r t y P a r t i e s 2 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G C O N T R A C T P AR T I CU L A R S U A E T er r i t o r y T h r e e ( 3 ) y e a r s f r o m the e f f e c t ive d a te of t h e f i r st W o r k O r d e r e x e c u t e d u n d e r t h i s A g r e e m e n t . I n i t i a l T e r m C L I E N T : N a m e : A m ir H e s hm a t p o u r T e l e p h o n e : + 1 - 310 - 7 2 1 - 43 91 E m a i l: a m i r @ n e o n c . c o m I R O S : N a m e : I s l a m E l t a n t a w a y T e l e p h o n e : + 9 7 1 5 45 3 5 3 5 51 E m a i l: is l a m . e lt a n t aw y @ i r os. a i R e l at i o ns h i p Ma n a ge r A M u l t i - S i t e , R a n do mi ze d , P h a s e 2 b / 3 S t u dy E va l u a t i ng O v er a l l S u r v i v a l (O S ) o f I n t r a n a s a l N E O 1 00 in P a t i e n t s w i t h P r o g r e s s ive o r R ec ur r e n t G r a de I I I A st r o c y t o m a s a n d G l i o b l a s t o m a M u lt i f o r m e (G BM ) , S t r a t i f i e d by ID H 1 M u t a t i o n S t a t u s , C o m p ar e d t o B e s t S t a nd ar d o f C a r e T i t l e o f f i r st S t u dy un d e r f i r s t WO F o r C L I E NT : A d d r e s s : 2 3 9 75 P a r k S o r re n t o , S u i t e 205, C a l a b a s a s, CA 9 1 30 2, U nit e d S t a t e s E m a i l: jn e m a n @ n e o n c . c o m A t t e n t io n : J o sh N e m a n , P h D F o r I R O S : A d d r e s s : M B ZUA I c a mpus i n M a s d a r C i t y , G r ou n d L e v e l, O f f i c e U nit G 19 , I n c ub a t o r B u i l d i ng , M a sd a r P O B O X 1 127 7 8, A b u Dh a bi, Un it e d A r a b E m i r a t e s E m a i l: i s l a m. e l t a n t a w y @ i ro s . a i , w i th a c opy to l e g a l @ m 4 2 .
a e A t t e n t io n : I sl a m E l t a n t a w a y A d d r e ss F o r N o t i ce s E X E C U T I O N V E R S I O N WH E R E A S A. I R OS i s a Co n t r ac t R e s e a r c h O r g a n i z a t ion ( CR O ) p r o v i d i ng c l i n i c a l r e s e a r c h s e r v i ce s. B. C L I EN T i s a c lin i c a l - s t a ge lif e s c i e n c e s c o m p an y f o c u s e d on t h e d e v e l o p m e n t a n d c omm e r c i al i za t i o n of ce nt r a l n e r v o u s s y s te m th e r a p e u t i c s t h at a r e d e s i g n e d t o ad dr e s s t he p e r s i s t e n t c h a l l en g e s i n o v e r c o mi n g t he bl o o d - br ai n b a r r i e r a nd ac t s a s t h e s p o n sor o f c e r t a i n c l i n i c a l tr i a l s in the T e r ri to r y . C. The P a rt i e s d e s i r e t o e n te r i n t o t h i s A g r ee m e nt t o p r o vi de t he t e r m s a n d condit i o n s u p o n w h i ch C L I EN T m ay en g a g e I R O S, fr o m t i me t o t i m e , t o p r o v i de C R O s e r v i c e s f o r t he m an a g e m e n t of c l i n ic a l d r u g s t ud y (i e s ) s p onsored b y C L I EN T u n d er t his A g r ee m e n t ( ea c h a S t u d y S t u d i e s ) by e x e c ut i n g a WO ( a s d e f i n e d b e l o w) s p e c i f y i n g t h e d e t a i l s o f t h e s er v i ce s a n d t he re l a t e d te r m s a n d condi t i o n s . N O W, T H E R E F O R E , t he P a r t i e s agre e a s f o l l o w s : 1 . D E F INI T I O N S 1 . 1 T his Agr e e m e n t s h all b e i n t e rp ret ed i n a c c o r d a n c e w i t h t he pro vi s i o ns on i n t e rp r e tat i on s e t out i n S c h e d u l e 1 (D e f i n i t i o n s & I n t e r p r e t a t i o n ) a n d ca p i t a l i zed w o rd s s h a ll h a v e t h e m e a n ing g i v e n t o th e m i n S c h e d u l e 1 ( D e f i n i t i o n s & I n t e r p r et at i o n ), unle s s t h e c o nt e x t r e q u i r e s ot h e r w i s e . 2 . S E R V I C E S . 2 . 1 S c o p e o f A g r e e m e n t . P ar t i e s t o c o n t r ac t f or mul t iple S t u d i e s th r o ugh t he i s s u a n c e o f mult i p l e W O s ( a s d e f i n e d b e l o w ) , w i t h o u t h a vi ng t o r e - n e g otiate t he b a s ic t e r m s and co n dit i o ns c o n t a i n e d h e r e i n . T h i s A g r e e m e n t co v e r s t he p r o v i s i on o f C R O s e r v i ce s b y I R O S t o C L I E N T a n d , a c co r di ng l y , thi s Ag r e e m e n t r e pre s e nts a v e hi c l e b y w h ic h C L I EN T can e f f i c i e n t l y co n t r a c t w i t h I R OS f o r C R O s e r v i ce s . 2 . 2 W o r k O r d e r s . T he s p e c i fic d e t a i l s of t he S e r v i c e s to b e p e r f o r m ed b y I R OS f o r ea c h S t u d y s h all be s epar a t e l y n e g o t i a t ed a n d s p ecifi ed in wr i t i ng on t e r m s a nd i n a fo r m a cce pt a ble t o the P a r ti e s ( ea c h s u c h WO , a f o r m of w hi ch i s a t t a c h e d a s S c h e du le 2 ( W or k O r d e r ) . Ea c h W O w i l l s e t o u t a s ap p ro pr i a t e , t he n a t u r e a n d s c o pe of w o r k, S t u dy - s p e c i f ic a ss u mpti on s , the s c h ed u l e of w ork t o b e p e r f o r m e d or S e r v i c e s t o be p rov id e d d u r i n g t h e c o ur s e of a S t u d y, t he I R O S P e r s o n n el, t he b u d g e t, th e r e le v a nt P r ot o c o l a n d t he p aym e nt s ch ed ul e, o r g a ni za t i on of f o l lo w - up a c t iv i tie s a n d /or , a s a pp l i c a b le, any o t h e r t e r m s r e qu i r ed f o r t he p e rfo r m a n c e o f t h e S e r vi c e s . W h e n a p pli c a b l e , e a c h WO s h a l l c o nt a i n a l i s t o f o b l i g a t i ons a n d r e s p o ns i bil i tie s b e i n g d e le g a t e d to I R OS i n c o nj u n c t i on w it h the r e le v a nt W O . On c e e x e c u t ed b y e a c h P a r t y, each WO s h a l l be s u bj e c t t o a ll o f t h e t e r m s and c o n d i t i o n s of th i s Ag r ee m e n t, i n a ddi ti on t o t h e s p e c ific d e tail s s et for t h i n t he W O . T o t he e x te n t a ny t e r m s or p ro vis i o ns of a W O co nf l i c t w i t h t he t er m s a n d p r o vi s i ons of thi s A g r ee m e nt , t h e ter m s and p r ov i s i o n s of t h i s Ag r ee m e n t s h a l l p r e v a i l , e x ce p t t o t h e e x t e nt t h at t he a p pl i c a b l e W O ex p r e s s l y a n d s p e c i fic a l l y s t a te s an inte n t t o s u per s e d e the A gr ee m e n t o n a s p e c ific m a t t er . 2 . 3 A W O s h all c o m m en ce a s of t he c omm e n ce m e nt d a t e, s e t f o rt h i n t h a t W O a n d s h a l l r e m a i n in for c e u nt i l t he c o mp l e t i o n of the S tudy or t h e ap p l i c a b le S e r vi c e s, unle s s t e r mi n a t ed e a rlie r a s pr o v i d e d f or i n Cl a u s e 2 6 . 2 . 4 E a ch WO s h a ll s t and al o ne w it h r esp e c t t o a ny o t h e r WO e n t e r e d und e r th i s Ag r e e m e nt . T he p e r fo r m a n c e of o bli g a tio n s u n d er a ny o n e W O sh a ll n ot a f f e c t, and s h a l l at a l l t im e s be u n r e l a t ed t o , the p er f or m a n c e of a n y o t h e r W O e n t e r ed i n t o u n d e r t his Agr e e m e n t . The e xpira t ion or ea rl y t e r m i n a t i o n of o n e WO s h a l l n o t ( u n l e s s e x p r e s s l y a gr e e d ot h e r w i s e by the P a rt i e s) im p a c t a n y o th e r W O , wh i ch s h all r e m a in i n f u ll f o r c e and e f f e ct . 2 . 5 N a t u r e of S e r v ic e s . T h e s er vi c e s c o v e r e d b y thi s A gr ee m e nt m ay i n c lu d e s t r a t e gic p lan n i n g, ex p ert co n s ultati on, c l i ni c a l t r i a l s e r vi c e s, r e g u l a to r y , p r oj e ct m a n a g em e n t and o t h e r r e s e ar c h a n d d ev el o p m e nt s e rv i ce s r eq u e s t e d b y C L I EN T and a g r ee d t o b y I R OS a s s et f o rt h i n t he r e l e v a n t W O( c o l l ecti v e l y, t he S e r vi c e s I R OS s h all r ep o r t on the p r o g r e ss o f e ach S t udy t o C L I EN T on a m o n th ly b a s i s or m o r e f re q u e n t l y w h e r e a g r eed i n a W O . I R O S r easo n a b le r equ e s t.
3 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N 2 . 6 C lie nt ' s A ut h o r i z a t i o n . A ny re s p o ns i b il i t i e s n o t e x p l i c it l y tr an s fe rred t o I R OS un d e r a s i g ned W O s ha ll r e m a i n t h e le ga l a nd r egu lat o r y r e s p o n s i b i l i t ie s of C l i en t . E xcep t a s o t h er w i s e a g r eed b y t h e P a rt i e s i n wr i t ing, Cli e nt is a nd a t a ll t i m e s r e m a i n s, i n a l l g e o gr a ph i c a l r e gi o n s w h e r e a S t u dy is b e ing p e rf o r m e d, 2 . 7 Cha n g e O r d e r s . 2.7 . 1 An y m a t er i a l chang e i n t h e de t a i l s o f a W O or t h e a s s u m p t ions s p e c if i e d i n t h e W O upon w h ic h the W O i s b a s e d ( i n c l u din g , but n ot l im i t e d t o , c h a n g e s i n a n a gr e e d s t ar ting d a te f or a S t u dy o r s u s p e n s i on of t h e S t udy by CL I EN T ) m ay r eq u i r e cha n ge s i n t h e b u d g e t an d / or t i m e l i n e s , and s h a l l r equ ir e a wr i t t en a m e n d m e n t t o th e W O i n t h e f orm o f a c h a n g e or de r ( ea c h , C O O s h a ll de t a i l t h e r e q ue s te d c han g e s to t h e a p p l i cab le ta s k, r e s p on s i b i li t y , d ut y, b udg e t, t i m e line a nd o t h e r m a t t e r s . Th e C O w ill b e come ef f ec t i ve upon t h e e x ecu t i on of th e C O by b o t h P a r t i e s (u n le ss s o m e ot h e r e f f ec t i v e da te i s s e t o u t i n w r i t i n g in the C O) , a nd I R O S s h a ll u s e rea s on abl e e ff o r ts to i m pl e m e n t the c h an g e s a s s o on a s i s r easo n a b l y p ra c tic a b l e . B o th P a rt i e s a g r e e to a c t i n go o d f a i t h and p r o m pt l y wh e n co n s i de ri ng a C O reque s te d by t h e o t h e r P a r t y . W i t h ou t l im it i ng t h e f o r eg o i n g : ( a ) CL I E N T ag r ee s t h a t it w i l l no t u n r e a s o nab l y w it hh o l d a pprova l of a C O , e ven i f it i n v o l v e s a f i x e d p r i c e c o n t r a c t , i f t h e p r o p o s ed c h a n g e s i n b u d g e t s or t i m e li ne s r e s u lt f rom m a t e r i a l ch a n ge s i n t h e a s s u m p ti ons u p o n wh i c h t h e i n i t i a l bud g et or t im eli ne s w e r e ba s e d, i n cl u d in g , bu t no t l i m i t e d t o, t h e a s s u m p t i o ns s et f or t h in t h e b u d g e t or t i m e l i n e s ; and ( b) I R OS ag r ee s t h at i t n o t h a v e t h e c a p a b i l i t y t o i m p le m e n t t h e change ; ( i i ) t h e c ha n g e wo uld pl ac e I R O S i n b r ea c h of l a w ; o r ( i i i ) th e pa rt i e s a r e u nab le t o a g r e e o n t h e b u d g e t and o t h e r c o m m e r c i al te r m s of t h e C O . 2.7 . 2 Su b ject t o Cla u se 2.7 . 3 , I R O S s ha l l n o t p e r f o r m o u t - o f - s cop e S e r v ic e s in t h e ab s e n c e of a n execu t ed C O . I R O S r e s e rv e s t h e ri gh t t o p o s tp o n e e f f ec t i ng m a t er i a l chan g e s i n th e S t u d y s co p e un t i l s u c h ti me a s th e P a r tie s a g re e t o a n d exe c u t e t h e c orr e s pond i ng C O , p r o vided t ha t any r ea s o n a b le c os t s in c u r r ed i n s o d o i n g a r e born e b y I R OS and a n y d e a d li ne s s p e c ifi ed can s t i l l b e m e t . For a n y C O t ha t af f ec t s t h e s c o p e of t h e re g u l a t or y o b l i gat i o ns t h at h a v e be e n t r a ns f e r re d t o I R O S , I R O S and C L I E N T s h all ex e cu te a co r r e s po n d i ng a m e n dm e n t to th e w r i t t e n transfe r of o b li ga t i ons s et o u t i n t h e a p p l i c a b le W O . 2.7 . 3 I R OS m u s t de v i a te f rom Cl a u s e s 2 . 7 i f a mo d i f i c a t ion r ea s o n a b ly in v o l ve s t h e s a f e t y of a h um an s u b je c t or t h e i n t e grit y of t h e S t u dy d at a , i n w h i ch c a se I R OS s h a l l q u i ck l y ac t o n th e r eq u e s te d ch a n ge , and w hen p r a c tica b l e , g i v e n o t i c e pro mp t l y t o CLIE N T by tel ep h o n e or e l ec tr o n i c c o m mu n i c a t io n t h a t such s c op e c h a n g e occ u r re d an d a C O m ay b e r e q u i r e d . CLIE N T a n d I R O S w i l l w o r k i n g ood f a i t h t o p r om p t l y e x e c u te t h e r e l eva n t C O . 3 . P E R S O NN EL 3 . 1 E ac h P a rt y s h a l l a p p o i n t : 3.1 . 1 a r e lati o n s h i p m ana g e r i n r e s p e c t o f t hi s A g r ee m ent , w ho sh a l l b e na m ed i n t h e Con tra c t P a r t i c u l a r s ; a n d 3.1 . 2 a p r o j ec t re p re s e n t a t iv e m a nage r f o r ea c h W O , w h ic h per s o n w i l l b e i d e n t ifi ed i n t h e ap p l i c a b le W O . T h e r e lati o n sh i p m an a g e r and t h e W O p r o ject r ep r e s e n t a t i v e , h o w e v e r, s h all n o t hav e a u t h o rit y t o co n t r a c t ua l l y b in d th e P a r t i e s i n t e r m s o f s i g n i n g a n y v a r i at i on t o t h i s Ag r e e m e n t or a ny W O o r C O . I R OS sha ll u s e re asona b l e e n d e a v o ur s t o en s ur e t h a t t h e s ame pe r s o ns ac t a s t h e I R O S r e l a t i o ns h i p m ana g e r and a s W O pro j e c t r e p r e s e n t a t i v e s t h r ou g h o u t t h e t e r m of t h i s A gr ee m en t o r t h e r e l e v a n t W Os, b u t m a y r e p l a c e s u c h pe r s o n s f rom t ime t o t i me w her e r ea s o n a bly nec e ss a r y in t h e i n t e r e s t s o f I R O S' b u s i ne s s .
4 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N 3 . 2 I R OS r ep r e s e n t s , w a r r an t s and u n d e rt a k e s t ha t: 3.2 . 1 i t s h all us e pe r s on n e l ( in c lud i n g w i t h o u t l imi t a ti on i nd e p e n d e n t con tr ac t o r s , c o n s u l t a nt s , e m p l o y e e s and a ge n t s ) a s i t dee m s nec e ss a r y t o p e r f o r m t h e S e r v i ce s t o t h e r e q u i s i t e s ta nd a r ds ( the I R O S P e r s o n n el w h o a r e a pp ro pr i a te ly tra in e d, qu a l i f i e d b y e d uc ati o n a n d e x p e r i en c e d t o p e r for m I R O S 's o bl i g atio n s un de r t his Ag r e e m ent . I R O S s h all be re s p o nsible f o r mo n i to r i ng t h e p e rfo r m a n c e o f s u ch pe r s onne l w ho a r e en g a ged i n t h e p erf or m anc e o f S e r v i c e s ; 3 .2 . 2 t he I R O S P e r s o nn e l h av e, a nd a t a l l t i m e s d u r i n g t he te rm of this A g r e e m e n t sh a l l h a v e , ap p ro pr i a t e l i c en s e s, approv a l s a nd c e r t i fi c atio n s nece s s a r y t o s a f e l y , a d e q u at e l y a nd la w f u l ly pe r fo r m t he i r o b l i ga t i o ns u nd e r th i s Ag re e m e n t and a n y W O ; and 3.2 . 3 I R OS s h all b e r e s p o n s i b l e f o r m o n it o r i n g t h e p e r f o r m a n c e a nd c o m p lia n c e w it h A pp li c a b l e L a w s of s u ch I R OS P e r s o nne l w ho a r e e n g ag e d in t h e p e r f o r m a n c e of S er v ic e s . 3 . 3 I R OS w i ll b e s o l e l y re s p o n s i b le f o r t h e w age s /f e e s and e m p l o ym en t r e lat ed lia b i l i t i e s a s s o c i a t ed w i th t h e e mplo y m e nt o f a ny I R O S P e rs o nn el wo r k i ng on the WOs . 4 . D E B A R M E N T 4 . 1 E ac h P a r t y r e pr e s en t s , w a r r a nt s a n d u n de rt ake s t ha t ne it he r i t n or any o f i t s r e s pec t i v e p e r s on n e l t ha t i t en g a g e s w h o ar e t o p e r f o r m any of it s ac t i v it i e s i n c o nn ecti on w i t h t h i s A gr ee m e n t ha v e b e e n ( i ) p r o h i b i t ed f r om p ro v i d i ng m e d ic a l o r cli n ic a l r e s ea r c h s e r v i c e s o r d eb arr ed by any G ove r n m en t a l Ent i t y of any k i nd i n a n y j u ri sd i c t i on or ( i i ) c onvi c t ed o f a c r ime for w h i c h a p e rson c a n b e proh i b it ed f ro m p r o v i d i n g m e dic a l or c l i n i ca l r e s e a r ch s e r v i c e s or d e ba r r e d i n a ny j ur i s di c t io n . 4 . 2 E ac h P a r t y al s o re pr e s e n t s , w arr a n t s and u n d e r t a k e s t ha t n eit he r it nor any of i t s r e s p ecti v e e m p l oye e s h a v e b e en (i ) t hr e a t en e d to b e d e b a r re d o r o t he r w i s e p r oh i bi t e d f ro m p r ov i d i ng m e d i c al o r c l i n i c al r e s e a rch s e r v i ce s b y any Go v er nm ent al E n ti t y of a n y k i n d i n a n y j u ri sd i c t i o n , or ( i i ) in d i c t ed f o r a c ri m e or o t he rw i se en g a g ed i n c o n d u ct fo r w h i ch a pe r s on can b e p ro h i b i t ed f r o m p r o v i d i ng m e d i ca l o r c l i nic a l r e s e a rch s e r v i ce s o r d e ba r re d u n de r a ny A p p l i ca b l e L a w s or r e g u l a t i on i n a ny j u ri sd i c t i on r e g u l a t i ng t h e pe r f o r m a n c e of S e r v i ce s re l a t i n g t o p h a r m a c e u t i c a l p r o d uc t s o r c l i n ical s tud i e s . 5 . A N T I - B R I B E R Y A N D A N TI - C O RR U P T I O N . 5 . 1 I n c ar r y i ng o u t i t s r e sp o ns i b i l i ti e s u n d e r t h i s A g r ee m e n t, n ei t he r P a rt y n o r a ny of i t s r e s pe c t i v e off i c er s, e m p l o y e e s , su b - co n t r a c t o r s , r e pr e s e n t a t i v e s or a g e n t s w ill p a y , o f f e r o r p r o m i s e t o p a y, or a uth o riz e t h e pa ym e n t o f, a ny m o n e y, o r g i v e or p r om i s e t o g i v e, o r a u t hor i z e t h e giv i ng o f, any s e r v ic e s o r a n y t h i ng e l s e of v a lu e , e i the r d ir ec t l y or t h r o u gh a t h i rd par t y, t o a ny o ff ic i a l o r e m p l o ye e o f a n y G o v e r n m e n t a l E n ti t y , or of any a g e n c y o r s u b d i v i s ion t he r e o f , or to a n y p o li t ic a l par t y or o f f i c ial t h e r e o f o r t o any cand i da te f o r p o l it i ca l off i c e c o r ru p t l y for t h e p u r p o s e of i m p r o pe r l y (i ) i nf l uenc i ng a ny a c t or d e c i s i on of t ha t person i n h i s off i c ia l c a p a c i t y, i nc l u d i ng a d e c i s i on t o f a il t o pe r fo r m h i s of fi c i a l f u nc t i o ns w i t h s u c h G o v e r n m e n t a l E n ti t y or su c h p o li t ic a l pa rt y, ( i i ) i n d u c i ng such pe r s o n t o us e h i s i nf l u e n c e w i t h s u ch G o v e r n m e n t a l En ti t y or su c h p o l it i ca l pa rt y t o a f f ect o r infl ue n c e a n y ac t o r d e c i s ion t h e r e o f , or ( ii i ) s ecur i ng a n y i m p r o p e r a d van t ag e . Ea c h P a r t y s h a ll r e p or t a n y vio l a t i on of i t s ob l ig a t i o ns u n de r Cl aus e 5 . 1 p r o mp t l y t o t h e o t he r P a r t y . 6 . C O OP E R A T I O N ; D I S C L O SU R E OF H A Z A R D S . 6 . 1 CLIE N T s h all f o r w ard t o I R O S i n a t i m e l y m a n n e r a ll d o c u m e n t s , m a t er i a l s a n d i n f or m a t i o n i n CL I EN T p o s s e s s i on or c o nt r o l r ea s o n a b l y n e ce s s a r y f or I R OS t o c o n d u ct t h e S e r v ic e s . CLIE N T s h a l l p r o v i d e I R OS w i t h a l l in f orm a t i on a v a i l ab le t o it r e g a r d i ng kno w n or p o t en tial haza r ds a s s o ci a t e d w it h t h e u s e of any su b s t a n c e s , i nc l u d i n g a n y S tudy D rug, or e q u i p m e n t s u ppl i ed t o I R OS or t o a n y S t u d y s i t e by CLIE N T , and CLIE N T s h a l l co m p l y w it h all A p p lica b l e La w s co n c e r n i ng t h e s h i p m e n t o f s u c h s u b s t ance s .
5 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N 6 . 2 CLIE N T sh a l l : 6.2 . 1 de l ive r a l l S tu d y D r u g s , e q u i p m en t or o t h e r c l i n i c a l s u p p lie s t ha t m ay b e r e q u i r e d f or a S t u d y and wh i ch C L I E N T ha s a g r e ed t o p r o v i d e p ur s ua n t to a Cl i n i c a l T ri a l A gr e e m e n t ( t h e ) t o e ach r e l evan t I ns t i t u ti on t i m e o us l y . 6.2 . 2 u s e a l l r easo n a b le e ff o rt s t o s u pp l y s u f f i c i e n t q u a n t i t i e s of t h e a p p lic ab le S tu d y S u p p l i e s a s n ece s s a ry t o c o n d uc t t h e S t udy s e t f or t h i n t h e W O . A ll ne ce s s a ry a p p r o v al s for th e im p o r t a ti on of s u c h d ru g s or e q u i p m en t in t o t h e Ter ritor y s h a ll b e o b tai n e d by C L I E N T ( a t i t s e x p e n s e) . 6 . 3 I n no e v e n t s h a l l any S t udy S u pp lie s b e u s ed by I R OS f o r a n y p u r pos e o t he r t h a n a s e xp r e s s l y s et f o r t h i n t h e a p pl i c abl e P r o t o c o l. 6 . 4 W ithin 6 0 ( s ixty) d a ys a f t e r t he c o m p le tion of a S t udy, I R O S w ill p r o vi de to CL I E N T a w r i t te n a c co u n t i n g of all cli n i c al s u pp lie s s u pp li ed by CLIE N T t o I R O S t o m a nag e w it h t h e I n s t it u t i o n ( s ) a s p a r t of t h e S t u d y S u p p l i e s . I R OS w ill u s e a l l r e a s onab le e f f o rt s t o r e t u r n or proc u r e t h e r e t u r n, of a l l u n used S tu d y S u p p l ie s p r o v i d e d by CLIE N T t o In s t i t u tio ns i n ac c o r da n c e w i th r e q ui r e m en t s i n th e a p p l i c a b le Cl i n i ca l T r i a l Agr ee m en t o r a s oth er wise inst r u ct e d b y CL I E N T . D ur i n g ea c h S t u dy, I R O S w ill p r ocu r e tha t t h e In s t i tu ti ons and I n v e s t i g at o r s m a i n t a in r eco r d s o f (i ) t h e d at e s a n d a mo u n t s of a l l S t u d y S u p p l i e s r ec ei v e d by I nve s t i g a t o r s ; ( i i ) t h e da te s, a m oun t s a nd s u b j ec t s t o w h om S tu d y D r ugs h a v e been d i s p e n s ed ; (i i i ) th e da t e s and a m o u n t of S t udy D r u gs s p i l l e d o r lo s t ; and ( i v ) th e da t e s and a m ou n t s of S tu d y Dr u gs be i ng re t u r n e d or d e s t ro y e d . 7 . D E L A Y S A N D E X TE N S I O N O F TI M E L I N E S . 7 . 1 I R OS i s n o t ac c o u n ta b le f or d el ays i n th e pe rf o r m a nc e of it s o b l i ga t i o ns un d e r t h i s A g r e e m en t or u n d e r a W O t o t h e e x te n t t ha t s u c h de l a y i s d u e s o l e l y to (i ) t h e a c tio n s , e r r or s o r o mi s s i o n s of a n y G o v e r n m e n t a l E n ti t y ; ( i i ) r e g u l a t o r y or ex t e r n al e t h ic s c o m m i tte e e nc u m br a n c e ; ( i i i ) S t udy e n r o l m e n t f or cli n ic a l s t ud i e s a t t h e S i t e s i f I R OS can p r o v i d e w ri t t e n ev i d e n c e t ha t i t ha s f u l l y p e r f o r m e d i t s S e r v i ce s r e l a t ed t o co n t ac t i n g a n d m a in t a i n i ng c o n t ac t w i t h I n s t i t ut i on s ; ( i v ) a s a c o n s equenc e of F or c e M a j eu r e ; o r ( v ) a s a r e s u l t o f any d el ay o r f a i l ur e by t h e C L I E N T t o pe rf or m a n y o f i t s o bl i ga t i o n s u n d e r t h i s Ag re e m e n t or any Cl i n i ca l Tr i a l A g r ee m e n t ac t i o n s or o mis s i o ns o f C L I E N T or a n y oth e r d i r e c t o r in d i r ec t c on t ro l, i nclu d i ng cha n ge s i n P r o t oc o l r e que s te d by I n v e s t i g at or s , R eg u l at o ry A u t h o r i t i e s , ex t e r n al e t h ic s c om m i t t e e s or f a i l u r e of CLIE N T t o t i m e l y p r ov i d e d o c u m e n t s, m a t e ri a l s o r i n f o r m a t i on or to o t h e r w i s e c o o p e r a te w i t h I R OS wh er e t h i s i s r easo n ab l y req u i r e d f o r I R OS t o t i m e l y a n d p r ope rl y p e r f or m t h e S e rv ice s i n ac c o r da n c e w it h th e t im e l i n e s d e s c r i b e d i n t h e a p p l i cab le W O . I n t h e eve n t o f a n y d e l ay a s co n t e m p l at e d u n de r t h i s Cl a u se 7 . 1 , I R OS sh all p r o v i d e n o t i c e t o C L IE N T a s s oon a s r e a sona b l y pr a c ti c a b le a n d u s e co mm e r ci a l ly r ea s o n a b le e f f or t s t o c o nt i n u e p e r f orm an c e of t h e S e rv i c e s n o t a f f ec t ed by s u c h d el ay i n ac c o r da n c e w it h t h i s A g r ee m e n t . 7 . 2 I n t h e e v e n t I R OS i s u na b l e t o co mp ly w it h i t s o b l ig a t i o n t o m e et any t i m el i n e s s e t ou t in a W O or Cli n ic a l T rial Ag r e e m e n t d u e s o l e l y t o CLIE N T f a i l u r e to p e r fo r m it s o b l i g ati o n s un d e r t h i s Ag re e m e n t or any C l i n i c a l T r i a l Ag r ee m e n t or i s d e l a y e d i n s u c h p er fo r m an c e , t h e t i m e l i n e s s e t o u t i n t h e W O s h all b e m o d i f i ed a s de s c r ib e d i n C l a us e 2 . 5 ( Chang e O rde r ) a n d ex t en d e d by t h e l eng t h of t h e d el a y , u n l e s s CLIE N T ag r ee s i n w ri t i ng t o pa y a n y a ddi t i o n a l c o s t s t h at w o u l d b e r e q u i r e d t o m ee t t h e or i g i na l tim e l i ne . I n a d d it i o n , C L I E N T w i ll p a y a l l n o n - cance l ab le cos t s and e x p e n s e s i ncu r r e d b y I R OS in ac c o r d a n c e w i t h t h e r e l e v a n t W O and any no n - can c e l ab le c os t s and ex p e n s e s i ncu r r ed by Su b c o n tra c to r s t ha t w i l l b e pa s s ed t h ro ugh t o I R O S, d u e t o s u c h de la y . I R OS s h all us e r ea s o nabl e e f f o r t s t o m i ti ga t e a n y lo s s e s a ri s i ng p u r s u a n t t o t h i s p a r a gr a p h . 7 . 3 S u bj e c t t o C l a u s e s 7 . 1 a nd 7 . 2, I R OS a ckn o w l e d g e s th at it sh all p r o v i d e th e S e r vi ce s i n ac c o r d a n c e w it h t h e de a dl i n e s spe cif i e d i n t h e W O or C O(s ) , or a s m a y b e su b s e q u e n t l y ag r e ed i n w ri t i ng by t h e P ar t i e s . 7 . 4 I f t h e P a rtie s agr e e i n w rit i ng to e x t e n d th e t i m e l i ne s s e t ou t i n W O , t h e P a rti e s w ill n e g o tiate i n g o od f a i t h t h e r e - ad j us t m en t of f e e s , i f a n y, in c o n s i de r a t i o n of t h e a g r eed re vi s e d dead li ne s and d o c u m e n t such ag r ee m en t i n a C O .
6 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N 7 . 5 I n t h e ev e n t t ha t any S tu d y i s p lac ed on ho l d fo r a p e r i o d o f t h i r t y ( 3 0 ) da y s or m or e f or r e a s o ns no t a t tr ib u ta b l e to I R OS or it s S u b c o n t ra c t o r s , CLIE N T w i ll c o m pen s a te I R OS f o r co s t s or e x pe n s e s i n c u r r e d f o r t h e pe r fo r m a n c e o f the S t u d y t h at c a n n ot r ea s o n a b l y be a v o i d e d or m i t ig a t e d i n c u r r e d during t h e hold p e r i o d i n a cc o r d a n c e w i t h t he W O . I f the d ela y i s lo n g e r t h a n t h i r t y ( 3 0 ) d a y s a n d t h e C L I E N T w i s h e s f o r any I R OS P er s o n n e l t o c o nt i n u e t o b e a l l o c at ed t o t h e S t u d y a nd p r o v i d e d th at I R OS h a s t h e s o l e d i s c r e t i o n t o ag r e e t o s u c h r eq u e s t (w h i c h w i l l no t b e u nr e a s ona b l y w i t hhe l d ) , t h e P a r t i e s s h a l l ne g o tiate a co mm e r c i a l l y r e a s o n a ble f e e to c ompe n s ate I R O S f o r th a t c o n t i n ue d allo ca t i o n , s h o u l d I R O S a g r e e to s u c h r e q ue s t . Such co mp e n s a t i o n s hal l b e s e t f ort h i n a C O . 8 . F O R C E M A J E U R E . 8 . 1 I n t h e e v e n t th at e i t h e r P a r ty sh a l l b e d e la y e d o r h i nde re d i n or p r e v en t e d f r o m th e p e r f o r m anc e o f a n y ac t r eq u ire d he r eun d e r a s a r e s u lt o f a Forc e M a je u r e E v e n t o cc u rr in g , t h e n p erf o r m a n c e o f s uch a ct s ha ll b e e xcu s e d for t h e pe ri od of s u c h de la y, p r o v i ded t ha t : 8.1 . 1 th e P a rt y cl a i m i n g F o r c e M a j e u r e n o t i f i e s th e o t he r P a rt y i n w r it i n g pro m p tl y on b e co mi n g a w a r e t h a t s u c h Fo rc e M a j e u r e E v en t h a s o c c u r r e d; 8 .1 . 2 t he P a r ty c l a i ming F o r c e M a j e u r e us e s re a so n a b le e f fo r t s t o m i tig a t e the e f f ec t s o f t h e F o r c e M aj e ur e Eve n t u pon t h e p erf or m anc e of i t s o b l ig a t i ons un d e r th i s Ag r ee m e n t a n d / or W O ; 8.1 . 3 w i th i n f i v e ( 5 ) ca l e n da r d a y s a f t e r t h e ce s s ati on of t h e Fo r c e M a j eu r e E ve n t , t h e P ar t y c l a imi ng F o r c e M a j e u r e n o t i f i e s th e o t he r P a r t y i n w r iti ng o f t h e ce s s a t ion o f th e F o r c e M aj e ur e E ven t a nd r e s u m e s p er f o r m a nc e of a ll i t s o b l i g a t io n s u n d e r t h i s Ag r ee m e n t ; and 8.1 . 4 th e P a rt i e s a g r e e a nd ackno w l e d g e t ha t fi nanc ial di ff i c u l t y s h all ne v e r b e dee m e d a F o rc e M aj e ur e Eve n t . 8 . 2 A n o n - af f ec t e d P ar t y s ha ll a l l ow t h e a f f ec t e d P ar t y a p e r i o d n o t exce e d i n g s i x t y ( 60 ) ca le n da r d a ys f r o m t h e da te o n w h i ch n o t i f i cati on of Fo r c e M a j eur e Eve n t i s r e c e ived b y t h e no n - a f fe c t e d P a rt y d u ri ng w h i c h t h e aff e c t ed P a r t y sha ll u s e re a s o nab le e n de a v o ur s t o m i t i g ate t h e e ffe c t of t h e F or c e M a j e u r e Ev e n t and t o ca rr y o u t i t s o b l i g ati o n s unde r t h i s A gr e e m e n t . I f su c h d e la y o r f a i l ur e p e r s i s t s for m o r e t han s i x t y ( 6 0 ) c a l e n da r days t hen t h e no n - a f fec t e d P a r t y m a y , i n i t s s o l e d i s c r e t i o n, t e r m i n ate t h i s A gr e e m e n t w i t h im m e d i a te e ffec t by w rit t e n n o t i c e t o t h e af f e ct e d P ar t y w it h o u t f urt he r lia b i l i t y t o e i t he r P a r t y, i n ac c o r da n c e w it h C l aus e 2 6 . 4 . 3 . 8 . 3 T h e corr e s pond i ng o b l i g a t ions o f t h e o t he r P a rt y w i l l b e s u spe n de d, a n d i t' s ti m e f o r pe rf o r m a n c e o f s uch o b l i g a t ions e x t ende d, t o t h e s a me e x t e n t a s t h os e of t h e P a rt y af f ec te d by t h e F or c e M a jeu r e E ve n t . 9 . V I S I T S A N D A UD I T S 9 . 1 T h e P arti e s a g r e e t ha t C L I E N T , i t s r e g ul a t o r s and th e i r ap p oin t ed re p r e s en t a t i v e s m ay v i s i t t h e S i t e s wh e r e t h e S t u d y i s be i ng c o n du c t e d . D u r ing t h e t e r m o f t h i s A g r ee m en t o n g i v i n g no t l e s s t han f o u r t een ( 1 4 ) da y s p r ior n o t i c e i n w rit i ng ( un l e ss s h o r t e r no t i c e i s requ ire d by a re g u l a t o r ) , C L I ENT , i t s r eg u l a to r s an d / o r th e i r s u i t ab l y q u ali f i e d r e p r e s en tati v e s m a y d u rin g r eg u l a r b u s in e ss h o u r s and at m u t ua l l y ag r eeab le t i m e s ( ea c h p a r ty a c t i n g r ea s o n a b l y ) , v i s it any s u c h S i t e w h e r e S e rv ic e s a r e be i ng p er for m e d or S t ud i e s a r e b e ing c o n d u c t ed i n o r d e r t o b e a s s u r ed t ha t s uch S e rv i c e s a n d / o r S t u d i e s co m p ly w i t h Ap p lic a b l e L a w s, i nc l u d i n g , a s a p p l i cab l e , Go od Cl i n i ca l P r ac t i ce s, t h i s Agr e e m e n t , a n d any C L I E N T s p e c i f ica t i o n s . A n y s uch i nspec t i on s ha ll b e f or t h e C L I E NT ' s ac c o u n t s av e t ha t I R OS s h a l l n o t b e e n ti t l e d t o re i mb u r s e m e n t of i t s o w n c o s t s incu r r e d i n p a r t i c i p ati ng i n a S i te v i s it i f s uch S i t e v i s it occu r s w it h i n t h e E mi ra te of Ab u D h a b i . I R O S s ha l l us e r ea s o n ab le e ff or t s t o pro c ur e ac c e ss t o a ny S i t e w h i c h m ay b e s u b ject t o an a u d it f or t h e p u r pos e s o f ena b l in g s u c h au d i t, a n d ag r ee s t o coop e ra te w i t h t h e a u d i to r s d u r i ng t h e p r oce s s . No t w i t h s t a n d i ng t h e f or go i n g , C L I E N T a ck n o w l e d ge s t h at a cce s s t o a n y S ite i s s u b j ec t t o t h e a p p r ova l a nd ac c e ss co n d i ti o ns of t h e t h ir d - pa r ty S i t e . 9 .
2 D ur i n g t h e ter m of t h i s A gre e m ent , CLIE N T or i t s s u i t ab l y q u a l if i e d re p r e s e n t a t i v e s h a l l h a v e th e r i g h t , no m o r e t h a n t w ic e a y e a r (u n le ss r eq u i r e d by a r eg u lato r ) , d u ri ng o rd i n ar y b us i ne ss hou r s a n d u pon f o u rt e e n ( 1 4 ) ca l e n da r days p r ior wr it t en n o t i c e ( u n l e s s s h o r t e r n o t i c e i s re q u i r e d b y a regu l a t o r ) , ga i n ac c e ss t o a n d au d it I R O S b o o k s , r e c o r ds and p r oced u r e s t ha t ar e re l e v a n t to 7 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N ( i ) v e r i fy c o m p l ia n c e w i th t h is A g r e e m e n t a nd a n y Ap p l i ca b le L a w s , ( iii) id e n t i f y o r i n v e s t i g a t e s u s pec t ed fr a u d , a n d / or ( i v) r e vi e w I R OS CLIE N T or i t s au d i to r s s h all p r o v id e a s pe c i f ic l i s t of d o c u m e n t s t h a t w i l l b e re q u e s t ed f o r t h e a u di t t o a l l ow I R O S to com p i le t h e r ec o r ds a n d c on te s t an y r eq uir e m e nt t h a t would b e i rr el e v a n t in the c o n te xt of s u c h a u di t . Th e c o s t s o f t h e a ud it i s th e re s pon s i b i li t y o f CL I EN T s a v e t ha t I R OS s h a l l no t b e e n t i t l ed t o r e i m b u r s e m en t of i t s o w n c o s t s i n c ur r ed i n pa rtici pa ti ng i n a n au d i t i f s u c h a u d i t o c c u r s r e m o t e l y o r w it h i n t h e E mi ra te o f Ab u Dh ab i u n l e ss th e r esu lt s o f s uch au d i t d i s c l o s e a m a t e r i a l v i o l at i o n of t h i s Agr e e m e n t or of a n y Ap p l i c a b l e La ws i n wh ic h c a s e I R OS s ha ll r ei m b u r s e C L I E N T f or i t s o w n re a so n a b le c o s t s a n d ex p e n s e s i n c urr e d . A ll i n fo r m ati on ob t a i n e d a s a r e s u lt of s u ch a u d it s h a l l b e C o n f i d e n t i a l In f o r m a t i o n t o t h e ex t en t s u c h i n f o r m a t ion m ay b e h e l d con f id e n t i a l l y u n de r A p p l i cab le L a w s . An y s u i t ab l y q u a l i f i ed r e p r e s e n ta tive a p p o i nt e d by for p ur p o s e s o f t h i s c l au s e 9 . 2 s h a ll b e s u bj e c t to c o n f i d e n t i a l ity o blig a t io n s no l e s s r e s tr i c t iv e t h a n t h os e s et f o rt h i n Cl au s e 1 7 w it h r esp e c t t o s u c h C o n f i d e n t i a l I n f o r m at i o n . 9 . 3 I R OS r e s e r v e s t h e r i g h t to l i m it d i s c l o s ur e of i t s p ro p r i et a r y i n f o r m a t i o n t o any th ir d - p a r t y C R O or p ha r m a ce ut i ca l d e v e l o p m e n t s e r v i ce s p r o v i d e r . 1 0 . S T A NDA R D S O F S E R VI C E S A N D R EG U L A T O R Y C O M P LI A N C E . 1 0 . 1 I R OS u n de rt ake s t ha t i t s S er v i c e s w i l l b e c o n d uc t e d i n c o m p l i anc e w it h t h e dead li ne s s e t ou t in t h e r e le v an t W O , G ood Cli n ic a l P r a ctic e s , t h e P r o t o c o l a nd Ap pli c a b l e L a w s r e le v an t t o t h e s c o p e o f wo r k en v i s a g e d unde r t h e app l i c a b l e W O . I n p a r t i cu l a r, I R O S s ha ll c omp l y w i t h, a n d s h all p r o c ur e t ha t I R OS P e r s o n n el co mp l y w it h, th e f oll o w i n g l eg i s l a t i o n , r eg u latio ns and g uid e l i n e s ( a s m a y b e a m en d e d f r o m t i me t o t im e ) i n t h e c o nduc t o f t h e S t u d ie s : 1. D O H S T A ND A R D O N H U M A N S U B J E CT R E S E A R C H ( D O H / QD / S D / H S R / 0 . 9 ) ; 2. D O H C o n s e n t G u i de l i n e ; a n d 10.1 . 3 Gu ide l ine s f or c o n d uc t i ng Cl in i c a l T ri a l w i t h inv e s t i g ati o n a l p r o d u ct s a n d m ed i c al dev i c e s ( M O H A P ) . 10.1 . 4 D O H Gu i d eli ne s for Co n d u c t i ng C l i n i c al T r i a l s w i t h I n ve s ti ga t i o n a l P rod u ct s and M e d ic a l D e v i ce s . 10.1 . 5 In t e r n ati o n a l C o u n c i l f o r H a r m on i s a t i o n of T echn ic a l R e q uir e m en t s f o r P ha r m ac eut i c a l s f o r Hum an U se G u i d e l i ne s f o r G ood Cl i n i c a l P r actic e E6 ( R 3 ) . and w i t h th e a dd iti ona l r e q u ire m en t s spec ifie d i n S c h e d u le 3 ( F D A R e q u i r e m e n t s ). 1 0 . 2 CLIE N T r ep r e s e n t s t h at it w i ll c o ope r a te i n go o d f a i t h w i t h I R OS i n ta k ing a ny ac t io n s t h a t I R OS r easo n a b l y b e l i e v e s a r e n e c e ss a r y f o r I R O S t o co mp l y w i t h t h e r e g u l a t o r y o b li ga t ions t h at h a v e b een t r a ns f e r re d t o I R OS and s h all u s e it s co m m e r c iall y rea s o n able e ff o rt s in t a k i n g s u c h a ctio ns . L i ke w i s e , I R OS r epr e s e n t s t ha t i t w i ll c o o p e r ate in good fa i t h w i t h CL I EN T i n t aking any ac t i o n s t ha t C L I E N T r easo n a b l y be l i e v e s ar e n e c e s s ary f or CLIE N T t o c o m p l y w it h re g u lat or y o b l i g a t i o n s re l a ted t o th e S e r v i c e s and s h all u s e i t s c o mm e rc i a l l y re a s o n a b l e eff o r t s i n t a k i ng s u c h a c t i o n s . 1 0 . 3 I R OS s h all i n f orm C L I E N T of a l l nec e s s a ry a m e n d m en t s t o t h e P r o t oc o l o r a n y de v i a t i o ns f r o m t h e P r o t oco l wh ic h a r e i m p e r at i v e t o a v o i d i m m ed i a t e d a n g e r t o t h e s u b j e ct s pro m p t l y on beco m i n g a w a r e o f t he se a m e n d m e n t s o r d e v i at i on s , a n d i m m ed i a t e l y t a k e a n y nece ss ary p r ec a u t i ons f o r th e p r o t e c t ion of a l l te s t su b je c t s . 1 0 . 4 I R OS ackn ow l ed g e s t h at any r ev i s i on t o t h e P r o t oc o l m u s t b e a p prov e d i n wr it ing b y CLIE N T and ap p ro v ed b y t h e r e le v an t Regu l a tory A u t ho ri t i e s b e fo r e a n y c han g e c a n b e m a d e t o t h e P r o t o c o l . 1 1 . R E P R E S E N T A T I O N S A N D W A R R A N TI E S 1 1 . 1 E ac h of C L I E N T a n d I R OS h e r e b y r e p r e s en t s, w arr an t s, and co v e nan t s t o t h e o t h e r at t h e E f f e ct i v e D a te and a s a t t h e e x ec u t i o n o f e a ch W O : 8 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N 1 1.
1 . 1 i t h a s the f ull r i g ht a nd a u t hor ity to e nt e r i n t o th i s Ag re e m e nt, a n d th a t n o c o n s e n t or au t h or i z at i o n no t ob t a i n e d p r i o r to th e E ff e c ti v e D a te a n d / or t h e d ate t h e r e l e v a n t W O i s execu t ed ( a s app lic a b l e) , i s n e c e s s a r y t o b e o b tai n e d ; an d i t i s n o t a w ar e o f a ny i m pe d i m en t w h ic h w o u ld su b s t a n t i a l l y imp a ir i t s a bil i t y to p e r f or m the t e r ms a n d c o n d i t i o ns imp o s e d on it by t h i s Ag r ee m e n t ; a nd 11.1 . 2 i t i s a c orp o r a t i o n val i d l y o r g a n iz ed u n d e r th e l a w s o f i t s i n c orpo r at i on a n d i s a u t ho r i ze d t o do bu s i n e s s t o t h e e x te n t n e c e s s a r y t o f u l f i ll it s o b l ig a t i o ns h e r e u nd e r . 1 1 . 2 CL I E N T r e p r e s e n t s a n d w a r r a n ts th a t it h a s o b t a i n e d or w i ll o b t a i n an y r eq u i re d c o n s e n t or a ut h or i z a t ion r eq u i re d by t h e approp ri a t e Re g u l a t ory A u t h o ri t y w it h r esp e c t t o t h e S tud y . 1 1 . 3 T he w a r r a n t ie s i n th i s Cl au se 1 1 s h all b e d e e m e d g i ve n a g a i n on t h e d a te the P ar tie s e x e c u te a W O . 1 2 . I N S PE C T I O N S. 1 2 . 1 D u r i ng t h e t er m o f this A g r ee m e n t, I R O S s h a l l n o t i fy C L I E N T p r omp t ly o n b ec o ming a ware of a ny ac t u a l or n o t ifi ed i ns p e c tio n of I R O S's p r e m i s e s or S i t e ( s) or i nq u i r y o r ac t i on by a ny Go ver n m e nt al E n t i t y wh e r e t ha t i ns p e c ti on, i n q u i r y or a cti on d i r e ct l y r e lat e s t o a S t u dy be i ng p e r f orm ed b y I R OS u n de r t h i s Ag r ee m e n t . I R OS s h all pr o m p t l y f u r n i s h c o p ie s o f a ll c o rr e sp o n d e n c e s, lette r s, n o t i fi c atio n s rel a t i n g t o s u c h ac t i o ns, i n sp e c t i o ns or i n q u i r ie s t ha t in v o l v e s uch S t u d y , and I R OS s h all p e r mit CL I E N T t o rev i e w and c o m m en t on r e s p o n s e s g i ven t o t h e G o v e rn m en t a l En ti t y p r i o r t o m a k i ng r espo n s e s . 1 2 . 2 I n t h e e ven t of a n i ns p e c t i on re q ue s t ed by a G ove r n m e n t a l E n t i ty a s pe r C l aus e 1 2 . 1 , I R OS s h a l l a r r a n g e ac c e ss t o t h e S i t e a n d t h e t h i r d p a rt y a n d s h all p e r mit s uch off i c er s t o c o py a n d v e r i f y a n y da ta r eco r ds and r e p o r t s i n I R O S . It i s un d e r s tood by t h e P a r t i e s t ha t i n t h e c a se o f a n y i n spec t ion o n S i t e , a n I R OS q u a l i t y a g e n t s ha ll b e pr e s en t . CLIE N T s h a l l hav e t h e r i g h t t o b e pr e s en t f o r and o b s e r v e a n y i n s p e c ti on r e l at e d to a ny S i t e ( o r o t h e r re l at e d v e n do r s) b y any Go v er n m en t al En t it y p ur po s e . 1 2 . 3 O n beco mi ng a w ar e o f any ac t i on ta k en by a n y G o v e rnm e n t E n t i t y t h at m a y a dv e r s el y im p a c t t h e S e r v i c e s i n a m a t e r i al m an n er , I R OS a g r ee s t o n ot if y C L I E N T a s s oo n a s r e a s o n a bly pr a c tic a b l e o f such a d ve r se im pac t ir r e spec t i v e o f w he t he r t h e a c t ion r e l a t e s di r ec t l y to a S t u dy be i ng p e r f o r m e d by I R OS u nd e r th i s Ag r ee m e n t . 1 3 . R E C O R D S A N D M A T E R I A L S . 1 3 . 1 I R OS s h a l l m ai n t a i n r e lev a n t R ec o r ds f o r a p e r i o d r e q u ire d by A pp l i cab le La w s a n d i n a c c o r d a n c e w i t h i t s o b l i ga t i o ns of c on f i d e n t i a l i t y a nd n o n - u s e i n t h i s Ag r e e m en t . S u c h r e c o r ds s ha ll b e m a i n t a i n e d i n a p r o p e r a n d orde r ed m a n n e r . C L I E N T s h all b e e n t it l ed to o b t ain co p i e s of any of th e Re c o r ds on r easo n a b le no t i c e i n wr it i n g , i nclu d i n g af t e r t e r mi n a ti on of t h i s Ag r ee m en t . 1 3 . 2 W it h o u t p r e j u d i c e t o C l a u se 26.1 1 . 2 , at t h e c o m p l e t i on of th e S e r v i ce s by I R O S , all m a t e r i a l s , i n f o r m at i on and a l l o t h e r d ata o w ned by C L I E NT , r e g a r dl e ss of t h e m et hod o f s t or ag e or r e t r i e v a l , s ha ll b e de l i v e red t o C L I E N T i n s u c h f or m a s i s t hen c u r r e n t l y i n t h e p o s s e ss i o n o f I R O S . A l t e rn a t i ve l y, a t CL I EN T w r i t t e n r e q ue s t , s u c h m at e ria l s a nd d a t a m ay b e r e tai n e d b y I R O S f o r CL I EN T f o r an ag r ee d - upon ti m e pe ri o d, or d i s p o s ed o f p ur s uan t to th e w r i t t en d i r e ct i ons of CL I EN T . C L I EN T s h a ll pay t h e r ea s o n a b le co s t s a ss oci a t ed w it h any o f t h e a b o v e o p t i o n s . 1 4 . C LI N I C A L T R I A L A GRE E M E N T S 1 4 . 1 T h e P a r tie s a gr e e t h at C l i n i c a l Tr i a l A g r ee m en t te mp lat e s sha ll b e u s e d b y t h e P ar t i e s wh e n co n t r a c t ing w it h I n s t it u t i o ns i n t h e Te rr i t o r y , u nl e ss e x pr e s s l y a g r e e d othe r w i s e and s p e ci f i ed i n a WO . 1 4 .
2 A s s e t f or t h i n a W O , I R O S ( a t it s c o s t ) m ay neg o t i a te t h e Cl i n i c a l Tr i a l Agr e e m e n t te r m s an d /or othe r S t u d y - t o p r o v i d e t im e l y f e edback i n c o n n e c t ion w i t h a n y s u c h n e g o t i a t i o n s, a n d I R OS sha ll n o t b e r e s p o n s i b l e 9 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N f o r a ny und u e d el a ys a t t r ibut a b le to C LI E N T ' s fa i lure to p r ov i de a p p r o v a l s a nd tim e ly r e s p o n s e s . I R O S m u s t s ecu r e C L I E N T a p pro v a l of a l l C l in i c a l T rial A g r e e m e n t s p ri or to e x e c u t i o n. 1 5 . P A Y M E N T OF FE E S AN D E X P E N S E S . 1 5 . 1 I n c on s i d e r a t ion for t he p er f o r m an c e o f t h e Se r vi c e s b y I R O S i n a cc ord a n c e w ith t h is A g r e e m en t a nd t h e r e le v an t W O , C L I EN T w i l l p ay I R OS f o r f ee s, e x pe n s e s a nd p a ss - t h r o ugh e x p e nse s in a cco r dan c e w i t h t h e b udge t a n d p a y m e n t s c h e du le c o nt a i n e d i n each W O or a s s oc i a t ed C O . U n l e s s o t h e r w i s e a g r eed i n a p a r t i c u l a r W O , the f o l lowing s h a ll a p p l y : ( i ) I R O S w i l l invoi c e C L I E N T monthly fo r t h e f ee s , e xp e n s e s and pa s s - th r o u g h exp e n s e s ( s u bj ect t o c l a u s e 1 5 . 2 ) inc u r r ed i n p e r fo r m i n g t h e S e r v i ce s ; a n d, ( i i ) CLIE N T s h a l l p a y e ach in v o i c e w i th i n t hi rt y ( 30 ) d a y s o f t h e d a t e o f r ece i p t o f s u c h i n v oic e . 1 5 . 2 F o r t h e a v o i da n c e o f dou b t th e CLIE N T w i ll b e s o l e l y r e s p on s i b l e f o r m ak i ng d ir ec t p a ym e n t of a n y f ee s , ex p e n s e s o r o t h e r c o s t s t ha t ar e paya b l e t o a n I n s t it u t i o n u nde r a C l i n i c al T r i a l A gr e e m en t t o e ach s u c h I n s t i t ut i o n , s av e wh e r e ex p r e s s l y agr e ed o t he r w i se u n d e r a W O . I R O S s h a l l hav e n o lia b i li t y for a n y f a i l u r e by C L I E N T t o m ak e p a ym e n t s t o I n s t it u t i o ns u n d e r e ach C l in i c a l T rial A g r e e m e n t . Each Cl in i c a l T r ial A g r ee m e n t s h all c ont a i n a stat e m e nt t o th a t e ffe c t . 1 5 . 3 A ll su m s p a y a b le t o I R OS u nd e r th i s A g r e e m e n t : 15.3 . 1 ar e e xc l us i v e of V A T , eq u i v a l e n t s a l e s t ax or a ny ot h e r ta xe s, cha r g e s , l e v i e s a ss e s s m en t s and o t he r f ee s of a n y k i n d i m p osed on th e S e rv i ce s and C L I E N T s h a l l i n a d d it i o n p a y an a m o u n t e q ua l t o a ny V A T ch ar g e a b le on t h os e su m s o n de l i v e r y of a V A T i n v o i ce ; and 15.3 . 2 s h all b e p a id i n f u ll w i t h o u t a n y s et - off , coun t e r c l a im , d e du cti on o r w i t h h o l d i n g (o t h e r th an any d e d u c t ion o r w i t h h o l d i ng o f t ax a s r e q u i r e d by A pp l i ca b le La w s ). 1 5 . 4 W it h o u t p r e j u d i c e t o any o t he r ri g h t or re m e dy t ha t i t m a y h a ve , i f C L I E N T f a i l s t o p a y : 15.4 . 1 I R OS a n y s u m d u e unde r a n y W O on t h e d u e d at e : ( i ) a nd CLIE N T h a s s t i l l n o t m a d e pa ym e n t w it h i n th irt y ( 30 ) d a ys of a w ri t t en re m i n d e r f r o m I R O S t o m ak e pay m e n t , I R OS m ay s u s pend t h e S e r vic e s u n d e r th e r e l e v a n t W O u n t i l p a y m e n t ha s be e n m ad e i n f u l l ; a n d ( i i ) CL I EN T s ha l l p ay i n t e r e s t o n t h e o v er d u e su m fr o m th e du e da t e u n t il p a y m e n t of t h e o v e rd u e s u m , wh et h e r b e f or e or af t e r j udg m en t . I n t e r e s t unde r t h i s cl a u se w ill ac cr u e ea c h d ay at 2 % a y e a r a b o v e t h e C e n t r a l B ank of t h e U A E ' s b a s e r a te fr o m time t o t im e, b u t at 2 % a y ea r f or any pe r i od w h e n t h at b a se r a te i s be l ow 0 % ; and /o r 15.4 . 2 an I n s t i t u ti on i n a c c o r d a n c e w it h t h e t e r m s of t h e a p pl i c a b l e Cl i n i ca l T ri a l A g r e e m e n t , I R OS m ay s u spe n d th e S e r v i c e s und e r t h e rel eva n t W O i n r e s p e c t of such I n s t i t ut i o n , u n t i l p a y m e n t ha s been m a d e i n f u l l . 1 5 . 5 I f CLIE N T i n good fa i t h w i she s t o d i s p u te an i nvo ic e i s s u e d un d e r th e t e r m s of t hi s A g re e m e n t a n d t h e ap p l i c a b le W O , CLIE N T s h all n ot i f y I R OS of any d i s p u t ed a m o u nt s w i t h i n t en ( 1 0 ) days of t h e da t e of D i s p ut e No t i c e CLIE N T d i s p u t e s o n l y a p o r t i on of a n in v o i c e/ p a ym e n t r eq u e s t, t hen t h e CLIE N T s h all p a y t h e u n d i s p u t ed a m o u n t s a s i n a cco r danc e w it h t h e te r m s of t h i s Ag r ee m e n t a n d t h e a pp lic a b l e W O and t h e P a r t i e s s h a l l u s e g ood f a i t h e f fo r t s t o r e c o nc i l e t h e d i s p u te d a m o u n t a s s o o n a s te a m s w i ll u se g ood f ait h e f fo r t s t o re s o l v e such d i s p u te w i t h i n t en (10) d a ys of t h e da te of C L I E N T ' s D i s p u te No t i ce . T h e P a rt i e s a g r e e t ha t t h e r e s u l t o f t h e se d i s cu s s i o ns w i l l b e b i nd i ng o n bo t h P a r t i e s. I f no a g ree m e n t c an b e r ea c h e d by th e p a r tie s i n r el a t i on t o CLIE NT ' s D i s p u te No t i ce , c l au s e 36.3 of t h i s Ag r ee m e n t w i ll a p p l y. 1 5 . 6 Up on t h e rea s o n a b le re q ue s t o f I R O S , C L I E N T agr e e s t o p r o m p t l y p r ov i d e w r it t en a s s u r anc e t ha t CL IE N T i s i n p os s e s s i o n of t h e fi n a n ci a l re sourc e s s u ff i c i e n t t o m ee t a ll an tici pa t ed fi na n c i a l o bl i ga t i o n s t o c om ple t e t h e S tu d y a n d t o de m o n s trate i t s fi n a nc ial a b i l i t y t o m ee t i t s f in a nci a l o b l iga t i ons u n d e r t h i s Ag r ee m e n t and e ach W O . A ny f i na n ci a l s t a t e m en t s o r o t h e r i n f orm a t io n p ro v i ded t o I R OS u n de r t h i s C l a u s e s h all b e k e p t co n fi d e n t i a l .
10 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 1 6 . F O R EI G N C U R R E N C Y E X C H A N GE 1 6 . 1 T h e c u r r e n c y t o b e us e d f o r in v o ic e a nd p ay m e n t s ha ll b e th e c u r r e n c y s tat ed i n t h e W O . 1 7 . C O N F I D E N T I A L I T Y . 1 7 . 1 E ac h Par t y un d e r t a k e s to t he o th e r P a r ty t o t r ea t a s c onf i d e n ti a l a l l Conf id e ntial I n f o r m ati o n p r o vi d e d to t ha t P a rt y by a n y o t h e r P a r t y . A P art y sh a l l n o t di s c l o se any C o nf i d e n t i a l I n f or m a t i on it r e c ei v e s f rom t h e o t h e r P a r t y un d e r t h i s A g re e m e n t , u nl e ss oth e r w i s e agr e ed b y t h e o t he r P ar t y or a s p e r mit t ed unde r this Cl au se 1 7 . 1 7 . 2 W h e n CLIE N T i s ac t i n g in th e c o n t ex t o f a S tu d y o n b e ha l f o f a th ir d par t y en ti t y w ho s e p r oduc t i s t h e s u b ject of t h e S t u dy, C L I EN T s h all hav e th e r i g h t t o d i s c l os e any C o n f i d e n t i a l In f o r m a t i o n r e ce i v ed f r o m I R OS u n de r t h i s A gre e m en t a n d / or a W O , t o t h e e x t en t n e c e s s a ry f or t h e purp o s e s o f t h e co n d u ct of t h e S tu d y, an d pr ovid e d th a t su c h e nti t y is m a d e a w a r e o f s u c h c o n f i d e n t i a l i ty o b l ig a t i ons a n d is b o u nd by s i mi l a r c o nf i d e n t i a l i t y obl i g a t i o n s t ow a r d s CLIE N T . 1 7 . 3 T o t h e e x t en t t ha t a ny C o n f i d e n t i a l In f o r m a t i o n i s requ ir ed t o b e d i s c l o s ed b y Ap p lic a b l e L a ws , r eg u l at i o n or a n y g o ve r n m e n tal or co m p et e n t r e g ula t o r y a uth o ri t y ( i n cl u d i ng any s e c u r i t i e s e x c han g e ) , a P ar t y m a y d i s c l o s e s u c h Co nf i den tial I n fo r m a t i on p r o v i d e d t ha t, t o t h e e x te n t re a s ona b l y pr a c tic a b l e and l e g a l l y p e r m i s s i b l e , t h e P a r t y req u ire d t o m a k e such d i s c l os ur e s h a ll c o n s u lt i n a d vanc e w it h ( a n d ta k e i n to ac c o u n t th e r ea s o n a b le r e q ue s t s o f ) t h e o t he r P a rt y on t h e p r opo s e d f o r m , t i mi ng, con te n t and p u r p o s e of t h e d i s cl o su r e . 1 7 . 4 E ac h P a rt y u n de r t a k e s t o : 17.4 . 1 di s c l os e t h e o t he r P a r t y's Co n f i d e n t i a l In fo r m a t i o n o n l y to t h os e o f i t s o f f i c e r s , e m p l o ye e s, age n t s , co n s ul t a n t s , p r o f e s s i ona l a d v i sor s, A f f i liat e s and c o n tr ac t o r s t o w h o m and t o t h e ex t en t to wh i c h such d i s c l os ur e i s ne ce s s a ry f o r t h e pu r po s e s co n t e m p l a te d unde r thi s Ag r ee m e n t, and p ro v i d e d t h a t s uch pe r s o ns a r e u n de r a s i m ila r o b li ga t i on of conf i de n t i a l ity ; 17.4 . 2 p r ocu r e tha t s uch pe r s o n s a r e m ad e a w a r e o f t h e o b l i ga t i o ns u n de r t h i s C l a u se 1 7 ; a n d 17.4 . 3 b e r e s p on s i b l e f o r all ac t s a n d o mi s s i o n s of s u c h p er s o n s w ho a r e g i v e n a cce s s t o t h e C o n fi dent i a l In f o r m a t i on a s tho u g h t hey w er e i t s o w n ac t s or o m i ss io n s u n de r t h i s Ag r ee m e n t . 1 7 . 5 T h i s C l a u s e 1 7 s h all n o t a p ply t o a n y i n f o r m a t i o n wh ic h : 17.5 . 1 a t t h e t i me of it s d i s c l o s u r e b y ( o r on beha l f o f ) a P a r t y i s i n, or s u b s e q u e n t l y c om e s i n t o, th e p u b l i c do m a i n , e x c e p t th r o ugh b r e ach o f a ny o f t h e un d e r ta k i n gs s et o u t i n t h i s Agr ee m e n t; 17.5 . 2 i s a lr eady i n t h e l a w f u l p os s e s s ion of a P a r t y , a s e v i denced by wr i t t en d o c u m e nt a t ion m a i n tai ned pri or t o t h e d i s c l o s u r e of t h e Co n f i den t i a l I n f o r m ati on or w h i ch i s i n d e p e n d e n t l y d i s co v e r ed by a P ar t y, a f t e r t h e da te h e r eo f, w i thou t t h e ai d, a p p lic a t i on, or u s e of t h e C o n fi dent i a l I n f o r m a t i o n o f t h e o t h e r P a r t y , a s ev i denc e d b y w r i tte n r ec o r d s ; o r 17.5 . 3 s u bs e q u e n t l y c om e s l a wf u l ly i n t o t h e p o s s e s s i on of a P a r t y fro m a t h i rd p a r t y w h o d oe s no t o w e th e d i s c l o s i ng P a r t y an o bli ga t i on of con fi denc e i n r el a t i o n t o it a n d w h o d i d n o t o b ta i n 1 7 . 6 W it h o u t af f ec t i n g a n y oth e r r i g h t s or r e m e d i e s t h a t a P a r t y m ay ha v e, e ach P a r ty ackno w l ed g e s t ha t t h e o t he r P a r t y m ay b e i r r e p ar a bl y h ar m e d b y any b r e a c h of it s t e r m s a n d t ha t d a m a g e s al o n e m a y no t nece s s a r i l y b e an a d e q ua te re m e dy . A c c ord i ng l y, each P a r t y a c k n ow le dge s ( w i t h o u t p r o of o f a c t u al da m a g e s ) t ha t i n j u nc t i v e r e l i e f , s pec if i c per f o r m a n c e o r o t h e r eq u i t ab le r e l i e f i n fa v o r of th e o t he r P a rt y t he r eof m a y b e a n a p p r o pr i a t e a n d nec e ss a ry r e m edy fo r an y t h r ea te n e d or a c t u a l br e ach of t h e t er m s o f t h i s Cl a u se 1 7 .
11 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 1 7 . 7 T h e c o n f i d e n tiali t y o b l i g ati ons u n d e r t hi s Cl a u se 1 7 s h all s u r viv e t h e ex p i r y or ea r l y t e r m i na t i o n of t hi s Ag r ee m e n t f or a p e r i od o f f i v e ( 5) y ea r s a fte r exp ir y o r t e r m i n ati on o f t h e la s t W O . 1 8 . P U B L I C A T IO N . 1 8 . 1 S tu d y r e sults m a y n ot be pu b l i s h e d or r e f er re d t o , in w h ole or i n p a r t, by I R O S w ith o ut the pr i o r e xp r e s s w r i t t e n c o nse n t o f CLIE N T . N e i t h e r P a rt y w ill u s e th e o t he r P p u b l i c a t i o n o r p r o m o tio n w i t h o u t t h e o t h e r P 1 8 . 2 N e i t he r Pa r t y s h a l l b e p e r m i tt e d to i ss u e a ny in f o r m a t i o n o r s t a t e m e n t to t h e pr e s s or p u b lic r e l a ting to t he i r c o l l ab o r a t i on i n t h e c o n te x t of t h e A g r ee m en t w it ho u t pr i or r e v ie w a n d wr i t t en a p p r ova l o f t h e oth e r P a r t y, wh i ch co n s en t s h all n o t b e un r e asona b l y w i thh e l d . 1 8 . 3 N e i t h e r P a rt y sh a l l b e p e r m i tte d t o u s e t h e n a m e s o r l o g o s o f t h e o t h e r P a r ty i n a ny p u b l i c i t y , a d v er t i s i ng or n e w s r el ea s e, i n r e la tion to a S t u dy o t he r s o ci a l m e d i a w i t h o u t t h e p ri o r c o n s e n t of t h e oth e r P ar t y , wh ic h co n s e n t s h all n o t b e u n r ea s o nab l y w it h h el d. 1 9 . O W N E R S H I P OF I N T E LL E C T U A L P R O P E R T Y A N D D A T A . 1 9 . 1 T h e Ba ck g r o und I P of e a c h P a r ty i s a nd s h all r e m a i n t h e p r o p e rt y of th at P a rt y or i t s Af f i l i a te s or t h i r d p a rt y l i ce n sor s, a s a p pl i c ab l e . Excep t a s s e t o u t i n t h i s A g r e e m e n t , nei t h e r P a r t y, n o r a n y o f i t s A f f i l i a te s , . 1 9 . 2 A ll m at e r ia l s, d o c um e n t s , i n f or m a t i o n a nd da t a , i n c l u d in g G e nera t e d D at a, s u pp li ed t o I R O S by C LIE N T or g e n e r a t ed on b e h al f of C L I E N T i n t h e p e rfor m a n c e o f t h e S e rv i c e s u n d e r t h i s A g r e e m e n t ( ) w ill b e t h e s o le a nd exc l us i v e p r oper t y o f t h e C L I E N T . CLIE N T : 19.2 . 1 i s r e q ui r ed t o ob t a i n a l l a p p li c a b l e l i c e n s e s r e l a t ed t o a n y s c a le , a s s e s s m en t, q u e s t i o nna i r e , m ea s ur e or simi l a r i ns tr u m e n t t ha t C L I EN T r e q u e s t s I R OS t o u s e f o r a n y S t ud y ; 19.2 . 2 g r a n t s t o I R OS a no n - exc l u s i ve , r o ya l t y - f r e e lic e n s e, w i t h a r i g h t t o su b l i cens e t o I R O S A ff i l i a t e s , I R OS P e r s o n n el and Sub c o n t rac t o r s , t o u se C LIE N T B a c k g r ou n d I P , C L I E N T P r o p e r t y a n d Re s e a r c h I P to t h e ext e n t need e d t o a ll ow IR O S t o p e r f o r m t h e S e r v ic e s a n d exe r c i se a n y o t h e r r ig h t s o r p erf o r m a ny o t h e r o b l i g ati ons u n d e r t h i s A gr e e m ent . 1 9 . 3 I R OS s h all p r o m p tl y di s c l os e t o C L I EN T a n y I n t e l l ec t u a l P r oper t y or ( i i ) C L I EN T P r ope r t y , in e a ch c a s e wh ic h w a s co n c e i v e d or g e n era t ed by I R O S , I R O S P e r s o n ne l or S u bco n tra c t o r s w h ile p ro v i d i n g t h e S e r v i c e s unde r t hi s A g r e e m e n t or b y I n s t i t ut i ons i n pa r t i c i p ati ng i n a S t u d y ( t h e ) . T h e re f o r e , i n co n s ide r a t i o n of t h e p a y m en t of t h e f ee s u n de r t h e r e l eva n t W O , I R O S he r eby exc l u s ive l y a s s i g n s to CLIE N T , wor l d w ide , and f or any pu r pos e w ha t soeve r, a ll Re s e a r c h I P w it h e f f e c t f rom it s c r ea t i o n , f or t h e e n t i r e d ura t i on o f such In t e l l e c t u a l P r o p e r t y Ri g h t s, a n d u n der t ak e s t o pe r f o r m , a t a l l ac t s d ee m e d n e ce s s a r y o r de s ir ab le b y C L I E N T or it s s ucce s s o r s to pe r mit a nd a s s i s t i t i n o b t a i n i ng a n d e nf o r c i n g t h e f ul l b e n efi t s, e n j o y m e n t , r i gh t s a n d t i t l e t h r oug h o u t t h e w or l d i n s u ch In telle c t ua l P r o pe r t y, i n c l u d i n r eq u e s t . Dur i ng a n y p e r io d i n w h i ch s u ch a s s i g n m e n t o f f u t ur e In t e l l e c t u a l P r ope r ty i s n o t ef fe c t i v e p ur s u a n t t o a p p l i c a b le l a w , t h e I R O S s h a ll l i c e n c e t h e u se of s uch I n t e l l e ctu al P r o p e r ty t o C LIE N T o n a wo r ld w i d e , exc l u s i ve , pe r pe t u al, s u b lic e n s a b le and r o y a l t y - f r e e b a s i s . 1 9 . 4 1 9 . 5 I R OS r e pr e s en t s and w a rr a n t s t ha t t h e R e s ea rch I P be i ng c r e a t ed by I R OS P e r s o nnel , S u b co n t r ac t or s a nd I n s t i t ut i ons u n de r t h i s A g r e e m ent , a r e or s h all b e a s s i g n e d to I R OS on w r i t t en t e r m s ve s ti ng o w ne r s h i p of t h e R e s ea r ch I P to I R OS ( and l i c ensed t o I R O S d ur in g a n y pe r i o d i n w h i c h s uch a s s i g n m e n t i s i ne f fe c t i v e ) , s o a s no t t o l i mit t h e In telle c t ua l P ro p e r t y a s s i g n e d an d /or l i c e n s ed t o CLIE N T p ur s u a n t t o 1 9 . 4 . 1 9 .
6 No t w i t h s t a n d i ng t h e f o r e g o i n g , t h e C L I E N T ac k n o w le d g e s t ha t I R O S B a c k g r o u n d I P , i n cl ud i ng ana l y tic a l m e t h o d s , p r o c e d ure s a n d t e c h n i q ue s , co m pu t e r te c h n i c a l e x p e r t i s e, ha r d w ar e and sof t w a r e , 12 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N m a y be u s e d i n t h e c ou r se of p r ovid i n g t h e S e r v i ce s . To t he e x t e n t s u c h I R O S Ba c k g ro u nd I P is u s e d , im p ro v e d o r m od i f ie d by IR OS u n de r o r du r ing t h e t e r m o f th i s Agr e e m e n t , s uch im pro v e m e n t s o r m o d i f i ca t i o ns s h all b e d ee m ed t o b e I R O S Back g r ound I P . F or t h e av o i d a n c e of d o u b t : 1 9. 6 . 1 s t i t l e in a n y d e l i v e ra bl e s s t emming fr om t he S e r vi c es, a nd a ny r ig h t s in I nt e l l e c t u a l P ro pe r t y e m bo d i e d i n t h e d e l iv e r a b l e s, sha ll n o t ex t end t o a n y I R OS B a c k g r o u n d I P i nc l u ded i n s u c h d eli ver a b l e s b y i mp l i c ati on or o t he r w i s e . W i t h r e s p ect t o s u ch I R O S B a c k g ro und I P , I R OS g r a n t s th e CLIE N T a n o n - e xc l us i ve , n o n - t r a nsf e r a b l e l i c e n se t o us e the I R O S Ba ck g r o u n d I P to t he ex t en t n ec e s s a ry t o m a k e u s e o f su c h de l iv e r ab l e s a nd to a l l o w us e of s u c h d eli v er ab l e s by t hi r d pa r t i e s p ro v i ded th at a ll u s a g e r e m a i n s in ac c o r da n c e w it h t h e t e r m s o f t hi s A g r e e m e n t ( a s a p p l i c a b l e ) a nd in c o m p l i anc e w it h all a p p lica b l e la w s ; a nd 19.6 . 2 n o t h i ng in t h i s C l aus e 1 9 s h all b e c o n s t ru e d so a s t o prev e n t I R O S fr o m u s i ng i t s kn ow - h o w g e n e r at ed d uri ng t h e per f o r m a nc e of t h e S e rv i ce s i n t h e f u r t h e r anc e o f i t s nor m a l ac t i v it i e s , P r o p e r t y or C o n fi d e n t i a l I n f o r m a t i o n. 2 0 . I N SU R A N C E . 2 0 . 1 I R OS m u s t s e c u r e a n d m a i n t a in i n fu ll f o r c e and e f f e c t t h ro ugh o u t t h e t e r m of ea c h W O ge n e r al a n d p r o f e s s i o n a l l i ab il i t y co v e ra g e of a m o u n t s i n a cc o r d a n c e w it h ge n e r all y a cc e p t ed s t a n d a r d s by C R O s, t o co v e r a l l l os s e s , d a m a g e , li a bil i t y o r co s t s w i t h r e s pec t t o wh i ch it i s lia b le u n d e r t h i s Ag r ee m e n t . I f CLIE N T s o r eque s t s i n wr it i n g, bu t n o m o r e f r e q u e nt l y t h a n onc e e v e r y t w e l v e ( 1 2 ) m o n t h s , I R OS w i l l p r odu c e a c e r t if i ca te o f i n s u r a n c e f or r ev i e w or s uch oth e r d ocu m e n t e v i d e nc i ng t h at i t ha s ade q ua t e co v e r a g e c on s i s t en t w it h h u m a n c l in i c a l trial i n d u s t ry s t an d a rds t o co v e r i t s o b l i g atio n s he re u n d e r , a n d i n no e v e n t l e s s t han th e mi n i m u m a mo u n t o f i n sur a n c e r e q ui re d by A p p l i cab le La w . 2 0 . 2 CLIE N T or t h e t h ir d pa r ty en ti ty o n be h al f of w h i ch t h e S t u dy i s c o n d uc t e d m u s t s e c u r e a n d m a i n t a i n i n f u l l for c e and e f fe c t t hro u g ho ut t h e te r m of ea c h S t ud y , and w i t h a r e p u ta b le in s ur e r , a n i n s u r a n c e p o l i c y t o c o v e r a n y i n jur y o r d a m a g e s s uff e r e d b y S tu d y s ub j ec t s r e s u l t i n g f r o m t h e p e rf o r m anc e o f t h e S tu d y w it h r e s pec t to wh i ch th e s p o n s o r i s l i ab le u n d e r t h i s Agr e e m e n t , of a mo u n t s i n a cc or d a nc e w i t h Ap p lic a b l e L a w s and g e n e r a ll y acc e p te d s t an d a r ds f o r sp o n s or s i n c o n n e c t ion w it h th e ad mi n i s t r ati on o f i nve s t i ga t i o na l c o m poun d s or cli ni c a l t r i a l s . Such i ns u r anc e sha ll n o t c o n t a i n e x c l u s i ons t ha t wo uld p r e c l u d e c l a i m s b y p a r t i c ip a t i n g S t u d y s u bj e c t s wh ic h a r i se f r o m th e S t u d y i n r el a t ion t o t h e i nve s t i ga t i o na l p ro d uc t, w h e r e t h e S t u d y p a r t i c i p a n t h a s r ea s o na b l y c o m p l i ed w i th t h e P r o t o co l . 2 0 . 3 W it h o u t l i mit i n g t h e g e n e r ali ty o f t h e f oreg o i n g C L I EN T s ha l l m a i n t a in f or t h e t e r m o f t h i s A gr e e m en t and for a p e r i o d of 3 (t hre e ) y e a r s f r om t h e e x p ir a t io n or t e r m i na t i o n o f t h e l a s t WO , c l i n i c al t r i a l l i ab il i t y or p ro d uct s l i a b i l i t y i ns u r anc e w i t h co v e r a g e e q ua l t o t h e g re a t e r of : ( i ) n o t l e s s th a n $ 1 0 , 00 0 , 0 0 0 U S D p e r occurr e nce /a g g r e g at e , ( i i ) t h e s ta t u t o ri ly m a n da t ed c o ve r ag e a n d ( ii i ) t h e m i n i m u m a mo u n t o f i ns u r anc e cove r ag e d i c t a t e d by a n y e t h ic s c omm i t t e e or in depen d en t r e v i e w b o a r d . 2 0 . 4 I R OS and it s A f fi l i a t e s s ha ll b e i d e n t i f i ed a s add i t i o n al i n s ur e d s o n C L I E N T CLIE N T and i t s A f fi l i a t e s sha ll b e i den ti f ie d a s ad d i t iona l i n s u re d s on p o l i c y. 2 0 . 5 Up on w r itte n req u e s t , ea c h P a r t y s ha l l p r o v i d e t h e o t he r w i t h a c o py of it s e ffe c t iv e c er t i fi ca t e o f i ns u ra n c e or s uch o t he r d o c u m e n t e v i d e n c i ng t ha t it ha s a d e qua te c ove r a g e c on s i s t en t w i th h u m a n c li n ic a l t ri a l i nd u s tr y s t a n d a r d s to co v e r it s o bl i ga t i ons he r eun d er, a n d i n n o e v en t l e ss t han t h e m i n i m u m a m ou n t of i ns u r anc e r e q u ire d by A pp lica bl e La w s . C L I E N T he r eby a ut h o riz e s I R OS t o pr o v i d e i t s S u b c o n tra c t or s w it h a c o py o f ce r t ifi c ate of i n s u r anc e . D A T A P R O TE C T I O N A N D S E C U R I T Y 2 1 . 2 1 . 1 Bo t h P a rt i e s h a v e th e o b l i ga t i o n t o a b i d e by t h e pr in c i p le of m e d i ca l c o n f i d e n t i a l i t y f o r t h e s ub j e ct s p a rt i c i p a t ing in a S t ud y . 2 1 . 2 F o r t h e pu r p o s e of t h i s A g re e m en t, e ac h P a r t y s h a ll p r o v i d e t o t h e o t h e r P ar t y o n ly A non y m i zed D a t a r e lat ed t o t h e S t u d y s u b j e c t s .
13 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 2 1 . 3 E ac h P ar t y ack n o w l edge s a n d ag r e e s t ha t , a n d s h all p r ocur e t h a t i t s d i r e cto r s , e m p l o yee s a n d a u t ho r i z ed s u bco n t r a c t o r s : 21.3 . 1 s h all c om p l y w i t h t h e t e r m s o f U A E F ede r a l L a w N o 2 o f 2019 o n t h e Us e o f th e I n fo r m atio n a nd C ommu n i c at i o ns Tec hn o lo gy in Health F i e lds (a s a m e n d e d or u p d a t e d f r o m t i me to t i m e ) a nd a ny oth er a ppl i ca ble P r iv ac y L a w s ; 21.3 . 2 s h all a t a ll t im e s en s u r e t h e p r o t e cti on of t h e pr i v a cy o f hu m an s u b j e ct s , c o m p l y w i th a ll h ea l t h inf or m a t ion a nd Ano n y m i z e d D a t a ; a nd 21.3 . 3 s h all o n l y u se S t u d y and t h e An ony m i ze d D a ta f o r t h e p u r p o se of t h e r el a t ed S t u dy a n d n o t f o r a ny o t he r p u r p o s e or i n a n y w a y c o n tr a r y t o l e ga l r e q u ire m e n t s. 2 1 . 4 S u bj e c t t o c l a u s e 2 1.1 and t o th e e x t e n t th at I R O S p r o c e s s e s P e r s o n al D a ta r e la t ed t o th e S t u dy S u b j e ct, in r e sp e c t o f t h i s P er son a l D a t a a nd t he Ge n e r at e d D a t a , I R O S s h a l l : 21.4 . 1 o n l y u s e t h e P e rso n al D a ta and t h e G e n e r at e d D a ta f or th e p u r p o s e of th e r e l a t ed S t u d y i n ac c o r da n c e w i th t h e p r o v i s i ons o f t h i s A g r e e m e n t , and n o t f o r any o t h e r p u r po s e or in a ny w ay c o nt r a r y t o le g a l r equ ire m en t s, a l w a ys i n co m p l i a nc e w i t h all a p p l i cab le P ri v a cy L a w s ; 21.4 . 2 t a k e ap p ro p ri a t e s t eps t o pro te c t t h e c o n f i d e n t i a l i t y a nd s e c u r i t y of t h e P e r s o n al D a ta and t h e G e n e r at ed D a ta wh i l e i n i t s p o s s e ss i o n or co n t r ol ; 21.4 . 3 s u b je c t t o c l a u s e 21.4.4 be l o w , n o t t o d i s c l o s e P e r s ona l D a ta and G en e ra t e d D a ta to any t h i r d p a rt y exc e p t : ( a ) t o any a utho riz ed ind i v i dua l s i n vo l v e d in t h e S t udy to w ho m d i s c losur e i s s tr i c t l y n ece s s a ry i n ord e r fo r t h e p erf o r m a n c e of it s o b li ga t i o ns u n de r th i s Agr e e m e n t p r o v i d e d t ha t s u c h in d i v id u a l s ar e obl i ged t o pr o c e ss t h e P e r s o n al D a t a a n d G e n e r at ed D a ta i n ac c o r d a n c e w i t h t h e p r ov i s i o n s of t hi s Ag r ee m en t ; o r ( b ) i f r e q u ir ed t o do s o b y a n y l e g a l r e q u i r e m e n t s, i n c l uding w i t h r e spec t t o prov i d i ng t h e P e r so n al D a t a t o any c o m pe te n t G o v er n m e n t a l En ti t y p r o v i d e d t h at I R OS o n l y p r o v i d e s t h e m in im u m P e r s o n a l D a t a nece s s a r y t o s a t i s fy t h e r eq u ire m e n t . 21.4 . 4 n o t tra n s f e r any P e r s on al D a t a o u t s i d e o f t h e U A E u n l e s s p e r mit t ed b y , a nd in a cco r dan c e w it h t h e r equ i re m e n t s o f, a ppl i c ab le P r i v acy L a w s , o r i f in s t ru c t e d by a ny c o m pe t en t au t h or i t y ; 21.4 . 5 i m p le m e n t a nd m ai n t a i n a p p r o p r i a t e p h y s i c al, a d m i n i s tr a t i v e, and te chn i c a l s a f egua r d s t o p r o t e c t t h e P er s o na l D a ta a nd t h e G ene r a te d D a t a f ro m i n ad v e r t en t or u n a u t h or i z e d a cc e s s, d i s c l o s ur e , u s e, o r m o d i f i ca t i on D a t a B r e a c h , t a k i n g i n t o a c c o u n t th e s en s i ti v i t y o f s u c h d a t a ; 21.4 . 6 p r o m p t ly a n d i n any ev e n t w i t h i n t w e n t y - f o ur ( 24 ) ho ur s i n f orm t h e CL I EN T u p o n be c o m i n g a w a r e of a D ata B r each or a r e q u e s t f r o m an i n d i v i d u al t o e x e r ci se a r i g h t u n de r a p p l i c a b l e P r i v ac y L a w s or a ny o t he r th ir d p a r t y r e q u e s t / en q u ir y i n r el a ti o n t o t h e P e r s o na l D at a . I R OS s h a l l r e s po n d t o th e a fo re m e n t i o ned o c c ur a nce s i n a cc o r d a n c e w i t h a p p l i cab le P r i vacy La ws and p r o vid e t h e C L I E N T w i t h s u c h in f orm a t i on and a s s i s t anc e w it h r e s p ect t o t h e a f o r e m t n i o e d o cc u r re n ce s a s t h e C L I E N T m ay r e asona b l y r e q ue s t . 2 2 . L I A B I L IT Y AN D I ND E M N I F I C A T I O N . 2 2 . 1 22.1 . 1 in r e spec t o f a n y in d e m n i f i ca t i o n o b li g ati on a ri s i ng p u r s u a n t t o t h i s Ag r ee m e n t; 22.1 . 2 in r e spec t o f f r a u d u l e n t mis r e p r e s e n t a t i on or f r au d ; 14 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 2 2.
1 . 3 i n the e v e nt o f i n j u r y t o o r d e a th of , a ny p er s o n c a us e d b y its n e g l ig e n c e o r t h a t of i ts e m p l o y e e s o r a g en t s a n d fo r w h i ch it i s r e sp o ns i b l e ; o r 2 2 . 1 . 4 wh er e s uch l i m itati on or e x c l us i on w ou l d cont r aven e A p p l ic abl e La w s . S u bj e c t t o Cl a u se 2 2 . 1 , ne it h e r P a r ty s h a l l b e l i a b l e o r r e s pon s i b l e t o t h e o t h e r P a r t y f or a n y i nd i re c t or co n s e q u e n t i a l loss (i nc l u d i ng l o s s o f g o o dw il l , l o s s of p r of it, l o s s of any co n t r a c t, l o s s of o p p o r t u n i t y, l o s s of a n t i c i p a t ed pro fit s o r r evenu e o r c o s t s of c a p i t a l ) , and i n ea c h c a se ho w s oe v e r cau s ed w he t he r a r i s i n g u n de r c o n t r a c t, t o rt ( i n c lud i ng n e g l i g e n c e a nd b r ea c h of s t a tu t ory d u t y ) or o t he rw i s e, e v en i f it ha s be e n a d v i s e d o f t h e p o s si b i li t y o f s u c h los s . 2 2 . 2 2 2 . 3 S a v e a s p r ov i ded u n d e r Cl a u s e s 2 2 .4, C L I E N T s h all i n d e m n i f y, de f end a nd hold h ar ml e s s I R O S and it s A ff i l i a t e s , a g e n t s a n d S u bcon t r a c tor s f r om and a g ai n s t any L o s s e s s uf f e r ed a s a r e s u l t o f: 22.3 . 1 ad m i n i s tr a t i o n of t h e S t udy D r ug (i nc l u d i ng d ur ing t h e S tudy) , or t h e p e r fo r m a n c e of a ny p r oc e d u re r e q ui r e d by t h e Pro t o c o l fo r t he pe r f o r m a n c e o f t h e S t ud y , i n c o m p l i anc e w i t h t h e P r o t o c o l ( a s ap p r o v e d by C L I EN T a n d t h e r e le va nt Re g u l a to r y Autho r i t i e s ) ; 22.3 . 2 t h e S e r vi c e s i n f r i n g e s I n t e l l e c t u a l P ro p e r t y ; 22.3 . 3 22.3 . 4 C L I E N T ne g l i ge n c e , f r a u d or w i l l fu l m i s co n duc t in conne c t i o n w i t h t h i s Agr ee m e n t ; 2 2 . 3 . 5 C L I E N T CLIE N T da m a g e or L o s s e s t o t h e e x t e n t c a used b y 2 2 . 4 C l a u s e 22.3 . 1 t o 22. 3 .4 doe s n o t a p ply t o i n j ur y, l i a b i l i t i e s , : 22.4 . 1 fa i l u r e t o pro v i d e t h e S e rv i c e s a s r e q u i r e d p ur s ua n t t o a W O or t o a d he r e t o th e P ro t oco l (a s ap p ro v ed b y C L I EN T and t h e r e le v an t R eg u l a t ory A u t hor it i e s ) ; 22.4 . 2 f a i l u r e t o c om p l y w it h A pp lica b l e L a w s ; 22.4 . 3 ne g l i ge n c e , f r a u d o r w il l fu l m i s co n d u c t i n t h e p er f o r m a nc e of th e S erv i c e s ; o r 22.4 . 4 b r ea ch of i t s o b l ig a t i o ns unde r t h i s Ag r e e m e n t ( and / or a n y W O ) . 2 2 . 5 T h e C L I E N T i n Cl au s e 22.3 . 2 i s l i m i t ed t o t h e a m o u n t s a w a r ded i n f i na l j ud g e m e n t or ag r e ed i n s e tt l e m en t w i th t h e t hi r d p a r t y and t h e r ea s o n a bl e c o s t s a n d ex p e nse s in c urr e d by p r o p e r t y rig h t s i n f r ing e m e n t i n c o nn e c t i on w i t h t h i s A g r e e m e n t . 2 2 . 6 I R OS s h a ll ind e m n i f y, d e f e n d a n d h o l d ha r m l e s s C L I E N T and i t s A ff i l i a t e s , I n d e m n i fi e d P a r t y L o s s e s a r i s i ng o u t o f : C L IE N T 22.6 . 1 CLIE N T a nd t h e r e le v a n t Reg u l a t o r y A u t ho r i t i e s ); 22.6 . 2 Ap p lic a b l e L a w s ; 22.6 . 3 I R OS , fr a ud o r w i l l f u l mis c o n duc t in t h e p e rfo r m a nc e o f t h e S e rv i c e s a s r eq u i re d p u r s u a n t t o a W O ; o r 22.6 . 4 I R OS b r e ach o f i t s w a r ra n t i e s and r e p r e s en t a t i o ns unde r t h i s Agr e e m e n t ( an d / or a n y W O ).
15 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 2 2 . 7 2 2 .5 d o e s n o t a pply t o i n j u r y, l i a b i li t i e s , d a m a g e o r L o s s e s to t h e e x t e n t ca u s ed b y: 2 2 . 7 . 1 C L I E N T 2 2 . 7 . 2 C L I E N T , f raud or w il l fu l m i s c o n d u ct i n t h e p e r f o r m a nc e of i t s o b l i ga t i o n un d e r t h i s A g r ee m e n t (and / or a ny W O) ; or 2 2 . 7 . 3 C L I E N T S u bj e c t to c la u s e 2 2 . 1 and w it ho u t p r e j udi c e t o c l a u s e 22 . 2 , t o t h e m a x i mum ex t en t p er mi t t e d un d e r A p plic ab l e L a w , the a g g re g a te lia b i l i t y o f ea c h P a r t y in r e s p ec t of a ny W O ( i n cl u di n g a s a n y s u c h W O m ay b e a m e nded by a n y a s so c i a t ed C O ) s h all n o t i n any ci r c um s t a n ce s wh a t s o e v e r ex c eed a g g r ega te a m o u nt s pa i d o r paya b l e by CL I EN T fo r p e r f o r m a n c e of t h e S e r v i ce s r e l a t ing t o s uch W O . 2 2 . 8 2 2 . 9 T his Cl a u s e 2 2 s h all r e m a i n i n f ull f o r c e a n d e f f e c t n otw i t h s ta n ding a ny t e r m i n a tion or e x p i ry o f t his Ag r ee m e n t. 2 2 . 10 Up on r e aso n a b le r e q u e s t b y I R O S or a n I n s t i t ut i on u ti l i z ed in c onnec t i o n w i th a W O , C L I E N T s h a l l execu te a n d pr o v i d e a s epar a t e l et t e r o f i n de m n i f i c a t ion t o I R OS t h a t c a n b e p r o v i d e d t o I n s t it u t i o ns, i n a f o r m m u t ua l l y a ccep ta b le t o th e P a rt i e s . 2 3 . I N D EM N I F I C A TI O N PRO C E D U R E . 2 3 . 1 T h e i n d e m n i f ica t i o n ob li ga t i on o f ea ch P a r t y u nde r Cl au s e 2 2 i s su b je c t t o t h e i n d e m n ifie d P a r t y n ot if y i ng t h e i n d e m n i f y i n g P a r t y a s soon a s p ra c tica b l e a f t e r beco mi n g a w a r e of t h e r el ev a n t c l a i m , a l l ow i ng t h e i nde m n if y i ng P a r ty t o t ak e c o n t r o l of t h e d e f e n s e a n d s ett l e m e n t o f t h e c l a i m , a nd ta k i ng a l l ac t i o n r easo n a b l y r e q ue s te d by t h e i n d e m n if y i n g P a r t y to a v o id, c om pro mise o r d e f end t h e c l a i m a n d a n y p r o c e e d in g s i n r esp e c t of t h e c la i m . Th e i n d e m n i f i e d P art y sh a ll p r ov i d e a ny s u p p o rt re a son a b l y r e q ue s te d by t h e ind e m n i f y i n g P a r ty t o d efe n d th e c la im . D I S C L A I M E R 2 4 . 2 4 . 1 CLIE N T ackn ow l ed g e s t hat : 24.1 . 1 th e r e s u l t s of t h e S e r v i ce s t o b e p ro v i ded a s o u t l i ned h e r e in a r e i n h e re n tl y u n c er t a i n an d t h at , ac c o r d i n g l y, the r e c a n b e n o a s s ur an c e , repr e s e n t a t i on or w a rr a n t y by I R OS t ha t t h e S t u dy D rug w i l l b e ap pr o v e d a n d / o r s u c c e s s fu l l y m a r k et ed by C L I E NT . 24.1 . 2 I R OS s h all n o t b e r e s po n s ib le for th e a u t he n t i c i t y or s u c c e s s f u l o u t co m e of t h e S t u d y Dr u g . 24.1 . 3 th e S e r v i c e s t o b e p r o v i d e d b y I R OS a s o u t l i ned he r e i n a r e b a s ed u p o n i n f o r m a t i o n supp li ed b y I R OS and C L I E N T , a s w e l l a s o t he r s , a n d t h a t I R O S doe s n o t g uaran t e e o r w a r ra n t t h e r e s u l t s of s u c h S e rv i c e s , w it h t h e excep ti on t ha t d a t a c o l l ec t ed in s u p p or t o f S tu d i e s , w i l l b e ac c u r a t e , l e g i b l e , r e l i ab le a n d s u i t ab le f or u s e i n t h e S tu d y and o t he rw i se in a c c o r da n c e w i t h t h e t er m s of t h i s A g r ee m e n t a n d a ny a p p l i c a b le W o r k O r d e r s . F o r t h e a v o i d a n c e of d ou bt, I R OS sha ll n o t b e r e s po n s i b le f or t h e a ccu rac y , c om ple t e n e s s , o r i n t eg r i t y o f a n y i n f orm a t i on, r eco r d s , or da ta s u p p l i ed by C L I E N T , I n s t it u t i o ns, or t h i rd p a r t i e s . 2 5 . T E R M OF A G R E E M E N T . 2 5 . 1 T h i s Ag r ee m e n t sha ll co mm e nc e a s o f th e E f f e c t i v e D a te a n d s h all co n t i n u e f o r th e In it i a l T er m f r om tha t da te, u n le s s e ar l i e r t e r m i na t e d by e i t h e r P a rt y in a cco r da n c e w it h C l a u s e 2 6 be l ow . 2 5 . 2 A t t h e e nd of t h e I n it i a l T er m , t h e P a r t i e s m ay e x t e nd t h e A g ree m en t b e yo n d t h e In it i a l T e r m for a d u r a t io n E x t e n d e d T e r m Ag r ee m e n t s i g ned b y b o t h P a r t i e s , a t l ea s t 1 5 ( f ift e e n ) d a y s pr i or t o th e e nd o f t h e I n i t ia l T er m .
16 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 2 6 . T E RM I N A T I O N . 2 6 . 1 T h e P ar t i e s m ay dec i d e t o t e r m i na t e th i s A g r ee m en t by m u t u a l co n s e n t i n w r i t i ng w it hou t t h e need fo r a co u rt o r d e r . 2 6 . 2 I R O S m a y t e r m in a te this A g r ee m e n t or a ny W O und e r t h i s A g re e m en t w i t h o u t c au s e a n d w ith o ut the need f or a c o u rt o r de r a t a n y t i m e d u r i n g t h e t e r m of t h e A gre e m en t o n t h i r t y ( 3 0 ) days pr i o r w r i t t en n o t ic e t o CL I EN T . I R O S s ha l l re i m bu r s e th e C L I E N T f o r i t s r e a s o nab le a n d d i r e c t co s t s a nd e x p ens e s i nc ur re d by t he C L I E N T i n c o n n ec t i on w i th e n g a g i ng a n ew C R O s e r vi c e s p r o v i d e r f o l lo w i n g t e r m in a t i o n b y I R OS p ursuan t t o t h i s c l a u s e . 2 6 . 3 W O s c u rr e n t ly i n e ff e c t . 2 6 . 4 E i t h er P a r ty m a y t e r m in a te a ny W O in re l a t ion t o a S tudy b ef o r e t he b e g i n ni n g of s u c h S tu d y i m m e d i a t e l y by wr it t en no t i c e t o t h e o t h e r : 26.4 . 1 in t h e e v e n t of f a i l ur e by C L I E N T t o s e cur e a p p r o v al f r o m t h e r e le v a n t R eg u l a to r y A uth o r it i e s for the c ond u ct of the S tu d y; 26.4 . 2 th e S t udy can n o l o n g e r b e c on d uc te d d u e t o l oca l r e gul a t i o n s or gove r n m en t re s t r i c t i o ns ; 26.4 . 3 th e S t udy i s te r m i n at ed fo r a ny r ea s o n t ha t i s no t t h e fa u lt o f t h e t e r m i na ti n g P a r t y in c l u d in g d u e t o a s i gni fi c a n t c h an g e i n t h e s a m p le s i z e ga t he r ed i n t h e r e l e v a n t t e r ri to r y ( i e s ) i n co mp a r i s on to t h e s a m p le r equ ire m e n t s a s s e t ou t i n t h e P r o t o c o l wh ic h pr e v e n t s t h e S t udy f rom be ing s u cc e s s f u l l y c on d u ct e d ; a nd 2 6 . 4 . 4 in t h e e v en t t h at f o r w h a t e v e r r ea s on C L I E N T i s no l o n ge r th e s p o n s or o f t h e r e l e v a n t S t u d y , i n wh ic h c a s e n e i t he r P a r t y s ha ll b e l i ab le t o t h e o t he r P a r t y f or a n y Lo s s e s , c la im s , d a m a g e s , f e e s, l i a b i l i t i e s , co s t s or ex p e n s e s su f f e r e d or i nc ur re d by t h e o t h e r P a r ty on t h e a ccou n t of such t er mi na t i o n . 2 6 . 5 An y W O sha ll t er mi na te im m e di a t e l y u p o n w r i tte n n o t ic e o f o n e P a r t y t o t h e o t h e r , i f t h e r e l e v a n t R eg u l a t o r y A u t h or it i e s h a v e de c i d e d to t e r m i n ate th e c o r re s p on d i n g S t u d y du e t o a ny caus e r e l a t ing t o t h e s a fe t y of th e s u b je c t s or any e t h ic a l r easo n , in w h i c h c a se n e i t he r P a r ty s h a l l b e l i a bl e t o t h e o t he r s f o r any Loss e s , cl a ims, d a m a g e s , f ee s , l i ab il i t i e s , c o s t s o r e x p e n s e s s uf f e r ed or i n c ur r ed by t h e o t h e r o n t h e ac c o u n t of such t e r m i n a t i o n . 2 6 . 6 E ac h P a r t y s h all ha v e t h e rig h t , w i t h o u t pre ju d i c e t o i t s o t he r r i g h t s o r r e m e d i e s , i n cl u d i ng t h e r i g h t t o r eq u e s t f o r d a m age s, t o te r m i n a t e t h i s A g r ee m en t (a n d a l l r e l at ed W O ) i mm e d i a tel y b y wr i t t e n n o t i c e t o t h e o t he r 2 6 . 6 . 1 i f t h e o t h e r P a r t y ha s m a d e any f a l se m a te ri a l re p r e s en t a t i o n or w a r ra n t y i n t h i s A g r e e m en t ; 26.6 . 2 i f t h e o t he r P a rt y ( i ) su s p e n ds or t h r ea te n s t o su s p end, p a y m e n t of i t s de b t s or i s u nab le t o p ay it s d eb t s a s t h e y f a l l d u e or a d mi t s i nab i l i t y to pay i t s d e b t s , or ( i i ) beco m e s in s o l v e n t or a p e t it i o n i s f i l e d , a n o tic e i s giv e n , an o r de r i s m ad e or a r e s o l u t i on p a s s ed for t h e ad mi n i s tr a t i o n, w i ndin g - up or d i s so l u t ion o f t h e othe r P a rt y ( o t he rw i se t han f o r t h e p u r pose s of a s o l ven t a m a l ga m a t i o n or re c on s t r u c t i on ) , or (ii i ) an a p p l i ca t i o n i s m a d e t o c o u rt, or a n o r d e r i s m a d e to appo i n t a n ad mi n i s tr a t i v e o r o t he r r e ce i ve r, m a n a ge r, l i q u i d a t or , ad mi n i s tr a t o r, tr u s t e e o r simi l a r o ff ic e r ove r all or a n y s u b s ta n t i a l pa rt o f th e a s s e t s o f t h e o t he r P ar t y, or (i v) t h e o t he r P a r t y e n t er s in t o or p r opo s e s a n y c o m p o s i t ion o r arr an g e m e n t w it h i t s c r e d i t o r s gene r a l l y , or (v ) a n y t h in g an a logo u s t o th e f o r e g o i ng o c c ur s i n a ny ap p l i c a b le ju ri s d i c t i o n . 2 6 .
7 E ac h P a r t y s h all ha v e t h e rig h t , w i t h o u t pre ju d i c e t o i t s o t he r r i g h t s o r r e m e d i e s , i n cl u d i ng t h e r i g h t t o r eq u e s t f o r da m a g e s , to t e r m i n a t e a W O i m m ed i a t e l y b y w r it te n not i c e t o t h e othe r i f t h e o t he r P a rt y i s i n b r e ach of a ny o f i t s m a t e r i a l o b l i g a t i ons u n d e r th at W O or thi s A g r ee m e n t ( w i t h r e s p e c t t o t ha t WO ) a n d 17 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N e i t h e r t h a t b r each i s i n c a p a ble o f re m e dy or t he o t h e r P ar t y s h a ll h a v e f a i l ed t o re m e dy t h at b re ach w i t h i n 30 ( t h i r t y ) d a ys a f t e r r e c e ivi ng w r i tte n n otic e r e q u i r i n g it t o r e m edy t h a t br e a c h . 2 6 . 8 W it h o ut a ff ec t i n g a n y o t h e r r i g h t or r e m e dy av a i l a b l e t o it, I R OS m ay t e r mi n a te a W O w i th imme di at e e f f e c t by givi ng wr i t t e n n o t i c e t o t he C L I E N T : ( i ) i f t h e C L I EN T f a i l s to p a y any a m ou n t d ue un d e r t h a t WO on t he d u e d a te f or p a y m e n t ; (ii ) I R O S h a s e x e r c i s ed it s r i ght t o s u s p e nd t h e S er v i c e s und e r C l a u s e 1 5 . 4 . 1 a n d not i f i ed t h e C L I E N T o f it s i n t e n t ion t o t e r mi n a te the W O i f p a ym e nt i s n o t m ade w i thi n a f u rt h e r t hi rt y ( 30 ) d a y s ; ( i ii ) t he C L I E N T a n d r e m a i n s i n d e f a ult t h i rt y ( 30 ) d a ys a ft e r c omm e n c e m e n t o f t he s us p e n s i o n . 2 6 . 9 T e r mi n a t i o n of t h i s A gre e m ent o r o f a W O , a s a p plic a b l e , s h a l l b e e f f e ct i v e imm e d i a t e l y or o n the d a te s e t o ut i n a t e r m i n atio n n otic e a s t h e ca se m ay b e , w i t hout t he n e ed o f a c ou r t o r d e r. 2 6 . 10 I n t he e v e nt of n o t i c e o f te r m i n a t i on b e i n g g i v e n b y eit h e r P ar t y a s d e s c r i b e d a b o v e , t he P ar t i e s ag r e e t o co o p e r a te i n g o o d fa i t h i n r esp e c t of t h e tra ns i t i on o f o n g o i ng S e r vi c e s d u r i n g t he p e r i od of noti c e a n d t h e c l o s e - o u t p eri od r e f err ed t o i n Cl au s e 2 6 . 12 (w hi c h m ay e x te n d b e y ond t he e f f e c t ive d a t e of t e r mi n a t i o n ) . 2 6 . 11 O n e ar l y t e r mi n a t i on or e x p i r y of th i s Ag r ee m e nt o r a W O , a s ap p l i c a b l e : 26.11 . 1 the r i g hts g r a n t ed by o ne P a r t y t o t h e ot h e r u nd e r thi s A g r e e m e n t or the WO , a s a p p l i ca bl e , s h a l l cea s e ( ex c e pt a s ex pr e ss ly a ut hor ize d by t he o t h e r P a r t y f o r t r a n s i ti on pu r p ose s ) ; 26.11 . 2 each P a r t y s h all p ro mp t l y d e l i v e r to t he o t h e r o r d e s tr oy, u pon i t s re q u e s t, all Co n f i d e nt i a l I n f o r m ati o n , a n d , i n t h e c a se o f I R O S, all C L I EN T P r o p e r t y t h a t a r e i n i t s p os s e s s i on or u n d e r i t s c o nt r ol . No t w i t h s t a n di ng t he f o r eg o i n g, t he r ec e i vi ng P a r t y sh a ll be p e r mi t t ed t o r e tai n o n e c o p y o f Co n fi d e ntial In f o r m a t i o n a n d , i n t he c a se of I R O S , C L I EN T P r o p e r t y, t o t he e xt e nt r e q ui re d to c o m p l y w it h A p p l i c a b l e La w s ( in c l u d i n g t he r ul e s of a n a p pl i ca b l e s to c k ex c h a n g e ) or b o n a f i de i n t e r n a l d o c u m e nt r et e nti on p o l i c i e s a n d s h a l l n o t be r eq u i r e d t o d e s tr o y , d e let e , o r m o d i fy a n y b a ckup t a p e s or o t h e r m e d i a c o n t a i n i ng s u c h C o n fi d e n t i a l I n f o r m ati on or C L I EN T P r o p e rt y p u r s u a nt t o a u t om a t ed a r c h i v a l p ro ce s s e s in t he o r d in a r y co u r se o f it s bus i n e s s , pr o v i d e d t h a t s u c h Co nf i d e ntial In f o r m a t i on an d , i n t he c a se of I R O S, C L I EN T P r o p e r t y w ill not be u s ed o r a c c e s s ed f o r a ny o t h er pu r p os e and s h all r e m a i n su b j e ct t o t h e t er m s of t his A g r e e m e n t . 2 6 . 12 te r m i n a t io n n o t i c e in r e l a ti on to a WO f o r a n y r e aso n , t h e P a r t i e s s h a l l m ee t t o p r ep a r e a clo s e - o u t s c h e d u l e, a nd I R OS s h a l l c e a se p e r f o r m i n g a l l w o r k n o t n e ce s s a ry f o r t h e o rd e r l y cl o s e - o u t o f t h e S e r v i ce s or r eq u i r e d by l a w s o r r egul ati o n s . Ea c h P a rt y sh a l l c o mply w it h i t s o bli g a t i o n s i n t he a g r eed c l o s e - o u t S ch e d u l e fo r t he p e r i od r e f e r r e d to i n it ( w hi c h s h all be at l e a s t s ixt y ( 6 0) d a y s u n l e s s a s h o r t e r p e r i o d i s re q ui re d by t h e C L I EN T ) . 2 6 . 13 Un le s s ot h erw i se s t a ted i n t he n o t i c e of t e r m in a t ion, t e r m ina t i o n or ex p i ry of t his A gre e m e nt s h a l l n o t a f f e c t t he v a l i d i ty of any WO h e r e u n d e r th e n in ef f ec t , a nd a ll t he t e r m s of th i s Ag re e m e n t s h all s u r v ive and c o n t i n ue to a p p l y t o s u c h WO u n t i l i t s c o mpl e t i on or ter m i n a t io n . 2 6 . 14 I f thi s A g re e m e nt or a ny W O i s t e r mi n a t e d, C L I EN T sh a l l p a y I R OS f o r a l l S e r v i ce s p e r f or m e d i n ac c o r d an c e w i t h th i s A gr e e m e nt or any W O up t o t h e t e r m i n a ti on d a t e , p r o v id e d t h at I R OS h a s c om pl i ed w it h i t s o b l i g a t i o ns u n d e r t he Pro t o c o l and a n y P r o t o c ol i n h a n di ng ov e r any on g o i ng S t udy t o C L I EN T or a r e pl a c e m e n t C R O pro vi d e r . I f p aym e n t s a r e u n it or mi l e s t o ne b a s e d, a n d t h e A g r e e m e nt or a W O i s te r m i n a t e d a fte r a g r e e d co s t s h a ve b e e n i n c urr e d to w ard ac hi e v in g p or ti ons o f o n e or m o r e i n c om p l e t e un i t s or m i l e s t o n e s, C L I EN T w ill p a y I R OS t he a gr eed f ee s f o r a c t u a l wo r k p er fo r m ed t o w ard t hos e i n com p l e t e uni t s o r m i l e s t on e s u p t o t he d a t e o f te r m i n a t i o n , in ad d i t i on t o p ay i n g f o r c o m p l e te d u n i t s or m i l e s t o n e s . I f p a y m e n t s a r e u nit o r m i l e s t o ne b a s e d, and the Ag r ee m e nt or a WO i s te r m i n a t e d , C L I EN T w i l l o n l y be r eq u i r e d t o p a y I R O S f o r com pl e ted u ni t s o r mi l e s t o n e s . 2 6 . 15 An y te r m i n a t i o n o f t h i s A gr e e m e n t (ho w s o e v e r o c c a s i on e d ) s h a ll n o t a f f ec t a n y a c c r u e d r i g h t s or l i a b i l i t i e s of e i t h e r P a r t y, n o r s h a l l it a ff e c t t he co m i ng in t o f o r c e or t he cont i n u a n c e i n forc e of a n y p r o v i s i on of th i s A g r e e m e n t w hi ch i s e x p r e s s l y or by i m p l i cat i o n inte nd e d t o c o me i n t o fo r c e o r c o n t i n u e i n f o r c e on or a f t e r ter m i n a t i on .
18 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N 2 7 . N O T I C E A N D D E L I V E R I E S . 2 7 . 1 An y n o t i c e r e q u ire d o r pe r mit t ed t o b e g i ven h e r e u n d e r by e it h e r P a r ty he r e u n d e r s h a l l b e i n w ri t i ng a n d s h a l l b e dee m e d g i ven on t h e d a t e r e c e i ved i f de l i ve r e d p e r s o n a l l y o r by a r e p u t a b l e o v e r ni g h t de l i v er y s erv i ce , o r s e v en t y - t wo ( 72 ) hours a f ter t h e d ate p o st m a r k e d if s e n t b y reg is t e re d o r c e r ti f i e d m a il, r et u r n r ec ei p t r eq u e s te d , p o s ta g e p re pa i d t o t h e phy s i ca l ad d r e s s , or on t h e d ate of t h e e m a il i f s e n t b y e m ail t o t h e e m a i l ad dr e ss e s s e t o u t f or ea c h P a rt y i n th e Co n t r ac t P a r t i cu l a r s . 2 7 . 2 I f CL I E N T d el iv e rs , s h ip s , o r m a ils m a te r i a l s or d o cu m e n ts t o I R OS, or r e q u e s t s th a t I R O S d e liv e r s, s h i p s , o r m a il s m a t e r i al s o r do c u m e n t s t o CLIE N T or t o t h i rd par t i e s , t hen t h e e x p e n s e and ri sk of lo s s f o r s u c h de l i v e ri e s , s h i p m en t s, or m ai l i n gs s h all b e b o r n e by C L I EN T , p r o v i d e d t h at I R O S f o l l o w e d CLIE N T w r i t t e n i n s t ruc t i o n s f or t h e m a t e ri a l s t ha t w e r e d e l iv e r e d , s h i p pe d, or m a i l e d . I R O S di s c l a i m s any lia b i l i t y f o r t h e a c t ions o r o m i s s i o n s of t h i rd - pa rt y de liv e r y S e r vic e s o r c ar r i e r s . 2 8 . I N D E P E ND E N T C O N T R A C TOR R EL A T I O N S H I P . 2 8 . 1 F o r t h e pu r p o s e s o f t hi s Agr e e m e n t , t h e P a r t i e s h e r e to a r e i n d e p en d e n t c o n t r a c t o r s a n d no t h i n g co n t a i n e d in t h i s A g r ee m e nt s h a l l b e c o nst r u e d to c o n st i tut e , c r ea t e , or in a ny w a y be i n t e r p r e t e d a s , a joi n t v en t ur e o r pa r t n e r s hip be t w een t h e P a r tie s . 2 9 . S U B C O N T R A C T I N G . 2 9 . 1 A s p a r t of t h e S erv i c e s , i f s e t fo rt h i n a W O , I R OS m ay e n g a g e a t h ir d - pa rt y p r o v i d e r f o r th e p r ov i s i on of S e r vi c e s wh ic h a r e e i t he r i ) n o t c u s t o m ari l y per f o r m ed b y I R O S , or ii ) r eq u i red to b e p e rf o r m e d i n te rr i t o r i e s o u t s id e of t h e U A E wh e r e I R O S d oe s n o t c u s t o m ari ly o p er a t e ( a S u b co nt r a c t o r ) . I R OS w i l l s ecur e t h e w r it t en a p p r ova l of C L I E N T to e n ga g e a S u b c o n tr a ct o r w h ic h w i l l n o t b e u n r e a s ona b l y w it h h el d . I R O S s h all r e m a i n f u l ly re s p o ns i b le f or t h e pe rf o r m a n c e by i t s Su bco n t r a c t o r s of any S e r v i ce s a s i f it had p e r f o r m ed t h e S e r v i ce s it s e l f . I R O S ' s du t y w i t h r e spec t to s u c h Su b c o n tra c to r s s h all b e t o co o r dina te t h e i r a c t iv it i e s a nd t o m a k e t h e c o r r e spond i ng p a y m en t s , a f t e r r ec ei p t of suff i ci en t f u n ds f r o m CL IE N T , i n a cco r dan c e w i t h t h e r el e v an t W O . F o r t h e p u r p o s e s o f c la r i t y , a n I n s t it u t i o n c o n d uc t i ng a S t u d y p u r s uan t t o a C l i n i c a l Tr i a l A gr e e m e n t i s n o t a S u b c o n tr ac t o r of I R OS f o r t h e pu r p ose s o f t h i s Ag r ee m e n t or a W O . 3 0 . B I N D I N G A G RE E M E N T AN D A S S I G N M E N T . 3 0 . 1 T h i s Agr e e m e n t sha l l b e b i n d i ng u pon and i n u r e t o t h e be n ef i t of C L I EN T and I R O S and t h e i r r e s p e c t iv e s u c ce s s or s a n d pe r m i tte d a s s i g n s . 3 0 . 2 E x c e p t pu r s u a n t t o Cl a u se 2 9 ( S ub c o n tr a ctin g ) o r i n t h e ca s e of : 3 0 . 2 . 1 an a s s ign m e n t to a n A ff i liate o f t h e P a r t y ; o r 30.2 . 2 in c o n n e c t i o n w i t h th e m e r g e r , c o ns o l i da t i o n o r s a l e o f s ub s t an ti a l l y all of a P a r ty a s s e t s r e lat ed t o t h e S t u d y , ne it he r P a rt y m ay a s s i g n , t r a n s f e r , c h ar g e o r d e a l i n a n y o t h e r m a nn e r w it h a n y of it s r i g h t s or o b l iga t ions u n de r t h i s A g r e e m e n t w it hou t t h e p r i o r w r i tte n c o n s e n t of th e o t h e r P a r t y. 3 0 . 3 I f I R O S h a s t r a n s f err e d ri g h t s an d / or ob l i g ati o n s unde r t h i s A g r e e m en t pu r s u a n t t o Cl a u se 30 . 2 . 2 and t h e CL IE N T ob j e cti o n s t o t h e i d e n t it y o f t h e a s s i g n e e on th e b a s i s t ha t it i s a c o m pe t i t or of th e C L I E N T o r t h e CLIE N T ha s r e a s o n a b l e g r o u n d s t o be l i e v e th at t h e a s s i g n e e i s no t f i n a n c i a l l y s o u n d, doe s n o t h a v e t h e r e s ou r c e s of c a p ab il i t y t o co m p l y w i t h t h i s Agr ee m en t o r p r e s en t s re p u t a t i o n a l , r eg u l a to ry o r o p e r a t i o n a l r i s k t o t h e CLIE N T , t h e CLIE N T m ay ter mi na t e t h i s Ag r ee m e n t on wr it t en n o t i c e t o I R OS and t h e a s s i gnee . 3 0 . 4 T h e P a rt i e s ac k n o w l e d g e a nd a g r e e t ha t : ( i ) t h i s Agr ee m en t ha s been en t e re d i n t o i n con te m p lati on of t h e i nco r po rati on of a n op e r ati ng s u b s i d i ary o f t h e C L I E N T i n t h e U ni t e d A r ab Em i r a t e s t o s p o n s or t h e S t u d i e s i n t h e U n i t ed Ar ab E m i r at e s ; and ( i i ) imm e d i a t e l y f o l lo w i n g i n c o r p o r a t i on, t h e C LIE N T sha ll t r a ns f e r al l o f i t s r i g ht s a n d o b l i ga t i o n s u n d e r th i s Agr e e m e n t t o s uch s u b s i di a ry ; a nd (ii i ) t h e P a r t i e s s ha ll 19 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N e x ec ute ( a n d the C L I E N T sh a l l p r o c u r e e x e c u t i o n b y t he s u bsidi a r y o f ) a ny d o c u m e n t s n e c e ss a r y t o give e f f e c t t o s u c h tra n s f e r.
3 1 . GO V E R N I N G L A W . 3 1 . 1 T his Ag r e e m en t a nd a ny d i spute o r cl a i m ( i n c l u d i ng no n - c o n t r a c t u a l d i s p ut e s o r c la ims) s h a ll b e co n s tr ue d, g o v e r n e d, i nt e r p r e t e d, and a pp li ed i n ac c o r d a nc e w i t h t h e l a w s of t h e A b u D h a b i G loba l M a r ke t . 3 2 . S E V E R A B I L IT Y . 3 2 . 1 I f an y p r o v is ion or p a r t of a p r o v i sion of t h i s A g r ee m e nt i s d e c l a r e d in v a l i d, i l l e g a l , or un e nf or c e a b l e , t h e i nva li di t y , i l l ega l i t y, or u n e n f o r c e a b i li t y t he re o f w i ll n o t a f f ec t t h e r e m a i n in g pa rt of t ha t p ro v i s i on a nd a l l o t he r p r o v i s i o n s of t h i s A g r e e m e n t . 3 3 . V A R I A T IO N 3 3 . 1 S u bj e c t t o Cl a u s e 2.6 , no v ari a t i on o f t h i s A gr e e m e n t s ha ll b e e f f ec t i v e u n le ss i t i s i n w ri t ing a nd s i gned by t h e P a rt i e s ( o r t h e i r au t hor i s ed r epr e s e n t a t i ve s ) . 3 4 . W A I V E R . 3 4 . 1 F a i l ur e or de l a y by a P a r t y t o e xer c i s e a n y r i g h t or r e m e d y p r o v i d e d u n d e r t h i s Ag r ee m e n t o r by la w sh a l l n o t c o n s t it ut e a w a i v e r of t h at o r any o t h e r ri g h t or re m e d y , n o r s h a l l it p r e v e n t or r e s t r i c t a n y f u r t h e r exe r c i se o f t h at o r any o t he r r i g h t o r r e m e d y . 3 4 . 2 A w a i ve r o f a n y rig h t or r e m e d y unde r th i s A g r e e m e n t or by l a w i s o n l y e f f e c t i v e i f g i v e n i n wr it ing a n d s h a l l n o t b e d e e m e d a w a i ve r o f a n y s u b s e q uen t ri gh t o r r e m e d y . 3 5 . S U R V I V A L . 3 5 . 1 O n t e r m i na t i o n o r e x p i r y of t h i s A g r e e m e n t , all ex i s ti ng W O s h a ll c o n ti nu e un l e ss e x p r e s s l y t e r mi na t e d a s pe r t h e r e qui r e m en t s o f Cl a u s e 2 6 . 3 5 . 2 An y p r o v i s i on of t h i s A g re e m e n t t ha t exp r e s s l y o r by i m p li c a t i on i s i n t e n d e d t o c ome i n t o or c o n t i n u e in f o r c e on or af t e r t e r m i n ati on or e x p i r y o f t h i s A g r ee m en t s h all r e m a i n i n f u ll f o r c e a nd effe c t. 3 6 . D I S P U TE R E S O L U T I O N . 3 6 . 1 I n t h e e v en t of a n y d i s pu te or dif fer e n c e b e t w e e n t h e P ar tie s a r i s ing ou t o f or i n c o n n e c t i o n w i t h or r e l a t i n g t o t h i s A gre e m en t o r a ny W O ( a " D i s p ut e" ), e i t h e r P a rt y s h a l l g i v e t o t h e o t he r wr i t t e n n o tic e o f t h e D i s p u te, s et t ing o u t it s na t ur e and f u ll p a r t i cu l ar s ( a d o cu m e n t s. O n s e r v ic e o f t h e D i s p u t e No t i ce , t h e i n g o o d f ait h t o r e s o l v e t h e D i s pu t e . ), t oge t he r w i t h r el ev a n t s u p p o rtin g s h a l l a tte mp t 3 6 . 2 te n ( 10 ) c a l e n da r days of r ec ei p t of t h e D i s p u te N o t i c e , t h e D i s p u te s ha ll b e r e f e r re d i n w r i ti ng t o t h e A m i r H e s h m a t p our of t h e CL IE N T a n d t h e C h i e f Exe cuti v e O ffic e r of I R O S . T he s e r e p r e s e nt i ve s s h all, w i t h i n t e n ( 1 0 ) c a l en d a r d a y s o f t h e r e f e rr a l o f t h e D i s p u t e , ho l d a m e e t i n g ( a "D i s p ut e M e e t i n g ") e i t he r in pe r son o r v i r t ua l l y in an e f f o rt t o r e s o l v e t h e D i s p u t e . 3 6 . 3 An y D i s p u te wh ic h i s n o t r eso l ved w it h i n t h i r t y ( 3 0 ) c a l end a r d a ys a f t e r th e s e rv i c e o f a D i s p u te N o tic e , wh e t h e r or n o t a D i s p ut e M ee t i ng ha s be e n h e l d , m ay b e s u b mit t ed by a P a r t y t o th e c o u r t s o f Ab u D h a b i G l o ba l M a r ke t , i n t h e E mi rate of Ab u Dh a b i, U A E , wh ic h s h a l l hav e e x c l u s iv e j u r i s d i c t io n to d e cid e o n any d i sput e a r i s ing our or i n c on n ec t i on w i t h t h i s A g ree m en t and a ny W O .
20 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N 3 7 . E N T I R E A G R EE M E N T AN D M O D I F I C A TI O N . 3 7 . 1 T h i s A gre e m e nt , t o g e t h e r w i t h t h e W O and C Os , co n t ains t h e en ti r e u n de r s t a n d i ng of t h e P a rt i e s w i t h r e s p ect t o th e su b j ec t m a t t e r he r e i n, a n d s u p e r s ede s all p r ev i o u s a g r ee m e n t s ( o r a l a n d wr it t e n) , l e t t e r s of int e nt, n e g otia tions a n d d is c u s sion s . A ny m o di f ic a tions t o t h e pr o v i sio n s h e r e i n m u s t be i n wr i t i ng a nd s ig n e d by t h e P a rt i e s . 3 8 . TH I R D P A R T Y R IG H T S 3 8 . 1 U n le s s i t e x p r e s sly s tat e s ot h e rw i s e , this a gree m e nt d o e s n o t g i v e r is e t o a n y r ig h t s ( w h e t he r st a t utory or o t he r w i s e ) t o a ny t h i r d pa r ty w h o i s n o t a p a r t y to t h i s a gr e e m en t to e n f or c e a n y t e r m o f t h i s ag r e e m e n t . 3 8 . 2 T h e r i g h t s of t h e pa rtie s t o re s c ind or va r y t h i s a g r ee m en t a r e n o t su b je c t t o th e c o n s en t o f any o t he r p e r s on. 3 9 . C O UN T E R P A R T S. 3 9 . 1 T his A gre e m e n t, a W O a n d / o r a CO m a y be e x e c u t e d i n a n y n umbe r o f c o u nt er p a r ts ea c h o f w hi c h, w h e n execu t e d, s h all c o n s t i t u te an o ri gina l, b u t a ll t h e c o un t e r p art s t oge t he r s ha ll c on s t it u te a s i ng le b i n di n g le g a l d oc u m e n t . T h i s Agr ee m en t m a y b e e x e c u t ed th ro u gh t h e u s e of a n e l e c t r o n i c s i g na t u r e . T r an s m i s s i on o f t h e e x e c u te d s i g n a t u r e p a g e o f a c o u n t e r p a r t o f th i s A g r e e m e n t b y ( a ) f a x or ( b ) e m a il ( in PD F , JP E G or othe r ag r e ed f o r m at ) t o a noth e r P a r t y s h all t a k e e f f e c t a s d e l i v e r y o f a n e x e c u te d co u n te r p a rt of t h i s A gr e e m e n t . I f e i t h e r m e t h o d of d eli ve r y i s a d o p t e d , w i thou t pr ej u di c e t o t h e va l i d i t y of t h e Agr e e m e n t t h u s m a d e , ea ch P a r t y s h a l l p r ovid e t h e o t h e r s w i t h t h e or i g i n a l of s u c h c o u n t e r p art a s s o on a s rea s o n a b l y p o s s i b l e t he r ea f te r . N o coun t e r par t s ha l l b e e f f e c ti v e u n t i l ea c h P a r t y h a s e x e c u te d and d e l i ve re d a t l ea s t o n e c o u n te rpart . S i g n a t u r e C l a u s e f o llo w s.
21 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N I N W I T N E SS WH E R E OF , D U L Y A U T H OR I Z E D R E P R E S E N T A T I V E S O F TH E P A R T I E S H A V E E X E C U TE D A N D D E LI V E R E D T H I S A G R E E M E N T , I N D U PL I C A T E , A S O F T H E EF F E C TI V E D A T E . A CK N O W LE D G E D , A C C EP T E D A N D A G R E E D T O : N E O N C TE CH N O L OG I E S H O L D I N G S , I N C .
I N S I G H T S P H A R M A C E U T I C A L R E S E A R CH L L C By: B y: N a m e : T i t l e : T i t l e : D a t e : D a te : 3 October 2025 22 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G 4 October 2025 E X E C U T I O N V E R S I O N S C HE D U LE 1 D E F INI T I O N S A N D I N TE R P R E T A T I O N D ef i n e d T e r m s Aff i l i a t e m ea ns a ny p e r son di re c t l y C o nt r o l ling, C on t r o l l e d by or und e r d i r ec t o r i n di rec t C o nt r ol w i t h s u c h P ar ty ; A ff i l i a t e o f I R O S m eans M u b ada la I n v e s t m e n t Co m p a ny P JSC and G r oup 42 H o l d i ng Lt d a n d ea c h o f t he i r Con t r ol l e d e nti t i es, p r o v i d e d t h at f o r all p u r pos e s h e r e of , M u b a d a la Ca pital L L C , A b u Dh ab i I n v e stm e nt C o un c i l PJ S C or a n y t h ir d par t y c ap i t a l m ana g e m e n t f u n d s and t he i r re s pec t i v e d i r e ct l y a n d i n d i r e c t l y C o n t r o lle d s u b s i di a r ie s, a cco u n t s, col l e cti v e i n v e s t m en t f u n ds, i n ve s tm e n t h o l d i n g c o m p a n i e s or o t he r s im i l a r e n t i t i e s Con t r o l l e d , m a n a g e d or a d v i s e d by a ny o f th e m s h a ll n ot b e d ee m e d to b e a n A f f i l i at e of I R O S ; Ag r ee m e n t m eans t h i s a gr e e m ent ; A n o n y m i ze d D a t a m eans a n y dat a t h at h a s been i r r eve r s i b l y an o n ym i zed t o e x c l u d e i den t i f y i ng inf o r m a t i on r e lat ed t o a n a t u r al p er s o n a nd a n y o t he r i nf o r m ati on t h a t c o n s t it u te s P e r s o na l D a t a , w h i c h w ill b e p r o v i d e d b y I R O S to C L I E N T i n re l at i o n t o a S t u dy s ubj e ct ; A p p l i c a b le L a ws m eans any s u p r a - na ti ona l, f e der a l , na t i ona l, s tat e , m u n ici pa l o r l oca l s t a t u t e , la w , o r d i nance , r eg u l a t ion, r u l e , c o d e , orde r o r any o t h e r o rd e r o r j udg m e n t i s sue d , p r o m u l ga te d b y a ny G o v e rn m e n t a l En t i t y or any ru le or r equi r e m en t of a ny na ti ona l s e c u ri t i e s excha n g e , a s a n y o f t h e f o r e g o in g m a y b e a m en d e d f ro m t ime t o t i me and w h ic h a r e a p p l ic a b l e to a P ar t y or t o t h e sub je c t m atte r o f th i s Ag re e m e n t , in c l u d i n g P r i va c y La w s a n d Go od C l i n ical P ra c t ic e s ; B a c k g r o un d I P m eans i n r el a t i on t o a P a r t y , any In telle c t u a l P r o p e r t y, k n o w - h ow , i n f o r m ati on a n d m at e rial s (i ) o w ned b y o r lic en s e d t o t h at P a r t y o r i t s Af f i liat e s , p r i o r t o t h e c o m m enc e m e n t o f t h e A g r e e m e n t o r a W O (i i ) c r ea t ed d ur i n g t h e te r m o f t h e A g r e e m en t or W O b u t o u t s i d e t h e s c o p e of i t s a c t iv i t i e s u n d e r t h e S t u d y , a nd w h ic h a r e u s ed by s u c h P a rt y i n r e lati on to t h e S t u dy or t h e S e r v i c e s or ar e o t he r w i se m ad e a v a i l a b le t o t h e o t h e r P art y i n c o n n e c tio n w i t h t h e S t udy or S e r v ic e s . I t i n cl u d e s a n y i m p r ove m e n t s t he r e t o, w i thou t u s i ng or re fer enc i ng a n y ; C L IE N T I n d e m n if i e d P a r t y ha s t h e m e a n i n g g i ven t o i t i n C l a u s e 2 2 ; C li n i c a l T r i a l A g r e e m e n t s h all m e an t h e c o n t r a c t ua l a gr e e m e n t t ha t h a s b e en or w ill b e e n t e r ed i n t o b y C LI EN T and I R O S w i th a n I n s t i t u t ion f o r t h e con d uc t o f a S t udy by t h at I n s t it ut i o n ; C O ha s t h e m e a n i ng g i v e n t o i t i n C l a u se 2 . 6 ; C o n f i d e n t i a l I n f o r m a t i o n m e ans a l l s u c h in f orm a t i o n di s c l os e d pu r s ua n t t o t h i s A g r ee m en t an d / o r a W O , w he t he r f u r n i s h e d b e f o r e o r a fte r t h e d a t e h e r e of , w he t he r or al o r w r i t t e n , i nc l u d i ng t h e ter ms of t h i s Agr e e m en t . Co n fi dent i a l I n f o r m ati on m a y i n cl u de , bu t no t b e l i mi t ed t o, fi na n ci a l i n fo r m a t i on, kno w - h ow , tra d e s e c r et s, r e s e a rch ach i eve m e n t s , pr o duc t i o n m e th o ds, te c h n i q u e s , q ua l i t y c ont r o l, t e s t i ng m e t h o d s, s o ft w a r e , c ha rt, p r o g ra mm i n g spec ific a t i o ns, d eve l o pm en t p r o c e s s e s , s t e p s , i de a s, i nt e l le c t u a l p r o p e rt y (w he t h e r o r n o t re g i s t e r e d or p a t e n t e d ), b u s i ne s s p l an s , c u s t om e r l i s t s (p o t en t i a l o r e x i s t in g ), and o t he r i nfo r m a t i o n re l a ted to c u s t o m e r s , m a r k e t ing s trat eg i e s, th e te s t vac ci ne s , a n d o t h e r bu s i ne ss i n f o r m a t i on t h a t a r e d i s cl o s e d b y e i t h e r P art y ( or i t s A ff i l i a t e s ) fo r u s e i n o r i n c onnec t i on w it h t h e A g r ee m e n t a n d/or t h e S t u di e s .
Conf i d e n t i a l I n f o r m a t i on doe s n o t i nc l u d e any inf or m a t i o n wh i c h t h e r e ce i v ing P a r t y can rea sona b l y d e m o n s trate t h at (i ) w a s l a w f u ll y k n o w n t o t h e r ec ei v i n g P a rt y p r ior t o r ec e i ving t h e s ame w i t h o u t r e s t ricti on a s t o u se o r d i s c l o s ure ; (ii ) i s or be c o m e s ge n eral l y ava i l a b l e t o t h e p u b lic ( t h r o u g h n o b re a ch o f t h i s A g r e e m e n t ) ; ( i i i ) w a s o b t a i ned by th e rec e i v i ng P ar t y f r o m a t h i rd p a r t y fr e e of any o b l i g at i on o f c o n f i den tial i t y a t t h e t im e of di s cl o su r e ; ( i v) i s re q u ire d t o b e di s c l os e d b y la w or r e gu l a t i o n ; C o n t r a c t P a r t i c u l a r s m eans t h e C o n t ra ct P a r t i c u l a r s s e t ou t i n t h e f ron t - e n d of t h e A g r e e m e n t ; C o n t r o l m eans t h e p o w e r t o d i re ct t h e m a n a g e m e n t a n d po li c i e s o f a per s o n, d i re c t l y or i n d i re c tl y, wh et h e r t h r ough o w ne r s h i p o f v o t i ng s ecu ri t i e s, by c o n tra c t o r o t h e r w i s e ; C R O ha s t h e m e a n i n g g i ven i n th e R e ci t a l s ; 23 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G E X E C U T I O N V E R S I O N E ff ec t i ve D a t e m e a ns the d a t e s e t o ut in the la s t sig n a tu r e in r e s p ect o f t his A gr e e m e n t i s r ec ei v e d ; E x t e n d e d T e r m ha s t h e m e a n i n g giv e n t o it i n C l au s e 2 4 ; F o r c e Ma j e u r e m eans a n y e xt e rna l e v e n t beyond t h e c o n t ro l of a P a r t y , i nc l u d i n g b u t n o t lim i t ed to, f lo o d, d r oug h t , e a r t hqua k e or o t h e r n a t u r al di s a s t e r ; t e r ro ri s t a t t a c k, c i v il w a r, c i v il co m m o t i o n , p a n de mic o r e p i d e m i c , or r i o t s , w ar , a r m e d c on f l i c t , i m p osit i o n of s an c t i o n s , e m b ar g o , o r b r e ak i n g o f f of di plom at i c r e l a t i o n s ; or a n y l a w or any a c t ion ta k e n by a G o v e r n m e n t a l E n ti t y , i nc l u d i ng w it ho u t l i m itati on im p o s i ng a n e x p o rt o r i m po rt r e s tricti o n , q u o ta or pr o h i b i ti o n , w h i ch a r e n o t r ea s o n a b l y fo r e s e ea b le ; G e n e r a t e d D a t a m eans all d a t a r e lat ed t o o r a r i s ing ou t o f t h e c o ndu ct of e a c h S t u d y , inc l uding r e s u l t s, c o n cl u s i o n s , dis c o v e r ie s , d e ta i l s , summa r i e s or co p i e s o f i n f o r m a t i o n, m at e r i a l s , a nd d o c um e nt a t i o n b ut e x c l u d i n g a ny I R O S B ac k g r o und I P ; G o o d C l i n i c a l P r a c t ice s m e a n s curr e n t g o o d c l in i c a l pr a c tic e s g u i de l i n e s of t h e In t e r na t i o na l C on f e r e n c e o n H armoniz a t i on of Tec h n i ca l R e q ui r e m e nts for Re g is t r a tion of P h ar m a c euti c als f or H u m a n U se To p ic E 6 : Gu i de l i ne s o n G o od Cli n ic a l P rac t ic e, toge t he r w i t h s u c h o th e r G o o d C l i n i c a l P r a c t i c e req u i r e m e n t s a s m ay ap p ly w it h i n t h e Te rri t o ry or such o t he r te r ri t o r y wh e r e a S tudy i s b e i n g c o n duct e d, 2 0 0 8 s e t f o r th in th e H el s i n k i D e c l a r ati on of t h e Wo rl d M e d ic a l C o n g r e s s, a n d a l l i mp o r t a n t g u id i ng pr i nc i p le s r e lat ed to d r ugs a n d cli ni cal t r i a l s t h at t a k e e f fe ct im m ed i a t e l y ; G o v e r n m e n t a l E nt i t y m eans a n y co u rt, a dm i n i s tr at i v e bod y , l oca l a u t ho r i ty or o t h e r g o ve r n m e nt a l o r q u a s i - g o ve r n m en t a l en tit y w i t h c o m p e t en t j u ri sd i c t i o n , a n y s u p r a - na ti onal , n ati o n a l, fe de r a l, s t a te, m u n ici pa l, p r ovin c i a l or l oc al g o ve r n m en t a l , re g u l a t o r y o r a d mi ni s t r a t iv e a u t ho r it y, a g enc y, c ommi s s i o n , c o u r t , t r i b una l, a rb i tr a l b o d y, s el f - r e g u l a ted e n t i t y, p r i v a te b o d y e x e r ci s i ng any r e g u l a t o r y , t ax i ng, i m p or t i ng or o t he r g o v er n m en t a l or q u a s i - g o ve r n m en t a l au th or it y or oth e r g o v e r n m e n t al e n t i t y, i nc lu d i ng any r el eva n t Reg u l a to r y A u t h o r i t y ; I n i t i a l T e r m ha s t h e m e a n i n g g i ven t o it i n in t h e C o n tra c t P ar tic u l a r s ; I n t ell e c t u a l P r o p e r t y m eans pa t e n t s , u ti l i t y mo de l s , r i g h t s t o i n v en ti ons, c o p y ri g h t a nd n ei g h b or i ng and r e lat ed r ig h t s , t r a d e m a r ks, bu s i n e s s n a m e s a nd do m a in n a m e s, r i g h t s i n g e t - up a n d t r ad e dr e s s , good w i l l a n d t h e r i g h t t o s u e for p a ss i n g o f f , r i g h t s i n de s i g n s , ri ght s i n c o mp u t e r s o f t w a r e, d a t a b a s e r ig h t s , r i g h t s t o u s e , a n d p r o t ec t t h e co n f iden tiali t y of, c o n fi den t i a l i n fo r m a t ion (i nc lu d i ng k no w - h ow and t r ad e s ec ret s ) , and a l l ot h e r i n t e l l ec t u al p r o p e r t y ri g h t s , i n e a c h c a se w h e t h e r r e g i s t e r ed o r u n r e g i s t ered a n d i nc l u d i ng all ap p l i ca t i o n s a n d r i g h t s t o a p p l y f o r a nd b e g r an te d, re ne w al s o r ex te n s io n s o f, and r i g h t s t o c la im p ri or it y f r o m , a ny r i g h t s a n d a ll s i m i l a r o r eq u i v al en t rig h t s o r for m s o f p r o t e ct i on th at s u b s i s t o r w ill s u bs i s t now o r i n t h e f u t ur e i n a n y pa rt of t h e wor l d ; I n t ell e c t u a l P r o p e r t y R i g ht s m eans r ig h t s s u b s i s t i n g i n t h e I n t e l l e c t ua l P r o p e rt y ; I n s t i t u t i o n m eans any i n s t i t u t i on a p p o i n te d by C L I E N T t o de s i gn a n d c o n d u ct a S t u dy a t a S t u d y s i t e ; I n v e s t i g a t o r s m eans t h e i ndiv i d ua l( s) ap p o i nted by t h e I n s t i t u t i on a n d i s re s p o ns i b le f or th e co n d u c t o f a S t u d y a t S i t e s I R O S P e r s o n n el ha s t h e m e a n i n g g i ven t o it i n C l a u se 3 ; L o s s e s m ean s , c o l le c t iv e l y, a l l l o s s e s , d a m a g e s, lia b i li t i e s, r ea s o nabl e a tt o r n e y fe e s, c o ur t c o s t s , and e x pen s e s ; P e r s o n a l D a ta m eans m e an a n y i n fo r m a t i on r e la t i ng t o a n i d e n t i fi ed or i d e n t ifia b le na t u ral per s o n a n d any o t he r i n fo r m a t i on t h a t c ons tit ut e s pe r s o nal l y i d e n t i fi ab le i nfo r m a t i o n u n de r a ny P ri v a c y L a ws . T h i s w i l l i nc l u d e n um ber , and pr o t e c t e d h ea l t h i nfo r m a t i o n ; P r i v a c y L a w s m eans a l l A p p li cab le La w s r el a t ing t o p r i va c y and P e r s o na l D a t a prot e c tio n i n t h e UA E , i nc l u d i n g F e d e r al L a w by D e c r e e N o . 45 of 2 0 2 1 on t h e P ro te c t i o n o f P e r s o na l D a ta a n d t h e E x e c u t i v e R eg u l a t i o ns r e lati ng t o i t, F e d e r al L a w N o . 2 of 2019 o n t h e U se o f t h e I n f or m a t i on a n d C o m m u n ic a ti on Tec h no l o g y i n H e a lt h F iel ds and Ca b i n et D ec i s i o n No . 3 2 / 2 0 20 on t h e I m p l e m e n t i ng Re g u lati on of F e d e r a l L a w N o . 2 of 20 1 9 and M i n i s t e r i a l R e s o l u t ion N o .
( 5 1 ) o f 2 0 2 1 on C a s e s w he r e H ea l t h D a t a and I nfo r m a t i o n m a y b e s t or ed or t r a n s f err e d o u t s i d e t h e S t a t e , a s a m e n ded fr o m t i me t o t i m e , and any o t h e r r e l e van t j ur i s d icti o n , i n cl u d i ng th o se r el a t ing s p e c ific a l l y t o s u b ject i nf or m a t i o n a n d co n s e nt ; 24 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N P r o t o c o l m ea ns a ny St u d y p ro to co l a t t ac h e d to t h e r e l e v a n t W O ; R eco r d s m eans da ta r ec o r ds p e r t a i ning t o t h e S e rv i ce s p e r f o r m e d ; R e g u l at o r y A u t h o r i t y m ea n s a n y i n t e r na ti ona l, na t i o na l , o r o t h e r g o v er nm e n tal, reg u l a tor y, or a d m in i s t r a t i v e au t h or i t y , or ot h e r b ody c o m p e t e n t t o g r a n t a p pro v al s , r e g i s t r a t io n s , or o t h e r c o n s en t s f or t h e co n d u ct of cli n i c al t r i a l s or f o r t h e m a nu f ac t u r e , i m p o r t a t ion a nd d i s t rib u t ion of i n v e s t i g a t i o n al m e d ic i n a l p r odu c t s ; R e s e a r c h I P ha s t h e m e a n i n g g i ven i n C l a u s e 1 9 .3 ; S e r v i c e s ha s t h e m e a n i n g g i v e n t o i t i n C l a u s e 2.5 ; Si t e m ea ns a ny I n s t i t utio n ' s si t e w h e re t h e S t u d y is b e i n g c ond u c t e d ; S t u d y ha s t h e m e a n i n g g i ven t o i t i n t h e R ec i t a l s ; S t u d y D r u g m ea ns CL I E N T ( o r s u c h oth e r ph a r m a c eutic a l s p onsor w h o i s au t ho r i zi ng C L I E N T ) ph a r m ac e u t i ca l f o r m of an ac t i v e i n g r ed i en t or p l acebo or c o m p a ra t or p ro d u c t be i ng t e s te d or u s ed a s a r e f e r e n c e i n a S t u d y a s s e t o u t in a P ro t o c ol ; S t u d y S u p p l i e s ha s t h e m e a n i n g giv e n t o it i n C l au s e 6.2 . 1 ; S u b co nt r a c t o r ha s t h e m e a n i n g g i v e n t o i t i n C l a u s e 2 9 ; T e rr i t o r y ha s t h e m e a n i ng g i v e n t o i t i n t h e C o n tr ac t P a rtic u la r s ; U A E m eans t h e U n ite d Ar a b E m ir a t e s ; U A E C i v il C o d e : m eans F e d e r a l L a w N o. (5 ) o f 1985 on t h e Ci v il T r a n s ac t i o n s L a w of t h e U. A . E . V A T m eans t h e v a l u e - ad d e d t ax a s ap p l i ed i n t h e U A E; a nd W O ha s t h e m e a n i n g g i ven t o it i n C l a u s e 2.2. I n t e r p r e t a t io n 1. An y a m b i g u i t i e s i n t h e t e r m s o f t h i s A g r ee m e n t w i ll no t b e pre s u m p t i v el y c o ns tr ued for or a g a i n s t e i t h e r p a rt y . 2. H e adin g s a r e for conv e ni e nc e o n l y . 3. Th e s ched u l e s and e x h i b it s f o r m p a r t of t h i s A g r ee m en t. A ny r e f e re n c e to t h i s A g r ee m e n t i n cl u de s t h e s che d ul e s , e x h i bi t s a nd e x e c u te d W O s and C O s . 4. A s u s ed i n t h i s Ag re e m e n t i ng i ng w i t h o u t l im i t a t i o n . 5. Un le ss t h e c o n t ex t o t he r w i se r e q ui r e s , w or d s i n t h e s in g u la r s ha l l i nc l u d e t h e p l ur al and i n t h e p l u r a l s h a ll i nc l u d e t h e s i n g u l a r. 6. Un le ss ex p re ss ly p r ov i ded o the r w i s e i n t h i s A g r e e m e n t , a r e f e re n c e t o l e gi s l a t i on o r a leg i s lati v e p r o v i s i on i s a r e f e r e n c e t o i t a s a m e n d e d, e x t e n d e d or r e - enac t e d f ro m time t o t i m e . 25 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G E X E C U T I O N V E R S I O N S C HE D U LE 2 F O R M OF W O R K O R D ER T o be a tt a c h e d i n a s e p a r a t e c o v e r : 26 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G
S C H E D U L E 2 F O R M A T O F W O R K O R D ER T h i s W or k O rd e r N o . [ 1] ( W O C omm e r cia l s b e l ow b y a n d b et w ee n : t h e C o m m e n ce m e n t D a t e s e t o u t i n t h e K e y 1 ) [ T O B E CO M PLETE D ] C L I E N T ; a n d 2 ) I N S IGH T S P H A R M A C E U T I C A L R E S E A R C H LL C I R O S , p u r s u a n t t o t h e Ma s t e r S e r v ic e s A g re e m e n t d a t e d Ag r e e m e nt b et w ee n C L I ENT a n d IR O S . T h i s W O s p ec i f i e s t h e s e r v i ce s t o b e p r o v i d e d b y I RO S i n t h e T e rr i t o r y i n c o n n ec t i o n w i th t h e St ud y (t h e S e r v ice s ) a n d t h e d eta i l s f o r the fo ll o w in g : a) P r o t o c o l ( E x h i b i t A ) : b) S c o p e o f W o r k ( E x h i b i t B ) ( ; c) P r o je c t S c h e du l e ( E x h i b i t C ) ; d) P r o je c t B u dg e t ( E x h i b i t D ) ; a nd e) P a y m e n t S c h e d u l e ( E x h i b i t E ); a nd f) Cl i n i ca l T r ia l A gr ee m e n t te m p l at e ( E x h i b i t F ) . T h e P a r t i e s h e r e b y a g re e t h a t I RO S sh a ll p e r f o r m the S e rv i ce s i n t h e T e rr i t o r y a n d C L I E N T s h a l l p a y f o r s u c h S e r v i ce s, a l l i n acc or d a n c e w i t h t h e p r o vis i ons o f t he A gr e e m e n t a n d t h e te r ms o f t h i s WO. 1 . K E Y C O M M E R C I AL S I TE M D E T A I L S C o m m e n ce m e nt D a t e [ D a t e o f l a st s i g n a t u r e o f t h i s W O , p r o v i d e d b o t h P a r tie s s i g n / o r a s p eci f i e d d a t e i f a p p l ic a b l e ] T e r m C omm e n c e m e n t D a te u n t i l s at i s f a c t or y c o m p l e ti o n o f t h e Ser v i ce s , u n le ss t h i s W O i s t e rm i n at e d ea r l i e r i n ac c o r d a n c e w it h t he t e r ms of Ag r ee m e n t . P r o j ec t R e p r e s e n t at i v e M a n a g e r F o r C l i e n t : N a m e : [ In s e r t ] P o s i t i o n : [ In s e r t ] A dd r e ss: [ In s e r t ] T el e p h o n e : [ In s e r t ] E m a i l : [ In s e r t ] F o r I RO S : N a m e : [ I s la m E l T a nt a wy] P o s i t i o n : [ In s e r t ] A dd r e ss: [ In s e r t ] T el e p h o n e : [+ 97 1 5 45 3 5 3 5 5 1 ] E m a i l : [ is l am . e lta n ta wy @Se r vi c e P ro v i d e r .
a i ] S p o n s o r [ In s e r t d e t a i l s o f S p o nso r ] S t ud y T i t l e [ i n s e r t ] P r o t o c o l N u m b e r [ i n s e r t ] S t ud y D r u g s [ i n s e r t ] A n y R e q u i r e d E q u i p m e n t [ i n s e r t ] S t ud y A s s u m p t i o n s T h e k e y S t u d y a ss um p t i o n s on w h ic h t h i s W O h a s b ee n a g r ee d a r e a n d i n acc ord a n c e with w h ic h the S e r v ic e s s h al l b e p r ov i d e d a r e : N u m b e r o f S i t e s wi l l b e : [ i n s e r t ] R e c r u i t m e nt R a t e a ss u m p t i o n s : [ i n s e r t ] M i n i m um / M a x i m um T r i a l S u b j ec t s T o B e En r o l l e d : [ i n s e r t ] \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l 2 . D E F I N I T IO N S A N D I N T E R P R E T T IO N 2 . 1 Ca p it a lize d te r ms a r e a s d e f i n e d i n t h e A gr ee m e n t , u n l e ss o t h er wise d e f i n e d i n t hi s W O . T h e fo l l o w i n g w ord s s h a ll h a v e t h e fo ll o w i n g m e a nin g s f o r t h e p u r p o s e s o f this W O : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l D E T A I L S I TE M ] i n s e rt S i t e M a n a g e me nt A ss u m p t i o ns: [ ] i ns e rt ot h e r c a te go r i e s o f ap p l i c a b l e ass u mpt i o n s [ U A E Terr it o r y I R O S s h a l l p r o v i d e t h e S e r v i ce s i n t h e T er r i to r y i n acc o r d a n c e w i t h t h e S c o p e o f W o r k s e t o u t i n T a b l e 1 : S c o p e o f W o rk i n E x hib i t B . I R O S s h a l l d e l iv e r t h e S e rv ic e s a s p e r t h e a g r ee d ti m eli n e s s e t o u t i n t h e P r o je c t S c h e du l e a tt a c h e d h e r et o a s E x h i b i t C . T h e P a r t ie s ho w e v e r u n d e r s ta n d a n d a gr e e t h a t t h i s t i m el i n e is d e p e nd e n t o n t i m e ly a p p r ov a l o f k e y S t ud y d o c u m e n t s a n d a cti v i t ie s b y t h i r d p a r ti e s , i n c lu d i n g Re gu l a tor y Au t h o r iti e s, I R B a n d I EC a n d m a y n e e d t o b e a u t o m a t ica l l y e x t e n d e d i n a cc o r d a n c e w i t h Cla u se 7 o f t h e A gr e e m e n t or a m e n d e d b y f or m a l C O . S c o pe o f W o r k I R O S ' s ta nd a r d o p e r a t i n g p r o c e du r e s w i l l b e u s e d in p e rf o r m a n c e o f t h e S e r v ic e s t o t h e e x te n t a pp r o p r i at e , unl e s s o t h e r w i se s e t ou t i n t h e c o r r e s po n d i n g P ro t o c o l . A pp lic at i o n o f I R OS' SOPs I R O S, C L I E N T a n d In s t it u ti o n s h a l l e n t e r i n t o a t r i - p a r t it e c l i n i c a l t r i a l a gr ee m e n t ; a n d I R O S ' Cl i n i c a l T r ia l A g r e e m e nt te m p la t e w i l l be u s e d f o r c on t r act in g w it h In s t it u t i o n s. C l i n ic a l Tri a l Ag ree m e n t S h ou l d I R O S b e r e q u e s te d b y C L I E N T t o p e rf o r m a d d i ti o n a l s e rv ice s w h ic h a r e n o t i n cl u d e d in t h e s c o p e o f t h i s W O , t h e se s e rv ice s s h al l b e p r o vid e d by I R O S fo r a n a d d i t i on a l S er vi c e s F e e t o the S e r v i ce s F ee s s e t ou t in t h e P r o j ec t B u d g e t , w hi c h f e e s s h a l l b e m u t u al l y a g r e e d i n w ri ti n g i n a d v a n c e of t h e c o m m e n c e m e nt o f t h e a d d i ti on a l s e rv ice s . C L I E N T s h al l b e r e s p o n s i b l e fo r t h e c o st o f a ll P a s s - T hr ou g h Costs r e lat i n g to t h e s e a d d i ti o n a l s e rv ice s . A dd i t i o n a l S er v ice s s p on s o r o f t h e S t u d y t o r e m u n e r at e a n y In s ti t u t i o n s i n t h e T e rr i t o r y p a r tic ip ati n g i n the S t ud y a n d t h a t t h e CL I E N T w ill b e r e s p o n s ible f o r t h e d ir ec t p a y m e n t t o In s t it u t i o n s o f a n y f ee s, e x p e n s e s o r c o s t s i n c u rre d b y I n s ti t u t i o ns i n r e l ati o n t o t h e S t u d y . P a y m e nt o f f e e s , c o s t s a n d e x p e n s e s i n c u rre d by I n s t i t u t i o ns M e a n i ng D e f i n e d Ter m T h e S e r vi c e F ee s a n d P a s s - T hr ou g h C o s t s p a y a b l e b y C L I E N T to I R O S i n acc ord a n c e w i t h t h e P ro jec t B u d g e t s e t o u t i n E x h i b i t D a n d t h e P a y m e nt S c h e du l e s e t for t h in E xh i b i t E C h a r g e s T h e Ke y C o mm e r c i al s s e t o u t i n S ec t i o n 1 K e y C o mm er ci a l s T h e p a ss - t hro ug h c os t s s e t o u t i n P a r t 3 o f t h e P r o j ec t B u d g e t i n E xh i b i t D a n d s h a l l fo r t h e a v o i d a n c e o f d ou b t i n c l u d e a n y c os t s t h a t a r e n o t d ir ec t c o s t s i n c u r r e d b y I R O S ( su c h a s l a b o r c o s t s) i n t h e p e r f o r m a n c e o f S e rv ice s, i n cl ud i n g w it ho u t l i m it a ti on , c o s t s fo r S e r v i ce - r e l ate d t r a v e l a n d S u b c o n t r ac t o r s f ee s (o t h e r t h a n f or In s t it u t i o n s, w hi c h f ee s a r e p a y a b l e b y C L I E N T t o I n s ti t u t i o n d i r e ct l y ) f o r i t e ms s u c h a s pr i n ti ng , l a b or at o r y f e e s, s h i p p ing a n d f a c s i mi l e c o s t s , la ng u a g e t r a n s la t i o n , t e l e ph o n e c ha r g e s, a d v e r t i s i n g , i n v e s ti g a t o r m ee t i n g e xp e n s e s, a nd / o r o t h e r e xp e n s e s a ss o c i a te d wi th t h e c o n d u c t o f t h e Stu d y . T r a v e l c o s t s i n c lud e , bu t a r e n ot l i m i te d t o, t h o se a ss o cia t e d w i t h r e a s on a ble t r a n s p or tati o n ( E c o no my f a r e s fo r ai r p la n e t r i p s, 2 n d cla ss tr a v e l i n t r ai n s ) , l od g i n g ( 3 s t a r h o te l s m a x i m u m pr o v i d e d s u c h a r e a v a i l a bl e ) a n d m e a l s . P a ss T h r o u g h C o s t s T h e c urr e n c y c onv e r s i o n r a t e ( s) s e t o u t i n t h e P a r t 3 o f t h e P a y m e n t S c h e du l e at t ac h e d a s E x h i b i t E.
E x c h a n g e R at e 2. T h e E x h i b i t s t o t h i s W O fo r m a n i nt e g r a l p a r t o f th i s W O a n d a r e h er e b y i n c or po r a t e d b y r e f e r e n c e . 3. S a v e a s s p eci fi e d h e r ei n al l te r ms i n t h e A g r e e m e n t a r e d e e m e d i n c o r por ate d i n t h i s W O a n d s h a l l gov er n t h e p e r f o r m a n c e o f the P a r t i e s ob li g at i ons un d e r t h i s WO . 4. A n y c o n fl ic t b e t wee n t h i s W O a nd t h e A gr ee m e n t s h a ll b e r e s o l v e d in acc ord a n c e w i t h C l a u s e 2 . 2 o f t h e A gr ee m e nt . 5. W i t h r e s p ec t t o t he S e rv ice s p e rf o rm e d un d e r th i s WO, t h i s W O a n d t h e A gr ee m e n t , c o n t a i n t h e e n t i r e a gr ee m e n t of t h e Pa r t i e s i n re s p ec t o f t h e s ub j ec t m a t te r h e r et o . 3. P R O J E C T M A N A G E M E N T 1. C L I E N T h a s a pp o i n t e d t he C L I E N T Pr o je c t Re p r e s e nt ati v e w h o s h al l b e r e s p o n s i b l e fo r t h e c o ord i n ati o n o f al l m att e r s r e l a ting t o t h e S e r v i ce s . I RO S u n d e r ta k e s t o c omply w i t h t h e r ea s o n a b l e i n s t r u c tions o f C L I E N T a n d / o r CL I ENT , w hi c h m a y b e g i v e n f r om t im e t o ti m e i n w ri ti ng . 2. I RO S h a s a p p o i n te d the I RO S P r o je c t Re pr e s e n tat i v e w h o s h a ll b e r e s p o n s i b l e f o r t h e c o o rd i n a t i o n o f al l m at t e r s r e l a ting t o t h e d eli v e r y of S e r v i ce s on b e h al f o f I ROS . 3. T h e C L I E N T P ro j ec t Re p r e s e n t at i v e a n d t h e I RO S P r o jec t Re pr e s e n t ati v e s h a l l me e t a s of te n a s r ea s o n a b l y p r a cti c a b l e t o e n su r e e ff ic i e n t p e r f o rm a n c e o f the S e r v i ce s , [ a n d n o le ss t h a n o n c e in ea c h p e r i o d of t hr e e ( 3 ) m o n t h s und e r t h i s W O ] a t a pl ac e a n d ti m e t o be a g r ee d t o by t h e P r o j ec t Re pr e s e n t ati v e s . T h e se m eeti ng s m a y b e v i r t u al . 4. T h e I RO S P r o je c t Re p r e s e nt ati v e sh a ll: S e r v e a s a p r i m a r y p o i n t of c ommu n i cat i o n a n d r e s o u r c e f o r S tudy o v e r s i g h t f or C L I E NT , o t h e r s e r v i c e p r o v i d e r s a n d t h e S t u d y te a m ; C r eat e a m a n a g e m e n t fr a m e wor k t o op t i m iz e t h e s k il l s a n d p e r form a n c e o f fun cti o n a l le a d s, a n d dr i v i n g f o c u s a n d e x e c u t i o n o n t h e q u al i t y a n d e ffi cie n c y o f ind i v i du a l ta s k s; P r ov i d e pr o a cti v e le a d e r s h i p a nd d ir ect i o n t o t h e S t u d y t e a m, in cl u d i n g c o m p r e h e n s i v e p r o jec t p l a n s fo r mi le s t on e s , q u a li t y a n d bu d g e t a n d m ai n ta i n i n g c l ie n t - s p eci fi c g u i d el i n e s; D ir ec t t h e I R OS g l o b a l r i sk m a n a g e m e n t p r o c e s s, a dd r e s s i n g a n d mi ti g a t i n g po te n t ia l o b s tac l e s, a n d a ss u ri n g t i m el y a n d c os t - e ff ic i e nt pr o j ec t d el i v e r y ; U t il i z e I RO S s y s t e ms a n d p r o ce ss e s t o a ss u r e e ff ic i e n c y a n d a c c u r a c y t h r ough o u t t h e S tud y ; A t te n d r e g u l a r ca l l s w it h C L I E N T to d i s c u ss r ec r u i t m e n t , p ro t o c o l d e v i a ti o n s, s it e p e rf o rm a n ce , q u a l it y a n d ti m e l i n e s; a nd P r e p a r e a nd d e li v e r m o n thly r e p o r t s o n t h e p r og r e s s o f t h e S t u dy . 4. E X E C U T IO N 1. T h i s W O m a y b e e x e c u t e d i n a n y n umb e r o f c ou n t e rp a r t s e a c h o f w h ic h , w h e n e x e c u t e d , s h a l l c o n s t i tu t e a n o r igin a l, bu t a l l t h e c ou n te rp a r t s tog e th e r s h a l l c o n s t it u t e a s i n g l e b inding l e g a l d o c u m e n t . T h i s W O m a y b e e x e c u te d t h ro ug h t he u se o f a n el e ct r on i c s i g n a t u r e . T r a n s mi s s i o n o f t h e e x ec u te d s i gn at ur e p a g e o f a c o un te r p a r t of t h i s W O b y ( a ) f a x o r ( b) e m ai l (i n P D F, JPE G o r o t h e r a g r ee d f o rm a t ) to a n o t h e r P a r t y s h a l l t a ke e f f e c t a s d el i v e r y o f a n e x ec u te d c o un t e r p a r t o f t h i s W O . I f e i t h e r m et h o d of d e li v e r y is a d o p te d , w i t h o u t p r e j u d i c e t o t h e v al i d it y o f t h e W O t h u s m a d e , e a c h P a r t y sh a ll pro v i d e t he o t h e r s w it h t h e o ri g i n a l o f s u c h c ount e r p a r t a s s oo n a s r ea s o n a b l y p o ss i b l e t h e r e a f t e r . N o c o u n te rp a r t s h a ll b e e ff ec t i v e u n t i l eac h P a r t y h a s e x ec u te d a nd d e l i v e r e d a t l e a st o n e c o u n te r p a r t . [ S i g n a t ur e C l a u s e fo l l o w s] \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l T h e p r o t o c o l w i t h t h e p ro to c o l n u m b e r s p e c i f ie d i n t h e K e y C o mm e r cia l s a s a p p r o v e d b y C L I E N T, t h e E t h i c s C o mm i tt e e a n d t h e A b u D h a b i D e p a rt m e n t o f H e alt h , a n d a tt a c h e d a s E xh i b i t A . P r ot o c o l T h e c l i n ica l r e s e a r c h s e r vi ce s to be p r ov i d e d b y I RO S i n r ela t i o n t o t h e S t u d y u n d e r t h i s W O , t h e s c o p e o f w h i c h i s m o r e p a r t i c u l a r l y i d e n ti fi e d i n E x h i b i t B , i n cl ud i n g s er vi c e s w h i c h a r e i n ci d e n ta l o r a n ci l la r y t o s u c h s e r v i ce s . S er v ice s T h e s e r vi c e s f ee s s e t o u t i n P a r t 2 o f t h e P ro jec t Bu d g e t i n E x h i b i t D .
S er v ice s F e e I N W I T N E SS W H E R E O F , d u l y a ut h o r ize d r e p r e s e n t a t i v e s o f t h e P a r t ie s h a v e e x ec u t e d and d eli v e r e d t h i s A g r e e m e n t , i n du p l ic at e . A C K N O W L E D G E D , A C C E P T E D A N D A G R E E D T O: [ T O B E C O M P L ETE D ] I N S IGH T S PH A R M A C E U T I C A L R E S E A R C H LL C B y : B y : N a m e : T i t le : D a te : N a m e : T i t le : D a te : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l E X H I B IT A T HE P R O T O C OL \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l
E X H I B IT B S C O PE O F W O R K P A R T 1 : S E R V I C E S I RO S s h a l l pro v i d e t h e Se r vi c e s i n d i c ate d b y m a r k [ X ] i n r ela t i o n t o t h e S t u d y f o r t h e li f ec y cl e ( s ) o f t h e S t u d y s e t o u t in t h e c o l u mn t it l e d ' D u ra tio n ' , o r fo r s u c h oth e r p e r i o d a s m a y b e s p ec if ica l l y s t ate d i n C o l u mn 3 b el o w .
T a b l e 1 : S c o p e o f S e r v i ce s \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l S er v ice s A pp lic a b i li t y D u r at i o n U n i t P r i c e N u m b e r o f U n i t s T a s k P r i c e C l i n ic a l w r i t i ng [ i n s e r t ] ] [ i n s e r t ] [ i n s e r t c o st p e r ac t i v it y ] [ P la n n i n g ] [ X ] P r e p a ri n g p at i e n t i nfo r m a ti o n s h e e ts [ P la n n i n g ] P r e p a ri n g i n fo r m e d c o n s e n t f o r ms [ S ta r t - u p ] P r e p a ri n g S tudy p la n s P r e p a ri n g c li n ic a l s t u d y r e p o r ts i ns e rt o t h e r r e la te d [ e r vice s] s R e g u l at o r y Af f ai r s [ P la n n i n g ] P r e p a r a t i o n a n d m a n a g e m e n t o f cl i n i ca l t r ia l a p p l ica t i o n s [ P la n n i n g ] L o ca l E t h i c s C o mm it t e e S u b m i ss i o n a n d A ppr o v a l N a ti on a l In s t it ut i o n a l Re v ie w B o a r d S u b m i ss i o n [ P la n n i n g Cl o s i n g ] P r e p a ri n g a n d m a n a g i n g s u b s ta n t i a l a m e nd m e n t s [ Cl o s i n g ] P r e p a ri n g a n d s u b m i t ti n g e n d o f t ri a l n o t i f ic a ti on s t o Re g u l at or y A ut h or it i e s A nn u a l Re p o r t s t o E C s a n d Re gu la t o r y A ut h or it i e s i ns e rt o t h e r r e la te d [ e r vice s] s P r oj ec t M a n a g e m en t [ O n e ] m eet i n g d u ri n g S t a r t - u p K i c k - of f M ee ting T e r m of t h e A gr ee m e n t Cl i e n t I R O S m ee t i n g s a nd ca l l s [ M on t h l y ] Re p o rt i n g on S t u d y pr o gr e ss [ Rec ru it m e nt ] P r o je c t T ea m T r ai n i n g i ns e rt o t h e r r e la te d [ ] e r vice s s S t udy S i t e M a n ag eme nt and M o n i to ri ng [ S ta r t - u p ] S elec t i o n of S t u d y \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l T a s k P r i c e N u m b e r o f U n i t s U n i t P r i c e D u r at i o n A pp lic a b i li t y S er v ice s S ite ( s) Id e n t i f ic a ti o n a n d s ele c ti o n o f P r i n ci p a l In v e s t i g a t o r [ S ta r t - u p ] P r e - S t u d y Vi s i t [ Rec ru it m e nt ] S it e M a n a g e m e n t a n d C o - or d i n a t i o n [ S ta r t - u p ] S it e C o n t r a ct s In v e s t i g a t o r S i te F il e P r e p a r a t i o n [ Rec ru it m e nt ] S it e I ni t i a t ion V i s i t [o n e v i sit d u r i n g Rec ru it m e n t ] S it e M ai n te n a n c e V i s i t [ O n e v i s it dur i n g Cl o s u r e ] S it e Cl o s u r e V i s i t C o - or d i n a t i n g ac t i v it i e s ac r o ss t h e S t u d y S i t e s i ns e rt o t h e r r e la te d [ e r vice s] s C R O M a n a g e m e n t [ Rec ru it m e nt ] CR O - S p on s o r Call s i ns e rt o t h e r r e la te d [ e r vice s] s I n s u r a n c e [ S ta r t - u p ] A rr a ng i n g L o c a l In s ur a n c e Ce r t i f i ca te i ns e rt o t h e r r e la te d [ e r vice s] s R e g u l at o r y C ons ul t i n g i n re s p ec t o f In v e s ti g a t io n al M e d i ci n a l P r o d u c t ( I M P) [ S ta r t - u p Rec ru it m e n t ] Re g u l at or y c o n s u l t a n c y s e r v ice s i n r ela t i o n t o i m por tat i o n of IM P Re g u l at or y c o n s u l t a n c y s e r v ice s i n r el a ti o n t o s t or a g e a n d d el iv e r y o f I M P t o S tudy s i te s i ns e rt o t h e r r e la te d [ e r vice s] s I n fo r m e d C o n s e n t C ol lec t i o n C o llec t w ri tte n c o n s e n t o f eac h s u b je c t p a r t i ci p at i n g i n S t u dy , i n t h e f o r m a u t h o ri ze d b y t h e a p p l ica b l e Re g u l at or y A ut h or it i e s, i n cl ud i n g fo r c o lle c ti o n a n d u se o f s a m p le s a n d u se o f P e r s o n a l D ata .
i ns e rt o t h e r r e la te d [ ] e r vice s s R e c o r d s a nd Da t a M a n ag eme n t Ess e n t ia l D o c u m e n ta t i o n C o llec t i o n [ N o t e t o D r a f t e r : T a b le t o b e u p d a t e d t o i n c l u d e t h e s e r vi ce s t h a t I R O S wi l l b e p r ov i d i n g f o r t h e s p ec i f i c S t ud y . T h e s e r v i c e s n a m e d i n t h e t a b l e a r e n o t e x h a u s t i v e a n d s h o u l d b e a d d e d t o i f o t h e r s e r v i ce s a r e r e q u i r e d fo r a S t u d y . ] P A R T 2 : T R A N S F E R O F O B L IG A T IO N S L I S T T h e P a r t i e s h e r e b y a gr e e a nd ac k n o w l e d g e t h a t t h e C L I E N T t r a n s f e r s t o I RO S, wh o a s s um e s, r e s p ons i b i lity f o r t ho s e ac t i v it i e s s e t o u t i n T a b l e 2 : De l e g a t i o n o f A u t h o r i t y i n r e s p ec t o f wh i c h i t h a s e xp r e ss l y b ee n p r o v i d e d t h a t I RO S i s r e s po n s i b l e . C L I ENT s h a l l r e t a in r e s p o n s i b i l it y f o r al l o t h e r ac t i v it i e s . C L I E N T r e s e rv e s t h e r ight t o a ss u m e a n y o f t h e d u tie s d ele g at e d t o I R OS u nd e r t h i s W O a t a n y t i m e o n w ri tte n n o t ic e t o I RO S, i n w h i c h ca se T a b l e 1 : S c ope o f S e r v i ce s a n d t h i s T a b l e 2 : De l e g a t i o n o f A u t h o r i t y s h a l l b e a m e nd e d ac c o r din g ly .
T a b l e 2 : De l e g a t i o n of A u t h o r i t y F o r p u r p o s e s o f t h i s t a b le : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l T a s k P r i c e N u m b e r o f U n i t s U n i t P r i c e D u r at i o n A pp lic a b i li t y S er v ice s Rec or d S t o r a g e a n d A r c hi v i n g i ns e rt o t h e r r e la te d [ e r vice s] s S a f e t y M a n ag e m en t P r o ce ss i n g o f S e r i ou s A dv e r se E v e nts Re p o rt i n g of s e r i o u s u n e xp ecte d d r u g a d v e r se r eact i o n s ( S U S A R s) t o Re g u l at or y A ut h or it i e s, E th ic s C o mm it t ee s a n d In v e s t i g a t or s [ D e v e l o p s a f et y m o n i t or i n g p l a ns] i ns e rt o t h e r r e la te d [ e r vice s] s Qu a l i t y a nd C o m p l i a n c e T r ia l M a s te r F i l e P r e p a r a t i o n T r ia l M a s te r F i l e M a in te n a n c e Ret ur n o f T r i a l M a s t e r Fi l e Re v ie w o f s t a n d a r d o p e r a t i o n p r o c e d u r e s i ns e rt o t h e r r e la te d [ e r vice s] s R e cr u i t me nt of p a t ie n t s Rec ru it m e n t o f p ati e n t s [P a r tie s t o i ns e rt a ny o t h e r S e r vi ce s t h a t wi l l a pp l y t o t h i s W O ] F o ll ow - up A c t i v it ie s i ns e rt a n y f o l l o w - up [ ] cti v it i e s a ' R ' m ea n s ' Re qu e s te r ' ' A ' m ea n s 'App r ov e r ' ' I ' m ea n s [ i n s e r t ] . [ N ot e t o d r a f t e r: T a ble o f r e s po n s i b i l i t ie s t o be u p d a te d t o s u i t t h e sp ec i f i c S t u d y . T he l i s te d r e s p o n s i b i li ti e s a r e n o t e x h au st i v e . ] P A R T 3 : I R O S PE R S O N N E L I RO S s h al l m a k e use o f the f o l lo wi n g I ROS P e r s o n n e l f or p urp o s e s o f pr o v i d i n g t h e S e r v i c e s: ( A ) : E m p l oy ee s : ( B ) : C o n t r a c t o r s : ( C ) : C o n s u l ta n t s : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l R e s p o n s i b l e P a r t y I R OS C L I E N T Li f ec y cl e T a s k [I R O S] S t a r t - u p K i c k - of f M eet i n g [I R O S] S t a r t - u p P r o je c t M a n a g e m e nt [I R O S] S t a r t - u p S elec t i o n of S i t e s a nd I nv e s t i g at or s [I R O S] R S t a r t - u p P r e - s t u d y V isi t s [I R O S] R ec r ui t m e nt S it e M a n a g e m e nt a n d c o o r d i n at i o n [I R O S] R ec r ui t m e nt S i t e P a y m e n t P r o c e s s i n g a n d T r a c king [I R O S] R R ec r ui t m e nt T M F M a i n t e n a n c e [I R O S] R C l osu r e S it e Cl o s u r e V i s i t ( S C V ) [I R O S] R C l osu r e A nn u a l Re p o r t t o R A s a n d E C s [ Cl i e n t ] A I S t a r t - u p C R F D e v e l o p m e nt [ Cl i e n t ] I S t a r t - u p D a ta b a se S e t - up a n d V a li d a t i on [ Cl i e n t ] I S t a r t - u p E d i t C h e c k P ro g r a m i n g [ Cli e n t ] I Rec ru it m e n t D a t a Cle a n i n g a n d Q u e r y P r o ce ss i n g ( eCR F) [ Cl i e n t ] I R ec r ui t m e nt E x te rn a l D a t a T r a n s f e r R e c on c i l i ati o n [ Cl i e n t ] I R ec r ui t m e nt C o d i n g [ Cl i e n t ] I A C l osu r e D a ta b a se L o c k [ Cl i e n t ] I S t a r t - u p Ra n d o m iz a ti o n [ Cl i e n t ] I C l osu r e D B T r a n s fe r [ Cl i e n t ] I R ec r ui t m e nt eC R F Li c e n se Li f ec y cl e P o s i t i o n ] i ns er t [ Li f ec y l e D e t a i l s [ i ns er t ] Li f ec y l e D e t a i l s ] [ i ns er t P A R T 4 : S T U D Y S I T E S [ T h e S t u d y s h al l be ca rri e d o u t a c r o ss th e f o l l o w i n g S t u d y Si t e s: [ i n s e r t ] [ N ot e t o d r a f t e r : T h e a b o v e p r o v i s i o n s h o u l d b e po p u l a te d w i t h t h e p re - s ele c te d S t u d y S ite s if t h e C L I E NT i d e n ti fi e s t h e S t u d y S ite s t o w h i c h t h is W O a pp li e s a n d a c r o s s w h i c h S t u d y S it e s t h e S e r v i c e s s ha l l b e p r o v i d e d .] OR I RO S s h al l id e n t i f y [ i n s e r t nu m b e r ] a p p r op r ia t e s i te s i n the T e rr it or y fo r t h e c o n du c t i n g o f t h e St u d y , eac h s u c h s it e t o m ee t the s p e c i f ic a ti on s pr o v i d e d t o I RO S b y t h e C L I E N T . T h e r e s h o u l d b e [ o n e ( 1 ) ] S t u d y S i t e i n e a c h [ c o u n t r y ] i n t h e T e r r i t o ry , or su c h oth e r num b e r o f S t ud y S ite s a s m a y b e s p eci f i e d b y t h e C L I E N T i n eac h [ c o u n t r y ] i n t h e T e r r i t o r y o r i n eac h s p ec if ie d c ou n t r y i n t h e T e rr i t o r y b y t h e C L I EN T . [ N ot e t o d r a ft e r : t h e a b o v e p r o v i s i o n s h o u l d b e u s e d i f I R O S i s r e q u i r e d t o i d e n t i f y t h e S t u d y S i t e s a s a S e r v i c e u n d e r t h i s W O . ] \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l
E X H I B IT C P R O J E C T S C H E D U L E S T U D Y T IM E L I N E T h e t im el i n e ins e r t e d i n t h i s a t tac hm e n t in d i c ate s t h e a n t i ci p ate d du r at ion o f t h e p r i ma r y S t ud y act i v i ti e s . T h i s t im el i n e i s d e p e n d e n t o n t i m e ly a pp r o v a l o f k e y S t u d y d o c u m e n t s a n d a c tiv i ti e s by C L I E N T a nd ot h e r t h i r d p a r ti e s ( e . g . I R Bs/ I E C s/Si te s) a s n e c e ss a ry . A d just m e nts t o t h i s t im el i ne d u ri n g t h e i n i tia t i o n o f t h e S t u d y ma y h a v e a ca s ca d e e f f ec t o n t h e r e m ai n d e r of t h e ti m eli n e a n d t h e bu dg et . Thus, t h e S t u d y t im el i n e m a y b e a m e n d e d i f r e g u l at o r y a pp r ov a l i s d e l a y e d /e x p e d it e d o r if a n a m e n dm e n t t o the P ro t o c o l r e q u i ri n g I R B / I EC a ppr o v a l is m a d e o r i f r ec ru it m e n t d ela y e d /e x p e d i t e d ; t h e r e v ie w e d ti m e l i n e s sh o u l d b e a gr ee d b y t h e P a r t i e s i n a C O) . \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l M o n t hs D ay s T o F r o m Ph a se P l a n n i ng S t a r t - up R e cr u i t me nt V a cc i n at i o n / F o ll ow - up D ata b a se L o c k C l o s i n g T o t a l E X H I B IT D P R O J E C T BUD G E T P a r t 1 : C H A R G E S 1.
A l l C h a r g e s u n d e r t h i s E x hi b i t a r e to b e i n voi c e d a n d p ai d i n U S D , u s i n g the E x c h a n g e Ra t e . 2. A l l a mo u n t s li s te d h e r ei n a r e e x c l u d i ng V A T o r o t h e r s ale s o r w i t h h o l d i n g ta x e s . I R O S s h a l l b e p ai d t h e V A T i n a dd it io n t o t h e a m ou n t s s e t o u t i n t h i s E x h i b i t (o r a s p r ov i d e d i n T a b l e 1 : S c op e o f S e r v i c e s i n E x h i b i t B , a s a pp li c a b l e ) . 3. T h e t o ta l Ch a r g e s u nd e r t h i s W O ar e ca pp e d a t [ T O B E CO M PLETE D ] . P A R T 2 : S E R V I C E S F EE S S e r v i ce s F ee s will b e b a s e d o n a c t u a l n u mb e r o f S t ud y S ite s, s u b j e ct s r ec ru it e d a n d m a n - mo n ths . T h e S e r v i ce s F ee s s h a l l b e ca l c u l ate d a s t h e s um o f a l l a p p l i ca b l e ta sk pr i ce s s e t o u t i n T a b l e 1 : S c o p e o f S e r v i ce s i n P a r t 1 o f E x h i b i t B [ le ss a n y a gr ee d d i s c o u nt] , w h ic h a m o u nt s h al l b e a s fo l l o w s fo r p u r p o s e s o f t h i s W O : P A R T 2 : P A SS - T H R O U GH C O S T S T h e C L I ENT a gr ee s th a t al l e x p e n s e s i n c u r r e d b y I RO S in r elat io n t o t h e f o ll o w i ng ca t e go r ie s o f p a s s - th ro ug h c o s t s s h a l l b e d e e m e d t o be a p pr o v e d P a s s - T hr o u g h C o s t s fo r w h i c h t h e C L I E N T s h a l l b e l i a b l e du r i ng t h e te rm o f t h i s W O : [ N o t e to d r a ft e r : T a b l e d o e s n ot s e t o u t a n e x ha u s t i v e li st o f p a s s - t hr o u g h c o s t s . T h e se w i l l n ee d t o b e u p d a t e d o n a S t u d y - b y - S t u d y b a s i s . ] [ T h e i t e m pr ic e f o r eac h o f t h e c a te go r i e s o f P a ss - T hr o ugh C o s ts s e t o u t i n the t a b l e a bov e sh a l l b e a u t om a t ica l l y i n c r ea s e d i n l in e w it h a n y i n c r e a s e s i n t h e e xp e n s e s i n c ur r e d b y I RO S f or ca r r y i n g o u t a n y s u c h ta sk d ur i n g t h e te rm o f t h e W O , w i th e ff ec t fr om t h e d at e s u c h t a sk pr ic e h a s b ee n i n c r ea s e d . ] P a s s - T hr o ug h C o s t s w i l l b e p ai d b y t h e C L I E N T .
\ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l ] i n s e r t [ S u m of a l l T a s k P r i ce s ( U S D ) ] i n s e r t [ D i s c o unt ( i f a p p l i c a b le ) ] i n s e r t [ T o t a l S e r vi c e s F e e (af t e r d i s c o u n t i f a p p li c a b le ) I t e m Ex pe nse ( U S D ) N u m b e r o f U n i t s U n i t P r i c e ( U S D ) E x p e nse I t e m E t h i c s Co m m i tt ee s a nd R e g u l at o r y F e e s F i x e d M o n t h l y Ph o n e C o s t s S t udy I n s ur a n c e C o u rie r , P r i n t i ng & O t h e r S i t e V i s i t E x p e ns e s L a b o r at o r y f ee s L a n g u ag e t r an s la t i o n c o s t s A d v er t i s i ng c o s t s I n v e s t i g a to r m ee t i ng e x p e n s e s Tr a v e l c o s t s H o s p i ta l i t y T o t a l C o ul d w i th h o ld i ng t a x e s C o mm en t : C o mm e n t e d [ 1 ] : a p p l y in a n y c i r c u m s t a nce s i n r e l a ti o n to t h e Ch ar g es ? E X H I B IT E P A Y M E N T S C H E D U LE 1 . P A Y M E N T S C H E D U L E [I n r e s p ec t of eac h m on t h u nd e r t h i s W O ( w i t h e ff ec t fr o m t h e E ff ec t i v e D a t e ) , I R OS w i l l i nv o i c e C L I E N T fo r t h e S e r v i c e F ee s a n d P a s s - Th r o u g h C o s t s i n c u r r e d b y t he C L I E NT i n t h a t m o n t h . C L I E N T s h a ll p a y eac h i nv o i c e wi t h i n t h ir t y ( 3 0 ) d a y s o f t h e d a t e o f r ecei p t o f s u c h i n vo ice . O R : T h e P a r t i e s h a v e a g r ee d t h a t t h e S e r v ic e F ee s s h al l b e p a i d b y C L I E N T t o I R OS i n [ i n s e r t n umb e r ] i n s ta lm e n t s, eac h f o r t h e a m o u n t s s e t o u t b e low ( " S e r v ic e F e e I n s t a l m e n t s " ) . T h e fir s t S e rv ic e F e e In s t al m e n t s h a l l be p ai d t o I R O S i n a d v a n c e ( a n d a s a d o w n p a y m e n t f o r t h e S e r v i ce s) i n t h e a m o un t s e t o u t i n the ta b l e b e l o w . In s t all m e n t s s h al l o t h e rw i se b e p a y a ble i n r e s p e c t of c om p l et i o n a p p li c a b l e m il e s t o n e o n t h e t e r ms s e t out i n t h e t a b l e b e l o w . I n r e s p e c t o f ea c h s ub s e qu e n t S e rv ic e F e e In s tal m e n t , I R O S s h a l l b e e n t i tl e d to i n v o ic e C L I ENT fo r t h e r ele v a n t S e r vi c e F e e In s t al m e n t o n o r a f t e r t h e a sso c ia t e d m i l e s to n e a s d e f i n e d in t h e t a b l e b e l ow h a s b ee n ac h ie v e d . T o g e t h e r w it h t h e S e rv ic e F e e I n s t al m e n t, I R O S s h al l in v o ic e C L I E N T f o r al l P a ss - T hr o ug h C o s t s i n c urr e d d ur i n g t h a t p e r i o d [ a nd a s s e t out i n t h e t a b l e b el o w] . C L I E N T sh a ll p a y e a c h i n v o ic e w it h i n thi r t y ( 3 0 ) d a y s o f t he d a t e o f r e c ei p t o f s u c h i n v o i ce . M i le s t o n e C o s t T e r m s E x ec u ti o n of t h e W O D ow n P a ym e nt S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD [ S t u d y A p p r o v a l & Si te I n i ti a ti on ] S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD A ft e r 3 0 d a y s o f i nv o ic e s u bm i ss i o n [ i n s e r t ] S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD A ft e r 3 0 d a y s o f i nv o ic e s u bm i ss i o n [ i n s e r t ] S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD P A R T 2 : A D V A N C E D P A Y ME N T A n y p o r t ion o f a ny a dv a n c e p a ym e nt m a d e un d e r t h i s W O s h al l b e r e f u nd a b l e t o t h e C L I E N T t o t h e e x te n t t h e a mo u n t o f t h e a d v a n ce d p a y m e n t i s gr eate r t h a n t h e act u a l C h a rg e s d u e b y t h e C L I E N T f o r t h e Se r vi c e s c o mpl e t e d d u ri n g t h e p er i o d t o w h ic h t h e a d v a n c e p a y m e n t r e l ate s, p r o v id e d t h a t I R O S s h al l on l y b e r e qu i r e d to re i m b u r se t h e C L I E N T fo r t h e d i f f e r e n c e b e tw ee n t h e a m ou n t p ai d a s a n a d v a n c e p a y m e n t a nd t h e act u a l C h a r g e s d u e un d e r t h i s W O fo r t h e S e r v ic e s t o wh ic h the a dv a n c e p a y m e n t r ela t e s , o r t h e p e r iod t o w h i c h t h e a d v a n c e p a y m e nt r el a te s .
A ft e r 3 0 d a y s o f i nv o ic e s u bm i ss i o n \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l P A R T 3 : I N V OI C I N G 1 . I nvoi ce s a r e s u b j e c t t o t h e r e v ie w o f P r o j ec t Re pr e s e n t at i v e s a n d I RO S sh a ll pr o v i d e t h e n e ce ss a r y s u pp o rt i n g d o c um e n t s o r j usti f i ca tion i f r e qu e s t e d . 2 . I n vo ice s s h a l l b e a d d r e ss e d t o : p a y m e n t s@ g 4 2 . a i 3. E a c h i n v o i c e mu s t i n c l u d e t h e f o l l o w i n g m i n i m u m d e t a il s : - t h e fu l l b u s i n e s s n a m e a n d a dd r e s s of I RO S i n cl ud i n g t h e t a x / V AT re g i st r a t i o n n umb e r o f I RO S ( if a p p l ica b le ) ; - t h e ti m e p e r i o d t o w hi c h t h e i nv o i c e r ela t e s a n d t h e l o cati o n o f t h e s u p p l y ( i f a p p l ica b l e fo r t a x p u r p o s e s ) ; a nd - I RO S ' b a n k a nd acc o u n t d et a il s fo r p a y m e n t . P A R T 4 : E X C H A N GE R A TE 1 . F o r p u r p o s e s o f d et e r m ining a l l a m o u n t s to b e i n vo i ce d u n d e r t h i s WO, I R O S sh a ll m a k e u se of t h e [ i n s e r t / U S D ] e x c h a ng e r a t e d e t e rm i n e d by [ i n s e r t i n s t i t u ti o n / i n d e x] . I R O S s h a l l a pp l y t h e a pp lica b l e c urr e n c y c o n v e r s i o n r at e a s d e t e r m in e d b y [ i n s e r t i nst i t u tion / in d e x ] o n the d at e o f i n v o ic i n g . \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l E X H I B IT F C L I N I C A L T R I A L A G R EE M E N T T E M P L A T E \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l
E X E C U T I O N V E R S I O N S C HE D U LE 3 F D A R EQ U I R E M E N T S U n i t e d St a te s F o od an d D rug A d m i ni s t r a t ion Re g ul a t i ons f or C l ini c a l T r ials (Ti t le 2 1 CF R P a r t s 5 0 a n d 5 6 ) : T o b e a tt a c h ed i n a s ep a r a t e c o v e r : 2 7 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 21CFR5 0 (enhanced display ) page1 of 1 7 2 1 CFR Part 5 0 (Sept.
2 5 , 202 5 ) Th i s content is from the eCFR and i s authori tat i ve but u nofficia l . Title 2 1 - Food and Drugs Chapter I - F o od and Drug Admini s tration, Department of Health and Human Serv i c es S ubchapter A - General Part 5 0 .P. r ! . ! . --- .f.. . . !:: ! . . - . Q . . - J !i ! . s ubpart A - - r . ! . .P.rQY . ! . J g . - † 5 0 . 1 . † . <:?. . P. . : . † 5 0 . 3 P . . - . ! ! . . - . : . S ubpart B . ! . . f . Q . - . . g . Q . . :: ? . ! . . f . . . . - - . Q .. - J <:?.. ! . . † 5 0 . 20 - - - E . ! . E 9 . . ! r - ! . f r . ! . f9 . E . Q .. . - - ! . : . † 5 0 . 22 - £ P ! . . ! 2 n . fr . 2 . . ! . Q . f . 2 . r . . - . £2. Q . . n ! . . r . . 9 . . ! .r . . . Q ! . . f 2 r . . . . ! . Q . ! . . ! . . r i . . --- . ! . ! . . ! . £ . ! .. ! QY . . ! . . ! 9 . . ! . ! . 2 n . : . † 5 0 . 23 - 9 . P ! . ! . Q . . f . 2 . .. . 9 . . - r . ! . . . r . . 9 . . ! E . . . Q ! . . : . † 5 0 . 24 - 9 . P ! . . ! 2 . . fr . Q . . . ! . f . 9 . . . . . Q .. 9 . . . - - . .. . . 9 . . ! E . - ! . . . . f9 . r .. - r. 9 . Q'?.Y. . . . E . . : . † 5 0 . 25 . ! . . ! . 9 . . f . . ! . . f . 9 . r . . .. - - . Q . : . † 5 0 . 27 P . !:? . . - - ! ! ! . Q . . . . Q f .. ! f2 . . . - . . !?.2 . . - - . . : . Subpart C [Reserved] s ubpart D A . . . ! ! . 2 . . . ! . f . 9 . r . . . f r . . G . . ! . ! r . ...! . . . g . ! . ! . . ! . . ! . . ! .Y . . . . . ! . 9 . ! ! . Q . . † 5 0 . 5 0 . ! . R . -- - ! . . ! . . . : . † 5 0 . 5 1 _ g _ ! . ! . . ! . £ . ! J Y . . ! . . ! 9 . . ! . ! .!:? . . . · -- - ! . .. ! .Y . . ! .Y . . ! . Q 9 . . 9 r . ! . r . . ! . . -- · - ! . .! . . !... r ! . . : . † 5 0 . 52 _ g _ ! . ! . .!. £ ! . J Y . . ! . . ! 9 . . ! . ! .9 . . . . . ! . QY . Q . !Y . ! . . 9 . 9 . r . ! . - - ! . Q . . .! . . ! . . . ! . . r ! . - - · - ! . .P.r - - . ! . . 9 . . ! . - - Pr P ! 9 . . f... . ! . r . ! . - - f l . .Q..!. . .!.Y ! . . - . ! . . . - 1 £ ! . . : . † 5 0 . 5 3 . g . ! . ! . . ! . 9 . . ! J .Y . . ! . . ! 9 . . ! . ! . !:? . . . . . . ! . QY . Q . !Y . ! . 9 . . . 9 . . ! . -- . - . . . . ! . Q! . ! . .. ! . .. - . --- . Q . . P . 2 . P . . 9 . . 2 . ! . . Q . ! . . - - . - . . 9 . . . ! . Q . ! .Y . . ! . . . ! . . . . - j · - ! . . ! . . . . . . .. ! . ! . . ! .Y . . ! . Y . ! . ! . . 9 . . - . !.!. . ! . . - r:?..'!!. . ! . . 9 . . .. . - . . . . - - j ' . . .. - 2 . - . 9 !. . . £ 2 . . Q . ! ! . 2 Q . . . † 5 0 . 54 _ g _ ! . ! . Q . ! . 9 . . ! . . ! . .Y . . . ! . . ! 9 . ! . ! . Q . . --- - ! . . . . . ! . . . .P.P . ? Y . . . . ! . . . ! . . .P.r - - . . -- .P. P . !:? . . ! . . ! Y .. 2. - - - ! . . ! . - - - P. Y . . ! . ! . . 2 . . . . ! . ! . . Y ! . ! . . . . r 2 . . . P r . . ! . --- - f . f . ! . ! . Q . 9 . .. . h .. b . - ! . . 2 r . . - ! f r . .Qf chi l dre n . † 5 0 . 5 5 . .9 . . ! . . ! . . . . f . ? r . . P . r . ! . . . i . 2 . . . Y . . . P. . ! . . E . . 9 . . . - . ! . . Q . . . Q . . f . . .. . - ! . . Y . ... . ! E . . : . † 5 0 . 5 6 Wards. P ART S O - PR O TE C TION OF HUMAN SU B JE C T S Authority: . . } ... . : : . 9 . : .. ?. J . .. .. . - . - . . . Q . . . Q ? . ?.?.. - . . . . † . • . . 9 . .. - Q . . Qf, . . Q . . . . Q j _. ?. J . .. ? . - J . . : ? . . . : : . 9 . : . ? . 1 . .. ? . J . ? . ? . · S o urc e : - . E . . . 9 . .. May 3 0 , 198 0 , un l ess otherw i se noted.
pa g e2 of t7 21CFR5 0 . 3 (b)( 7 ) ( enha n ced display) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR SD.1 S ubpart A - General Provi s ions † 5 0 . 1 Scop e . ( a ) Th i s part applies to all c l i n i cal i nvest i gat i ons regu l ated by the Food and Drug Adm in i strat i on under sect i ons 505 ( i ) and 520( g ) of the Federal Foo d , Drug, and Cosmet i c Ac t , as well as clin i cal i nvest i gat i ons that support app l i cat i ons for research or market i ng perm i ts for products regu l ated by the Food and Drug Adm in i strat i o n , i nc l ud i ng foods, i nclud i ng d ietary supp l ements, that bear a nutr ient content c l a i m or a hea l th c l a i m , i nfant formu l as, food and co lor add i t i ves, drugs for hu man us e , med i cal dev i ces for human use, b i o l og i cal products for human us e , and e l ectron i c product s . Add i t i onal specific ob l i gat i ons and comm i tments of, and standards of conduct fo r , persons who sponsor or mon i tor cl i n i cal i nvest i gat i ons i nvolv i ng part i cu l ar test art i c l es may a l so be found i n other parts ( e . g . , parts 312 and 812) . Compliance w i th these parts is i ntended to protect the r i ghts and safety of subjects i nvo l ved i n i nvest i gat i ons fi l ed w i th the Food and Drug Adm i nistrat i on pursuant to sect i ons 403 , 406, 409, 4 1 2 , 41 3 , 50 2 , 50 3 , 50 5 , 51 0 , 5 13 - 51 6 , 518 - 52 0 , 7 2 1 , and 801 of the Federal Foo d , Dru g , and Cosmet i c Act and sect i ons 3 5 1 and 354 - 360 F of the Pub l i c Hea l th Serv i ce Act. ( b ) References i n this part to regu l atory sect i ons of the Code of Federal Regu l at ions are to chapter I of t i t l e 2 1 , un l ess otherwise note d . ( 1 . . . E . l . ! : . . ? . . ? . ! ! t May 30, 1980; . F . ! t Jan. 27, 198 1 , as amended at . . ? . . E . ?. . . . !.t May 13, 1998 ; . . 1 . . E . . ! Jan. 1999; . . . . F.. ? Q . !.t Apr. 2 4 , 2001] † 5 0 . 3 D e finition s . As used i n th i s part: (a) Act means the Federal Food, Dru g , and Cosmet ic Act, as amended ( secs. 201 - 90 2 , 52 Stat. 1040 et se q . as amended ( ? . . 1 . .. . : . : . : .. .1 . : . ? . )). (b) Application for research or marketing permit i nc l udes: (1) A co l or add i tive pet i t i o n , descr i bed i n part 7 1 . (2) A food add i t i ve pet i t i o n , descr i bed i n parts 1 7 1 and 57 1. (3) Data and i nformat i on about a substance subm i tted as part of the procedures for establish i ng that the substa n ce is generally recognized as safe for use that resu l ts or may reasonably be expected to resu l t, d i rect l y or i nd i rect ly , in i ts becom i ng a component or otherw i se affect i ng the character i st i cs of any foo d , descr i bed i n . † . † . . J . . ? . Q : 9 . . and . ?.9 . : . .Q. (4) Data and i nformat i on about a food add i t i ve s u b m i tted as part of the procedures for food add i tives perm i tted to be used on an i nter i m bas i s pend i ng add i t i onal stud y , descr i bed i n . † J . 9 . : J . : (5) Data and i nformat i on about a substance subm i tted as part of the procedures for establish i ng a to l erance for unavo i dab l e contam i nants i n food and food - packagi ng mater i a l s , descr i bed i n sect i on 406 of the act. (6) An i nvest i gat i onal new drug applicat i o n , descr i bed i n P. . . J . ? . . . 2 . . ! . . . £ . . l?. ! . f . · ( 7 ) A new drug applicat i o n , descr i bed i n part 31 4 .
2 1 CF R S 0 . 3 (b)(2s) (enhanced dis p l ay) pa g e3 of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S0 . 3 (b)( 8 ) (8) Data and i nformat i on about the b i oavailabil i ty or b i oequ i val ence of drugs for hu man use s u b m i tted as part of the procedures for i ssu i ng, amend i n g , or repea l i ng a b i oequ i va l e n ce requ ir e ment, descr i bed i n part 32 0 . (9) Data and i nformat i on about an over - the - counter drug for human use subm i tted as part of the procedures for c l ass i fyi ng these drugs as generally recognized as safe and effect i ve and not m i sbrande d , descr i bed i n part 330 . ( 1 O ) Data and i nformat i on about a prescri pt i on drug for human use subm i tted as part of the procedures for c l ass i fy i n g these drugs as generally recogn i zed as safe and effective and not m i sbrande d , descr i bed i n this chapter. (11) [Reserved] (12) An app l i cat i on for a b i o l og i cs l icens e , descr i bed i n p . . Q . } .. . ! . . . i . . . . .P . ! . - (13) Data and i nformat i on about a b i o l og i cal product subm i tted as part of the procedures for determ i n i ng that licensed b i o l og i cal products are safe and effect i ve and not m i sbranded, descr i bed i n part 601. (14) Data and i nformat i on about an i n v i tro d i agnost i c product subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for these product s , descr i bed i n part 809. (15) An Application for an lnvestigational Device Exemptio n , descr i bed i n part 81 2 . (16) Data and i nformat i on about a med i cal dev i ce subm i tted as part of the procedures for class i fying these dev i ces, descr i bed i n sect i on 513. (17) Data and i nformat i on about a med i cal dev i ce subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for these dev i ce s , descr i bed i n sect i on 514. (18) An app l i cat i on for premarket approval of a med i cal dev i c e , descr i bed i n sect i on 5 15. (19) A prod u ct devel opment protocol for a med i cal dev i c e , descr i bed i n sect i on 5 15. (20) Data and i nformat i on about an e lectron i c product subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for these product s , descr i bed i n sect i on 358 of the Pub l i c Hea l th Serv i ce Act. (21) Data and i nformat i on about an e lectron i c product subm i tted as part of the procedures for obta i n i ng a var i ance from any e l ectron i c product performance standar d , as descr i bed i n † . . . . . Q . . 9 : . · (22) Data and i nformat i on about an e lectron i c product subm i tted as part of the procedures for grant i n g , amend i n g , or extend i ng an exempt i on from a rad i at i on safety performance standar d , as descr i bed i n . † .J . 9 . . 1 . 9 . : . † . · (23) Data and i nformat i on about a cl i n i cal study of an i nfant formu l a when subm i tted as part of an i nfant for m u l a not i ficat i on under sect i on 4 12(c) of the Federal Foo d , Drug, and Cosmet i c Act. (24) Data and i nformat i on submitted i n a pet i t i on for a n utr i ent content cla i m , descr i bed i n . † . J . 9 . 1 . . † . . . f. ! . . ! .. . 9. P . ! E · or for a hea l th c l a i m , descr i bed i n † .. . } . 9 . 1 . : .?.. 9 . f. . . ! . . 9 . . .P . ! . - (25) Data and i nformat i on from i nvest i gat i ons i nvolv i ng ch il dren subm i tted i n a new d ietary i ngred i ent notif i cat i on, descr i bed i n . † . . . Q : . † . f. . ! . ! . . . P . ! . -21CFR5 0 . 3 ( m ) (enhanced disp l a y ) pa g e4of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 5o.3( c ) (c) Cli n ical in v estigation means any experiment that i nvo l ves a test art i c l e and one or more human subjects and that e i ther i s subject to req u i rements for pr i or subm i ss ion to the Food and Drug Adm i nistrat i on under sect i on SOS ( i ) or 520 ( g ) of the act, or i s not subject to requi rements for pr i or submiss i on to the Food and Drug Adm i n i strat i on under these sect i ons of the act, but the resu l ts of whi ch are i ntended to be subm i tted l ater to, or he l d for i nspect i on b y , the F ood and Drug Adm i n i strat i on as part of an app l i cat i on for a research or market i ng perm i t. The term does not i ncl ude exper i ments that are subject to the provis ions of P . . r . . . ? . . . ? .f. . . ! . S . P . . E · regardi ng noncli n i cal laboratory stud i es. (d) Investigator means an i nd i v i dual who actual l y conducts a c l i n i cal i nvest i gat i o n , i.e . , under whose i mmed i ate d i rect ion the test art i c l e is adm i nistered or dispensed t o , or used i nvo l v i n g , a subject , o r , i n the event of an i nvest i gat i on conducted by a team of i nd i v i dua l s, i s the respons i b l e l eader of that team. (e) Sponsor means a person who i n i t i ates a c l i n i cal i nvesti gat i o n , but who does not actually conduct the i nvest i gat i o n , i . e . , the test art i c l e is adm i nistered or dispensed to or used i nvo l v i n g , a subject under the i mmed i ate d i rect ion of another i nd i v i dual. A person other than an i nd i v i dual ( e . g . , corporat i on or agency) that uses one or more of i ts own emp l oyees to conduct a clin i cal i nvest i gat i on i t has i n i t i ated i s consi dered to be a sponsor (not a sponsor - i nvest i gator ) , and the emp loyees are cons i dered to be i nvest i gators. (f) Sponsor - investigator means an i nd i v i dual who both i n i t i ates and actually conduct s , a l one or w i th others, a clin i cal i nvest i gat i o n , i.e . , under whose i mmed i ate d i rect i on the test art i c l e i s adm i nistered or dispensed t o , or used i nvo l v i n g , a subject. The term does not i nc l ude any person other than an i nd i v i dua l , e . g . , corporat i on or agency. (g) Human subject means an i nd i v i dual who i s or becomes a part i c i pant i n researc h , e i ther as a rec i p i ent of the test art i c l e or as a control. A subject may be e i ther a hea l thy human or a pat i ent. (h) Institution means any pub l i c or pr i vate ent i ty or agency ( incl ud i ng Federa l , Stat e , and other agencie s ) . The word facility as used i n sect i on 520 ( g ) of the act i s deemed to be synonymous w i th the term institution for purposes of this part . (i) Institutional review board ( IRB ) means any boar d , comm i tte e , or other group formal l y des i gnated by an i nst i tut i on to rev i ew b i omed i cal research i nvo l v i ng humans as subject s , to approve the i n i t i at i on of and conduct per i od i c rev i ew of such research. The term has the same mean i ng as the phrase institutional review committee as used i n sect i on 5 2 0( g ) of the act. 0) T e st a nicle means any drug ( i nclud i ng a b i o l og i cal product for human use ) , med i cal dev i ce for human us e , human food add i t i v e , co l or add i t i v e , e l ectron i c product, or any other art i c l e subject to regu l at i on under the act or under sect i ons 351 and 354 - 360F of the P u b l i c Hea l th Serv i ce Act ( ? . . . Y . . : . : . : . . ? . ? . an d . ?. . ?.:::? . . !: )) . (k) Minimal risk means that the probabil i ty and magn i tude of harm or d i scomfort ant i c i pated i n the research are not greater i n and of themse l ves than those ord i narily encountered i n da i l y life or during the performance of routi ne phys i cal or psycho l og i cal exam i nations or tests. (I) Legally authorized representative means an i nd i v i dual or jud i c i al or other body authorized under applicab l e l aw to consent on beha l f of a prospect i ve subject to the subject's part i cpat i on i n the procedure(s) i nvolved i n the research. ( m ) F amily memb e r means any one of the follow i ng l egally competent persons: Spous e ; parents; children ( incl ud i ng adopted childre n ) ; brother s , s i ster s , and spouses of brothers and s i sters; and any i nd i v i dual re l ated by b l ood or affi n i ty whose c l ose assoc i at i on w i th the subject i s the equ i va l ent of a fam i l y re l at i onsh i p.
2 1 CF R s o . 22{ b ) (enhanced display ) page5of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0 . 3 (n) (n) Assent means a ch i ld ' s affirmative agreement to partic i pate i n a clin i cal i nvest i gat i o n . Mere fai l ur e to object shou l d no t , absent affirmat i ve agreement, be construed as assent. (o) Children means persons who have not atta i ned the l egal age for consent to treatments or procedures i nvolved i n c l i n i cal i nvest i gation s , under the app l i cab l e l aw of the jurisd i ct i on i n wh i ch the c l i n i cal i nvest i gat i on will be con d u cted. (p) Parent means a c h i l d's b i o l og i cal or adopt i ve parent. (q) Ward means a ch il d who i s p l aced i n the l egal custody of the State or other agenc y , i nst i tut i o n , or ent i t y , consistent w i th applicab l e Federa l , Stat e , or l ocal l a w . (r) Permission means the agreement of parent ( s ) or g uard i an to the part i c i pat i on of the i r child or ward in a clin i cal i nvest i gat i o n . (s) Guardian means an i nd i v i d ual who is author i zed under app l i cab l e State or l ocal l aw to consent on beha l f of a ch i l d to general med i cal car e . f '! . ? . . E. .. . ! ! t May 3 0 , 198 0 , as amended at 1 . E . ! ! . ? . ! ! t Jan. 27, 1981 ; . ?. . 1 : . . E . . Q ! ! t Mar. 3 , 7 9 8 9 ; . ?. . .. E . ? . . Q ? . . t June 18, 1991; . ! . E . 1 3 . . ? . . ? . ? . . . ? . ! ! t Oct. 2 , 1996 ; . . ? . . E . ! ! t July 2 3 , 199 7 · , . . E. . . t Jan. 5 , 1999 ; . . E. . ?.. ! ! t Oct. 2 0 , 1999 ; . . . E. . ? . 9 . ? . . . . !t Apr. 2 4 , 2001; ? . . E . t:! . . . T? . . ? . ! ! t Feb. 2 6 , 2013] S ubpart B - Informed Con s ent of Human S ubjects S o urc e : . X . . . ?.J . .. Jan. 2 7 , 198 1 , u n l ess otherw i se noted. † 5 0 . 20 General requirements for informed c on s ent. Except as prov i ded i n † . † . . . ? . . 9 . . : ? . ? . • . ?. Q : . ?. . and . ?. 9 : . ?. . no i nvest i gator may i nvo l ve a human be i ng as a subject i n research covered by these regu l ations un l ess the i nvest i gator has obta i ned the l egal l y effective i nformed consent of the subject or the subject's l egally author i zed representat i ve. An i nvest i gator shall seek such consent on l y under c i rcumstances that prov i de the prospect i ve subject or the representat i ve suffic i ent opportun i ty to consi der whether or not to part i c i pate and that m i n i m i ze the possi bility of coerc i on or undue i nfluenc e . The i nformat i on that is g i ven to the subject or the representat i ve shall be i n l anguage understandab l e to the subject or the representat i ve. No i nformed consent, whether oral or wr i tte n , may i nc l ude any excu l patory l anguage through wh i ch the subject or the representat i ve i s made to waive or appear to wa i ve any of the subject ' s l egal r i ght s , or re l eases or appears to re l ease the i nvest i gato r , the sponso r , the i nst i tuti o n , or i ts agents from liability for negligenc e . f . . . E. . ?. . ?.t Jan. 2 7 , 198 1 , as amended at . . ..E. ..!.9 . . ? t . Mar. 8 , 1999; . .E. . ? . ?. ! ! t Dec. 27, 2023] † 5 0 . 22 E x c eption from informed c on s ent requirements for minimal risk clin i ca l investi g ation s . The I RB respons i b l e for the rev i e w , approva l , and continu i ng rev i ew of the clin ical i nvestigati on descr i bed i n this sect i on may approve an i nformed consent procedure that does not i nc l ude or that a l ters some or all of the e l ements of i nformed consent set forth i n . † . . ?. 9 : . ? . . ? . ( . ). and. ( ) ..
or may wa i ve the requ i rement to obta i n i nformed consent, prov ided the I RB finds and documents the follow i ng: ( a ) The c l i n i cal i nvest i gat i on i nvo l ves no more than m i n i mal risk to the subjects; { b ) The c l i n i cal i nvest i gat i on cou l d not pract i cab l y be carr i ed out w i thout the requested wai ver or a l terat i on; page 6of 1 7 21CFR5 0 . 2 3 (d) ( 1 ) ( enhan c ed display) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 21CFR5 0 . 22( c ) (c) I f the clin i cal i nvest i gat i on i nvolves us i ng i dent i fiab l e pr i vate i nformat i on or i dentifiab l e b i ospec i mens, the c l i n i cal i nvest i gat i on cou l d not pract i cab l y be carr i ed out w i thout us i ng such i nformat i on or b i ospec i mens i n an i dent i fiab l e format ; (d) The wa i ver or a l terat i on will not adverse ly affect the r i ghts and welfare of the subject s ; and (e) Whenever appropr i at e , the subjects or l egally authorized representati ves will be prov i ded w i th add i t i onal pert i nent i nformat i on after part i c i pat i on. ( l?. . . . E . l . ! : .. ?. . 1 . ! ! t Dec. 21 , 2023} † 5 0. 2 3 Exception from g eneral requirement s . (a) The obta i n i ng of i nformed consent shall be deemed feas i b l e un l ess, before use of the test art i c l e ( except as provi ded i n P . r . 9 . ! . P . . ( ). of th i s sect i o n ) , both the i nvest i gator and a phys i c i an who i s not otherwi se part i c i pat i ng i n the c l i n i cal i nvest i gati on certify i n writ i ng all of the follow i ng: (1) The human subject i s confronted by a life - threaten i ng s i tuat i on necess i tat i n g the use of the test art i c l e. (2) I nformed consent cannot be obta i ned from the subject because of an i nability to commun icate w i t h , or obta i n l egally effect i ve consent fro m , the subject. (3) T i me i s not suffic i ent to obta i n consent from the subject ' s l egal representat i ve. (4) There i s avai l ab l e no a l ternat i ve method of approved or general l y recogn i zed therapy that prov i des an equal or greater l i ke l i hood of sav i ng the life of the subject. (b) I f i mmed i ate use of the test artic l e i s, i n the i nvest i gator ' s opi n i o n , requ i red to preserve the l ife of the subject, and t i me i s not suffic i ent to obta i n the i ndependent determ i nation requ i red i n P . ! 9 ! .P . . . ( ). of th i s sect i on i n a d vance of us i ng the test art i c l e , the determ i nat i ons of the c l i n i cal i nvest i gator shall be made and, with i n 5 work i ng days after the use of the art i c l e , be rev i ewed and eval uated i n wr i t i ng by a phys i cian who i s not part i c i pat ing i n the c l i n i cal i nvest i gat i on. (c) The documentat i on requ i red i n P . ! 9 . ! P . . . . ( ) or . ( ) . of th i s sect i on shall be submitted to the I RB w i th i n 5 work i ng days after the use of the test art i c l e . ( d ) (1) Under . . Q .. . : : . g . : . . 1 . J . . Q .?..CQ. the Pres i dent may wa i ve the pr i or consent requ i rement for the a d m i n i strat i on of an i nvest i gational new drug to a member of the armed forces i n connect i on w i th the member ' s part i c i pat i on i n a part i cul ar military operat i on. The stat u te spec i fies that on l y the Pres i dent may wa i ve i nformed consent i n th i s connect i on and the Pres i dent may grant such a wa i ver on l y if the Pres i dent determ i nes i n wr i t i ng that obta i n i ng consent: I s not feas i b l e; i s contrary to the best i nterests of the m i l i tary me m ber; or i s not i n the i nterests of nat i onal secur i ty. The statute f u rther prov i des that i n mak ing a determ i nat i on to wa i ve pr i or i nformed consent on the ground that i t i s not feas i b l e or the ground that i t i s contrary to the best i nterests of the military members i nvo l ve d , the Pres i dent shall app l y the standards and cr i ter i a that are set forth i n the re l evant FDA regu l at i ons for a wa iver of the pr i or i nformed consent requ i rements of sect i on 505 ( i ) ( 4) of the Federal Foo d , Dru g , and Cosmeti c Act ( ?. } . . . : † ! . : ? . . ?. (!) ( ).).
Before such a determ i nation may be made that obtai n i ng i nformed consent from military personnel pr i or to the use of an i nvest i gational drug ( i nc l ud i ng an ant i b i ot i c or b i o l og i cal product) i n a specif i c protocol under an i nvest i gat ional new drug app l i cat i on ( IND ) sponsored by the Department of Defense ( DO D ) and l i m i ted to specific m il i tary 2 1 CF R S 0 . 2 3 (d) ( 1)( xi ) ( enhanced display) p a g e7of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0 . 2 3 (d)(1)( i ) personnel i nvolved i n a part i cu l ar military operat i on i s not feas i b l e or i s contrary to the best i nterests of the m i l i tary members i nvo l ved the Secretary of Defense must first request such a determ i nati on from the Pres i dent, and cert i fy and document to the P res i dent that the follow i ng standards and cr i ter i a conta i ned i n P . . r . 9 . . P . . . . ( ) . (J J through . ( ) ( ) . of th i s sect i on have been met. ( i ) The extent and strength of ev i dence of the safety and effectiveness of the i nvest i gational new drug i n re l at i on to the med i cal risk that cou l d be encountered dur i n g the mi l i tary operat i on supports the drug ' s adm i n i strat i on under an I ND. The military operation presents a substant i al risk that military personnel may be subject to a chem i ca l , b i o l og i cal, nuclear , or other exposure l i ke l y to prod u ce death or serious or life threaten i ng i njury or illness. There is no availab l e sat i sfactory a l ternati ve therapeut i c or prevent i ve treatment i n re l at i on to the i ntended use of the i nvestigati o n al new drug. Cond i t i on i ng use of the i nvesti gat i onal new drug on the vol untary part i c i pat i on of each member cou l d s ign i ficant l y r i sk the safety and hea l th of any i ndiv i dual member who wou l d dec l i ne i ts us e , the safety of other military personne l , and the accomp l ishment of the mil i tary miss i o n . ( v ) A du l y const i tuted i nst i tuti onal rev i ew board { I R B ) established and operated i n accordance w i th the requ i rements of p r . 9 . r . .P . . . . ( ). ( ? . ). and . ( ) . ( ) . of th i s sect i on, respons i b l e for rev i ew of the stud y , has rev i ewed and approved the i nvest i gat i onal new drug protocol and the adm i n i strat i on of the i nvestigational new drug w i thout i nformed consent. D O D ' s request i s to i nc l ude the documentat i on requi red by . † . . ? . . : . J . . 1 . ( ) . ( ) .. f .. . ! . .. . P. ! . · DOD has exp l a ine d : ( i i ) ( ii i ) { i v ) ( v i ) (A) The context i n wh ich the i nvestigational drug will be ad m i n i stere d , e. g . , the sett i ng or whether i t will be self - adm i nistered or i t will be adm in i stered by a hea l th profess i ona l ; (B) The nature of the disease or cond i t i on for wh i ch the prevent i ve or therapeut i c treatment is i ntended; and { C ) To the extent there are ex i sti ng data or i nformat i on avai l ab l e , i nformat i on on cond i t i ons that cou l d a l ter the effects of the i nvest i gat i onal drug. (vii) DOD ' s recordkeep i ng system i s capab l e of track i ng and will be used to track the proposed treatment from supp l i er to the i nd i v i dual rec i p i ent. (viii) Each member i nvo l ved in the mil i tary operat i on will be g i ve n , pr i or to the adm i n i strat i on of the i nvest i gational new drug, a spec i f i c wri tten i nformat i on sheet ( incl ud i ng i nformat i on requ i red by .J. Q .. . : . : . : J.. J . Q? ( )) concern i ng the i nvest i gat i onal new dru g , the risks and bene f i ts of i ts use, potent i al s ide effect s , and other pert i nent i nformat i on about the appropr i ate use of the product. ( i x ) Med i cal records of members i nvolved i n the m i l i tary operat i on will accuratel y document the rece i pt by members of the notificati on requi red by P . r . 9 . P. . . . . ( ) . OJ ( Y . ! D . . of th i s sect i o n . ( x ) Med i cal records of members i nvolved i n the m i l i tary operat i on will accuratel y document the rece i pt by members of any i nvest i gat i onal new drugs i n accordance w i th FDA regu l at i ons i nc l ud i ng p . . .J . ? . . . . f... . . .. . P ! r. DOD will prov i de adequate followup to assess whether there are bene f i c i al or adverse hea l th consequences that resu l t from the use of the i nvest i gat i onal product. ( x i )
21CFR5 0 . 2 3 (d)(4) ( enhanced di s pla y ) pa g e 8 of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 21CFR5 0.2 3 (d) ( 1)( xii ) (xii) DOD i s pursui ng drug deve l opment, i nc l ud i ng a t i me line, and marketing approval w i th due d i l i gence. (xiii) FDA has concluded that the i nvest i gat i onal new drug protocol may proceed subject to a dec i si on by the Pres i dent on the i nformed consent waiver request. (xiv) DOD will prov i de trai n i ng to the appropri ate med i cal personnel and pote n t i al rec i p i e n ts on the specific i nvest i gat i onal new drug to be admi n i stered pr i or to i ts use. (xv) DOD has stated and just i f i ed the t i me per i od for w h i ch the wa i ver i s neede d , not to exceed one yea r , un l ess separatel y renewed under these standards and cr i ter i a. (xvi) DOD shall have a cont i nu i ng obligat i on to report to the FDA and to the Pres i dent a n y changed c i rcumstances re l at i n g to these standards and cr i ter i a ( i nclud ing the t i me per i od referred to i n .P . r . 9.t .P . . . . ( J ( . ) { ) . of th i s sect i on) or that otherw i se m i g h t affect the determ inat i on to use an i nvest i gat i onal new drug w i thout i nformed consent. (xvii) DOD i s to prov i de public not i ce as soon as pract i cab l e and cons i ste n t w i th classificat i on requ i reme n ts through not i ce i n the FEDERAL REG I STER descr i b i ng each wa i ver of i nformed conse n t determ inat i o n , a summary of the most updated sc i ent i f i c i nformat i on on the products use d , and other perti ne n t i nformat i o n . (xviii) Use of the i nvest i gational drug w i thout i nformed consent otherw i se conforms w i th app l i cab l e l a w . (2) The du l y const i tuted i nst i t u t i onal rev i ew boar d , descr i bed i n P. r. 9 .P . . ( ). ( J ) { y). of th i s sect i o n , must i nc l ude at l east 3 nonaf f 11iated me m bers who shall not be emp loyees or officers of the Federal Government (other than for purposes of membersh i p on the I RB ) and shall be requ i red to obta in a n y necessary secur i ty clearances. Th i s I RB shall rev i ew the proposed I ND protocol at a convened meeting at wh i ch a major i ty of the members are prese n t i nc l ud i ng at l east one member whose pr i mary concerns are i n nonsc i e n tific areas and, i f feas i b l e, i nc l ud i ng a major i ty of the nonaffi l i ated members. The i nformat i on requ i red by . † . . ? . . : . 1 . 1 . ?. ( ) . { ? . l. f . .. . ! . . . P . ! . i s to be prov i ded to the Secretary of Defense for further rev i e w . (3) The du l y const i tuted i nst i t u t i onal rev i ew boar d , descr i bed i n P. r. 9 .P . . ( )( J ) { y). of th i s sect i o n , must rev i ew and approve: ( i ) The requ ired i nformat i on sheet; ( i i ) The adequacy of the p l an to d i ssem i nate i nformat i o n , i nc l ud i ng d i str i but i on of the i nformat i on sheet to potent i al rec i p i e n ts, on the i nvest i gat i onal product ( e . g . , i n forms other than wr i tte n ) ; ( ii i ) The adequacy of the i nformat i on and p l ans for i ts d i ssem i nat i on to hea l th care prov i der s , i nc l u d i ng pote n t i al s i de effects, co n trai nd i cat i ons, pote n t ial i n teract i on s , and other pert i ne n t cons i derat i ons; and An i nformed consent form as requ ired by p r . . . . ? . . Q .. f . . . . ! .. . P . . E · i n those c i rcumstances i n wh i ch DOD determ i nes that i nformed consent may be o b ta i ned from some or all personnel i nvo l ved . ( i v ) ( 4 ) DOD i s to subm i t to FDA summar i es of i nst i t u t i onal rev i ew board meetings at wh i ch the proposed protocol has been rev i ewed.
page9of t7 2 1 CF R S 0 . 2 3 ( eX s ) ( enhanced dis p la y ) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 5 0 . 2 3 (d)( S ) ( 5 ) Noth i ng i n these cr i ter i a or standards is i ntended to preempt or l i m i t FDA's and DOD ' s author i ty or ob l i gati ons under app l i cab l e statutes and regu l at i ons. ( e ) ( 1 ) Obta i n i ng i nformed consent for i nvest i gat i onal i n v i tro d i agnost i c dev i ces used to i dent i fy chem i ca l , b i o l o g i ca l , radi o l og i ca l , or nuc l ear agents will be deemed feas i b l e un l ess, before use of the test art i c l e , both the i nvest i gator (e . g . , cli n i cal l aboratory d i rector or other respons i b l e i nd i v i dual) and a phys i c i an who i s not otherwise partic i pat i ng i n the c l i n i cal i nvestigat i on make the determ i nat i ons and l ater cert i fy i n wri t i ng all of the follow i ng: (i) The human subject is confronted by a l ife - threaten ing s i tuat i on necessi tat i ng the use of the i nvest i gational i n v i tro d i agnost i c dev i ce to i dentify a chem i ca l , b i o l og i ca l , rad i o l og i ca l , or nuclear agent that wou l d suggest a terror i sm event or other pub l i c hea l th emergency. Informed consent cannot be obta i ned from the subject becaus e : (A) There was no reasonab l e way for the person d i rect i n g that the speci men be collected to kno w , at the t i m e the speci men was collected, that there wou l d be a need to us e the i nvest i gat i onal i n v i tro d i agnost i c dev i ce on that subject ' s spec i me n ; and { B ) T i me is not suffic i ent to obta i n consent from the subject w i thout r i sk ing the l ife of the subject. T i me i s not suffic i ent to obta i n consent from the subject's l egally author i zed representat i ve. There is no c l eared or approved ava i l ab l e a l ternative method of d i agnosi s , to i dent i fy the chem i ca l , b i o l og i cal, rad i o l og i cal, or nuc l ear agent that prov i des an equal or greater l i kel i hood of sav i ng the life of the subject. ( i i ) ( i i i) ( i v ) (2) I f use of the i nvest i gat i onal dev i ce i s , i n the op i n i on of the i nvest i gator ( e . g . , c l i n i cal laboratory d i rector or other respons i b l e person ) , requi red to preserve the l ife of the subject, and t i me is not suffic i ent to obta i n the i ndependent determ i nat i on requ i red i n p r . 9 . r . P . . ( 20) of this sect i on i n adva n ce of us i n g the i nvest i gat i onal dev i ce, the determ i nations of the i nvesti gator shall be made an d , w i th i n 5 work i ng days after the use of the dev i c e , be rev i ewed and eva l uated i n wri t i ng by a phys i c i an who i s not part i c i pat i ng i n the c l i n i cal i nvest i gat i o n . (3) The i nvesti gator must subm i t the wr i tten certificat i on of the determ i nat i ons made by the i nvest i gator and an i ndependent phys i c i an requ i red i n P. 9 . r . . P . .. ( ) . { n_ or . ( ) . ( ? . ) . of th i s sect i on to the I RB and FDA w i th i n 5 work i ng days after the use of the dev i ce. (4) An i nvest i gator m ust disclose the i nvest i gat i onal status of the i n v i tro d i agnost i c dev i ce and what is known about the performance character i st i cs of the dev i ce i n the report to the subject's hea l th care prov i der and i n any report to public health author i t i es. The i nvestigator must prov i de the I RB w i th the i nformat i on requi red i n † .. . ? . Q : . ?.:? . . ( except for the i nformat i on descr i bed i n † . . ?. Q : . ?.:? . . ( ) ( ) ) and the procedures that will be used to prov i de this i nformat i on to each subject or the subject ' s l egally author i zed representat i ve at the t i me the test resu l ts are prov i ded to the subject ' s hea l th care prov i der and pub l i c hea l th author i t i es. (5) The I RB i s respons i b l e for ensur i ng the adequacy of the i nformat i on requi red i n . . ! 2 . . ? . 9 : . ?.:? . . ( except for the i nformat i on descr i bed i n † . .. Q : . . ? . . ( ). ( ) ) and for ensur i ng that procedures are i n p l ace to prov i de this i nformat i on to each subject or the subject's l egally author i zed representat i ve.
2 1 CF R s o . 2 4(a) ( s ) (enhanced dis p lay ) paget0 of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0 . 2 3 ( e )( 6 ) ( 6 ) No State or pol i t i cal subd i vis i on of a State may establish or cont i nue i n effect any l a w , ru l e , regu l at i on or other requi rement that i nformed consent be obta i ned before an i nvest i gat i onal i n v i tro d iagnost i c dev i ce may be used to i dentify chem ical, b i o l og i ca l , radi o l og i ca l , or nuc l ear agent i n suspected terrorism events and other potent i al p u blic hea l th e mergenci es that i s different fro m , or i n add i t i on to, the requi rements of this regu l at i o n . f . . . E ! . i . ?. . ?. . ?.! Jan. 27, 198 1 , as amended at . ? . . .E. . . ? ? . . ! . !.t Dec. 21, 1990 ; . . .E.. . . ? . ! Jan. 5 , 1999; . . E t:! . . ?. . ? . . † ! ! Oct. 5 , 1999 ; ? J .. . E . !i f. ? ? . ! . June 7, 2006; ? .. E t:! . . ? . ? ! . June 24, 2011] † 5 0. 24 Exception fro m informed c onsent requirements fo r emer g ency research. (a) The I RB respons i b l e for the rev i e w , approva l , and cont i nu i ng rev i ew of the clin ical i nvestigati on descr i bed i n th i s sect i on may approve that i nvestigati on w i thout requi r i n g that i nformed consent of all research subjects be obta i ned i f the I RB (w i th the concurrence of a l i censed phys i c ian who is a member of or consu l tant to the I RB and who i s not otherwise parti c i pat i ng i n the c l i n i cal i nvest i gati on) finds and documents each of the follow i ng: (1) The human subjects are i n a life - threaten i ng s i tuat i o n , avai l ab l e treatments are unproven or unsatisfactor y , and the collect i on of valid sc i entific ev i dence, wh ich may i nc l ude ev i dence obta i ned through random i zed p l acebo - controlled i nvest i gat i on s , i s necessary to determ i ne the safety and effect i veness of part i cu l ar i ntervent i ons. (2) Obta i n i ng i nformed consent is not feas i b l e because: ( i ) The subjects will not be ab l e to g i ve the i r i nformed consent as a resu l t of the i r med i cal condit ion; The i ntervent i on u nder i nvest i gat i on must be adm i n i stered before consent from the subjects' l egal l y authorized representat i ves i s feas i b l e; and There is no reasonab l e way to i dent i fy prospect ive l y the i nd i v i dua l s l i ke l y to become e l i g i b l e for part i c i pat i on i n the cl i n i cal i nvest i gat i o n . ( i i ) ( i i i) (3) Part i c i pat i on i n the research ho l ds out the prospect of d i rect benefit to the subjects because: (i) Subjects are fac i ng a life - threateni ng s i tuat i on that necess i tates i ntervent i on; ( i i ) Appropr i ate an i mal and other precl i n i cal stud i es have been conducted, and the i nformat i on der i ved from those stud i es and re l ated ev i dence support the potent i al for the i ntervent i on to prov i de a d i rect bene f i t to the i nd i v i dual subject s ; and ( ii i ) R i sks assoc i ated w i th the i nvest i gat i on are reasonab l e i n rel at i on to what i s known about the med i cal cond i t i on of the potent i al c l ass of subject s , the risks and benefits of standard therap y , if an y , and what is known about the risks and benefits of the proposed i ntervent i on or act i v i t y . (4) The c l i n i cal i nvesti gat i on cou l d not pract i cab l y be carr i ed out w i thout the wa i ve r . (5) The proposed i nvest i gational p l an defines the l ength of the potent i al therapeut i c w i ndow based on sc i ent i fic ev i denc e , and the i nvest i gator has comm i tted to attempt i ng to contact a l egally author i zed representat i ve for each subject w i th in that w i ndow of ti me an d , if feas i b l e , to ask i n g the l egally author i zed representat i ve contacted for consent w i th i n that w i ndow rather than proceed i ng w i thout consent. The i nvest i gator will summar i ze efforts made to contact l egally author i zed representat i ves and make th i s i nformat i on ava i l ab l e to the I RB at the ti me of cont i nu i ng rev i ew.
2 1 CF R S 0 . 24( c ) (enhanced dis p lay ) pagel1of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 5 0 . 2 4 ( a )( 6 ) ( 6 ) The I RB has rev i ewed and approved i nformed consent proce d ures and an i nformed consent document cons i stent w i th † . . . † . Q : . ? . - These procedures and the i nformed consent document are to be used w i th subjects or the i r l egally author i zed representatives i n s i tuat i ons where use of such procedures and documents i s feas i b l e . The I RB has rev i ewed and approved procedures and i nformat i on to be used when prov i di ng an opportun i ty for a fam i l y member to object to a subject ' s part i c i pat i on i n the c l i n i cal i nvest i gat i on cons i stent w i th P. ! ! 9.r . P . . . ( ). Q l (Y.). of th i s sect i on. ( 7 ) Add i t i onal protect i ons of the r i ghts and we l fare of the subjects will be prov i de d , i ncl ud i n g , at l east: ( i) Consu l tati on ( incl ud i n g , where appropr i at e , consu l tati on carr i ed out b y the I RB ) w i th representatives of the commun i t i es i n wh ich the clin i cal i nvesti gat i on will be conducted and from whi ch the subjects will be drawn; Public d i sc l osure to the commun i t i es in wh i ch the c l i n i cal i nvest i gati on will be conducted and from whi ch the subjects will be drawn, pr i or to i n i t i at i on of the cl i n i cal i nvestigati o n , of p l ans for the i nvestigati on and i ts risks and expected benefit s ; Public d i sc l osure of suffic i ent i nformat i on follow i ng comp let i on of the c l i n i cal i nvest i gat i on to appr i se the commun i ty and researchers of the stud y , i nclud i ng the demograph i c characterist i cs of the research popu l at i o n , and i ts res u l ts; Establis h ment of an i ndependent data mon i tor i ng comm i ttee to exercise overs i ght of the cl i n i cal i nvest i gati o n ; and ( v ) I f obta i n i ng i nformed consent i s not feas i b l e and a l egally authorized representative is not reasonab l y availab le, the i nvest i gator has com m i tted, i f feas i b l e, to attempt i ng to contact w i th i n the therapeut i c w i ndow the subject ' s fam i l y me m ber who is not a l egally author i zed representative , and ask i ng whether he or she objects to the subject's partic i pat i on in the cl i n i cal i nvest i gati on. The i nvest i gator will su m mar i ze efforts made to contact fam i l y members and make this i nformat i on ava i l ab l e to the I RB at the t i me of cont i nu i ng rev i e w . ( i i ) ( i i i) ( i v ) (b) The I RB i s respons i b l e for ensuri n g that procedures are i n p l ace to i nfor m , at the earliest feas i b l e opportun i t y , each subject, or if the subject rema i ns i ncapac i tate d , a l egally author i zed representat i ve of the subject, or if such a representat i ve is not reasonab l y availab l e , a family member , of the subject ' s i nclusi on i n the c l i n i cal i nvest i gat i o n , the deta i l s of the i nvest i gat i on and other i nformat i on conta i ned i n the i nformed consent document. The IRB shall a l so ensure that there i s a procedure to i nform the subject , or if the subject rema i ns i ncapac i tate d , a l egally author i zed representat i ve of the subject, or i f such a representat i ve i s not reasonably availab l e , a family membe r , that he or she may d i scont i n ue the subject ' s part i c i pat i on at any t i me w i thout pena l ty or l oss of benefits to wh i ch the subject i s otherwise ent i t l e d . I f a l egally author i zed representat i ve or family member i s to l d about the cl i n i cal i nvest i gat i on and the subject ' s cond i t i on improves, the subject i s a l so to be i nformed as soon as feas i b l e . I f a subject is entered i nto a cl i n i cal i nvest i gati on w i th wai ved consent and the subject d i es before a l egal l y authorized representat i ve or family me m ber can be contacte d , i nformat i on about the cl i n i cal i nvest i gat i on i s to be prov i ded to the subject ' s l egally authorized representat i ve or fami l y membe r , i f feas i b l e . (c) The I RB determ i nat i ons requ i red by P. ! ! 9.r . .P . . . { ) of this sect i on and the documentat i on requ i red by P . . r . 9 . r . P . . ( ). of this sect i on are to be reta i ned by the I RB for at l east 3 years after comp l et i on of the clin i cal i nvest i gat i o n , and the records shall be access i b l e for i nspect i on and copy i ng by FDA i n acc o rd a nee w i th . † . . . . :J.J . . { J . 9 . f. . . - ! . - - P ! r.
21CFR5 0 . 25( a ) ( 8 ) (enhanced di s p l a y ) page12 of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 cFR s o . 24(d) (d) Protoco l s i nvo l v i ng an excepti on to the i nformed consent requi rement under this sect i on must be performed under a separate i nvesti gat i onal new drug app l i cat i on ( IND ) or i nvest i gat i onal devi ce exempt i on ( I DE ) that c l ear l y i dent i fies such protoco l s as protoco l s that may i nclude subjects who are unab l e to consent. The submiss i on of those protoco l s i n a separate I ND/IDE i s requ i red even if an I ND for the same drug product or an I DE for the same devi ce a l ready ex i sts. App l i cat i ons for i nvest i gat i ons under this sect i on may not be subm i tted as amendments under † . † . . . . ? . : . Q . or . . ? . : . . ? . . 2f. . . . ! ... . . P ! . . · (e) I f an I RB deter m i nes that i t cannot approve a c l i n i cal i nvest i gati on because the i nvestigati on does not meet the cr i ter i a in the excepti on prov i ded under P. 9 E P . . . . ( ) . of this sect i on or because of other re l evant ethi cal concern s , the IRB must document i ts find i ngs and prov i de these find i ngs prompt l y i n wr i ti ng to the cl i n i cal i nvest i gator and to the sponsor of the cl i n i cal i nvest i gat i o n . The sponsor of the clin i cal i nvest i gat i on must pro m pt l y disclose th i s i nformat i on to FDA and to the sponsor' s c l i n i cal i nvest i gators who are part i c i pat i ng or are asked to part i c i pate i n this or a substant i ally equ i va l ent cl i n i cal i nvest i gat i on of the sponso r , and to other I RB's that have bee n , or ar e , asked to rev i ew this or a substant i ally equ i va l ent i nvest i gat i on b y that sponsor. [ 1 .. . f. B . . ? 1 . ? ? . ! Oct. 2, 1996] † 5 0 . 2 5 Elements of informed c onsent. (a) Basic elements of informed c o ns e nt. I n seek i ng i nformed consent, the follow i ng i nformat i on shall be prov i ded to each subject: (1) A statement that the study i nvolves researc h , an exp l anat i on of the purposes of the research and the expected durat i on of the subject's part i cipati o n , a descr i pt i on of the procedures to be followed, and i dent i ficat i on of any procedures wh i ch are exper i mental. (2) A descr i pt i on of any reasonably foreseeab l e risks or discomforts to the subject. (3) A descr i pt i on of any benef i ts to the s u bject or to others whi ch may reasonab l y be expected from the research. (4) A d i sc l osure of appropr i ate a l ternati ve procedures or courses of treatment, if an y , that m i ght be advantageous to the subject. (5) A statement descr i b i ng the exten t , if an y , to wh i ch confident i al i ty of records i dentify i ng the subject will be ma i nta i ned and that notes the poss i bil i ty that the Food and Drug Adm i nistrat i on may i nspect the records. (6) For research i nvo l v i ng more than m i n i mal risk, an exp l anat i on as to whether any compensat i on and an exp l anat i on as to whether any med i cal treatments are ava i l ab l e i f i njury occurs an d , if s o , what they consist of, or where further i nformat i on may be obta i ned. ( 7 ) An exp l anat i on of whom to contact for answers to pert i nent quest i ons about the research and research subjects' r i ght s , and whom to contact i n the event of a research - re l ated i njury to the subject. ( 8 ) A statement that part i c i pat i on i s vo l untar y , that refusal to partic i pat e will i nvo l ve no pena l ty or l oss of benef i ts to wh i ch the subject is otherw i se ent i t l e d , and that the subject may d i scont i nue part i c i pat i on at any ti me w i thout penalty or l oss of benefits to w h i ch the subject i s otherw i se ent i t l ed.
2 1 CF R S 0 . 27( bX2 ) ( enha n ced display ) page13of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S0.25(b) (b) Additional elements of informed consent. When appropr i at e , one or more of the follow i ng e l ements of i nformat i on shall a l so be prov i ded to each subject: (1) A stateme n t that the pa n i cu l ar treatment or procedure may i nvo l ve r i sks to the subject ( or to the embryo or fetus , i f the subject i s or may become pregna n t ) wh i ch are current l y unforeseeab l e. (2) A n t i c i pated c i rcumstances under wh i ch the subject ' s part i c i pat i on may be termi nated by the i nvest i gator w i thout regard to the subject ' s conse n t. (3) Any add i t i onal costs to the subject that may resu l t from part i c i pat i on i n the research. (4) The consequences of a subject ' s dec i s i on to w i thdraw from the research and procedures for order l y term i nat i on of pa n i c i pat i on by the subject. (5) A stateme n t that s i gnifica n t new find i ngs devel oped dur i n g the course of the research wh i ch may re l ate to the subject ' s w i llingness to co n t i nu e pa n i c i pat i on will be prov i ded to the subject. (6) The approx i mate number of subjects i nvo l ved i n the study. (c) When seek i ng i nformed conse n t for applicab l e cl i n i cal tr i a l s , as defined i n . . : . . : ... . G > . ( 1 1 ( ) .. the follow i ng stateme n t shall be prov i ded to each cl i n i cal tr i al subject i n i nformed consent doc u me n ts and processes. Th i s will not i fy the cl i n i cal tr i al s u bject that clin i cal tr i al i nformat i on has been or will be subm i tted for i nclus i on i n the cl i n i cal tr i al reg i stry databank under paragraph Q) of sect i on 402 of the Pub l i c Hea l th Serv i ce Act. The statement i s: HA descr i pt i on of th i s c li n i cal tr i al will be availab l e on !!P. l ! . : . 9. . ! ! !. .! . ! r . . ! . : . g g . '!! as requ i red by U . S . Law. Th i s Web s i te will not i nc l u de i nformat i on that can i dent i fy you. At most, the Web s i te will i nclude a summary of the resu l ts. You can search th i s Web s i te at a n y t i me: (d) The i nformed conse n t requ i reme n ts i n these regul at i ons are not i n tended to preempt any applicab l e Federal, Stat e , or l ocal l aws wh i ch requ i re add i t i onal i nformat i on to be d i sc l osed for i nformed conse n t to be l egally effect i ve. (e) Nothi ng i n these regu l at i ons i s i n tended to l i m i t the a u thor i ty of a phys i c i an to prov i de emergency med i cal care to the exte n t the phys i c i an i s perm i tted to do so under app l i cab l e Federa l , State, or l ocal l aw. ( 1 . . . E ! . i . !! . ?. . ! Jan. 27, 198 1 , as amended at ? . .E . ! i . ?!.. ! Jan. 4 , 2011] † 5 0 . 2 7 Documentation of informed consent. (a) Except as prov i ded i n † . . ? . † . : . J . . Q . . ( !?, ) . . i nformed consent shall be documented b y the use of a wr i tten conse n t form approved by the I RB and s i gned and dated b y the subject or the subject ' s l egally a u thor i zed representati ve at the t i me of conse n t. A copy shall be g i ven to the person s i gn i ng the for m . (b) Except as prov i ded i n † .. . ? . † . : . J . .Q .. ( !?, ) . . the consent form may be e i ther of the follow i n g : (1) A wr i tten consent document that embod i es the e l ements of i nformed conse n t requ i red by † . . . ?. Q . : ?.: · Th i s form may be read to the subject or the subject ' s l egally authorized representati ve, b u t, i n any event, the i nvest i gator shall g i ve e i ther the subject or the represe n tative adequate oppo n un i ty to read i t before i t i s s i gned. (2) A short form wr i tten consent doc u me n t stat i ng that the e l ements of i nformed conse n t requ i red by † . . ? Q : . ?.: ? . have been prese n ted orally to the subject or the subject's l egally a u thor i zed represe n tat i ve. When th i s method i s use d , there shall be a w i tness to the oral prese n tat i o n . A l s o , the I RB shall approve a wr i tten s u mmary of what i s to be sa i d to the subject or the representati ve.
On l y the short 21CFR5 0 . 52( c ) (enhanced dis p lay ) page 1 4of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 50.SO form i tself is to be s i gned by the subject or the representat i ve. Howeve r , the w i tness shall s i gn both the short form and a copy of the s u mmar y , and the person actually obta i n i n g the consent shall s i gn a copy of the su m mar y . A copy of the summary shall be g i ven to the s u bject or the representat i ve i n add i t i on to a copy of the short for m . ( 1 . . . f. . B . . ! ! ?. , ?. , Jan. 27, 198 1 , as amended at . .1. . . f. . B . . ? ! . ? . . . 9 , . Nov. 5 , 1996] S ubpart C [R e served] S ubpart D - Add i tional S afeguards for Children in Clinical Inv e stigations S o urc e : . . . E . . ?. 9 . ? . . . . Apr. 2 4 , 2001 , un l ess otherw i se noted. † S O . SO IRB duti e s . I n add i t i on to other respons i bilit i es ass i gned to I RBs under t h i s . l? . r.: ! .. . . . P . .. . ? . † . .9. .. . l . . 9 . . . I? . ! . . each I RB must rev i ew cl i n i cal i nvestigati ons i nvolv i ng ch ildren as subjects covered by th i s subpart D and approve on l y those c l i n i cal i nvest i gat i ons that satisfy the cr i ter i a descr i bed i n † . . . ?. 9 . : ?. J . .. † . . . ?. 9 : . ? . ? . . or † .. . ?. 9 : . ?. and the cond i t i ons of all other applicab l e sect i ons of t h i s subpart D. † S O . St Clinical inv e stigation s not involving greater than minimal risk. Any cl i n i cal i nvest i gat i on w i th in the scope descr i bed i n _ † . † . . . ? . 9 : . J . . and . ? . † : . J . . 9 . . J . .. f . ! . ! .. b . .P . ! . i n wh ich no greater than m i n i mal r i sk to ch ildren i s presented may i nvo l ve ch il dren as subjects on l y i f the I RB fmds that: (a) No greater than m i n i mal risk to ch i l dren is presente d ; and (b) Adequate provis ions are made for solic i t i n g the assent of the chi ldren and the permiss i on of the i r parents or guard i ans as set forth i n † . . . ? . 9 : . ? ? : f? . . . f... ] ? . . ? . . J . 1 Feb. 26, 2013] † S 0 . 52 Clinical inve s t i gations invo l ving greater than minimal risk but presenting the pro s pect of direc t benefit to ind i vidual s ubject s . Any c l i n i cal i nvest i gat i on w i th in the scope descr i bed i n . † . † . . . ? . 9 : . J .. and . ? . † : . J . . 9 . . J . . . f . ! . ! .. b . . P . ! . i n wh ich more than m i n i mal r i sk to ch ildren i s presented by an i ntervent i on or procedure that ho l ds out the prospect of d i rect bene f i t for the i nd i v i dual subject , or by a mon i tor i ng procedure that i s l i kely to contr i bute to the subject's wel l - be i n g , may i nvo l ve children as subjects on l y i f the I RB finds that: (a) The r i sk is just i fied by the anti c i pated bene f i t to the subject s ; (b) The re l at i on of the anti c i pated bene f i t to the risk is at l east as favorab le to the subjects as that presented by ava i l ab l e a l ternati ve approaches; and (c) Adequate provis ions are made for solic i t i n g the assent of the chi ldren and permiss i on of the i r parents or guard i ans as set forth i n . † . . . ? . . Q : . ?.? . · ( . . r n . 9 . . ? ' Apr. 2 4 , 2001. as amended at ?. . . . f.. . ' 3 J . ? . . ? . . ?., Feb. 26, 2013]
2 1 CF R s o . 54( b ) ( 2 )(lli) (enhanced dis p lay ) paget5of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0. 53 † 5 0 . 5 3 Clinical inve s t i gations inv o l ving greater than minimal risk and no prospect of direct benefit to ind i v i dual s ubjects, but like l y t o y i e ld g eneralizable knowledge about the sub j ect s ' disorder or condition. Any c l i n i cal i nvest i gat i on w i th in the scope descr i bed i n . † . † . . ? .Q:.J. . and . ? . † :.J . . 9 . .J . . f.. . . ! . . b . . P. . . i n wh ich more than m i n i mal r i sk to ch ildren i s presented by an i ntervent i on or procedure that does not ho l d out the prospect of d i rect benef i t for the i nd i v i dual subject, or by a mon i tor i ng procedure that i s not like l y to contr i bute to the well - be i ng of the subject, may i nvo l ve children as subjects on l y i f the I RB finds that: ( a ) The r i sk represents a m i nor i ncrease over m i n i mal risk; { b ) The i ntervent i on or proce d ure presents experi ences to s u bjects that are reasonab l y commensurate w i th those i nherent in the i r actual or expected med i ca l , denta l , psycho l og i ca l , soc i a l , or ed u cat ional s i tuat i on s ; ( c ) The i ntervent i on or proce d ure is li ke l y to y i e l d generalizab l e know l edge about the subjects' d i sorder or cond i t i on that i s of vital i mportance for the understand ing or ameliorat i on of the subjects' d i sorder or cond i t i o n ; and { d ) Adequate provis ions are made for solic i t i n g the assent of the chi ldren and permiss i on of the i r parents or guard i ans as set forth i n . † . . . ? . . 9 . : . ? . ? . · £ . . f.. . 9 . ? . ! ! 1 Apr. 2 4 , 2001, as amended at .! . . . f.. ) . ? . . . ?., Feb. 26, 2013] † 5 0 . 5 4 Clinical inve s t i gations not otherwise approvable that present a n opportunity to understand, prevent, o r alleviate a seriou s probl e m affecting the health o r welfare of children. I f an I RB does not be l i eve that a cli n i cal i nvest i gat i on w i th i n the scope descr i bed i n † . † . . . ? . . Q : . 1 . and . ? . . : . J . . 9 . . J .... f . ! . ! .9 . . .I?. . . and i nvo l v i ng children as subjects meets the requi rements of † . . ?. Q . . - . ?. J . . . † .. . ?. 9 : . ? . ?. : . or † . . . ? . 9 : . † . , the c l i n i cal i nvest i gat i on may proceed on l y if: (a) The I RB fmds that the c l i n i cal i nvest i gat i on presents a reasonab l e opportun i ty to further the understand i n g , prevent i o n , or allev i at i on of a seri ous prob l em affect in g the hea l th or we l fare of ch i l dre n ; and { b ) The Commiss i oner of Food and Drug s , after consu l tat i on w i th a panel of experts i n pert i nent discip l i nes ( for examp l e : sc i enc e , med i c i n e , educat i o n , ethi c s , l a w ) and follow i ng opportun i ty for pub l i c rev i ew and commen t , determ i nes e i ther : (1) That the c l i n i cal i nvest i gat i on i n fact sat i sf i es the cond i t i ons of . † . . . ?.9 . : . ? . 1 , † . . . ?. 9 : . ?.?.. or † . . . ?.9 . : . ? . .. as applicab l e , or (2) That the follow i ng cond i t i ons are met: ( i ) The clin i cal i nvest i gation presents a reasonab l e opportun i ty to further the understand i n g , prevent i o n , or allev i at i on of a ser i ous prob l em affectin g the hea l th or we l fare of children ; The clin i cal i nvest i gat i on will be conducted i n accordance w i th sound ethi cal pr i nci p l e s ; and Adequate prov i s i ons are made for so l i c i t i ng the assent of ch i l dren and the perm i ss ion of the i r parents or guard i ans as set forth i n † .. . ?.9 . . - . ?.? . · ( i i ) ( ii i ) £ - . f.. . 9 . . ? ! ! , Apr. 2 4 , 2001, as amended at .! . . . E. ) . ? . . . ?., Feb. 26, 2013]
21CFR5 0 . SS (g) (enhanced display) pa g e t6of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0. 55 † 5 0 . 5 5 Requirements fo r permi s s i o n b y parents o r guardians and for assent b y childre n . (a) I n add i t i on to the determ i nat i ons requ i red under other applicab l e sect i ons of th i s subpart D , the I RB must determ i n e that adequate provis i ons are made for so l i c i t i ng the assent of the children when i n the judgment of the I RB the c h i l dren are capabl e of prov i di ng assent. (b) I n determ i n i ng whether children are capabl e of prov i d i ng assen t , the I RB must take i nto account the age s , matur i t y , and psycho l og i cal state of the children i nvo l ve d . Th i s judgment may be made for all children to be i nvo l ved i n cl i n i cal i nvestigat i ons under a part i cu l ar protoco l , or for each child, as the I RB de e ms appropr i ate. (c) The assent of the children i s not a necessary cond i tion for proceed i ng w i th the c l i n i cal i nvesti gat i on i f the I RB determ i nes: (1) That the capabil i ty of some or all of the ch i l dren is so lim i ted that they cannot reasonab l y be consulte d , or (2) That the i ntervent i on or procedure i nvo l ved i n the cl i n i cal i nvest i gat i on ho l ds out a prospect of d i rect benef i t that is i mportant to the hea l th or wel l - bei ng of the children and i s availab l e on l y i n the context of the cl i n i cal i nvest i gat i on . (d) Even where the I RB determ i nes that the subjects are capabl e of assent i n g , the I RB may still wai ve the assent requi rement i f i t finds and documents that: (1) The clin i cal i nvesti gat i on i nvo l ves no more than m i n i mal r i sk to the subject s ; (2) The wa i ver will not adverse l y affect the r i ghts and we l fare of the subjects; (3) The clin i cal i nvesti gat i on cou l d not pract i cab l y be carr i ed out w i thout the wa i ver; and (4) Whenever appropr i at e , the subjects will be prov i ded w i th add i t i onal perti nent i nformat i on after part i c i pat i o n . (e) I n add i t i on to the determ i nat i ons requ i red under other applicab l e sect i ons of th i s subpart D , the I RB must determ i n e , i n accordance w i th and to the extent that consent is requ i red under part 5 0 , that the permiss i on of each child ' s parents or guard i an is granted. (1) Where parental permiss i on i s to be obta i ne d , the I RB may find that the permiss i on of one parent is suffic i ent for c l i n i cal i nvest i gati ons to be conducted under † . . ? . 9 : . ? 1 . or . † .. . ?. 9 : ? ? . · ( 2 ) Where cl i nical i nvest i gati ons are covered by . † . . ?. 9 : † . . or † .. . ?. 9 : . and perm i ss i on i s to be obta i ned from parent s , both parents must give the i r perm i ss ion un l ess one parent i s deceased, unknow n , i ncompetent, or not reasonab l y availab l e , or when only one parent has l egal respons i bil i ty for the care and custody of the child . ( f ) Perm i ss ion by parents or guard i ans must be documented i n accordance w i th and to the extent requ i red by † .. . ? . . Q . . . ?.Z : · ( g ) When the I RB determ i nes that assent is requi red, i t must a l so determ i ne whether and how assent must be documented. [ . . f. B . 9 . ? . ! Apr. 2 4 , 2001, as amended at ?. . . . f. . 13. J . ? . . . ?.! Feb. 26, 2013]
2 1 CF R S 0 . 56( b X4) (enhanced display) page 1 7of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR5 0 . 5 6 † 5 0 . 56 W a rds. (a) Ch i ldren who are wards of the State or any other agenc y , i nst i t u t i o n , or ent i ty can be i nc l uded i n c l i n i cal i nvest i gat i ons approved under † . . ?. Q . . . ? . . or † .. . ? . 9 : . ?. on l y if such c l i n i cal i nvest i gations ar e : (1) Re l ated to the i r status as wards; or (2) Conducted i n schoo l s , camps, hosp i ta l s, i nst i t u t i ons, or s i mi l ar sett i ngs i n wh i ch the major i ty of ch i ldren i nvo l ved as subjects are not wards. (b) I f the clin i cal i nvest i gat i on i s approved u nder p 9 . . . P . . ( ) of th i s sect i o n , the I RB must requ i re appo i ntment of an advocate for each ch i l d who i s a ward. (1) The advocate will serve i n add i t i on to any other i nd i v i dual act i ng on behalf of the child as guard i an or i n l oco parent i s. (2) One i nd i v i dual may serve as advocate for more than one c h i l d. (3) The advocate must be an i nd i v i dual who has the background and exper i ence to act i n , and agrees to act i n , the best i nterest of the child for the durati on of the child's part i c i pat i on i n the clin i cal i nvest i gat i o n . (4) The advocate must not be assoc i ated i n any way ( except i n the ro l e as advocate or member of the I RB ) w i th the c l i n i cal i nvest i gat i o n , the i nvest i gator(s ) , or the guard i an organizat i o n .
Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards page tof13 21CFR5 6 ( enhanced di s pla y ) 2 1 CFR P art 5 6 ( S e pt . 2 5 , 202 5 ) Th i s content is from the eCFR and i s authori tat i ve but u nofficia l . Title 2 1 - Food and Drugs Chapter I - F o od and Drug Admini s tration, Department of Health and Human Serv i c es S ubchapter A - General Part 5 6 Institutional Review Boards S ubpart A - - E . . .P.! . 2Y . ! . .! g . - † 5 6 . 1 0 1 9 . P . . : . † 5 6 . 1 02 .P. . . - . ! ! . 2 . . . : . † 5 6 . 1 03 . 9 . . ! E9 . . . - . ! . 9 . . . . ! . . . b ! . . . . ! . R : . .! .Y . . ! . . . ! . . E . . 9 . ! E . : . † 5 6 . 1 04 - P. ! . 2 . . - . f . 2 . . . ! . R : . . 9 . . ! . - - - . : . † 5 6 . 1 05 Y.Y . . . !Y . . . . 2 . f . .. . ! . R . . t 9 . . ! r . - - ! : . S ubpart B . 9 . . . 9 . . . ! . . ! . . ! 9 . . . . . . . . P . E † 5 6 . 1 06 . B . 9 . ! . ! . ! ! . 9 . . . : . † 5 6 . 1 07 . ! . R . . . . . . . ! . b . ! P . : . . . ! . S ubpart C . ! . . ... . ! .. 2 . i . . . . . . Q . P . ! ! . 2 . . - † 5 6 . 1 0 8 . ! . R . . . f . . . ! ! . 2 . . . . † 5 6 . 1 09 . ! . R . . . E Y . ! . . . Q . f . .. † 5 6 . 1 1 0 . . P . . ! . . . . Y . ! . . .. . 9 . . P r ! . ! . 2 . . . : . . ? . . ! . . : . . P . 2 . £ - . . . . f 2 . . . . . ! . ... ! n . . .. . 2. f .. . . - - 9 . bJ .Y . . 2 . 1 . x ! n 9 . . n 2 ... . 2 . J . n . E . . : . . . ! . . ! . . . ! . . E . ! . . . t. . . . f 2 E ... . ! . . 2 . r . . b . . . 9 . . ..! . .. P P . 2Y . . . .. !. † 5 6 . 1 1 1 . 9 . E . ! . ! . ! . . . f 2 . . . ! . R . . P P . 9.Y . . . ! . . . 2f. . . !. † 5 6 . 112 . B Y . . ! --- .Y. . . ! . . ! . . ! ! ! . Q . . : . E . . : . † 5 6 . 1 13 . . . P . . . ! . 2 . . . 2 . . . . ! . . ! . . ! ! . 2 . . . 2f . . ! . R . . P P . E2Y . . . ! . . . 2f . . !. . E . . : . † 5 6 . 1 1 4 . 9 . . 2 2 . P . . ! ! . Y . .. . E . . : . S ubpart D . R . 2 . ! . Q .. . . . . R P Q E ! . † 5 6 . 1 15 . ! . R . . . . 2 .! . . : . S ubpart E A . . . ! . . ! ! ! . . . !Y . . A . . ! 2 . . . f 2 . . . N . 2 . . 9 . . P ! . ! . g - . † 5 6 . 1 20 . . . . . . . . ! . . ! ! ! . ! . . ! Y . . . .. . ! . ! . 2 . . . : . † 5 6 . 1 2 1 .P . . ! . . 9 . . . ! . ! . f. - . ! . . 2 . f. . . . . . . ! . B . .. ! . . . . . . . ! . . . ! ! ! ! . 2 . . : . † 5 6 . 1 22 . P . . . . ! . ! . . ! . . 9 . ! . 2 . . . . . 2 f .. ! D f E . . ? . . ! . . . 9 . . . . . ! . 9 . . . ! Y . 2 ! ! . 2 . . : . † 5 6 . 1 23 . B . ! . . . ! . . . ! . . Q . f ... . . .. . ! . . . . 2 r . . J . ! . ! . ! ! . . . : . † 5 6 . 1 24 A ! . . ! 2 . .. . ! ! r . ! . . !Y . . 2 ! . .. 9 . . .!. . ! g - . ! . ! . . . ! q . . ! . ! . ! ! . . . : . P ART 5 6 - IN STITUTIONAL REVIEW BOARDS Authority: . ? . 1 ... . '. : . 9 : . . . . ? . 1 .. 4 . .. 4 . † .. . 4. .. . 4 . .. . . ?. 9 .. . . ?.9 ? . † ]. _ , . ?.? . . . . ? . . . . ?. ? . . . . 9 .. . 9 - . Q f . . . 9 .. . . 9 ! .. . † . Q j _, . . Q . : † . Q . .. ?. J . .. ?. . J . . ; 4 . ? . .. . '. : . 9 . : . . ?. J . . † .. ?.4. J . .. ? . ?? . · 21CFR5 6 . 1 02(b) ( 8 ) ( enhanced di s pla y ) p a g e2of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 5 6 . 1 01 S o urc e : - -- - -- . ? .. Jan. 2 7 , 198 1 , u n l ess otherw i se noted. S ubpart A - General Provi s ions † 5 6 . 1 0 1 S c op e . (a) Th i s part conta i ns the general standards for the compos i t i on, operat i o n , and respons i b i l i ty of an I nst i tuti onal Rev i ew Board ( I R B ) that rev i ews cl i n i cal i nvestigati ons regu l ated by the Food and Drug Adm in i strat i on under sect i ons SOS ( i ) and 520 ( g ) of the act, as well as cl i n i cal i nvesti gat i ons that support applicat i ons for research or market i ng permits for products regul ated by the F ood and Drug Adm in i strat i o n , i ncludi ng foods, i ncl ud i ng d ietary supp l ements, that bear a nutr ient content c l a i m or a hea l th cla i m , i nfant formu l as, food and co lor add i t i ves, drugs for hu man us e , med i cal dev i ces for human use, b i o l og i cal products for human us e , and e l ectron i c product s . Compl i a n ce w i th th i s part is i ntended to protect the r i ghts and we l fare of human subjects i nvolved i n such i nvestigati on s . (b) References i n this part to regu l atory sect i ons of the Code of Federal Regu l at ions are to chapter I of t i t l e 2 1 , un l ess otherwise note d . ( ' ! . E B . . !. Jan. 27. 198 1 , as amended at - - . E B . . . f Jan. 5 , 1999; . . . E B . . ?,; Q . . f Apr. 24 , 2001] † 5 6 . 1 02 Definit i on s . As used i n th i s part: (a) A ct means the Federal Food, Dru g , and Cosmet ic Act, as amended ( secs. 201 - 90 2 , 52 Stat. 1040 et seq . , as amended ( ? . J . . . . : . : . : .. ? . . . ? . . ? . )). (b) Application for research or marketing permit i nc l udes: (1) A co l or add i tive pet i t i o n , descr i bed i n part 7 1 . (2) Data and i nformat i on regard i ng a substance subm i tted as part of the procedures for establish i ng that a substance i s generally recogn i zed as safe for a use wh ich resu l ts or may reasonab ly be expected to result, d i rect l y or i nd i rect l y , i n i ts becom i ng a component or otherw i se affect in g the characterist i cs of any foo d , descr i bed i n † J . ? 9 : . ? · (3) A food add i t i ve pet i t i o n , descr i bed i n part 1 7 1 . (4) Data and i nformat i on regard i ng a food add i t i ve subm i tted as part of the procedures regardi ng food add i t i ves perm i tted to be used on an i nter i m bas i s pend i ng addit i onal stud y , descr i bed i n . † J .. Q:.J . . - (5) Data and i nformat i on regard i ng a substance subm i tted as part of the procedures for establish i ng a to l erance for unavo i dab l e contam i nants i n food and food - packagi ng mater i a l s , descr i bed i n sect i on 406 of the act. (6) An i nvest i gat i onal new drug applicat i o n , descr i bed i n P. .. . J . ? . . . qf . . ! . .. - . P. ! . · ( 7 ) A new drug applicat i o n , descr i bed i n part 31 4 . ( 8 ) Data and i nformat i on regard i ng the b i oava i l abil i ty or b i oequ i val ence of drugs for human use submitted as part of the proce d ures for i ssu i n g , amend in g , or repea l i ng a b i oequiva l ence requi rement, descr i bed i n part 320.
21CFR5 6 . 1 02( c) ( enhanced display) page3of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 56 . 1 02(b)( 9 ) ( 9 ) Data and i nformat i on regard i ng an over - the - co u nter drug for human use s u b m i tted as part of the procedures for c l ass i fyi ng s u ch drugs as generally recogn i zed as safe and effective and not m i sbrande d , descr i bed i n part 330. ( 1 O ) An app l i cat i on for a b i o l og i cs l icens e , descr i bed i n P . r. ! . . Q . 1 . .2f . . . . i . . . 2 b . .P . ! . - (11) Data and i nformat i on regard i ng a b i o l og i cal product subm i tted as part of the procedures for determ i n i ng that licensed b i o l og i cal products are safe and effect i ve and not m i sbranded , as descr i bed i n P . r . ! . . 9 . 1 . .. U . . ! . 2 b . . P . . t · (12) An Application for an l nvest i gational Dev i ce Exempt i on, descr i bed i n part 812. (13) Data and i nformat i on regard i ng a med i cal devi ce for hu man use subm i tted as part of the procedures for c l ass i fy i ng such devi ces, descr i bed i n part 860. (14) Data and i nformat i on regard i ng a med i cal devi ce for hu man use subm i tted as part of the procedures for estab l i sh i n g , amend i n g , or repealing a standard for such devi c e , descr i bed i n part 8 6 1 . (15) An app l i cat i on for premarket approval of a med i cal dev i ce for human us e , descr i bed i n sect i on 515 of the act. (16) A prod u ct devel opment protocol for a med i cal dev i ce for human us e , descr i bed i n sect i on 515 of the act. (17) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for such products, descr i bed in section 358 of the Pub l i c Hea l th Serv i ce Act. (18) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for obta i n i ng a vari a n ce from any e l ectron i c prod u ct performance standar d , as descr i bed i n † .. . 1. Q . 1 . Q : . · (19) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for grant i n g , amend in g , or extend i ng an exempt i on from a rad i at i on safety performance standard, as descr i bed i n . † . J . 9 . 1 . 9 : . † . · (20) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for obta i n i ng an exempt i on from notificati on of a rad i at i on safety defect or fai l ure of comp l i a n ce w i th a rad i at i on safety performance standar d , descr i bed i n subpart D of part 1003. (21) Data and i nformat i on about a cl i n i cal study of an i nfant formu l a when subm i tted as part of an i nfant for m u l a not i ficat i on under sect i on 4 12(c) of the Federal Foo d , Drug, and Cosmet i c Act. (22) Data and i nformat i on submitted i n a pet i t i on for a n utr i ent content cla i m , descr i bed i n . † . . 1 . 9 . . : . † . . gf ! . . ! .. . 9. . l? . ! E · and for a hea l th c l a i m , descr i bed i n † .. . 1 . Q. 1 . : .?.. Q . . gf.. . . ! . g . .P . ! . · (23) Data and i nformat i on from i nvest i gat i ons i nvolv i ng children subm i tted i n a new d ietary i ngred i ent not i ficat i on, descr i bed i n . † J . 9 : . † . f.. ! . ! . . b . .P. . . .
- ( c ) Clinical investigation means any experiment that i nvo l ves a test art i c l e and one or more human subjects, and that e i ther must meet the requ i rements for pr i or subm i ss ion to the Food and Drug Adm i nistrat i on under sect i on 505 ( i ) or 520( g ) of the act, or need not meet the requ i rements for pr i or subm i ss ion to the Food and Drug Adm i nistrat i on u nder these sect i ons of the act, but the resu l ts of wh i ch are i ntended to be l ater subm i tted t o , or he l d for i nspecti on b y , the Food and Drug Adm i nistrat i on as part of an app l i cat i on 21CFR5 6 . 1 02( m ) ( enha n ced display) pa g e4of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 1 02(d) for a research or market ing perm i t. The term does not i nc l ude exper i ments that must meet the provis i ons of part 5 8 , regard i ng nonc l i n i cal l aboratory stud i es. The terms researc h , clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part. (d) Em e rgency u se means the use of a test art i c l e on a human subject i n a l i fe - threateni ng s i tuat i on i n wh i ch no standard acceptab l e treatment i s availab l e , and i n wh i ch there i s not suffic i ent time to obta i n I RB approval. (e) Human subject means an i nd i v i dual who i s or becomes a part i c i pant i n researc h , e i ther as a rec i p i ent of the test art i c l e or as a control. A subject may be e i ther a hea l thy i nd i v i dual or a pat i ent. ( f) Institution means any pub l ic or pr i vate ent i ty or agency ( incl ud i ng Federa l , Stat e , and other agencie s ) . The term facility as used i n sect i on 520 ( g ) of the act i s deemed to be synonymous w i th the term institution for purposes of this part . (g) Institutional Review Board ( IRB ) means any boar d , comm i tte e , or other group formally des i gnated by an i nst i tut i on to rev i e w , to approve the i n i t i at i on of, and to conduct per i od i c review of, b i omed i cal research i nvolv i ng human subject s . The pr i mary purpose of such rev i ew is to assure the protect i on of the r i ghts and welfare of the human subjects. The term has the same mean i ng as the phrase institutional review committee as used i n sect i on 5 2 0 ( g ) of the act. (h) Investigator means an i nd i v i dual who actual l y conducts a clin i cal i nvest i gat i on ( i . e. , under whose i mmed i ate d i rect ion the test art i c l e is adm i nistered or dispensed t o , or used i nvo l v i n g , a subject ) o r , i n the event of an i nvest i gat i on conducted by a team of i nd i v i dua l s, i s the respons i b l e l eader of that team. (i) Minimal risk means that the probabil i ty and magn i tude of harm or d i scomfort ant i c i pated i n the research are not greater i n and of themse l ves than those ord i nar i l y encountered i n da i l y l ife or during the performance of routi ne phys i cal or psycho l og i cal exam i nat i ons or tests. G) Sponsor means a person or other entity that i n i t i ates a c l i n i cal i nvestigati o n , but that does not actually conduct the i nvest i gation, i.e . , the test art i c l e i s adm i n i stered or d i spensed to, or used i nvolv i n g , a subject under the i mmed i ate d i rect i on of another i ndiv i dual. A person other than an i nd i v i dual ( e . g . , a corporat i on or agency) that uses one or more o f i ts own emp l oyees to conduct an i nvest i gation that i t has i n i t i ated is consi dered to be a sponsor (not a sponsor - i nvestigator ) , and the emp loyees are cons i dered to be i nvest i gators. (k) Sponsor - investigator means an i nd i v i dual who both i n i t i ates and actually conduct s , a l one or w i th others, a clin i cal i nvest i gat i o n , i.e . , under whose i mmed i ate d i rect i on the test art i c l e i s adm i nistered or dispensed t o , or used i nvo l v i n g , a subject. The term does not i nc l ude any person other than an i nd i v i dua l , e . g . , i t does not i nc l ude a corporation or agency. The obligat i ons of a sponsor - i nvest i gator under th i s part i nc l ude both those of a sponsor and those of an i nvest i gator. (I) T e st article means any drug for human us e , b i o l o g i cal product for human us e , med i cal dev i ce for human use, human food add i t i v e , co l or add i tiv e , e l ectron i c product, or any other art i cle subject to regu l at i on under the act or under sect i ons 351 or 354 - 360F of the Publ i c Hea l th Serv i ce Act. ( m ) IRB approval means the determ i nat i on of the I RB that the cl i n i cal i nvestigati on has been reviewed and may be conducted at an i nst i tuti on w i t h i n the constra i nts set forth by the I RB and by other i nst i tuti onal and Federal requi rements . ' 1 . .E. . . ! Jan. 27, 1981, as amended at . 1..E . ! i . . Q ? . ! ! ! Mar. 3, 1989; † . ..E.. . . ? . . Q ? . ! June 1 8 , 199 1 ; ¥. : . .E.. . ? . . ! Jan. 199 9 ; ¥. : . . E! . i . ! Oct. 20, 199 9 ; . . .E.. . ? . :!..9 . ? ! . Aug. 29, 2000; . . . . E . ! i . ? 9 . . . ! Apr. 24, 2001; ? 1..E . ! i . ? . ? . ! ! ! Jan. 15 , 2009]
21CFR5 6 . 1 0 5 ( enha n ced display ) pa g e5of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 56 . 1 03 † 5 6 . 1 0 3 Circumstanc e s in which IRB review i s required (a) Except as prov i ded i n † . † . . ? . . :. 1 .Q4. and . ? . . :. 1 . Q † . , any c li n i cal i nvest i gat i on wh i ch m ust meet the requ i rements for pr i or subm i ss i on (as requ ired i n parts 31 2 , 81 2 , and 813) to the Food and Drug Admi n i strati on shall not be i nit i ated un l ess that i nvest i gat i on has been rev i ewed and approved b y , and rema i ns subject to co n t i nu i ng rev i ew b y , an I RB meeting the requ i reme n ts of th i s part. (b) Except as prov i ded i n † . † .. . ? . . . : . .94 . and . ? . . : . 1 . Q † . . the F ood and Drug Adm i n i strat i on may dec i de not to cons i der i n support of an applicat i on for a research or market i ng perm i t a n y data or i nformat i on that has been der i ved from a c l i n i cal i nvest i gat i on that has not been approved b y , and that was not subject to i n i t i al and conti nu i ng rev i ew b y , an I RB meeti ng the requ i reme n ts of th i s part. The deter m i nat i on that a clin i cal i nvest i gat i on may not be cons idered i n support of an applicat i on for a research or market ing perm i t does no t , howeve r , rel i eve the applicant for such a perm i t of any obligat i on under a n y other applicab l e regu l at i ons to subm i t the resu l ts of the i nvest i gat i on to the Food and Drug Adm i n i strat i o n . (c) Compl i ance w i th these regul at i ons will i n no way render i napp l i cab l e perti nent Federal, Stat e , or l ocal l aws or regu l at i ons. £ 1 . . E B . . ! Jan. 27. 198 1 ; 4 . F. . !J. }. 1: 9 ! Feb. 27. 1981} † 5 6 . 1 04 Exempt i ons from IR B requirement. The follow i ng categor i es of cl i n i cal i nvest i gat i ons are exem p t from the requ i reme n ts of th i s part for I RB rev i ew: (a) A n y i nvest i gat i on wh i ch commenced before Ju l y 2 7 , 1 981 and was subject to requ i reme n ts for I RB rev i ew under FDA regu l ations before that dat e , prov i ded that the i nvest i gat i on rema i ns subject to rev i ew of an I RB wh i ch meets the FDA requ i reme n ts i n effect before Ju l y 2 7 , 1981. (b) A n y i nvest i gat i on commenced before J u l y 2 7 , 1 981 and was not otherw i se subject to requ i rements for I RB rev i ew under Food and Drug Admi n i stration regu l at i ons before that date. (c) Emergency use of a test art i c l e , prov i ded that such emergency use i s reported to the I RB w i th i n 5 work i ng days. Any subsequen t use of the test art i c l e at the i nst i tut i on i s subject to I RB rev i e w . (d) Taste and food q u a l i ty eva luat i ons and consumer acce p tance st u d i es, i f who l esome foods w i thout add i t i ves are consumed or i f a food i s consumed that co n ta i ns a food i ngred i ent at or be l ow the l evel and for a use found to be saf e , or agr i cu l tura l , chem i ca l , or environmental contam i nant at or be l ow the l evel found to be saf e , b y the Food and Drug Adm i nistrat i on or approved b y the Envi ronmental Protect i on Agency or the Food Safety and I nspect i on Serv i ce of the U . S. Department of Agr i cu l ture. £ 1 . . E . ! i . . ! Jan. 27. 1981, as amended at - ..E . !J . . ? . . Q ? . t June 1 8 , 1991} † 5 6 . 1 0 5 W a i ver of IR B requirement. On the applicat i on of a sponsor or sponsor - i nvest i gato r , the Food and Drug Adm i n i strat i on may waive any of the requ i reme n ts conta i ned i n these regu l at i on s , i nc l ud i ng the requ i rements for I RB rev i e w , for spec i fic research activ i t i es or for c l asses of research act i v i t i e s , otherw i se covered by these regul at i ons.
S ubpart B - Organization and Personnel 21CFR5 6 . 1 06( e ) ( enha n ced display ) pa g e6of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 56 . 1 06 † 5 6 . 1 06 Registrat i on. (a) Who m u st register? Each I RB i n the Un i ted States that rev i ews c li n i cal i nvest i gat i ons regu l ated by FDA under sect i ons 505{i ) or 520( g ) of the act and each IRB i n the Un i ted States that rev i ews clin i cal i nvest i gat i ons that are i ntended to support app l i cat i ons for research or market i ng perm i ts for FDA regu l ated products m ust reg i ster at a s i te ma i ntai ned by the Department of Hea l th and Human Servi ces ( HHS ) . ( A research perm i t under sect i on 505(i ) of the act i s usually known as an i nvest i gat i onal new drug app l i cat i on ( I ND ) , while a research perm i t under sect i on 520 ( g ) of the act is usually known as an i nvest i gat i onal devi ce exempt i on ( IDE ) . ) An i ndiv i dual author i zed to act on the I RB ' s beha l f must subm i t the registrat i on i nformat i on. All other I RBs may reg i ster vo l untar i l y . (b) What information m u st an IRB register? Each I RB must prov i de the follow i ng i nformat i o n : (1) The name, ma i l i ng addres s , and street address ( if d i fferent from the mailing address) of the i nst i tut i on operat i ng the I RB and the nam e , mailing addres s , phone numbe r , facs i m i l e nu m be r , and e l ectron i c mail address of the seni or officer of that i nst i tuti on who i s respons i b l e for oversee i ng act i v i t i es performed b y the I RB; (2) The I RB's nam e , mailing ad d res s , street address ( i f different from the mailing addres s ) , phone n u mbe r , facs i mile nu m be r , and e lectron i c mail address; each I RB cha i rperson's nam e , phone numbe r , and e l ectron i c ma i l addres s ; and the nam e , ma i l i ng addres s , phone numbe r , facs i m i l e numbe r , and e l ectron i c mail address of the contact person prov i d i ng the regi strat i on i nformat i o n . (3) The approx i mate number of act i ve protoco l s i nvo l v i ng FDA - regu l ated products rev i ewed. For purposes of th i s ru l e , an Hact i ve protoco l · is any protocol for wh i ch an I RB conducted an i nitial rev i ew or a cont i nu i ng rev i ew at a convened meeti ng or u nder an exped i ted rev i ew procedure dur i ng the preced i ng 12 months; and (4) A descr i pt i on of the types of FDA - regu l ated products (such as b i o l og i cal prod u cts, co l or add i tive s , food add i t i ves, human drug s , or med i cal dev i ce s ) i nvo l ved i n the protoco l s that the I RB rev i ews. (c) Whe n must an IRB register? Each I RB must subm i t an i n i t i al registrat i on. The i n i t i al re g i strat i on must occur before the I RB beg ins to rev i ew a cl i n i cal i nvest i gati on descr i bed i n p r , g . r . P. . . ( ) . of this sect i on. Each I RB must renew i ts registrat i on every 3 year s . I RB reg i strat i on becomes effect i ve after rev i ew and acceptance by HH S . (d) Wh e re can an IRB register? Each I RB may register e l ectroni cally through ! I P ! !.. . ! P . . : . ! ! . : ! . :!. . : 9. Y ( . ' ! 0 !. : I f an I RB l acks the abil i ty to register e l ectron i call y , i t must send i ts regi strat i on i nformat i on, i n wr i tin g , to the Office of Good C l i n i cal Pract i c e , Office of Speci al Med i cal Program s , Food and Drug Adm in i stration, 10903 New Hampsh i re Av e . , B l dg. 3 2 , Rm. 5 1 2 9, S i l ver Spr i n g , MD 2 0993. (e) How does an IRB revise its registration information? I f an I RB's contact or cha i r person i nformat i on change s , the I RB must revise i ts regi stration i nformat i on by subm i tt i ng any changes i n that i nformat i on w i th i n 90 days of the chang e . An I RB's decis i on to rev iew new types of FDA - regu l ated products (such as a decis i on to rev i ew stud i es perta i n i ng to food add i tives whereas the I RB prev i ous l y rev i ewed stud i es perta i n i ng to drug product s ) , or to d i scont i nue rev i ew i ng cli n i cal i nvest i gat i ons regu l ated by FDA i s a change that must be reported w i th i n 30 days of the change. An I RB ' s dec i s i on to d i sband is a change that must be reported w i th i n 30 days of permanent cessat i on of the I RB ' s rev i ew of research . All other i nformat i on changes may be reported when the I RB renews i ts registrat i o n . The rev i sed i nformat i on must be sent to FDA e i ther e l ectron i cally or i n wr i ti ng i n accordance w i th p r . . 9 . E . P . . . J ) . of this sect i on. f? . 1 . .E. !! . . ? . . ! ! t Jan. 15 , 200 9 , as amended at .! . .E . B ..! . 1 . Q . t Mar. 15 , 2013]
21CFR5 6 . 1 0 8 (8) ( 3 ) ( enhan c ed display ) pa g e7of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR5 6 . 1 07 † 5 6 . 1 0 7 IRB membershi p . (a) Each I RB shall have at l east five members, with vary ing backgrounds to promote comp l ete and adequate rev iew of research act i v i t i es common l y conducted by the i nst i tuti on. The IRB shall be suffic i ent l y qualified through the exper i ence and experti se of i ts members, and the d i versity of the members, i nclud i ng consi derat i on of rac e , gende r , cu l tural background s , and sensitivi ty to such i ssues as co m mun i ty att i tudes, to promote respect for i ts adv i ce and counsel in safeguard i n g the r i ghts and we l fare of human subjects. I n add i t i on to possess i ng the profess i onal co m petence necessary to rev i ew the specific research act i v i t i e s , the I RB shall be ab l e to ascerta i n the acceptabili ty of proposed research in terms of i nst i tut i onal comm i tments and regu l at i ons, app l i cab l e l a w , and standards of profess i onal conduct and pract i c e . * * * The IRB shall therefore i nc l ude persons know l edgeab l e i n these areas. I f an I RB regu l ar l y rev i ews research that i nvolves a vul nerab l e category of subject s , such as children , pr i soner s , pregnant wome n , or handicapped or mental l y d isab l ed person s , cons i derat i on shall be g i ven to the i nclus i on of one or more i nd i v i dua l s who are know l edgeab l e about and exper i enced i n work i ng w i th those subject s . (b) Every nond i scr i m i natory effort will be made to ensure that no I RB consists ent i re l y of men or ent i re l y of wome n , i nc l ud i ng the i nst i tuto n ' s cons i derat i on of qualified persons of both sexe s , so l ong as no sel ect i on i s made to the I RB on the bas i s of gender. No I RB may cons i st ent i re l y of me m bers of one profess i o n . (c) Each I RB shall i nc l ude at l east one member whose pr i mary concerns are i n the sc i ent i f i c area and at l east one member whose pr i mary concerns are i n nonsc i ent i fic areas. (d) Each I RB shall i nc l ude at l east one member who i s not otherwise affi l i ated w i th the i nst i tuti on and who i s not part of the i mmed i ate fam i l y of a person who is affiliated w i th the i nst i tut i o n . (e) No I RB may have a member part i c i pate i n the I RB' s i n i t i al or cont i nu i ng rev i ew of any project i n wh i ch the member has a confli ct i ng i nteres t , except to prov i de i nformat i on requested b y the I RB. ( f) An I RB ma y , i n i ts d i scret i on, i nv i te i nd i v i dua l s w i th competence i n spec i al areas to ass i st i n the rev i ew of comp l ex i ssues wh i ch requi re experti se beyond or i n add i t i on to that ava i l ab l e on the I RB. These i ndiv i dua l s may not vote w i th the I RB. f . . . E . - !.. Jan. 27, 198 1 , as amended at - ..E. . . Q f. 1 June 1 8 , 199 1 ; † . . E. . .! . . 1 June 28, 1991; .!. . . E.. . t Q . J . 1 Mar. 15 , 2013] S ubpart C - IRB Functions and Operations † 5 6 . 1 08 IR B funct i ons and operations .
I n order to fu l fill the requ i rements of these re g u l at ion s , each I RB shall: (a) Follow wr i tten procedures: (1) For conduct i ng i ts i n i t i al and cont i nu i ng rev i ew of research and for report i ng i ts find i ngs and act i ons to the i nvest i gator and the i nst i tuti o n ; (2) for determ i n i ng wh ich projects requ i re rev i ew more often than annually and wh i ch projects need ver i f i cat i on from sources other than the i nvest i gator that no mater i al changes have occ u rred s i nce prev i ous I RB rev i ew; (3) for ensur i ng prompt report i ng to the IRB of changes i n research act i v i t y ; and 21CFR5 6 . 1 09( e ) ( enha n ced display ) page8of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 5 6 . 1 08 ( a ) ( 4 ) ( 4 ) for ensur i ng that changes i n approved researc h , dur ing the per i od for wh i ch I RB approval has al ready been give n , may not be i n i t i ated w i tho u t I RB rev i ew and approval except where necessary to el i m i nate apparent i mmed i ate hazards to the human subjects. (b) Follow wr i tten procedures for ensuri ng prompt report i ng to the I R B , appropr i ate i nst i t u t i onal offic i a l s , and the Food and Drug Adm i n i strat i on of: (1) Any unant i c i pated prob l ems i nvo l v i ng r i sks to human subjects or others; (2) any i nstance of ser i ous or co n t in u i ng noncompl i ance w i th these regu l at i ons or the requ i rements or determ inat i ons of the I RB; or (3) any suspens ion or ter m i nat i on of I RB approval. (c) Exce p t when an exped i ted rev i ew procedure i s used (see † . . ? . . : 1 . J . . Q ) , rev i ew proposed research at convened meeti ngs at wh i ch a major i ty of the members of the I RB are present, i nc l ud i ng at l east one member whose pr i mary concerns are i n nonscient i fic areas. I n order for the research to be approved, i t shall rece i ve the approval of a major i ty of those members present at the meet i ng. f 1 . .E . f! . . . ! Jan. 27, 1981, as amended at . .E . . ? . ? . . Q ? . t June 18, 199 1 ; .!. . .E. . . † . ? . . Mar. 4, 2002} † 5 6 . 1 0 9 IRB review of researc h . (a) An I RB shall rev i ew and have author i ty to approve, requ i re mod i ficat i ons i n ( to secure approva l ) , or d i sapprove all research activ i t i es covered b y these regu l at i ons. (b) An I RB shall requ i re that i nformat i on g i ven to subjects as part of i nformed consent i s i n accordance w i th † . . . Q : ?.:?. · The I RB may requ i re that i nformat i o n , i n add i tion to that spec i fically me n t i oned i n † . . ?. Q . - . f. : † . , be g i ven to the subjects when i n the I RB's judgment the i nformat i on wou l d mean ingfully add to the protect i on of the r i ghts and we l fare of subjects. (c) An I RB shall requ i re documentation of i nformed consent i n accordance w i th † . . Q . . . ? . :? . . 2 f. . ! . ! . h .P . ! t · exce p t as follows: (1) The I RB ma y , for some or all subjects , wa i ve the requi reme n t that the subjec t , or the subject's l egally a u thor i zed represe n tat i v e , s i gn a wr i tten consent form if i t finds that the research presents no more than m i n i mal r i sk of harm to subjects and i nvolves no procedures for wh i ch wr i tten conse n t i s normally requ i red o u ts i de the research context; or (2) The I RB ma y , for some or all subjects , find that the requ i reme n ts i n † . .. Q . . . ?.: 4 . . 2 f . ! . ! .. h . P . ! . r. for an exception from i nformed conse n t for emergency research are met. (d) I n cases where the documentat i on requ i reme n t i s wa i ved under P . . ! . 9 ! P. b . . .C 9 X J of th i s sect i o n , the I RB may requ i re the i nvest i gator to prov i de subjects w i th a wr i tten stateme n t regard i ng the researc h . (e) An I RB shall notify i nvest igators and the i nst i t u t i on i n wr i t i ng o f i ts deci s i on to approve or d i sapprove the proposed research act i v i t y , or of modificat i ons requ i red to secure I RB approval of the research act i v i ty. I f the I RB dec i des to d i sapprove a research act i v i t y , i t shall i nc l ude i n i ts wr i tten not i ficat i on a statement of the reasons for i ts deci s i on and g i ve the i nvest i gator an opportunity to respond i n person or i n wr i t i ng. F or i nvest i gat i ons i nvo l v i ng an except i on to i nformed conse n t under . † . . . 9 : . ? . . 4 . . f.! . ! . . b . P . . t .
an I RB shall prom p t l y notify i n wr i t i n g the i nvest i gator and the sponsor of the research when an I RB determ i nes that i t 21CFR 5 6 . l l O(d.) ( enhanced display ) pa g e9of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 1 0 9 (f) cannot approve the research because i t does not meet the criteri a i n the except i on prov i ded under † . . 9 : ?.4 ( ) . . 5 ? .f.. . ! .. . P. . . or because of other re l evant ethi cal concerns. The wr i tten not i f i cat i on shall i nclude a statement of the reasons for the I RB' s determ i nat i on. ( f) An I RB shall conduct cont i nu i ng rev i ew of research covered b y these re g u l at i ons at i nterva l s appropr i ate to the degree of risk, but not l ess than once per yea r , and shall have author i ty to observe or have a t h i rd party observe the consent process and the research . (g) An I RB shall prov i de i n wr i ting to the sponsor of research i nvo l v i ng an except i on to i nformed consent under † . . ?. 9 : . ?.4 . . . f. . . ! ... . P. . E a copy of i nformat i on that has been public l y disc l osed u nder † . . 9 : . ? . . . ( ) ( ?} . ( ! .! ) . and ( ) . ( !. l . Q . ! . ! l. f. . . ! .. . P ! . - The I RB shall prov i de th i s i nformat i on to the sponsor prompt ly so that the sponsor i s aware that such d i sc l osure has occurred. Upon rece i pt, the sponsor shall prov i de cop i es of the i nformat i on d i sc l osed to FDA. (h) When some or all of the subjects i n a study are children , an I RB must determ i ne that the research study i s i n comp l i ance w i th P . r. ! . . ? . . Q , ... . . f? . . . t ! ? . . . 2 J . . ! .. . 9 . . . f ? ! . . · at the t i me of i ts i n i t i al rev i ew of the research. When some or all of the subjects i n a study that was ongo i ng on Apr i l 30, 2001 , are ch i l dre n , an I RB must conduct a review of the research to determ i ne compliance w i th P . r. ! . . ? . . Q , ... . . P . . . . . !? . . . 2 ! . . . ! .. . . P. . . . e i ther at the t i me of cont i nu i ng rev i ew o r , at the d i scret i on of the I R B , at an earlier dat e . f 1 .E . ! i . . !. Jan. 27, 198 1 , as amended at . . 1.E . ! i .. . ? . . ? . . 1 Oc t . 2, 1996 ; . . . F B . . ? . 9 . . . 1 Apr. 24, 2007; .? . .E . ! i . . ? . ? . . . ? . . ? . 1 Feb. 26, 2013] † 5 6 . 1 1 0 Expedited review procedures fo r certain kinds of re s earc h i n volving no more than minimal risk, and fo r minor chan g e s i n approved re s earch. (a) The Food and Drug Adm in i strat i on has estab l ishe d , and published i n the FEDERAL REG I STER, a l ist of categor i es of research that may be rev i ewed by the I RB through an exped i ted rev i ew procedure. The list will be amended, as appropr i at e , through per i od i c repub l i cat i on i n the FEDERAL REG I STER. (b) An I RB may us e the exped i ted rev i ew procedure to rev i ew e i ther or both of the fol l ow ing: (1) Some or all of the research appear i ng on the l i st and found by the rev i ewer( s ) to i nvolve no more than m i n i mal r i sk, (2) m i nor changes i n prev i ous l y approved research dur i n g the peri od (of 1 year or l es s ) for wh ich approval is author i ze d . Under an expedi ted rev i ew proced u r e , the rev i ew may be carr i ed out by the I RB cha i rperson or by one or more exper i enced rev i ewers des i gnated by the I RB cha i rperson from among the members of the I RB. I n rev i ew i n g the researc h , the rev i ewers may exercise all of the author i t i es of the I RB except that the rev i ewers may not disapprove the research. A research act i v i ty may be d i sapproved on l y after rev i ew i n accordance w i th the nonexped i ted rev i ew procedure set forth i n † . . . ? . † .: J . . 9. . { !?. ) . - (c) Each I RB wh i ch uses an exped i ted rev i ew procedure shall adopt a method for keep i ng all members advi sed of research proposa l s wh i ch have been approved under the procedur e . (d) The Food and Drug Adm in i strat i on may restr i ct, suspend , or term i nate an i nst i tuti o n ' s or I RB' s use of the expedi ted rev i ew procedure when necessary to protect the r i ghts or we l fare of subjects. £ 1 . . E B . . . ! Jan. 27, 7987, as amended at . . . EB . ?. . . Q ?,g June 18, 1991]
research i f i t has not been approved by an I RB. 21CFR 5 6 .11 2 { enhanced display ) page 1 0of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 111 † 5 6 . 1 1 1 Criteria for IRB approval o f re search. (a) I n order to approve research covered b y these regu l at ions the I RB shall determ i ne that all of the follow i ng requ i rements are satisfied: (1) Risk s to s u bjects are m i n i m i zed: (i) By using procedures whi ch are consistent w i th sound research des i g n and wh ich do not unnecessar i l y expose subjects to risk, and (ii) whenever appropr i ate, by us i ng procedures already be i ng performed on the subjects for d i agnost i c or treatment purpose s . (2) Risk s to s u bjects are reasonab l e i n re l at i on to anti c i pated bene f i t s , i f an y , to subject s , and the i mportance of the know l edge that may be expected to resu l t. I n eva l uat i ng r i sks and benef i ts, the I RB shou l d cons i der on l y those risks and benefits that may resu l t from the research (as distin g uished from risks and benefits of therap i es that subjects wou l d rece i ve even i f not part i c i pat i ng i n the research) . The I RB shou l d not cons i der possi b l e l ong - range effects of app l y i ng know l edge ga i ned i n the research ( for example, the poss i b l e effects of the research on public pol i c y ) as among those research r i sks that fall w i th i n the p u rv i ew o f i ts respons i bil i ty . (3) Se l ect i on of subjects is equ i tab l e . I n mak i ng this assessment the I RB shou l d take i nto account the purposes of the research and the sett i ng i n wh i ch the research will be conducted and shou l d be part i cu l ar l y cogn i zant of the speci al prob l ems of research i nvolv i ng vu l nerab l e popu l at i ons, such as ch i l dre n , prisoner s , pregnant wome n , hand i cappe d , or mentally d isab l ed person s , or econom i cally or educat i onally d i sadvantaged person s . (4) I nformed consent will be sought from each prospect i ve subject or the subject ' s l egally authorized representat i v e , i n accordance w i th and to the extent requi red by part 50. (5) I nformed consent will be appropr i ate l y documente d , i n accordance w i th and to the extent requ i red by . † . . ? . 9 : ?.:? . .. (6) Where appropr i at e , the research p l an makes adequate prov i s i on for mon i tor i ng the data collected to ensure the safety of subject s . ( 7 ) Where appropr i at e , there are adequate prov i s i ons to protect the privacy of subjects and to ma i ntai n the confident i ality of data. (b) When some or all of the subject s , such as ch i ldren, pr i soners, pregnant wome n , hand i capped, or mentally d i sab l ed person s , or econom i cal l y or educat i onally disadvantaged persons, are l i ke l y to be vul nerab le to coerc i on or undue i nfluence add i t i onal safeguards have been i nc l uded i n the study to protect the r i ghts and welfare of these subjects. (c) I n order to approve research i n wh i ch some or all of the subjects are children , an I RB must determ i n e that all research is i n comp l i ance w i th P . r. ! .. . Q , ... !:. ' . P . . . . Q . . 2 . . . ! .. 2 . . P . ! . · { 1 . . E B . . !. Jan. 27. 198 1 , as amended at . . .fB . . ?..? . .Q? . g June 1 8 , 7997; † . . . r n . ?..9 . . ? . ? . . , Apr. 2 4 , 2001] † 5 6 . 1 1 2 Review b y institut i on. Research covered by these regul at ions that has been approved by an I RB may be subject to further appropr i ate rev i ew and approval or d i sapproval by offic i a l s of the i nst i tuti on.
Howeve r , those offic i a l s may not approve the pagellof13 21CFR5 6 . ll S ( c ) ( enhanced di s pla y ) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR5 6 . 113 † 5 6 . 1 1 3 Suspension o r termination of IRB approval of research. An I RB shall have author i ty to suspend or term i nate approval of research that i s not be i ng conducted i n accordance w i th the I RB ' s requ i reme n ts or that has been associated w i th unexpected ser i ous harm to subjects. A n y suspens i on or term i nat i on of approval shall i nc l ude a stateme n t of the reasons for the I RB ' s act i on and shall be reported prompt l y to the i nvest i gato r , appropr i ate i nst i t u t i onal officia l s , and the Food and Drug Admi n i stratio n . † 5 6 . 1 1 4 C ooperative re s earch. I n comp l y i ng w i th these regu l at i ons. i nst i t u t i ons i nvo l ved i n mu l t i - i nst i t u t i onal studi es may use jo i nt rev i e w . reliance u pon the rev i ew of another qualified I RB, or s i milar arrangeme n ts a i med at avoi dance of duplicat i on of effort. S ubpart D - Re c ords and Reports † 5 6 . 1 1 5 IRB record s . (a) An i nst i tut i o n , or where appropr i ate an I RB, shall prepare and ma i n ta i n adeq u ate docume n tat i on of I RB act i v i t i e s , i nc l ud i ng the fol l ow i ng: (1) Cop i es of all research proposa l s rev i ewed, sc i e n t i f i c eval uat i on s , if an y , that accompa n y the proposal s , approved samp l e consent documents , progress reports subm i tted by invest i gator s , and reports of i njur i es to subjects. (2) M i n u tes of I RB meetings wh i ch shall be i n suffici e n t deta i l to show attendance at the meet i ng s ; act i ons taken b y the I R B ; the vote on these act i ons i nc l ud i ng the nu m ber of members vot i ng fo r , aga i nst, and absta i n i ng; the bas i s for requ i r i ng changes i n or d i sapprov i ng research; and a wr i tten summary of the d i scuss i on of controverted i ss u es and the i r reso l ut i on. (3) Records of cont inu i ng rev i ew act i v i t i es. (4) Cop i es of all correspondence between the I RB and the i nvest i gators. (5) A list of I RB members i de n t i f i ed by nam e ; earned degrees; representati ve capac i ty; i nd i cat i ons of exper i ence such as board certificat i ons, license s , etc . , suffici ent to descr i be each member ' s ch i ef a n t i c i pated co n tr i but i ons to I RB de l i berat i ons; and a n y emp l oyment or other re l at i onsh i p between each member and the i nst i t u t i o n ; for examp l e: ful l - t i me empl oyee, part - t i me emp l oyee, a member of govern i ng panel or boar d , stockho l de r , pa i d or unpa i d consu l ta n t. (6) Wr i tten procedures for the I RB as requ i red by . † . . ? . . : J . . Q . . . C ) and. { ) . ( 7 ) Stateme n ts of s i gn i ficant new find i ngs prov i ded to s u bject s , as requ i red b y † . . ? . 9 : . ? : (b) The records requ ired b y th i s regu l at i on shall be reta i ned for at l east 3 years after comp l et i on of the researc h , and the records shall be access i b l e for i nspect i on and copy i ng by author i zed represe n tatives of the Food and Drug Adm i n i strat i on at reasonab l e t i mes and i n a reasonab l e manne r . (c) The Food and Drug Admi n i strati on may refuse to cons i der a cl i n i cal i nvest i gat i on i n support of an app l i cat i on for a research or market i ng perm i t if the i nst i tut i on or the I RB that rev i ewed the i nvest i gat i on refuses to allow an i nspect i on under t h i s sect i on. £ 1 . . E B . !J . ?. Jan. 27, 198 1 , as amended at - ..f. _ ?..f ! . . 9. . ? . . ! June 1 8 , 199 1 ; † 7...f. . . . † . f! . _ ? ! . Mar.
4, 2002} S ubpart E - Administrat i ve A ctions for Nonc omplian c e 21CFR5 6 . 1 2 1 ( c ) ( enhanced dis p lay) page12of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 120 † 5 6 . 1 2 0 L e sser administrative action s . (a) I f apparent nonco m pliance w i th these regu l at i ons i n the operati on of an I RB i s observed b y an FDA i nvest i gator dur i ng an i nspect i o n , the i nspector will present an oral or wr i tten summary of observat i ons to an appropr i ate represe n tative of the I RB. The Food and Drug Ad m i n i strat i on may subsequen tly send a l etter descr i b i n g the noncompliance to the I RB and to the parent i nst i t u t i on. The agency will requ i r e that the I RB or the parent i nst i t u t i on respond to th i s l etter w i th i n a t i me per i od specified by FDA and descr i be the correct i ve act i ons that will be taken by the I R B , the i nst i t u t i o n , or both to ach i eve compliance w i th these regu l at i ons. (b) On the bas i s of the I RB ' s or the i nst i t u t ion ' s respons e , FDA may schedu l e a re i nspect i on to confi rm the adequacy of correct i ve act i ons. I n add i t i on, u n til the I RB or the pare n t i nst i tut i on takes appropr i ate corrective act i o n , the Agency may requ i re the I RB to: (1) W i thho l d approval of new stud i es subject to the requ i rements of t h i s part that are conducted at the i nst i tut i on or rev i ewed b y the I R B ; (2) D i rect that no new subjects be added to ongo i ng stud i es subject to th i s part; or (3) T erm i nate ongo i ng studi es subject to th i s part when do i ng so wou l d not endanger the s u bjects. (c) When the apparent noncompliance creates a s i gn i fica n t threat to the r i ghts and we l fare of human subjects , FDA may not i fy re l eva n t State and Federal regu l atory agenc i es and other parti es w i th a d i rect i nterest i n the Agency's act i on of the def i c i enci es i n the operation of the I RB. (d) The pare n t i nst i tut i on i s presumed to be respons i b l e for the operati on of an I R B , and the Food and Drug Admi n i strat i on will ord i narily d i rect any a d m i n i strat i ve act i on under th i s subpart aga i nst the i nst i t u t i o n . Howeve r , depend i ng on the ev i dence of respons i bil i ty for deficienci es, determ i ned dur i n g the i nvest i gat i o n , the Food and Drug Admi n i strati on may restr i ct i ts adm i n i strative act i ons to the I RB or to a compone n t of the pare n t i nst i t u t ion determ i ned to be respons i b l e for formal des i gnat i on of the I RB. f . . . f. . !i . . ! Jan. 27. 198 1 , as amended at J .. . f. . !i..! . . Q ? . . 1 Apr. 4, 2016] † 5 6 . 1 2 1 Disqualif i cation of an IRB or an inst i tution. (a) Whenever the I RB or the i nst i t u t ion has fai l ed to take adequate steps to correct the noncompliance stated i n the l etter sent b y the agency under † ... f?. J . ? . . Q . ( ) .. and the Comm i ssioner of Food and Drugs determ ines that th i s noncompliance may just i fy the d i squa l i fication of the I RB or of the parent i nst i t u t io n , the Comm i ss i oner will i nst i tute proceed i ngs i n accordance w i th the requ i rements for a regu l atory hear i ng set forth i n part 1 6. (b) The Comm i ss ioner may d i sq u alify an I RB or the pare n t i nst i tut i on i f the Comm i ss i oner determ i nes that: ( 1 ) The I RB has refused or repeated l y failed to comp l y w i th any of the regu l ations set forth i n th i s par t , and ( 2 ) The noncomp l i ance adverse l y affects the r i g h ts or welfare of the human subjects i n a c l i n i cal i nvest i gat i o n . (c) I f the Comm i ss i oner deter m i nes that d i squalificati on i s appropri at e , the Comm i ss ioner will i ssue an order that exp l a i ns the bas i s for the determ i nat i on and that prescr i bes any act i ons to be taken w i th regard to ongoi ng cl i n i cal research conducted under the rev i ew of the I RB.
The Food and Drug Adm i n i stration will page13of13 21CFR5 6 . 12 4 ( enha n ced display) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 56J2 1 (d) send not i ce of the d i squa l ificat i on to the IRB and the parent i nst i tut i o n . Other part i es w i th a d i rect i nterest, such as sponsors and cl i n i cal i nvesti gators, may a l so be sent a not i ce of the disqua l i ficat i on. I n add i t i on, the agency may e l ect to publ i sh a not i ce of i ts act i on i n the FEDERAL REG I ST E R. ( d ) The Food and Drug Adm in i strat i on will not approve an app l i cat i on for a research perm i t for a c l i n i cal i nvest i gat i on that i s to be under the rev i ew of a d i squalified I RB or that i s to be conducted at a d i squali f i ed i nst i tut i o n , and i t may refuse to cons i der i n support of a market i ng perm i t the data from a clin i cal i nvest i gat i on that was rev i ewed by a d isqualified I RB as conducted at a disqual i fied i nst i tuti o n , un l ess the I RB or the parent i nst i tuti on i s re i nstated as prov i ded i n † . . ? . † . : 1 . ? . .. † 5 6 . 12 2 Publ i c disc l osure of information re g arding revocat i on. A determ i nat i on that the Food and Drug Adm i n i strat i on has disqual i fied an i nst i tut i on and the adm i n i strat i ve record regard i ng that determ i nat i on are d i sc l osab l e to the pub l i c under part 2 0 . † 5 6 . 1 2 3 Reinstatement of an IRB or an institution. An I RB or an i nst i tuti on may be re i nstated if the Comm i ss i oner deter m i nes, upon an eva l uat i on of a wri tten subm i ss ion from the I RB or i nstitut i on that exp l a i ns the correct i ve act i on that the i nstitut i on or I RB p l ans to tak e , that the I RB or i nst i tut i on has prov i ded adequate assura n ce that i t will operate i n comp l i ance w i th the standards set forth i n this part. Not i ficat i on of re i nstatement shall be prov ided to all persons not i fied under † .. . ?. † . : . . ? . . H2 ) : † 5 6 . 12 4 Act i ons alternative or addit i onal to disqualifi c ation. D i squa l ificat i on of an I RB or of an i nst i tut i on is i ndependent of, and ne i ther i n lieu of nor a precond i t i on to, other proceed i ngs or act i ons author i zed by the act. The Food and Drug Adm i nistrat i on ma y , at any t i m e , through the Department of Just i ce i nst i tute any appropr i at e jud i c i al proceed i ngs (c i v i l or cr i m i nal) and any other appropr i ate regul atory act i o n , i n add i t i on to or i n l i eu of, and befor e , at the t i me of, or afte r , disqualificat i o n . The agency may a l so refer perti nent matters to another Federal, Stat e , or l ocal government agency for any act i on that that agency determ i nes to be appropr i ate.
Exhibit 99.1
NeOnc Technologies’ Subsidiary, NeuroMENA, Signs Master Services Agreement with M42’s IROS and
Expands Board of Directors
CALABASAS, Calif. and ABU DHABI, United Arab Emirates – NeOnc Technologies Holdings, Inc. (NTHI) (“NeOnc” or the “Company”), a multi-Phase 2 clinical-stage biopharmaceutical company pioneering therapies for central nervous system (CNS) cancers, has announced two major strategic developments that solidify its expansion into the Middle East. Its wholly owned subsidiary, NuroMENA Holdings Ltd., has signed a Master Services Agreement (MSA) with Insights Research Organization and Solutions (IROS), a UAE-based contract research organization, part of the M42 group – a global health company powered by Artificial Intelligence (AI), technology and genomics.
In a concurrent strategic move, NeOnc is expanding the NuroMENA Board of Directors, appointing key partners from Quazar Investment to drive regional governance and growth.
The MSA with IROS provides NuroMENA with access to a world-class health ecosystem to accelerate the clinical development of NeOnc’s innovative cancer therapies. This partnership with an M42 entity represents a powerful validation of NeOnc’s scientific platform and anchors its clinical trial operations within one of the world’s most advanced healthcare infrastructures.
To guide this new phase of growth, the NuroMENA board will be expanded to include two new members: Waleed K. Al Ali, the CEO of Quazar Investment, and the Chairman of Quazar Investment. They will serve alongside current NuroMENA directors Amir Heshmatpour, Dr. Ishwar K. Puri and Bader Al Monawer, creating a formidable leadership team to oversee the company’s regional strategy.
“Signing an agreement with IROS, an entity backed by a global force like M42, is a transformative event,” said Amir Heshmatpour, Executive Chairman and President of NeOnc Technologies. “This MSA provides the elite infrastructure needed to fast-track our clinical trials. By simultaneously installing a powerful board with our partners at Quazar, we are establishing a premier foundation for both operational excellence and strategic leadership in the Middle East. Together, these actions will dramatically accelerate our mission to bring novel cancer treatments to patients.”
Commenting on the agreement, Islam Eltantawy, General Manager at IROS, said: “At IROS, we are proud to provide the platform, infrastructure and expertise that enable companies like NeOnc to accelerate the development of breakthrough cancer therapies. Through Abu Dhabi’s world-class health ecosystem that is fully aligned with international standards, we are able to conduct clinical trials with exceptional speed, quality and integrity. This partnership reflects our shared commitment to advancing research that brings new hope to patients and positions Abu Dhabi as a global hub for clinical excellence and innovation in oncology.”
-Ends-
About IROS
IROS, part of the M42 group, a global tech-enabled health powerhouse, is a pioneering UAE-based Clinical Research Organization (CRO) dedicated to advancing excellence in clinical research and real-world evidence. Its mission is to leverage cutting-edge technologies to innovate in health and drive breakthroughs in clinical research. By conducting high-quality research and achieving groundbreaking insights, IROS aims to improve patients’ lives and shape the health landscape.
IROS’ comprehensive offerings spans all therapeutic domains, positioning it as a leader in regional medical research. With a team of high-caliber experts committed to precision, IROS offers both full-service solutions and tailored services to meet the unique needs of its partners. The organization continually integrates the latest technologies and techniques to drive innovation and excellence.
For more information, please visit, https://iros.ai/ M42 is a global health champion powered by artificial intelligence (AI), technology and genomics to advance innovation in health for people and the planet.
About M42
Headquartered in Abu Dhabi, M42 combines its specialized, state-of-the-art facilities with integrated health solutions like genomics and biobanks, and harnesses advanced technologies to deliver precise, preventive and predictive care, to impactfully disrupt traditional healthcare models and positively impact lives globally.
Established in 2023, following the coming together of G42 Healthcare and Mubadala Health, M42 has more than 480 facilities in 26 countries and over 20,000 employees. M42 includes renowned healthcare providers including Cleveland Clinic Abu Dhabi, Danat Al Emarat, Diaverum, Imperial College London Diabetes Centre, Sheikh Sultan bin Zayed Hospital, and Moorfields Eye Hospital Abu Dhabi. As well as operating the Emirati Genome Programme, M42 runs Abu Dhabi BioBank and Abu Dhabi Health Data Services (ADHDS), a global tech-enabled healthcare company operating Malaffi.
About NuroMENA Holdings Ltd.
NuroMENA is a UAE-based subsidiary of NeOnc Technologies Holdings, Inc., established as part of the UAE structure to oversee regional clinical operations, partnerships, and innovation in the Middle East and North Africa. Upon closing of the $50 million investment and execution of the change of control, NuroMENA will be majority-controlled by Quazar Investment, with joint governance oversight and strategic alignment between NeOnc and Quazar to assist accelerating breakthrough CNS therapies across the region. NuroMENA was officially incorporated under ADGM on August 6, 2025.
ABOUT NEONC TECHNOLOGIES HOLDINGS, INC.
NeOnc Technologies Holdings, Inc. is a clinical-stage life sciences company focused on the development and commercialization of central nervous system therapeutics that are designed to address the persistent challenges in overcoming the blood-brain barrier. The company’s NEO™ drug development platform has produced a portfolio of novel drug candidates and delivery methods with patent protections extending to 2038. These proprietary chemotherapy agents have demonstrated positive effects in laboratory tests on various types of cancers and in clinical trials treating malignant gliomas. NeOnc’s NEO100™ and NEO212™therapeutics are in Phase II human clinical trials and are advancing under FDA Fast-Track and Investigational New Drug (IND) status. The company has exclusively licensed an extensive worldwide patent portfolio from the University of Southern California consisting of issued patents and pending applications related to NEO100, NEO212, and other products from the NeOnc patent family for multiple uses, including oncological and neurological conditions.
For more about NeOnc and its pioneering technology, visit neonc.com.
Important Cautions Regarding Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements can be identified by terminology such as “may,” “will,” “should,” “intend,” “expect,” “plan,” “budget,” “forecast,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “evaluating,” or similar words. Statements that contain these words should be read carefully, as they discuss our future expectations, projections of future results of operations or financial condition, or other forward-looking information.
Examples of forward-looking statements include, among others, statements regarding whether a definitive agreement will be reached with Quazar. These statements reflect our current expectations based on information available at this time, but future events may differ materially from those anticipated.
The “Risk Factors” section of our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, along with other cautionary language in that report or in our subsequent filings, outlines important risks and uncertainties. These may cause our actual results to differ materially from the forward-looking statements herein, including but not limited to the failure to finalize the agreement with Quazar, modifications to its terms, or alternative uses of proceeds.
We assume no obligation to revise or update any forward-looking statements, whether as a result of new information, future developments, or otherwise, except as required by applicable securities laws and regulations.
“NEO100” and NEO “212” are registered trademarks of NeOnc Technologies Holdings, Inc.
Company Contact:
info@neonc.com
Investor Contact:
James Carbonara
Hayden IR
(646)-755-7412
James@haydenir.com