IND COMPARISON OF REGULATORY REQUIREMENT FOR IND APPLICATION:

US EU INDIA

1. One Regulatory authority – FDA- CDER/CBER

1. Central Regulatory authority - EMEA (Europe Medical Agency) &Many CAs (Competent Authorities)[UK- MHRA: Medicines andHealthcare products Regulatory agency]

1. One Regulatory Authority - DCGI

2. Investigational New Drug (IND) Application

2. Clinical trial authorization (CTA) Application

2. Application for permission to import/manufacture New Drug or to undertake Clinical Trial -Form 44

3. Follow Code of Federal Regulations (CFR)-21 CFR 312.20-38

3.Follow EU Clinical Trials Directive –EU Directive 2001/20/ECwhich came in to force on 1/05/04

3. Follow Schedule Y under Drugs & Cosmetics Act, 1940 (DCA)

4. Approvals required-Ethics Committee-FDA

4.Approvals required-R&D Committee -Research Ethics Committee -Regulatory Authority/Competent Authority

4. Approvals required-Ethics Committee-DCGI

5. ------ 5. EUDRACTEUDRACT database –Apply for database –Apply for EUDRACTEUDRACT number is must. number is must.

5. ------

6. US “Resident US Agent” US “Resident US Agent” required by non-US sponsors in required by non-US sponsors in USUS

6.Sponsor EU Legal 6.Sponsor EU Legal RepresentativeRepresentative

6. ---------

7.Insurance of subjects is not mandatory for the trial.

7.Insurance of subjects is mandatory for the trial.

7.Insurance not mandatory

8.Trials conducted in normal volunteers require government approval

8.Trials conducted in normal volunteers do not require approval.

8.Trials conducted in normal volunteers require approval

9. -------- 9.If a randomized controlled trial then register with the database of randomized controlled trials and obtain an ISRCTN(International Standard of Randomised Controlled Trial Number) & a fee to be paid.

9. -------

10. There are four types of IND-Investigational, Treatment and Emergency IND.

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11.IRBs give approval/disapproval/approval with revision.

11.Some ECs give opinions only11.Some ECs give opinions only 11. -------

12.Sponsor has limited communication with IRB.

12.Sponsor has free 12.Sponsor has free communication with ECcommunication with EC

12. -----

13.One-part consent-contains all information for subject

13.Two-part consent-Plain 13.Two-part consent-Plain language information sheet and language information sheet and consent to participateconsent to participate

14.Subjects are also given a copy of consent

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15. Investigational New Drug (IND)-Form 1571

15. Clinical Trial Authorization (CTA) Application-Annex 1

15.Sch Y- Form 44

16. IND Application has to be submitted in triplet-One original and two photocopies.

16. One paper CTA & an electronic version XML file to be submitted to CA; supporting docs can be submitted electronically.

16.Paper Application only

17. IND Application:

A. Cover sheet (Form FDA–1571)

B. A table of contents.

C. Introductory statement

D. General Investigational plan

E. Investigator’s brochure.

F. Protocols -Study protocol -Investigator data -Facilities data -IRB data

G. Chemistry, manufacturing, and control information-Composition, stability, controls

H. Pharmacology and toxicology information-Pre clinical data

18.Previous human experience with the investigational drug.

J. Additional information.

17. Clinical Trial Authorization application:-Cover letter, confirmation of EudraCT number & authorization for applicant to act for Sponsor

-Application form (Annex 1) & fee A.Trial identification (EudraCT number)18.Sponsor id.18. Applicant id.18. Info.on the IMPs –IMPD18. Info. On the Placebos18.Sites responsible for IMP

release G. General Info. On the trial18. Pop. Of trial subjects18.Proposed sites in the

Member State18.Ethics Committee/MS

Competent Authority K. Check list

-IMP Dossier (IMPD)

-Accompanying documents Investigator Brochure EC opinion (if available) Protocol & protocol

summaryManufacturing/import licence

Insurance Sample label Financial issues Informed consent form

17. Form 44-Particulars of New Drug: Description of drug & therapeutic class. -Data to be submitted(A) Chem. & Pharmaceutical info.(B) Animal Pharmacology(C) Animal Toxicology(D) Human/Clinical Pharmacology

(Phase I) (E) Exploratory Clinical Trials

(Phase II)(F) Bio-availability, dissolution

and stability study Data(G) Regulatory status in other

countries(H) Marketing information:

(a) Proposed product monograph

(b) Drafts of labels and cartons

(I) Application for test license

18.Timelines:FDA sets a timeline for assessment of IND of 30 days

18. Time lines:Clinical Trial directive sets a timeline for assessment of CTA of 60 days.

18.Timelines

19. Pre IND meeting-Can be requested by sponsor to obtain guidance on data

necessary for IND submission

Table 1. Reduced information requirements for IMPs known to the concerned competent authority

Types of Previous Assessment Quality Data Non-clinical Data Clinical Data

The IMP has a MA in any EU Member State and is used in the trial:

-Within the conditions of the SmPC

-Outside the conditions of the SmPC

-With a change to the drug substance manufacture or manufacturer

-After it has been blinded

SmPC

SmPC

S+P+A

P+A

SmPC

Yes (if appropriate)

SmPC 6

SmPC

SmPC

Yes (if appropriate)

SmPC

SmPC

Another pharmaceutical form or strength of the IMP has a MA in any EU Member State and:- The IMP is supplied by the MAH P+A Yes Yes

The IMP has no MA in any EU Member State but drug substance is part of product with a marketing authorisation in a MS and:- is supplied from the same manufacturer-is supplied from another manufacturer

P+AS+P+A

YesYes

YesYes

The IMP has a previous CTA in the MemberState(s) concerned :-no new data available since CTA-new data available since CTA

NoNew Data

NoNew Data

NoNew Data

The IMP is a placebo P+A No No

(S: Drug substance data; P : Drug product data; A : appendices of the IMPD; SmPC: summary of product characteristics)