Ind Differences

IND COMPARISON OF REGULATORY REQUIREMENT FOR IND APPLICATION: US

EU

INDIA

1. One Regulatory authority – FDA- CDER/CBER

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

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/EC which 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

4. Approvals required -Ethics Committee -DCGI

-Research Ethics Committee -Regulatory Authority/Competent Authority 5.

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5. EUDRACT database –Apply for 5. EUDRACT number is must.

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

6.Sponsor EU Legal Representative

6.

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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.

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

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

11.Some ECs give opinions only

11.

12.Sponsor has limited communication with IRB.

12.Sponsor has free communication with EC

12.

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

13.Two-part consent-Plain language information sheet and consent 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:

17. Clinical Trial Authorization application: A. Cover sheet (Form FDA–1571) -Cover letter, confirmation of EudraCT number & authorization B. A table of contents. for applicant to act for Sponsor 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 informationComposition, stability, controls H. Pharmacology and toxicology informationPre clinical data

-Application form (Annex 1) & fee A.Trial identification (EudraCT number) 18. Sponsor id. 18. Applicant id. 18. Info.on the IMPs –IMPD 18. Info. On the Placebos 18. Sites responsible for IMP release G. General Info. On the trial 18. Pop. Of trial subjects 18. Proposed sites in the Member State 18. Ethics Committee/MS Competent Authority K. Check list

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

-IMP Dossier (IMPD) 18. Previous human experience with the investigational drug. J. Additional information.

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

18.Timelines: FDA sets a timeline for

Manufacturing/import licence

Insurance Sample label Financial issues Informed consent form

18. Time lines: Clinical Trial directive sets a

18.Timelines

assessment of IND of 30 days 19. Pre IND meetingCan be requested by sponsor to obtain guidance on data necessary for IND submission

timeline for assessment of CTA of 60 days.

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

SmPC

SmPC

SmPC

-Outside the conditions of the SmPC

SmPC

-With a change to the drug substance manufacture or manufacturer

S+P+A

Yes (if appropriate) Yes (if appropriate) SmPC 6 SmPC

-After it has been blinded

P+A

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 P+A -is supplied from another manufacturer S+P+A

Yes Yes

Yes Yes

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

No New Data

No New Data

No New 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)