2. Contents
• Introduction
• Criteria for INDs
• Types of IND
• Guidance Document of INDs
• Format and Contents of INDs
• Withdrawal of IND
• IND review flow chart
• IND process in India
3. INTRODUCTION
The Federal Food, Drug and Cosmetics act regulated
through Title 21 of U.S Code of federal Regulations,
requires a new drug to be approved by FDA before
legally getting introduced into the market.
In India, a new drug may be approved as regulated
by Schedule Y to the Rules of Drugs and Cosmetics
Act, 1940 and Rules 1945.
5. INVESTIGATIONAL NEW DRUG (IND)
INVESTIGATIONAL NEW DRUG (IND)
Investigational New Drug is defined under 21 CFR
312.3(b) as ‘ a new drug or biological drug that is
used in clinical investigation’. The term also includes
a biological product used in vitro for diagnostic
purposes.
An IND is a submission to the FDA requesting
permission to initiate a clinical study of a new drug
product.
6. IND…(cont.)
IND is required any time you want to conduct trial of
an unapproved drug.
The IND application provides the FDA with the data
necessary to decide whether the new drug and the
proposed clinical trial pose a reasonable risk to the
human subjects participating in the study.
7. IND…(cont.)
The sponsor submits the application for conduct of
human clinical trials called Investigational New Drug
(IND) application to FDA or DCGI .
Once IND application is submitted , the sponsor
must wait for 30 days before initiating any clinical
trial.
Clinical trials in humans can begin only after IND is
reviewed by the FDA and a local institutional review
board (IRB).
8. IND…(cont.)
If the FDA accepts the IND request within 30 days of
submission, clinical testing of the new molecule on
human may begin by the investigator.
At this point, the molecule under the legal status of
FDA becomes a new drug subject to specific
requirements of drug regulatory system.
If at any time during clinical testing, the data
furnished to FDA indicate the IP to be toxic under
the criterion of FDA’s Benefit/Risk ratio, FDA can
terminate clinical trial and its actions are not subject
to any judicial review.
9. Criteria for IND application
Criteria for IND application
➢A new indication Change in the approved route
of administration or dosage level.
➢ Change in the approved patient population
(vulnerable subjects e.g. pediatrics, elderly, HIV
+ ve , immunocompromised )
➢Significant change in the promotion of an
approved drug.
A clinical study is required for an IND if it is intended
to support
10. TYPES OF INDs
TYPES OF IND
COMMERCIAL INDs
These are applications that are submitted primarily by the
companies to obtain marketing approval for a new product.
NONCOMMERCIAL (Research)INDs
These INDs are filed for noncommercial research.
These are
➢ Investigator’s IND- It is submitted by a physician who both
initiates and conducts an investigation and who also administers
and dispenses the IP. A physician might submit a research IND to
propose studying an unapproved drug or an approved drug for new
indications or in new patient population .
11. TYPES OF INDs (cont.)
➢ Emergency Use IND-This IND allows FDA to allow
the use of an experimental drug in an emergency
situation that does not allow submission of an IND in
accordance with 21 CFR Sec312.23 or Sec 312.34.
➢ Treatment IND- Also called Expanded Access IND this
IND may be submitted for experimental drugs showing
promise in clinical testing of serious and immediately life
threatening conditions while the final clinical work is
conducted and the FDA review takes place (21 CFR
312.34).
12. The IND application must contain
information in 3 broad areas
Animal Pharmacology and toxicology
studies-Preclinical data to assess if the product is
reasonably safe for initial testing in humans. Also ,
included are any previous with drug in humans.
Manufacturing information- Information
pertaining to composition, manufacturer, stability
and controls used for manufacturing drug product to
ensure that the company can adequately produce
and supply consistent batches of the drug.
13. Information in 3 broad areas(cont.)
Clinical Protocol and Investigator information
Detailed protocols for proposed clinical studies to make
sure subjects are not exposed to undue risks.
Also, information on the qualifications of the
investigators (chiefly physicians) if they fulfill their
clinical duties.
Finally, commitments to obtain informed consent from
all research subjects, to obtain review of the study by an
IRB and to adhere to the investigational new drug
regulations.
An IND must also include The Investigator’s brochure.
14. Format and content of IND
Format and content of IND
Cover sheet ( Form FDA 1571)
✓ Name, address,t elephone of sponsor
✓Identification of phases
✓Commitment not to begin CT until IND approval
✓Commitment by IRB- Form 56
✓Commitment for conducting CT- accordance with regulations
✓Name,t itle-person(s) for reviewing
✓Name, address of CRO, if any
✓Signature of sponsor
Table of contents.
Introductory statement and General Investigational Plan.
Investigator’s Brochure.
15. Format and content of IND (cont.)
Study Protocols.
Chemistry, Manufacturing and Control information.
Pharmacology and Toxicology Information.
Previous human experience with IP.
Additional Information.
16. WITHDRAWAL OF AN INDA
WITHDRAWAL OF AN IND SPONSOR
At any time a can withdraw an effective IND .
In such a case,
➢FDA and IRB shall be so notified with reasons for
withdrawal,
➢all clinical studies ended,
➢ all current investigators and subjects notified,
➢all stocks of drug returned to the sponsor or
otherwise disposed off on request of sponsor in
accordance with 312.59.
17. IND PROCESS IN INDIA
IND PROCESS IN INDIA
IND has been defined under Rule 122-DA (3) of Drugs
and Cosmetics Rules 1945 as a chemical entity having
therapeutic indication but which have never been earlier
tested on humans.
No clinical trial for new drug for any purpose be
conducted without permission , in writing, of the
Licensing Authority (DCGI).
Application for conducting clinical trials in India require
submission by the sponsor on Form 44 along with
requisite fee ( Rs 50k) and documents as provided under
Schedule Y to Drugs and Cosmetics Act 1940.
18. IND PROCESS IN INDIA (cont.)
Data to be submitted along with the application on Form44
to conduct clinical trials (2 hard copies and 2 soft copies
i.e., CDs in PDF format)
Application on Form 44
Introduction of the drug
Fee Rs 50K through challan form
Chemical and Pharmaceutical information as per
Appendix I of Schedule Y
Animal Pharmacology as per Appendix IV
Animal Toxicology as per Appendix III
Human/Clinical Pharmacology data as per Appendix I
Regulatory status in other countries as per Appendix I.
19. IND PROCESS IN INDIA (cont.)
It takes 4-6 months for the approval but it is not
documented.
The Ethical Committee also requires 1-3 months
time.
Thus , it almost takes 7-9 months for approval of
INDA from DCGI.
For international applicants, import license to
import IP samples and permission from Director
General Foreign Trade to export blood samples is
also needed.
20. IND PROCESS IN INDIA (cont.)
After receiving the application, the CDSCO headquarters in
New Delhi refer it to the new drug division.
The new drug division where it is reviewed by IND committee.
The committee submit ted the report to DCGI along with its
recommendations.
If the report by committee is favorable, DCGI approves the
INDA.
23. Drug Review Steps Simplified
Preclinical (animal) testing.
An investigational new drug application (IND) outlines what the sponsor of a new drug
proposes for human testing in clinical trials.
Phase 1 studies (typically involve 20 to 80 people).
Phase 2 studies (typically involve a few dozen to about 300 people).
Phase 3 studies (typically involve several hundred to about 3,000 people).
The pre-NDA period, just before a new drug application (NDA) is submitted. A common
time for the FDA and drug sponsors to meet.
Submission of an NDA is the formal step asking the FDA to consider a drug for marketing
approval.
After an NDA is received, the FDA has 60 days to decide whether to file it so it can be
reviewed.
If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor’s
research on the drug’s safety and effectiveness.
The FDA reviews information that goes on a drug’s professional labeling (information on
how to use the drug).
The FDA inspects the facilities where the drug will be manufactured as part of the
approval process.
FDA reviewers will approve the application or issue a complete response letter.
