This document provides an overview of Investigational New Drug Applications (INDAs), which are required for clinical trials of unapproved drugs in the US. It defines INDAs and explains why they are needed, the types of INDAs, contents of an INDA submission, resources for preparing INDAs, the INDA review process, and the phases of investigation that can occur after an successful INDA. The goal of an INDA is to obtain permission to ship an experimental drug and begin human clinical trials before the drug is approved for marketing.

1. Investigational New Drug Applications
Prepared by
ASHISH
M.S. Pharmaceutics
Dept. Of pharmaceutics
NIPER-Raebareli

2. CONTENTS
INDA-definition
Why INDA required ?
Types of INDA
Contents of IND
Resources of INDA
INDA procedures overview
FDA receipt of INDA
INDA REVIEW
Phases after INDA

3. Investigational new drug application-Definition
Investigational New Drug (IND) program is the means by which a pharmaceutical company
obtains permission to start human clinical trials and to ship an experimental drug across state
lines (usually to clinical investigators) before a marketing application for the drug has been
approved.
The IND is the means through which the sponsor technically obtains this exemption from the
FDA.
Current Federal law requires that a drug be the subject of an approved marketing application
before it is transported or distributed across state lines.

5. USFDA DRUG APPROVAL PROCESS

6. When INDA Required ?
INDA is required if any pharmaceutical company wants to conduct clinical trails of an
unapproved drug.
INDA would be required to conduct clinical trails if the drug is
• New chemical entity , not approved for indication under investigation in new dosage
form.
• Being administered at new dosage level.
• In combination with another drug which is not approved.
• All clinical studies where new drugs are administered to human subjects , regardless
of the whether the drug is commercially developed , require an IND.

7. TYPES OF IND
1)Investigator IND
This is submitted by a physician who both initiates and conducts an investigation, and
under whose immediate direction the investigational drug is administered or
dispensed. A physician might submit a research IND to propose studying an unapproved
drug, or an approved product for a new indication or in a new patient population.
2) Emergency Use IND
It allows the FDA to authorize use of an experimental drug in an emergency situation
that does not allow time for submission of an IND in accordance with 21CFR , Sec.
312.23 or Sec. 312.20. It is also used for patients who do not meet the criteria of an
existing study protocol, or if an approved study protocol does not exist.

8. 3) Treatment IND
This is submitted for experimental drugs showing promise in clinical testing for serious or
immediately life-threatening conditions while the final clinical work is conducted and the
FDA review takes place.

9. CONTENTS OF INDA
Animal Pharmacology and Toxicology Studies
Preclinical data to permit an assessment as to whether the product is reasonably safe
for initial testing in humans. Also included are any previous experience with the drug in
humans.
Manufacturing Information
Information pertaining to the composition, manufacturer, stability, and controls used for
manufacturing the drug substance and the drug product. This information is assessed
to ensure that the company can adequately produce and supply consistent batches of
the drug.

10. Clinical Protocols and Investigator Information
Commitments to obtain informed consent from the research subjects, to obtain review of
the study by an institutional review board (IRB), and to adhere to the investigational new
drug regulations.
Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any
clinical trials. During this time, FDA has an opportunity to review the IND for safety to
assure that research subjects will not be subjected to unreasonable risk.

12. Resources for IND Applications
• Pre-INDA Consultation Program
Done by CDER (center for drug evaluation and research) to provide early
communications between sponsors and new drug review divisions to provide guidance
on the data necessary to warrant IND submission.
• Guidance Documents for INDs
Guidance documents represent the Agency's current thinking on a particular subject.
These documents provide FDA review staff and applicants/sponsors with guidelines to
the processing, content, and evaluation/approval of applications and also to the design,
production, manufacturing, and testing of regulated products.

13. Laws and Regulations
• Code of Federal Regulations (CFR)
The CFR is divided into 50 titles that represent broad areas subject to Federal
regulations.
Section 21 of the CFR contains most regulations pertaining to food and drugs. The
regulations document all actions of all drug sponsors that are required under Federal
law.
• The following regulations apply to the IND applications:

14. NUMBER REGULATIONS
21CFR Part 201 Drug Labelling
21CFR Part 312 Investigational New Drug Application
21CFR Part 314 INDA and NDA Applications for FDA Approval to
Market a New Drug (New Drug Approval)
21CFR Part 316 Orphan drugs
21CFR Part 50 Protection of Human Subjects
21CFR Part 54 Financial Disclosure by Clinical Investigators
21CFR Part 56 Institutional Review Boards
21CFR Part 58 Good Lab Practice for Nonclinical Laboratory
[Animal studies]

15. • IND rewrite was published by FDA in 1987, which resulted in a logical flow of
information.
• IND has 8 to 11 sections falling under four general areas-
1. Animal pharmacology
2. Manufacturing information on drug safety and drug product
3. Clinical protocols
4. Information on investigator qualifications

16. Overview of IND Application Procedures
 When submitting original IND applications, sponsors are expected to send
their applications in triplicate (one original and two copies). Electronic
submissions should be considered whenever possible.
 Each application should be accompanied by:
• Form 1571 (IND application cover)
• Form 1572 (Investigator’s statement)
• Form 3674 (certification requirement & mandatory registration and
reporting of results for applicable clinical trials)

17. Pre-IND Meetings(21 CFR 312.82)
• Request must be submitted in writing (fax is fine) and should include:
 Description of product
 Description of clinical indication and approach
 Identification of purpose, objectives, and draft of specific questions
• Suggested dates and times for meeting
• Pre-IND meetings are scheduled within 60 days from receipt of request.
• FDA will respond to request within 14 days of receipt of request.

18. • Meeting package must be submitted 4 weeks prior to meeting, includes:
 Pre-clinical data
 Product manufacturing scheme
 Data regarding product
 characterization/proposed specifications
 Proposed clinical protocol
 Specific questions grouped by discipline (product, pre-clinical, clinical).
• One hour formal meeting held by telephone unless unique situation.
• FDA issues official minutes to applicant within 30 days of formal meeting

19. Master File Submission(21 CFR 314.420)
• Alternative mechanism for submission of product & manufacturing information
• Does not include clinical protocol
• Permits holder to incorporate the information by reference when submitting an
IND
• To authorize other persons to reference information, without direct disclosure.

20. How and where to Send the Application
• The initial IND submission and each subsequent submission to the IND
should be accompanied by a Form FDA 1571 and must be submitted in
triplicate (the original and two photocopies are acceptable).
• Initial IND submissions are done at
• For a Drug:
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
• For a Therapeutic Biological Product:
Food and Drug Administration
Center for Drug Evaluation and Research
Therapeutic Biological products control room

22. FDA Receipt of the IND
• Upon receipt of the IND by FDA, an IND number will be assigned, and the
application will be forwarded to the appropriate reviewing division.
• The reviewing division will send a letter to the Sponsor-Investigator providing
notification of the IND number assigned, date of receipt of the original
application, address where future submissions to the IND should be sent, and
the name and telephone number of the FDA person to whom questions about
the application should be directed.
• Studies shall not be initiated until 30 days after the date of receipt of the IND
by FDA unless you receive earlier notification by FDA that studies may begin.

24. IND Review Team
Review team includes:
 Regulatory Project Manager
 Product Reviewer
 Pharmacology/Toxicology Reviewer
 Clinical Reviewer
 Statistical Reviewer
 If product includes a device or drug, consult reviewers from CDER are
assigned if needed, during initial processing.

25. Clinical Holds (21 CFR 312.42)
• Hold: An order issued by FDA to delay a proposed clinical
investigation or to suspend an ongoing investigation
Once active, an IND may be placed on hold if the grounds listed under
21 CFR 312.42(b) are met.
• Partial Hold: A delay or suspension of part of the clinical work under
an IND
e.g. IND has 2 protocols, one may proceed & one may not.

26. Phases of Investigation after successful INDA
oPhase I Investigational Studies- Designed to evaluate safety and side
effects
oPhase II Investigational Studies- Designed to evaluate efficacy and
dose ranging
oPhase III Investigational Studies- Expanded study, additional
information on efficacy and safety
oNew Drug Application

27. REFERENCES
1. https://www.fda.gov/drugs/types-applications/investigational-new-
drug-ind-application
2. S.K. Gupta , Basic Principles of Clinical Research and Methodology ,
1st Edition , Jaypee Brothers Medical Publishers (P) Ltd.