The document discusses the investigational new drug (IND) application process. It defines an IND as an application that allows sponsors to legally conduct clinical trials of investigational drugs in humans. The IND process involves preclinical animal testing, filing an INDA application including information on manufacturing and clinical protocols, a 30-day review period by the FDA, and oversight of clinical trials and reporting if approved. It provides details on the various sections, forms, classifications and reviews involved in the IND application and approval process.

1. Dr . D .Y. Patil Institute Of Pharmaceutical Sciences & Research Pimpri

2. Contents:
1. Drug development process
2. IND definition
3. Classification of IND
4. Types of IND
5. Format of INDA
6. FORM’S of INDA
7. IND review process

3. Drug Development Process:
Drug discovery
Preclinical(Animal
s)
1)Efficacy
2)Safety
3)4+years
Investigational New Drug
1)INDA submission
2)IND approval(30 days)
Clinical Trails(Humans)
Phase-1: Healthy Volunteers(28-80)(safety)
Phase-2: Patient volunteers(100-300)(expanded safety )
Phase-3:Patient volunteers(1000-3000)( safety &
efficacy)
NDA(2months)
1)NDA application
2)NDA approval
Phase-4
Post marketing
approval
Range:1-3 yrs, avg-18months
Range: 2-10 yrs
The overall process takes almost 10-15 years for drug to come in market

4. What is Investigational New Drug (IND):
 An IND is application which allows sponsor to
lawfully Use a investigational drug for conducting
clinical trials In humans .

5. Importance of INDA:
1. An INDA is required any time to conduct a clinical trail of an unapproved drug
2. An IND would be required to conduct a clinical trail if the drug is
a) If a drug is new chemical entity ,which is not approved for certain
indications.
b) Being administered at a new dosage level.
c) In combination with another drug and the combination is not approved.
3. All clinical studies where a new drug is administered to human subject, regardless of
whether the drug will be commercially developed, require an INDA.

6. Classification of IND:
• Commercial: Permits sponsor to collect data on clinical safety and
effectives needed for application for marketing in the form of NDA.
• Non commercial(Research):Permits the sponsor to use drug
in research ton obtain advanced scientific knowledge of new drug. NO plan
to market the product.

7. Research IND
• An Investigator IND 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.
Emergency
IND
• 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. 312.34
Treatment
IND
• 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
Types of IND applications:

8. Three Broad Areas of IND Application:
1. Animal pharmacology and toxicology studies:
Preclinical data to permit an assessment as to whether the product is
reasonably safe for initial testing in humans.
2. 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.
3. Investigator information:
It contains information about qualification of Investigator.

9. Format of INDA:
Cover Sheet:
1.Name of Sponsor
2.Sponsor Address
3.Name of Drug
4.Commitment of Sponsor
5.Signature of Sponsor

10. Table Content:
1. Description of the investigational drug
2. All active ingredients
3. Drug's pharmacological classification
4. Structural formula
5. Route of administration
6. Summary of previous human experience
7. Formulation of dosage forms
8. Objective and planned duration of proposed clinical
investigation.

11. Investigational plan:
 Description of clinical studies planned for the experimental drug
 Purpose of the study
 Indication to be studied
Types of trials to be initiated
1.Number of study subjects
2.Risks involved

12. Investigator Brochure:
1. Structural formula of drug
2. Summary of pharmacological, toxicological, pharmacokinetic
effects in animals.
3. Safety and efficacy
4. Purpose of study
5. Dose/dose frequency
6. Monitoring procedures

13. Protocol:
A clinical protocol describes how a particular clinical trial is to be
conducted.
It describes :
1. the objectives of study
2. the trial design
3. how subjects are selected
4. how the trial is to be carried out

14. FORM`S:
1)FORM 1571: Sponsor files the IND application in form 1571 to FDA for review once successful series of preclinical studies are completed.

15. 2) FORM 1572: Along with the IND application the sponsor submits the statement of the investigator (investigator`s
undertaking)

16. Once the INDA is submitted the sponsor must wait 30 calendar days
before initiating any clinical trails
The CDER( Centre For Drug Evaluation & Research) is division of the
FDA that reviews INDA to ensure that the drug is safe and effective
If the sponsor here nothing from CDER then on 31 day after
submission of INDA the study may proceed as submitted

17. 1. The sponsor should not initiate clinical study until 30 days until he receives the FDA
approval for IND.
2. The sponsor should not start clinical study when it’s placed on clinical hold.
3. The sponsor shall see that IRB do initial and continue approval of each study proposed
in the trial.
4. Conduction of investigation in accordance with all the other applicable regulatory
requirements.
5. He should conduct or supervise the investigation.
Commitments of sponsor:

18. Sponsor Responsibilities:
o Select qualified investigators
o Ensure that the investigation is conducted in accordance with the protocols in the IND
o Ensure proper monitoring of the investigation
o Maintain an effective IND
o Promptly inform FDA and all investigators of significant new adverse events
o Maintain adequate records, reporting and monitoring of the investigation to include
product accountability

19. Resources for IND Applications:
The following resources include the legal requirements of an IND application, assistance from CDER to help you
meet those requirements, and internal IND review principles, policies and procedures.
Pre-IND Consultation Program: Offered by CDER (Center for Drug Evaluation and
Research) to foster early communications between sponsors and new drug review divisions
in order to provide guidance on the data necessary to warrant IND submission.
Guidance Documents for INDS: documents are prepared for FDA review staff and
applicants/sponsors to provide guidelines to the processing, content, and
evaluation/approval of applications and also to the design, production, manufacturing, and
testing of regulated products
Laws, Regulations, Policies and Procedures

20. Code Of Federal Regulation(CFR):
 It’s the codification of the general and permanent rules and regulations published in the
Federal Register by the executive departments and agencies of the federal government of
the United States.
 The CFR is divided into 50 titles that represent broad areas subject to Federal regulations.
 The FDA's portion of the CFR contains most regulations pertaining to food and drugs comes
under CFR 21.
 21 CFR part 312: IND
 21 CFR part 314: INDA & NDA for FDA approval to market new drug.

21. INDA Annual reports
Sponsors should submit an annual report that provides the FDA with a
brief update on the progress of all investigations included in the IND.
It should contain the following:
1) Individual study information.
2) Summary of the study.
3) List of changes made in investigators broucher
4) Significant marketing developments like approval, withdrawal or
suspension in any particular country.

22. Applicant ( Drug Sponsor)
IND
(Review by CDER)
Medical Chemical Pharmacology/Toxicology Statistical
Safety review
INDA Review Process:

23. Safety acceptable for
study to proceed
Clinical hold decision
Complete reviews Notify sponsor
Reviews complete and
acceptable
Sponsor notified of deficiencies
No deficiencies Study ongoing
NO
YES
YES
NO
YES
YES

24. FDA Review of The INDA:
 Once the IND is stamped as received ,it is sent to the review division within CDER.
 On arrival at the review division, it is critically evaluated by several reviewers of
✓Chemistry
✓Biopharmaceutics
✓Medical
✓Statistics
✓Microbiology
✓Pharmacology/toxicology sections

25. Role of Pharmacologist in IND submission &
review:
This team is staffed by pharmacologists who evaluate the results of animal
testing and attempt to relate animal drug effects to potential effects in humans.
This section of the application should contain, if known:
 A description of the pharmacologic effects and mechanism(s) of action of
the drug in animals
 Information on the absorption, distribution, metabolism and excretion
(ADME) of the drug.