The document discusses Investigational New Drug (IND) applications, which are submitted to the FDA to obtain approval for human clinical trials of an experimental drug. An IND application includes preclinical animal data, manufacturing information, and clinical trial protocols. It allows 30 days for FDA review to ensure the trials will not expose subjects to unreasonable risks. The FDA reviews INDs from medical, chemistry, pharmacology and statistical perspectives and can notify the sponsor of deficiencies. Clinical trials can then proceed unless a clinical hold is issued.

1. INVESTIGATIONAL NEW DRUG
APPLICATION
Prepared By-
D.Mahendra,M.Pharm,(Ph.D),.

2. Contents
 Introduction
 Types of INDApplications
 Contents of INDApplication
 FORM 1571 & 1572
 Resources for INDApplications
 IND Review & Report
 Notification to the SPONSOR
 Exploratory IND studies

3. Introduction
 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.
 An investigational new drug (IND) application is to provide
the data showing that it is reasonable to begin tests of a new
drug on humans.

4.  FDA's role in the development of a new drug begins when the
drug's sponsor (usually the manufacturer or potential
marketer), having screened
pharmacological activity and
the new molecule for
acute toxicity potential in
animals, wants to test its diagnostic or therapeutic potential in
humans.
 At that point, the molecule changes in legal status under the
Federal Food, Drug, and Cosmetic Act and becomes a new
drug subject to specific requirements of the drug regulatory
system

5.  The IND application shows results of previous
experiments,
new studies will be
iii.
i. How, Where and by Whom the
conducted;
ii. Chemical structure of the compound;
How the compound is manufactured;
iv. Toxic effects in the animal studies.

6. CLASSIFICATION OF IND
COMMERCIAL
 Permits sponsor to collect data on clinical safety and
effectiveness needed for application for marketing in the form
of NDA
RESEARCH (non-commercial)
 Permits the sponsor to use drug in research to obtain advanced
scientific knowledge of new drug, No plan to market the
product

7. Type’s of IND Applications
1. Investigator IND application
2. Emergency Use IND application
3. Treatment IND application
4. Screening IND application

8. 1. Investigator IND Application
 Application 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 application to
propose studying of;
 An unapproved drug,
 An approved product for a new indication or
 An approved product in a new patient population.

9. 2. Emergency Use IND application
 Application allows the FDA to authorize use of an
experimental drug in an emergency situation that does not
allow time for submission of an IND application ,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.
 In such a case, FDA may authorize shipment of the drug for a
specified use in advance of submission of an IND application.

10. 3. Treatment IND application
 Application 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.
 A drug that is not approved for marketing, may be under
clinical investigation for a serious or immediately life-
threatening disease condition in patients for whom no
comparable or satisfactory alternative drug or other therapy is
available.

11. 4. Screening IND application
 Filed for multiple, closely related compounds in order to
screen for the preferred compounds or formulations.
 The preferred compound can then be developed under a
separate IND.
 Used for screening different salts, esters and other drug
derivatives that are chemically different, but
pharmacodynamically similar.

12. Contents 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.

13. 3. Clinical protocols and investigator information: Detailed
protocols for proposed clinical studies to assess whether the
initial-phase trials will expose subjects to unnecessary risks.
Also, information on the qualifications of clinical
of the
they are
investigators who oversee the administration
experimental compound—to assess whether
qualified to fulfil their clinical trial duties.

14.  Finally, commitments to obtain
a) Informed consent from the research subjects,
b) To obtain review of the study by an institutional review
board (IRB),
c) To adhere to the investigational new drug regulations.

15. FORM’S
 FORM 1571 : Sponsor files the IND application in Form
1571 to the FDA for review once successful series of
preclinical studies are completed.
 https://www.fda.gov/downloads/aboutfda/reportsmanualsform
s/forms/ucm083533.pdf
 FORM 1572 : Along with the IND application, the sponsor
submits the statement of the Investigator (Investigator’s
undertaking) in Form 1572.
 https://www.fda.gov/downloads/aboutfda/reportsmanualsform
s/forms/ucm074728.pdf

16. Form 1571

17. Form 1572

18.  Once the IND application is submitted, the sponsor must wait
30 calendar days before initiating any clinical trials.
 If the sponsor hears nothing from CDER (Center for Drug
Evaluation and Research), then on Day 31 after submission of
IND application, the study may proceed as submitted.
 The CDER is a division of the FDA that reviews New Drug
Applications to ensure that the drugs are safe and effective.

19. IND Review & Report
 During this time, FDA has an opportunity to review the IND
application for safety to assure that research subjects will not
be subjected to unreasonable risk.
iii.
i. Medical Review
ii. Chemistry Review
Pharmacology/Toxicology review
iv. Statistical analysis
v. Safety review

20. i) Medical Review
 During the IND application review process, the medical
reviewer evaluates the clinical trial protocol to determineif
(i) the participants will be protected from unnecessary risks;
(ii)the study design will provide data relevant to the safety and
effectiveness of the drug.
 Under Federal regulations, proposed phase I studies are
evaluated almost exclusively for safety reasons.

21. ii) Chemistry Review
 They address issues related to drug identity, manufacturing
control and analysis.
 The reviewing chemist evaluates the manufacturing and
processing procedures for a drug to ensure that the compound
is adequately reproducible and stable.

22. iii) Pharmacology/Toxicology review
 This team is staffed by pharmacologists and toxicologists 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.

23.  The regulations do not further describe the presentation of
these data, in contrast to the more detailed description of how
to submit toxicology data.
 A summary report, without individual animal records or
individual study results, usually suffices.
 An integrated summary of the toxicology effects of the drug in
animals and in-vitro the particular studies needed depend on
the nature of the drug and the phase of human investigation.

24. iv) Statistical analysis
 The purpose of these evaluations is to give the medical
officers a better idea of the power of the findings to be
extrapolated to the larger patient population in the country

25. v) Safety review
 Following review of an initial IND application submission,
CDER has 30-calendar-days in which to decide if a clinical
hold is necessary (i.e. if patients would be at an unacceptable
risk or if CDER doesn’t have the data to make such a
determination).

27. Sponsor will be Notified
 If other deficiencies are found in an IND application that the
review division determines are not serious enough to justify
delaying clinical studies, the division may either telephone or
forward a deficiency letter to the sponsor.
 In either case, the division informs the sponsor that it may
proceed with the planned clinical trials, but that additional
information is necessary to complete or correct the IND
application file.

28. Study Ongoing
 Once the CDER’s 30-day initial review period expires,
clinical studies can be initiated, unless a clinical hold has been
placed.
 Beyond the 30-day review period for an IND application,
subsequent clinical trials may begin immediately upon
submission of the clinical protocol to the IND application (i.e.
there is no 30-day waiting period for subsequent clinical trials
after the submission of the first clinical trial protocol).
 If the sponsor was notified of deficiencies that were not
serious enough to warrant a clinical hold, the sponsor
addresses these deficiencies while the study proceeds.

29. Exploratory IND studies
 Exploratory IND studies are intended to provide clinical
information for a new drug candidate at a much earlier phase
of drug development.
 These studies help to identify the best candidates for
continued development and eliminate those lacking promise.
 These clinical trials occur very early in phase I, involve very
limited human exposure and have no therapeutic intent.