Presenter; IHSANULLAH KHAN
To begin clinical studies on a drug product for human use,
a sponsor (generally a pharmaceutical company or a
research organization) must receive an exemption from
FDA from Act’s provisions prohibiting distribution of new
drugs not having approval from FDA.(21 U.S.C.335i)
Why IND Required
If it is intended to support a
1) New indication
2) Change in approved route of administration or dosage
3) Change in approved patient population e.g (pediatric) or
a population at increased or greater risk (elderly,HIV
+ve, immune compromised)
4) Significant change in promotion of an approved drug.
Types of IND
1) Investigator 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
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 use IND
1) Emergency Use 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.
2) 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.
• Treatment IND 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
Categories of IND
2) Research (non commercial)
Role of FDA
1) FDA role in development of new drug begins
When the drug sponsor (usually the mfgr or potential
marketer) having screened the new molecule for
pharmacological activity and acute toxicity potential in
2) Also wants to test it’s diagnostic or therapeutic potential
3) At that point the molecule changes in legal status under
the FDA and cosmetic Act and becomes a new drug
subject to specific requirements of the regulatory system.
How to get exemption from FDA
The sponsor supplies the FDA with IND application
a) Information on Drug
b) Protocols describing how the proposed clinical trials will
must contain 3 broad areas
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. Also included are any previous experience with
the drug in humans (often foreign use).
Manufacturing Information a) Information pertaining to the composition, manufacturer,
stability, controls used for manufacturing the drug
substance and the drug product.
b) This information is assessed to ensure that the
company can adequately produce and supply consistent
batches of the drug.
Clinical Protocols and Investigator
Detailed protocols for proposed clinical studies to assess
whether the initial-phase trials will expose subjects to
Also, information on the qualifications of clinical
investigators--professionals (generally physicians) who
oversee the administration of the experimental compound-to assess whether they are qualified to fulfill their clinical
Finally, 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.
Guidelines or Protocols for Application
Application for IND exemption to FDA contain
a) Cover sheet
b) Introductory statement and general investigational plan
c) Drug Master files
1) Type 1 include Mnfg site, facilities, operating procedures
2) Type 2 Drug substance, materials used in preparation or
3) Type 3 Packaging material
4) Type 4 Excipients, colorant, Flavor, Essence or material
used in their preparation or Drug product.
5) Type 5 FDA accepted reference information
d) Protocols outlying each study
e) Pharmacology and Toxicology information’s
f) Additional information's on drug dependence and abuse
potential of the drug.
(21CFR section 312.23)
Objective of FDA in Reviewing IND
A) To assure safety and rights of objects in all phases of an
B) In phases 2 & 3, to help assure that the quality of
scientific evolution of the drug is adequate to permit an
evaluation of drug effectiveness.
( 21 CFR 312.22)