The document discusses documentation required for Investigational New Drug (IND) applications submitted to regulatory authorities like the FDA. An IND application is required to get approval to start clinical trials of an investigational drug. It must include preclinical animal study and toxicity data, manufacturing information, clinical trial protocols, and prior human research data. If approved, the IND allows the sponsor to begin clinical trials to investigate safety and efficacy of the new drug in humans. The clinical trials are divided into four phases with increasing number of participants.

1. Documentation of drug trials and
regulatory filings
Dilsar Ilyas Gohil
Master in Pharmacy

2. What is Investigational New Drug
An Investigational New Drug (IND) is a drug or biological product
that has not been approved for general use by the Food and Drug
Administration (FDA). It is used in a clinical trial to investigate its
safety and efficacy. The term also includes biological products that are
used in vitro for diagnostic purposes.
After the successful completion of preclinical research, Drug developer
or sponsor, must submit an Investigational New Drug (IND) application
to respective regulatory authority such as FDA in order to start clinical
research.

6. Investigational New drug application (IND)
An IND is a submission to the food and drug administration (FDA)
requesting permission to initiate a clinical study of a new drug product.
The Federal Food , Drug and Cosmetic act requires that drugs have an
approved marketing application before they can be shipped in interstate
commerce.
The IND application allows a company to initiate and conduct clinical
studies for their new drug products.
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. The IND filing is the formal process by which a sponsor requests approval
for testing of a drug in human subjects. In the IND application, following
things are must included:
Animal study data and toxicity data
Manufacturing information
Clinical protocols (study plans) for studies to be conducted
Data from any prior human research
Information about the investigator
Any additional data After submitting IND, respective regulatory authority
reviewed all the data and if satisfied, they grant the sponsor to begin
clinical trial. It will take 30 -60 days after IND submission to get approval
for clinical trial from the FDA

8. TYPES OF IND
Investigator IND :
 Submitted by a physician who initiates and conducts an investigation,
and under whose immediate direction the investigational drug is
administered or dispensed.
 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
 Allows FDA to authorize use of an experimental drug in an
emergency situation
 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 FDAreview takes place

9. 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 o No
plan to market the product

10. CONTENT OF IND
In three broad areas:
Animal Pharmacology and Toxicology Studies :
An assessment as to whether the product is reasonably safe for initial
testing in humans.
 Any previous experience with the drug in humans
Manufacturing Information : composition, manufacturer, stability, and
controls used for manufacturing the drug.
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 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 - USFDA

11. Clinical trial : A systematic study of any new drug(s) in human
subject(s) to generate data for discovering and/or verifying the clinical,
pharmacological (including pharmacodynamic and pharmacokinetic),
and/or adverse effects with the objective of determining safety and/or
efficacy of the new drug.

12. Clinical trials consist of 4 phases
Phase I – Study Participants: 20 to 100 healthy volunteers Length of
Study: Several months to one year
Purpose: Safety and Dose range
Phase II – Study Participants: 100 to 300 volunteers with the disease.
Length of Study: Up to 2 years
Purpose: Safety and Efficacy
Phase III- Study Participants: 300 to 3,000 volunteers who have the target
disease Length of Study: 1 to 4 years

21. India Japan South Africa Australia
Protocol Yes
( English)
Yes
( in Japanese)
Yes
( English)
Yes
( English)
ICF
informed
consent form
Yes
( English and
other local
Languages)
Yes
( in Japanese)
Yes
( English )
Yes
( English)
Investigator
Brochure
Yes Yes
( in Japanese)
Yes Yes
Investigator’s
CV
Yes NO Yes Yes
Case Report
Form
Yes NO Yes Yes

22. India Japan South Africa USFDA
Case Report
Form
Yes NO Yes Yes
Study subject
compensation
documents
Yes NO Yes Yes
CMC
documents
Yes YES Yes Yes
GMP certificate
of the
investigational
drug
Yes NO Yes Yes
Development
Safety update
Report
Yes YES Yes Yes

23. Investigator’s Brochure
Acopy of the investigator's brochure, containing the following information:
I. A brief description of the drug substance and the formulation, including the
structural formula, if known.
II. A summary of the Pharmacological and toxicological effects of the drug in
animals and, in humans.
III. Asummary of the Pharmacokinetics of the drug in animals and in humans.
IV. A summary of information relating to safety and effectiveness in humans
obtained from prior clinical studies.
V. A description of possible risks and side effects to be anticipated on the basis
of prior experience with the drug under investigation or with related drugs, and
of precautions or special monitoring to be done as part of the investigational
use of the drug.

24. PROTOCOLS
I. An objectives and purpose of the study.
II. description of the dosing plan including duration, dose, or method
to be used in determining dose
• The name and address and a statement of the qualifications
A protocol contains the following, with the specific elements and detail of
the protocol reflecting the above distinctions depending on the phase of
study:
III.
(curriculum vitae or other statement of qualifications) of each
investigator, and the name of each sub investigator (e.g., research
fellow, resident)
IV. The criteria for patient selection and Exclusion and inclusion criteria.

25. V. Estimate of the number of patients to be studied.
VI. description of the design of the study, including the kind of control
group to be used, if any, and a description of methods to be used to
minimize bias on the part of subjects, investigators, and analysts.
VII.The method for determining the dose(s) to be administered, the
planned maximum dosage, and the duration of individual patient
exposure to the drug.
VIII.A description of the observations and measurements to be made to
fulfill the objectives of the study.
IX. A description of clinical procedures, laboratory tests, or other
measures to be taken to monitor the effects of the drug in human
subjects and to minimize risk.

26. CHEMISTRY, MANUFACTURING, AND CONTROL INFORMATION
This section describing the composition, manufacture, and control of the
drug substance and the drug product.
each phase of the investigation sufficient information is required to be
submitted to assure the proper identification, quality, purity, and strength
of the investigational drug.
Final specifications for the drug substance and drug product are not
expected until the end of the investigational process.
stability data are required in all phases of the IND to demonstrate that
the new drug substance and drug product
 Drug development proceeds

27. Drug substance
A description of the drug substance, including its physical, chemical, or
biological characteristics.
The name and address of its manufacturer; the general method of
preparation of the drug substance.
The specification and analytical methods used to assure the identity,
strength, quality, and purity of the drug substance.
Stability of the drug substance during the toxicological studies and the
planned clinical studies

28. Drug product
list of all components, which may include reasonable alternatives for
inactive compounds.
 Quantitative composition of the investigational drug product,
Brief general description of the manufacturing and packaging procedure
as appropriate for the product.
Specification and analytical methods used to assure the identity, strength,
quality, and purity of the drug product;
 Stability data
A brief general description of the composition, manufacture, and control
of any placebo used in a controlled clinical trial.
Labeling. A copy of all labels and labeling to be provided to each
investigator.

29. PHARMACOLOGYAND TOXICOLOGY INFORMATION
Adequate information about pharmacological and toxicological studies of
the drug involving laboratory animals or in vitro.
Pharmacology and drug disposition.
A section describing the Pharmacological effects and mechanism(s) of
action of the drug in animals, and information on the of the drug.
absorption, distribution, metabolism, and excretion
Toxicology
 summary of the toxicological effects of the drug in animals and in vitro.
The description is to include the results of acute, subacute, and chronic
toxicity tests; special toxicity test related to the drug's particular mode of
administration or conditions of use (e.g., inhalation, dermal, or ocular
toxicology).
 Any in vitro studies intended to evaluate drug toxicity.
Toxicology study that is intended primarily to support the safety of the
proposed clinical investigation.

31. Thank you