IND - drug development process, IND types and its application with processes in USA and India

1. INVESTIGATIONAL
NEW DRUG (IND)
By :- Vedanti Gharat
Student ID:- 7038

2. • Investigational New Drug Application (IND) is the document that should be filed
with the Food and Drug Administration (FDA) in USA, and the Therapeutic
Products Directorate (TPD) in Canada before studies can begin in humans.
• IND is submitted by the sponsor or on behalf of the sponsor.
• The IND application is the sponsor's request to perform studies of the drug or
biologic in human subjects to collect the necessary safety and efficacy data for a
New Drug Application (NDA) or Biologics Licensing Application (BLA).
• The FDA reviews the IND application within 30 days and may issue a clinical hold
if more data are required, or the trial may proceed if no issues arise.
• Even after preclinical trials, animal studies continue alongside clinical trials to
gather additional information.

4. Types of IND
• 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.
• Emergency Use INDs, are filed for emergency use of an
unapproved drug when the clinical situation does not allow
sufficient time to submit an IND in accordance with 21 CFR
section 312.23 or 312.20.
• Treatment INDs are filed to make a drug available for the
treatment of serious or immediately life-threatening conditions
prior to FDA approval.
• 2 IND categories:-
• Commercial INDs are filed by companies to obtain marketing
approval for a new drug.
• Research INDs are non-commercial INDs filed by researchers to
study an unapproved drug or to study an approved drug for a new
indication or in a new patient population.

5. What does and IND Application include?
• IND application should contain all currently
known information on the compound.
• Any previous experience in non-US / non-
Canadian studies.
• Chemistry of the Compound.
• Reports on Animal Pharmacology, Toxicology,
Pharmacokinetic, Reproductive Toxicity,
Genotoxicity, Carcinogenicity Studies.
• Manufacturing and Control Information.
• Well based answer whether the compound is
considerably and reasonably safe to start any trial
on humans.
• CRO (Contract Research Organization)
responsibilities if one is involved.
• Information on qualifications of investigators.
• IRB (Investigation Review board) responsible for
reviewing the future clinical trial.
• General Development Plan for the Drug.

7. IND in USA
• The authorization is required prior to interstate shipment and administration of any new drug that does not have an
approved new drug application.
• A Sponsor-Investigator is an individual who both initiates and conducts the clinical investigation and is directly
involved in administering or dispensing the investigational drug.
• Only one individual should be designated as the sponsor for administrative reasons.
• If a pharmaceutical company supplies the drug but does not submit the IND, they are not considered the sponsor.
• Certain information must be submitted with the IND, including manufacturing and controls information,
pharmacology and toxicology data, and data from prior human studies, unless previously submitted and authorized
by the original sponsor.
• If the investigational drug is modified or prepared after shipment, complete manufacturing and controls information
must be submitted.

8. • The protocol for the clinical investigation must be
submitted along with information on investigators,
facilities, and the Institutional Review Board.
• For pharmaceutical firms, the name of the person
responsible for monitoring the clinical investigation and
reviewing safety information should be provided.
• Upon receipt of the IND by the FDA, an IND number will
be assigned, and the application will be forwarded to the
appropriate reviewing division.
• The Sponsor-Investigator will receive notification of the
assigned IND number, date of receipt, address for future
submissions, and contact information for FDA questions.
• Studies should not be initiated until 30 days after the
FDA's receipt of the IND, unless the FDA provides earlier
notification.
• Treatment INDs and Treatment Protocols are special
cases not intended for single-patient use.
• If a marketed drug is used in the study without
modification to its approved packaging, specific
information about the drug product must be provided.
• Requests to charge and Treatment Protocols must be
submitted separately.
• For a Sponsor-Investigator IND, the investigator is
responsible for monitoring and evaluating safety
information.
• The IND submission is a critical step in the drug
development process to ensure the safety and regulatory
compliance of investigational drugs before human
testing.

10. IND in INDIA
1. Introduction
A brief description of the drug and the therapeutic class to which it
belongs.
2. Chemical and pharmaceutical information
2.1 Information on active ingredients
2.2 Physicochemical Data
a. Chemical name and Structure
b. Physical properties
2.3 Analytical Data
2.4 Complete monograph specification including
2.5 Validations
2.6 Stability Studies
2.7 Data on Formulation
3. Animal Pharmacology
3.1. Summary
3.2. Specific pharmacological actions
3.3. General pharmacological actions
3.4. Follow-up and Supplemental Safety Pharmacology Studies
3.5. Pharmacokinetics: absorption, distribution; metabolism; excretion
4. Animal Toxicology
4.1. General Aspects
4.2. Systemic Toxicity Studies
4.3. Male Fertility Study
4.4. Female Reproduction and Developmental Toxicity Studies
4.5. Local toxicity
4.6. Allergenicity/Hypersensitivity
4.7. Genotoxicity
4.8. Carcinogenicity
Format of data to be submitted for application to conduct clinical trials ( appendix- i)

11. 5. Human / Clinical pharmacology (Phase I)
5.1. Summary
5.2. Specific Pharmacological effects
5.3. General Pharmacological effects
5.4. Pharmacokinetics, absorption, distribution, metabolism,
excretion
5.5. Pharmacodynamics / early measurement of drug activity
6. Therapeutic exploratory trials (Phase II)
6.1. Summary
6.2. Study report(s)
7. Therapeutic confirmatory trials (Phase III)
7.1. Summary
7.2. Individual study reports with listing of sites and Investigators.
8. Special studies
8.1. Summary
8.2. Bio-availability / Bio-equivalence.
8.3 Other studies e.g. geriatrics, paediatrics, pregnant or nursing
women
9. Regulatory status in other countries
9.1. Countries where the drug is
a. Marketed
b. Approved
c. Approved as IND3
d. Withdrawn, if any, with reasons
9.2. Restrictions on use, if any, in countries where marketed
/approved
9.3. Free sale certificate or certificate of analysis, as appropriate.
10. Prescribing information
10.1. Proposed full prescribing information
10.2. Drafts of labels and cartons
11. Samples and Testing Protocol/s
11.1. Samples of pure drug substance and finished product (an
equivalent of 50 clinical doses, or more number of clinical doses if
prescribed by the Licensing Authority), with testing protocol/s, full
impurity profile and release specifications.

12. “The works must be conceived with fire in the
soul but executed with clinical coolness.”
-Joan Miro