Investigational new drug is defined as a new substance, chemical or biological entity that has not been approved by any regulatory authorities for marketing as a drug in any country. Investigational drug is often known as “study drug” or “experimental drug”.
According to, ICH GCP, Investigational Product is:
“A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.”
In India, the approval of manufacture/import of new drugs for marketing in the country is given by Central Licensing Authority (CLA). A permission to conduct clinical trials of new drugs including Investigational New Drugs is also given by CLA.
During early development phase of the drug, the safety and efficacy of the new product for use in human being should be established - this step is an essential aspect for getting approval for import or manufacturing and marketing of a drug in the country.
Rules and Regulation
In India, New Drugs & Clinical Trials Rules-2019 is applicable for submission of the information/ data required for approval of clinical trial and/or to import or manufacture of new drug/investigational.
The information is submitted online through CDSCO’s SUGAM online portal. The information submitted by the applicant is reviewed by the authorities at CDSCO and response is usually given within 90 working days.
Content of IND Application
Information required to be submitted for IND can be divided into three br/oad categories:
Animal Pharmacology and Toxicology Studies – The information in this section is generated through pre-clinical studies on animal and contains information to ensure that the drug is safe for human testing. Information related to history of use of the drug on humans is also required to be submitted.
Manufacturing Information – This contains information related to manufacturing unit to ensure that the manufacturer is capable for producing adequate batches of the drug of same property and quality.
Clinical Protocols and Investigator Information – Includes information related to investigational product form different resources to anticipate risk associated with initial testing in humans and the clinical protocol in accordance of which the clinical trials are conducted.
Phases of clinical trial for IND Application
A. For Phase I Clinical Trials the following are required:
1. Systemic Toxicity studies
Single dose toxicity studies
Dose Ranging Studies
Repeat-dose systemic toxicity studies of appropriate duration. This is required to support the duration of proposed human exposure.
2. Male fertility study
In-vitro genotoxicity tests
Local toxicity studies with proposed route of clinical application (in this case duration is dependent on the proposed exposure)
Hypersensitivity or test for allergy (for IND proposed to be used parenterally or local application)
Test for Photo-allergy or dermal photo-toxicity (if the IND or its metabolite is have an potential to cause photo-sensitivity)
B. For Phase II Clinical Trials the following are required:
Summary of non-clinical safety data (as listed above) submitted for Phase I trial permission and references for the same.
An application for directly starting a Phase II trial – complete safety data for Phase I trial must be submitted.
Repeat-dose systemic toxicity studies of appropriate duration. Required to provide evidence to support the duration of proposed human exposure.
In-vivo geno-toxicity tests.
Segment II reproductive or developmental toxicity study
C. For Phase III Clinical Trials the following are required:
Summary of non-clinical safety data submitted for Phase I and II trials, with references.
For an application for directly initiating a Phase III trial – complete non-clinical safety data needed for obtaining the permissions for Phase I and II trials
Repeat-dose systemic toxicity studies of appropriate duration to support the duration of proposed human exposure.
Reproductive or developmental toxicity studies
Segment I (if the study involves female of child bearing age), and Segment III (for drugs to be given to pregnant or nursing mothers or where the adverse effect on foetal development is aniticipated).
Carcinogenicity studies (if the drug is supposed to be carcinogenic or when the proposed treatment duration of the drug is more than 6 months).
D. For Phase IV Clinical Trials the following are required:
Summary of non-clinical safety data submitted for obtaining the permissions for Phase I, II and III trials, and references.
For an application for initiating the Phase IV trial, complete non-clinical safety data needed for obtaining the permissions for Phase I, II and III trials
Application of Good Laboratory Practices (GLP) –An accredited laboratory should be used for conducting all the animal studies , pharmacology studies, toxicology studies
Cliniexperts provide full-service regulatory support and assistance in navigating the various regulation steps for Investigational New Drug (IND). CliniExperts provide full spectrum services for the following types of Drug Clinical Trials:
Local Clinical Trial -Phase I Trial
Phase II Trial
Phase III Trial
and Phase IV Trial or Post Marketing Studies (PMS) (exclusively in India)
Global Clinical Trial -Phase I Trial
Phase II Trial
and Phase III Trial
New Drugs and Clinical Trials Rules, 2019, Ministry of Health & Fam. Welfare, Notification, G.S.R. 227(E), (March 19, 2019).