A detailed guideline for conducting clinical trials in India with the phases of clinical trials are explained.
CDSCO regulates the clinical trials for drugs and medical devices in India. Demonstration of safety and efficacy of the drug product for use in humans is essential before the drug product can be approved for import or manufacturing and marketing in the country. The Rules 122A, 122B and 122D, 122 DA, 122DAA, 122E of Drugs and Cosmetics Rules and Annexure A, B, C and D of Schedule Y, describe the information/data required for approval of clinical trials and/or to import or manufacture of new drug for marketing in the country.
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Document Requirements for Approval of Clinical Trials (Phase-I/II/III/IV).
For new drug substances discovered in India, clinical trials are required to be carried out in India right from Phase I. For new drug substances discovered in countries other than India, already conducted Phase I data is required along with the application. After submission of Phase I data generated outside India to the Licensing Authority, permission may be granted to repeat Phase I trials and/or to conduct Phase II trials and subsequently conduct Phase III trials.
For permission of such clinical trials the documents required to be submitted are as follows,
Form 44
Treasury Challan of INR 50,000 (for Phase- I) / 25,000/- (for Phase-II/III clinical trials)
Source of bulk drugs /raw materials
Chemical and pharmaceutical information including: Information on active ingredients:, Data on Formulation:
Animal Pharmacology
Animal Toxicology
Human / Clinical pharmacology (Phase I)
Therapeutic exploratory trials (Phase II)
Therapeutic confirmatory trials (Phase III)
Special studies – Bio-availability / Bio-equivalence.
Regulatory status in other countries
Prescribing information
Application in Form -12 alongwith T-Challan of requisite fees (in case of import of investigational products)
Below are the each phase described in detail. The number of study subjects and sites to be involved in the conduct of clinical trial will depend upon the nature and objective of the study.
Phase I Clinical Trials
Phase I clinical trials should usually be carried out by investigators trained in clinical pharmacology and having the necessary facilities to closely observe and monitor the subjects.
These may be carried out at one or two centers.
At least 2 subjects should be used on each dose.
The document required for Phase I Clinical Trials are,
Systemic Toxicity studies
Single dose toxicity studies
Dose Ranging Studies
Repeat-dose systemic toxicity studies
Male fertility study
In-vitro genotoxicity tests
Relevant local toxicity studies with proposed route of clinical application (duration depending on proposed length of clinical exposure)
Allergenicity / Hypersensitivity tests (when there is a cause for concern or for parenteral drugs, including dermal application)
Photo-allergy or dermal photo-toxicity test (if the drug or a metabolite is related to an agent causing photosensitivity or the nature of action suggests such a potential)
Phase II Clinical Trials
Phase II clinical trials should normally be carried out on 10-12 patients at each dose level.
These studies should usually be carried out at 3-4 centers by clinicians specialized on the concerned therapeutic areas and having adequate facilities to perform the necessary investigations for efficacy and safety.
The document required for Phase II Clinical Trials are,
Summary of all the non-clinical safety data (listed above) already submitted while obtaining the permissions for Phase I trial.
In case of an application for directly starting a Phase II trial – complete details of the nonclinical safety data needed for obtaining the permission for Phase I trial, as per the list provided above must be submitted.
Repeat-dose systemic toxicity studies of appropriate duration to support the duration of proposed human exposure.
In-vivo genotoxicity tests
Segment II reproductive/developmental toxicity study (if female patients of child bearing age are going to be involved)
Phase III Clinical Trials
If the drug is already approved/marketed in other countries, phase III data should generally be obtained on at least 100 patients distributed over 3-4 centres.
If the drug is a new drug substance discovered in India and not marketed in any other country, phase III data should generally be obtained on at least 500 patients distributed over 10-15 centres.
The document required for Phase II Clinical Trials are,
For Phase III Clinical Trials Provide a summary of all the non-clinical safety data (listed above) already submitted while obtaining the permissions for Phase I and II trials, with appropriate references.
In case of an application for directly initiating a Phase III trial – complete details of the non-clinical safety data needed for obtaining the permissions for Phase I and II trials, as per the list provided above must be provided.
Repeat-dose systemic toxicity studies of appropriate duration to support the duration of proposed human exposure.
Reproductive/developmental toxicity studies
Segment I (if female patients of child bearing age are going to be involved), and
Segment III (for drugs to be given to pregnant or nursing mothers or where there are indications of possible adverse effects on foetal development)
Carcinogenicity studies (when there is a cause for concern or when the drug is to be used for more than 6 months).
Phase IV Clinical Trial
Provide a summary of all the non-clinical safety data (listed above) already submitted while obtaining the permissions for Phase I, II and III trials, with appropriate references. In case an application is made for initiating the Phase IV trial, complete details of the non-clinical safety data needed for obtaining the permissions for Phase I, II and III trials, as per the list provided above must be submitted.
Permission to carry out these trials shall generally be given in stages, considering the data emerging from earlier Phase(s). CDSCO will initially examine such applications, if any particular data is lacking, the applicant will be informed or else the applications will be forwarded to the members of IND committee in case of Investigational New Drugs (INDs) or to the members of New Drug Advisory Committee (NDAC) in case of new chemical entities other than IND.
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A per Clause 1(3) of Schedule Y to Drugs & Cosmetics Rules, for drugs indicated in life threatening / serious diseases or diseases of special relevance to the Indian health scenario, the toxicological & clinical data requirements may be abbreviated, deferred or omitted, as deemed appropriate by the Licensing Authority. There is as such neither any definition of “life threatening / serious diseases” nor any list of such disease/disorders prescribed under the Drugs & Cosmetics Act & Rules. Diseases like Cancer, AIDS etc are generally considered as Serious /Life Threatening Diseases.
To conduct clinical trials in India contact us at [email protected]