Module 04: Clinical Trial Requirements and Documentation

Approval of New Drugs in India

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, Phase I data as 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 Phase III trials concurrently with other global trials for that drug. Phase III trials are required to be conducted in India before permission to market the drug in India.

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. 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.

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 centers primarily to confirm the efficacy and safety of the drug, in Indian patients when used as recommended in the product monograph for the claims made. 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 centers. In addition, data from clinicians on adverse drug reactions observed during clinical use in about 1,000 to 2,000 patients are required to be submitted as Phase IV.

Special studies: Special studies include bioavailability / bioequivalence studies or in vitro dissolution studies where data on formulations manufactured in the country need to be given. Data to explore the effects in the elderly or in patients with renal failure or expected drug interactions are to be provided as appropriate

Permission to carry out these trials shall generally be given in stages, considering the data emerging from earlier Phase(s). However, in case of new drugs approved in other countries, the requirement of submitting the results of local clinical trials for approval of a new drug may not be necessary if the drug is of such a nature that the licensing authority may, in public interest decide to grant such permission on the basis of data available from other countries.

The criteria of considering the clause of “public interest” may be as follows:

  1. In case the drug is indicated for serious/life threatening conditions.
  2. If the drug is indicated for a disease of special relevance to the Indian health scenario.
  3. The drug is indicated for a disease for which there is no or limited satisfactory therapeutic options.
  4. If the drug is indicated for a rare disease or a disease in which patient population is scanty and conducting clinical trial will take long time.
  5. Existence of significant unmet medical needs or significant public health issue
  6. The drug under evaluation is offering added significant advantage over the existing treatment modalities for a specific disease.

Also, as 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. “Life-threatening” diseases are generally considered as diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes. Diseases like Cancer, AIDS etc. are generally considered as Serious /Life Threatening Diseases.

In cases of life threatening / serious diseases, it is desirable to expedite the development, evaluation, and marketing of new therapies intended to treat persons especially where no satisfactory alternative therapy exists. In such cases patients / clinicians are generally willing to accept greater risks or side effects from products that treat life-threatening/ serious diseases, than they would accept from products that treat less serious illnesses.

CDSCO will initially examine such applications, if any particular data is lacking same will be informed to the applicant 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 and new fixed dose combinations (FDC’s). However, in case of applications for grant of approval of new dosage form, new indication, new route of administration etc. of approved drugs, the application will be examined by CDSCO. Wherever required, such applications may also be examined in consultation with expert / expert committees.

Further, all requests for exemption of toxicological & clinical data requirements will be considered on the basis of examination and scrutiny of the adequacy of data and in consultation with expert/expert committees. A legal undertaking in the form of an affidavit should be submitted by the applicant (competent person from the Company) stating that the data submitted along with the application is scientifically valid and authentic.

Permissions for conducting Clinical Trials

No new drug clinical trial can be carried out without the permission of the DCGI. Data appropriate to the phase of the trial along with the proposed protocol, case record form, names of investigators and centers have to be submitted for approval. The investigator has to have appropriate facilities and expertise and the trial is usually required to be carried out in teaching medical institutions. Protocols are to be reviewed and approved by the ethics committee of the institution. However, if an institution does not have an ethics committee, approval from DCGI is adequate to initiate the trial. Clinical trials in children may be permitted only after the phase III trials in adults are completed; however, if the drug has value primarily in diseases of children, early paediatric trials may be allowed.

Responsibilities of the investigator/Sponsor

Informed consent has to be obtained in the prescribed format. An annual status report must be done on current patients and those who have been terminated, with reasons for termination. Any unusual, unexpected or serious adverse reactions are required to be communicated.

In case the application is for clinical trial permission:-

i. adequate chemical and pharmaceutical information should be provided to ensure the proper identity, purity, quality & strength of the investigational product, the amount of information needed may vary with the Phase of clinical trials, proposed duration of trials, dosage forms and the amount of information otherwise available

ii. In case of applications for protocol amendments of already approved studies, applicants should submit copy of approval of protocol, amended new protocol, summarized list of all the new changes incorporated along with justification / reasons for the change.

iii. Ethics Committee Approval: Ethical approval should be obtained from Ethics Committee located in the same area where the clinical trial site is located.

iv. The proposed clinical trial study centers should be geographically distributed in the country and should also include clinical sites which have their own Institutional Ethics Committee.

Dr. Manoj Karwa

Auriga Research Ltd.
Email: [email protected]


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