The Drugs Controller General of India (DCG (I)) is the Regulatory Authority who grants permission for the conduct of clinical studies on human volunteers. This is in accordance with Rule 122-DA of Drugs and Cosmetic Rules, which states that no clinical trial for a new drug, whether for clinical investigation or any clinical experiment by any institution, shall be conducted except under, and in accordance with, the permission, in writing, of licensing authority.

Is it mandatory to obtain DCGI permission to conduct Bioavailability and Bioequivalence (BA/BE) studies?
To answer this, let us have a closer look of the Law. Rule 122-DA clearly states that clinical trials are not allowed on new drugs without permission from DCG (I). So now, we need to look at the definitions of 'Clinical trials' and 'new drugs'.

The Rule 122-DAA of the Drugs And Cosmetics Rules defines clinical trials as a systematic study of 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." The Bioavailability and Bioequivalence (BA/BE) studies fall within the purview of the definition of clinical trials as BA/BE studies involve verifying the pharmacokinetic effects. Hence it is required to obtain permission from DCG (I) to conduct BA/BE studies.

Now the next question would be whether all studies require DCG (I) permission. The answer is not all studies require permission but only those studies which are conducted with new drugs.

The Rule 122-E of Drugs and Cosmetics Rules gives the definition of new drug, according to which the following will be a new drug:

o a drug which has not been used in India to any significant extent and not been recognized as effective and safe in India.
o a drug already approved in India which is now proposed to be marketed with modified or new claims, namely, indications, dosage, dosage form (including sustained release dosage form) and route of administration.
o a fixed dose combination of two or more drugs, which are now proposed to be combined for the first time in a fixed ratio, or if the ratio of ingredients in an already marketed combination is proposed to be changed.

Under the same rule, it is also explained that a new drug shall continue to be considered as new drug for a period of four years from the date of its first approval or its inclusion in the Indian Pharmacopoeia, whichever is earlier. To comply with this rule, before conducting a clinical trial, a sponsor or a CRO is required to verify the status of the drug. A list of approved drugs is provided by the Central Drugs Control Standard Organization. There are inherent problems with this list. This list is not exhaustive as the date of first approval is only from the year 1999. This does not address the approval of drugs prior to 1999 and also does not mention the complete name of the drug up to 2003. This does little to help in the decision making process of adjudging the status of a drug, particularly in the case of bioequivalence studies.

A case may be made for the waiver of permission for the 'new drugs' in this four years period. i.e., which have been approved for marketing but not completed four years post approval.

These products will be used only in clinical studies on small number of volunteers and will not involve thousands of patients as is case with marketing of the product, where the safety of the drug may perhaps be a concern in the first four years as our country might not have had any experience with that particular new drug. In bioequivalence studies, the drugs are always given under very controlled conditions and under complete supervision of the clinical investigators who are medically qualified doctors who can monitor the study subjects very closely and as per the protocol approved by the competent ethics committee close supervision and monitoring in a non clinical trial setting is not possible and hence may be of concern to the regulatory authority.

What would this grant of waiver imply?
This would mean that drugs that have been granted approval by the DCG (I) in the last 4 years need not go through a re-approval process if a bioequivalence study is required on them . This would save an enormous amount of time and resource for both the industry and the regulatory authority.

(The author is senior executive - Regulatory Affairs, Lotus Labs Pvt. Ltd.)