We have an Ayush approval for a product, which is basically a plant extract. We are planning to take forward one of the components of this extract, which we have concentrated to purity level of 90% using organic solvents. This component is to be studied through an open label study to verify the proof of concept of its efficacy. Do we need a regulatory approval to undertake this study?
Unnikrishnan

Indian GCP section 7.5 gives guidance on the approach depending on the category of herbal product.
7.5.1. Categories of Herbal Products
a) A lot is known about the use of a plant or its extract in the ancient Ayurveda, Siddha or Unani literature or the plant may actually be regularly used by physicians of the traditional systems of medicine for a number of years. The substance is being clinically evaluated for same indication for which it is being used or as has been described in the texts.
b) When an extract of a plant or a compound isolated from the plant has to be clinically evaluated for a therapeutic effect not originally described in the texts of traditional systems or, the method of preparation is different, it has to be treated as a new substance or new chemical entity (NCE) and the same type of acute, sub acute and chronic toxicity data will have to be generated as required by the regulatory authority before it is cleared for clinical evaluation.
c) An extract or a compound isolated from a plant which has never been in use before and has not ever been mentioned in ancient literature, should be treated as a new drug, and therefore, should undergo all regulatory requirements before being evaluated clinically.

Please check in which category your product falls. This will give you an idea of the data to be generated before conducting clinical trial. You will need approval of EC for the protocol approval. The conduct of trial has to be as per DCGI guidelines and GCP guidelines. For category C all regulatory requirements have to be completed before it undergoes clinical evaluation.

Who could become an LAR of an illiterate subject?
Jeemut Parasar
Schedule Y
A legally acceptable representative is a person who is able to give consent for or authorize an intervention in the patient as provided by the law(s) of India
This usually includes parents, brothers, sisters or guardian (in case of minors) or someone who has been legally assigned a power of attorney.

What is the criteria for the selection of reference product for BA/BE trials conducting in India?
Harisankar S

Reference product (as per CDSCO guidelines for BE studies) is a pharmaceutical product which is identified by regulatory authorities as "designated reference product" and contains the same active ingredient as the new drug. The reference product is usually the global innovator's product.

If an innovator company is intends to launch a modified dosage form of their conventional dosage product, is it necessary to conduct pre-clinical studies?
Harisankar S

If the modified release form is a pharmaceutical modification which does not have potential to change the pharmacodynamic properties of the drug, there is no need for pre-clinical studies.

Povidone iodine is routinely used pre-op (5%) by almost every ophthalmologist as a prophylaxis against post-operative infection (endophthalmiltis). If a study is to be done on its efficacy in a specific type of conjunctivitis, and 0.3% is being used, can it proceed without DCGI?
Kannan Narayana

If povidone iodine falls into category of a new drug, you require DCGI approval. Pl check if povidone is approved for the indication of conjunctivitis by DCGI office and how many years have elapsed since approval. If it is not approved, Povidone iodine will fall into category of new drug as per Drugs & Cosmetics Rules 122 E. If it is approved as a new drug but 4 years have not elapsed, it will be considered a new drug as per Rule 122E of Drugs and Cosmetics Act.

Rule 122E defines a "new" drug as one which includes:
(a) Chemical, biological or recombinant biotechnological or such devices or delivery systems either in bulk or prepared dosage form intended for use in diagnosis, prevention, treatment or mitigation of disorders in human beings or animals, except during local clinical trials, has not been used in the country to any significant extent, and except during local clinical trials has not been recognized in the country as effective and safe for the proposed claim.
(b) A drug already approved for certain claims, 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.
(c) A fixed dose combination of two or more drugs, individually approved earlier for certain claims, 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, with certain claims, viz. indications, dosage, dosage form (including sustained release dosage form) and route of administration.
(d) All vaccines unless certified by licensing authority.
(e) A new drug shall 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.

Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, Mumbai.
Readers can send their queries at: arunbhatt@clininvent.com