The Prof C K Kokate-headed expert committee, constituted by the Union health ministry in February this year, to formulate policy guidelines and procedures for approval of fixed dose combinations (FDCs) has issued
draft policy guidelines for approval of FDCs in India.

The guidelines apply to the manufacture/ import and marketing approval of any FDCs in the country.

As per the guidelines, a clear justification with a valid therapeutic rationale of the particular combination of active substances proposed along with the appropriate data will be the basis for approval.  For granting manufacturing or marketing approval of a new FDC, it will have to be shown that it is rational to combine two or more APIs into a single product. An application should clearly state the basis of making the claim for the FDC; proposed dosing schedule with scientific evidence (if available) for the combination; and potential for clinically significant PK and/or PD interactions between the APIs proposed to be combined, leading to safety concerns.  Rationality will depend on medical, quality and bioavailability considerations.

The same quality standards that apply to single-component products will apply to FDCs. It will be necessary to demonstrate that the quality of the combination is similar to that of the individual ingredients.  Besides, there should be a medical rationale for combining the actives. If the actives in an FDC are intended to relieve different symptoms of a disease state, it is a prerequisite that these symptoms commonly occur simultaneously at a clinically relevant intensity and for a period of time such that simultaneous treatment is appropriate. Occurrence of the individual symptom in isolation should not be indications for the FDC.

The FDC should have demonstrably one or more of the features like increased efficacy in comparison to the individual components given at the same dose; the incidence of adverse reactions in combination is lower than in that component actives given alone, for dose of one component or a protective; dose reduction;  reduced cost; one drug acts as a booster for another (for example in the case of some antiviral drugs); improved adherence, simplified therapy; for antimicrobials, the combination of resistance; minimize abuse of other actives; and simplified logistics of procurement and distribution.

Dr Urmila Thatte, Bikash Medh, Dr R K Khar and Dr HG Koshia are the other members of the committee.

The terms of reference of the committee were to formulate policy guidelines and SOPs for approval of FDCs with special emphasis on requirements of clinical trial on Indian population; types of local clinical trial, its design, sample size, sites and their distribution etc in the clinical trial; requirements of post marketing (phase IV) trial to assess safely of FDCs in post marketing scenario; and to formulate guidelines and SOPs on the functioning of New Drug Advisory Committees (NDACs) in respect of FDCs.