The Drug Controller General of India (DCGI) has issued guidance for getting marketing approval of fixed dose combination (FDC) drugs in India. The draft has classified the FDCs into different categories and have stated various requirements for each in a detailed manner. These guidelines apply to manufacture, import and marketing approval of FDCs as a finished pharmaceutical product considered as new drug as per Rule 122(E) of Drugs and Cosmetics Act & Rules.

Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945) specifies the requirements for approval for marketing of various types of FDCs. The same is further elaborated in the draft to provide a detailed guidance for industry.

The aim behind elaborating the requirements for approval for marketing as mentioned in the draft was because, “FDCs should always be based on convincing therapeutic justification. Each fixed dose combination should be carefully justified and clinically relevant.” The draft guidance prepared by the government clearly put lots of focus on the importance on filing Form-44.

According to the draft when approval is sought for marketing investigational new drug (IND), data that are required to be submitted will be similar as per Appendix I of Schedule Y which is similar to data required for any new chemical entity (NCE).

However, for such FDCs clinical trials is required to be carried out right from Phase I and in order to get permission for marketing the new drug of such FDCs, along with other required documents. The draft also specifies that in case if the applicant does not have an approval from DCGI to manufacture any of the active pharmaceutical ingredient (API) which is considered as new drug, they can either import the API, manufacture it or obtain the API from another manufacturer which is not yet approved by DCGI provided the applicant files separate application in Form-44 along other requites.

Another feature highlighted in the draft is regarding the prerequisites for getting marketing approval, in case, one or more of the ingredients of the combination is a new drug and it is not approved individually in the country however the same is approved in other country.

The draft states, “If such FDC is marketed abroad phase III clinical trials are required to be conducted in India. In case, such a combination is not marketed anywhere in the world, clinical trials right from phase I as appropriate are required to be conducted in the country.”

Apart from fulfilling this criterion the companies or manufacturer's applying for marketing approval in India needs to submit data required for any new drug substance as mentioned earlier. However it states,“ In case of injectable formulation, sub-acute toxicity data conducted with the applicants’ product has to be provided.”

Another notable point highlighted in the draft is on the FDC's that are not marketed in India but the active ingredients are approved or marketed individually and it is likely to have significant pharmacokinetic or pharmacodynamic (PK/PD interactions. This group of FDCs includes those in which active ingredients already approved, marketed individually are combined for the first time for marketing in India, for a particular claim and where the ingredients are likely to have significant interaction of a PK/PD nature.

The draft mentions, “For the FDC that is not marketed anywhere in the world and the individual components are not concomitantly used in routine clinical practice and the ingredients are likely to have significant PK/PD interaction, clinical trials may be required.” And only after the successful completion of clinical trial(s), the following documents should be submitted to complete the marketing application the draft specifies.

There are many more changes and requirements that the draft has notified for the marketing approval of FDC's and the DCGI' office have already asked for comments and suggestions regarding this draft document, which the industry is expected to revert within in a months time.