Fixed Dose Combinations refer to products containing one or more active ingredients used for a particular indication(s). FDCs can be divided into the following groups and data required for approval for marketing is described below:
- The first group of FDCs includes those in which one or more of the active ingredients is a new drug. For such FDCs to be approved for marketing data to be submitted will be similar to data required for any new drug (including clinical trials) [see rule 122E, item (a)].
- The second group FDCs includes those in which active ingredients already approved/marketed individually are combined for the first time, for a particular claim and where the ingredients are likely to have significant interaction of a pharmacodynamic or pharmacokinetic nature [see rule 122E, item (c)]. If clinical trials have been carried out with the FDC in other countries, reports of such trials should be submitted. If the FDC is marketed abroad, the regulatory status in other countries should be stated. (see Appendix I, item 9).
- For marketing permission, appropriate chemical and pharmaceutical data will be submitted. In case such a combination is not marketed anywhere in the world but these drugs are already in use concomitantly (not as an FDC but individually) for the said claim, marketing permission may be granted based on chemical and pharmaceutical data. Data showing the stability of the proposed dosage form will also have to be submitted.
- For any other such FDCs, clinical trials may be required. For obtaining permission to carry out clinical trials with such FDCs a summary of available pharmacological, toxicological and clinical data on the individual ingredients should be submitted, along with the rationale for combining them in the proposed ratio. In addition, acute toxicity data (LD 50) and pharmacological data should be submitted on the individual ingredients as well as their combination in the proposed ratio.
- The third group of FDCs includes those which are already marketed, but in which it is proposed either to change the ratio of active ingredients or to make a new therapeutic claim. For such FDCs, the appropriate rationale including published reports (if any) should be submitted to obtain marketing permission. Permission will be granted depending upon the nature of the claim and data submitted.
- The fourth group of FDC includes those whose individual active ingredients (or drugs from the same class) have been widely used in a particular indication(s) for years, their concomitant use is often necessary and no claim is proposed to be made other than convenience. It will have to be demonstrated that the proposed dosage form is stable and the ingredients are unlikely to have significant interaction of a pharmacodynamic or pharmacokinetic nature. No additional animal or human data are generally required for these FDCs, and marketing permission may be granted if the FDC has an acceptable rationale.
RULES GOVERNING FIXED DOSE COMBINATIONS
The clinical trials are conducted in accordance with the Drugs and Cosmetics Rules. The specific Rules are-
- Rule 122 D -permission to import or manufacture fixed dose combination
- Rule 122 DA -Mandatory requirement of permission from DCG (I) for conduct of clinical trial of new drug;
- Rule 122 DAB-Provision for examination of serious adverse event (SAE) of injury and death and payment of compensation in clinical trial related cases. Provision for debarment of the applicant in case of failure to pay compensation;
- Rule 122 DAC -Conditions of permission for conduct of clinical trial which includes mandatory requirement to follow Good Clinical Practice (GCP) guidelines, guidelines and requirements specified in Schedule Y of Drugs and Cosmetics Rules and other applicable regulations. Provision for debarment of applicant and investigator in case of non- compliance;
- Rule 122 DD -Requirements and guidelines for registration of Ethics Committee;
- Rule 122 E-Definition of new drug;
- Schedule Y-Detailed guidelines and requirements for conduct of clinical trial and approval of new drug
- FDC Draft Guidelines -issued by CDSCO, Directorate General of Health Services, Govt. of India