Aiming to streamline the submission of application for approval of Fixed Dose Combination (FDC) drugs and their review by the drug authorities, the Drug Controller General of India (DCGI) has introduced a system of ‘preliminary scrutiny’ of such applications while receiving them to determine the acceptability for review by the DCGI office. This will come into effect from January 1, 2011.

The new system is intended to avoid unnecessary delays in approvals of FDC applications. So far, the applicants have used many different approaches in organizing the information and the differences in organization of data in each application has made reviewing more difficult and can also lead to omission of critical data or analyses which could result in unnecessary delays in approvals.

The preliminary scrutiny of the applications will be done by CDSCO officers based on checklists prepared for each of the several categories of FDC. During the preliminary examination, the CDSCO officers will scrutinize the applications to ensure that it contains all the required administrative as well as technical information in proper manner as per the checklist. If application submitted is not in accordance with the format and the checklist, it will not be accepted by CDSCO.

Once an application is accepted, the adequacy of the data will be reviewed by CDSCO as per the specified requirements and guidelines. In case the data submitted is not adequate or satisfactory, applicant will be requested to generate/submit adequate data for consideration and approval of the FDC.

The proposed fixed dose combination should be based on therapeutic rationale. The applicant is required to justify the combination based on the rationale. While submitting the rationale for a FDC, the applicant must address the issues like drug-drug interaction between the ingredients, food effects and dosage schedule of individual active ingredients vis-a-vis that of the FDC. Further, the indication/claim for the FDC should be such that the individual active ingredients makes a contribution to the claimed effect and the product should be formulated so that the dose and proportion of each substance in the FDC is appropriate.

Trial batches of new drugs for test and analysis/clinical trial/BE study purpose should be manufactured after obtaining Licence in Form 29 from the concerned State Licensing Authority and copy of the licence should be submitted along with the application.  While submitting reply to a query, the applicant should always enclose with the reply, a copy of query letter issued by CDSCO.

The applicant should submit stability data generated on 3 trial batches manufactured by them under Licence in Form 29 issued by State Licensing Authority (SLA). The stability data and the clinical trial protocol should be submitted as per the CDSCO format. In case of clinical trial/ bioequivalence study NOC, the applicant should submit the adequate chemical and pharmaceutical information. The applicant should always submit certificate of analysis, dissolution data (in case of oral dosages form, as appropriate), stability study data etc. in respect of formulation, duly signed by the In-charge/Manager QC.

Before preparing the application, the applicant must categorise their proposal and submit information as per the checklist for that category. Application in Form 44 should be complete in all respects and signed by the authorized person of the firm with name and designation. The TR challan receipt submitted by the applicant should mention the name of the FDC including correct head of the account, payable at, bank clearance, etc. The documents must be submitted with indexing and page number. Without indexing or page number, no application will be accepted. Clear and unequivocal information should be provided along with the application.