New Delhi : The Central Drugs Standard Control Organisation (CDSCO) has issued a notice seeking all the manufacturers of the 16 fixed dose combinations (FDCs) which were earlier considered as irrational in an expert panel report to submit the information in a prescribed format for further evaluation.

The decision is in connection with the decision of the 86th meeting of the Drugs Technical Advisory Board (DTAB) on April 13, 2021, which examined the expert committee report of Prof. Kokate Committee with respect to the FDCs considered as irrational. The meeting in principle agreed to the recommendations of the Committee and recommended that the sub-committee under Dr Nilima Kshirsagar, Emeritus Scientist, former Chair in Clinical Pharmacology, ICMR, Mumbai, shall examine the 16 irrational FDCs in detail as per the procedures.

In order to give an opportunity to the manufacturers of the said FDCs, and the concerned stakeholders for presenting the precise data with respect to these FDCs, the Subcommittee has desired that the manufacturers and other stakeholders submit the information in a prescribed format. The CDSCO, in its latest notice, released the format, which has to be submitted along with the supporting documents, for further action.

“Accordingly, all the manufacturers of said FDCs and the concerned stakeholders are hereby requested to submit the information in the prescribed format and the relevant supporting documents in hard copy as well as soft copy (i.e. in C.D form) to this office latest by April 30, 2023 till 5 pm,” said the FDC division of CDSCO.

The format for submission of information seeks details including the name and address of the applicant, the name and designation of the licensing authority, date and year of product license, whether the FDCs is approve by the Drugs Controller General (India), whether FDC is pre-1988 and if yes, details thereof, particulars of the drug, indications, copy of approved package insert currently provided, therapeutic details, one-page summary with highest level of evidence supporting the claim of postulated advantage or rationale, pharmacokinetic and pharmacodynamics rationality, regulatory status of the FDC in other countries, among others.

The list of 16 FDCS considered as irrational among the 294 FDCs recommended by the Prof Kokate Committee include combination of acetyl salicylic acid with ethoheptazine; aloe extract with aloe extract with allantoin, alpha tocopherol acetate, D-panthenol and vitamin A; Aloe extract with vitamin E, dimethicone and glycerine; aloe vera with jojoba oil and vitamin E; aloe vera with orange oil; aloe vera with jojoba oil, wheat germ oil and tea tree oil; aloe vera with vitamin E and herbal; dicyclomine with paracetamol and clidinium bromide; dicyclomine with paracetamol, clidinium bromide and chlordiazepoxide; gliclazide with chromium picolinate; paracetamol with lignocaine; amoxicillin with serratiopeptidase and lactobacillus sporogenes; amoxicillin with cloxacillin, lactic acid bacillus and serrapeptase; amoxicillin and serratiopeptidase; cefadroxil and probenecid; and cefurosime with serratiopeptidase.

The drug regulator received complaints from Consumer Associations in the year 2007 regarding FDCs not approved by the DCG(I) bug marketed in the country and as part of follow up action of complaints the DCG(I) prepared a list of 294 FDCs and directions were issued to all State and Union Territory drug controllers to withdraw these 294 drugs which were licensed without the approval of the central drug regulator. The manufacturers association, however, got a stay from the High Court of Madras in respect of the directions.

The matter was then placed in the DTAB in its 56th meeting held on January 16, 2008 and a subcommittee was constituted by the Board to examine these FDCs. According to the sub committee report, out of the 294 FDCs, for 17 it was reported that the data provided by the manufacturer was inadequate to prove its rationality, safety and efficacy, while for 49 it was reported that further data generation in terms of safety and efficacy by conducting clinical trial and other studies.

The Central government directed that these issues may also be dealt with by the Prof Kokate Committee and once the committee submits its report, it may be placed before the DTAB for further necessary action. Besides, another three FDCs were directed by the High Court of Maharashtra, Nagpur Bench, to be referred to the Prof. Kokate Committee.

Thus, the Committee examined these 17+49+3 FDCs and categorised them into three categories – 33 FDCs considered as rational, 20 FDCs requiring further data generation and 16 FDCs considered as irrational. The irrational combinations are proposed, not to be allowed for their continued manufacturing and marketing in the country.

The DTAB examined the Committee report dated March 12, 2021, in its 86th meeting and in principle agreed to the recommendations. It also recommended that the sub-committee under Dr Nilima Kshirsagar should quickly look at the 33 rational FDCs and 20 FDCs which need further deliberations, to see if there are any inconsistencies and revert to the Chairman of the DTAB. However, the sub-committee shall examine the 16 irrational FDCs in detail as per the earlier procedures, it added.