10-Dec-2018: ‘Many combination drugs not approved by regulator’

Of the 110 anti-TB (tuberculosis) Fixed Dose Combinations (FDCs) available in India, only 32 (less than 30%) have been approved by the Central Drugs Standard Control Organisation (CDSCO), the country’s drug regulator. In the case of malaria FDCs, only eight out of 20 (40%), have been approved.

These statistics, that give rise to safety and efficacy concerns, have been brought out in a study published online in the journal Tropical Medicine and International Health by researchers from the Manipal College of Pharmaceutical Sciences.

An FDC or combination product is a formulation with more than one active pharmaceutical ingredient (API) in a fixed ratio of doses formulated into a single dosage form.

Aimed at assessing the proportion and sales of unapproved FDCs of anti-tubercular, antimalarial and antiretroviral (anti-HIV/AIDS) medicines available in India, the study analysed the available FDCs for these diseases and screened them against the CDSCO database of approved FDCs.

An opaque regulatory framework and ambiguity over licensing powers have contributed to the problem. The rationality of unapproved FDCs should be reviewed and irrational formulations should be banned. As of April, the CDSCO had approved 1,288 FDCs. This is disproportionately high compared with the availability in a tightly regulated market like USFDA, which has only a few hundred approved FDCs.

Pointing out that even the World Health Organisation’s (WHO) list of essential medicines mentions only 24 FDCs; it is unfortunate that a majority of approved FDCs in the Indian market are irrational and lack scientific justification. The scientific rigour of the CDSCO in approving these FDCs has been questioned time and again in Parliamentary and academic reports.

The study quoted the Parliamentary Standing Committee on Health and Family Welfare, which in its 59th report in 2012, pointed out multiple deficiencies in the CDSCO’s approval process for FDCs. It highlighted institutional problems such as understaffing, lack of skills, and inadequate infrastructure. “However, the most significant observation concerned the issuance of manufacturing licenses by the State Licensing Authority without the prior clearance of the Drug Controller General of India DCG(I), the head of CDSCO. This is the main problem.

The problem of unapproved FDCs mainly affects those who get treated in the private sector. In the absence of a strong pharmacovigilance mechanism in India, there is no data on adverse events of these unapproved FDCs.

12-Sep-2018: Prohibition and restriction of manufacture, sale and distribution of Fixed Dose Combinations (FDCs)

The Ministry of Health and Family Welfare has prohibited the manufacture for sale, sale or distribution for human use of 328 Fixed Dose Combinations (FDCs) with immediate effect. It has also restricted the manufacture, sale or distribution of six FDCs subject to certain conditions.

Earlier, the Central Government had, through its notifications published on the 10th March, 2016 in the Gazette of India, prohibited the manufacture for sale, sale and distribution for human use of 344 FDCs under section 26 A of the Drugs and Cosmetics Act, 1940. Subsequently, the Government had prohibited five more FDCs in addition to the 344 under the same provisions.

However, the matter was contested by the affected manufacturers in various High Courts and the Supreme Court of India. In compliance with the directions given by the Supreme Court of India in its judgment dated the 15th December, 2017, the matter was examined by the Drugs Technical Advisory Board constituted under section 5 of the Drugs and Cosmetics Act, 1940 which furnished its report on these drugs to the Central Government. The Drugs Technical Advisory Board recommended, amongst other things, that there is no therapeutic justification for the ingredients contained in 328 FDCs and that these FDCs may involve risk to human beings. The Board recommended that it is necessary to prohibit the manufacture, sale or distribution of these FDCs under section 26 A of the Drugs and Cosmetics Act, 1940 in the larger public interest. With regard to six FDCs, the Board recommended that their manufacture, sale and distribution be restricted subject to certain conditions based on their therapeutic justification. Fifteen FDCs out of the 344 prohibited on the 10th March, 2016, which were claimed to be manufactured prior to 21stSeptember, 1988, have been kept out of the purview of current notifications.

Earlier, an Expert Committee appointed by the Central Government had also examined these FDCs and made recommendations in line with those of the Board as indicated above.

The Central Government considered the recommendations of the Expert Committee and Drugs Technical Advisory Board, and based on such consideration, it was concluded that it is necessary and expedient in public interest to prohibit the manufacture for sale, sale and distribution for human use of these 328 FDCs in the country.

Accordingly, the Ministry of Health and Family Welfare has, in exercise of powers conferred by section 26A of the Drugs and Cosmetics Act, 1940,prohibited the manufacture for sale, sale or distribution for human use of 328 FDCs through its gazette notifications dated 7th September 2018; it has also restricted the manufacture, sale or distribution of six FDCs subject to certain conditions. These notifications will take immediate effect.