India's apex drug regulatory body has taken decisive action against potentially harmful pharmaceutical combinations by ordering an immediate ban on 35 fixed-dose combination (FDC) drugs that were approved without proper safety evaluation.
The Central Drugs Standard Control Organisation (CDSCO) issued directives on April 11 to drug controllers across all Indian states and Union Territories to halt the manufacture, sale, and distribution of these unapproved combinations, which include painkillers, nutrition supplements, and anti-diabetic medications.
Regulatory Violations Identified
The Drugs Controller General of India (DCGI), Dr. Rajeev Raghuvanshi, highlighted that these FDCs—which contain two or more active pharmaceutical ingredients in fixed ratios—were licensed for commercial distribution without undergoing mandatory safety and efficacy evaluations required under the New Drugs and Clinical Trials (NDCT) Rules, 2019.
"It has come to the notice of this directorate that certain FDC drugs have been licensed for manufacture, sale, and distribution without prior evaluation of safety and efficacy as per the provision of NDCT Rules 2019 under the Drugs and Cosmetics Act 1940. This poses a serious risk to public health and safety," Dr. Raghuvanshi stated in the official communication.
The regulatory body emphasized that approving such unapproved combinations compromises patient safety and may lead to adverse drug reactions, dangerous interactions, and other health hazards due to the absence of scientific validation.
Affected Medications
Among the banned combinations are several widely used formulations including:
- Metformin hydrochloride 500 mg (extended release) with glimepiride 3 mg and dapagliflozin 10 mg
- Dextromethorphan hydrobromide 10 mg with phenylephrine hydrochloride 5 mg per 5 ml syrup
- Diphenhydramine hydrochloride 12.5 mg with phenylephrine hydrochloride 5 mg per 5 ml syrup
- Rosuvastatin calcium IP equivalent to rosuvastatin 20 mg (immediate release pellets) with clopidogrel bisulphate IP equivalent to clopidogrel 75 mg (immediate release pellets) and aspirin 150 mg (gastro-resistant pellets)
Longstanding Regulatory Concerns
This action follows a series of communications dating back to January 2013, when the DCGI first raised concerns about state licensing authorities granting manufacturing permissions for FDCs that qualify as "new drugs" without obtaining mandatory central approval.
Despite multiple warnings over the years, including the most recent letter issued in February 2024, compliance issues persisted. When manufacturers received show-cause notices, many claimed they had not violated any rules since the licenses were granted by respective state drug licensing authorities.
"This has resulted in a lack of uniform enforcement of the provision of NDCT Rules 2019 under the Drugs and Cosmetics Act 1940 across the country," the DCGI noted in the letter.
Strengthening Regulatory Oversight
The CDSCO has now directed all state and territory drug controllers to:
- Review their approval processes for FDCs
- Ensure strict compliance with the Drugs and Cosmetics Act 1940 and associated rules
- Prevent the manufacture, sale, and distribution of the 35 listed FDCs and any other unapproved combinations
- Conduct investigations and take necessary regulatory action
- Report compliance measures back to the DCGI's office
This regulatory intervention represents part of a broader effort to address irrational drug combinations in the Indian pharmaceutical market. Previous similar actions have led to litigation from pharmaceutical companies challenging the drug regulatory organization in various courts across the country.
Public Health Implications
Healthcare experts emphasize that FDCs require particularly careful evaluation because combining multiple active ingredients can alter the pharmacokinetics, efficacy, and safety profiles of individual components. Without proper clinical testing, these combinations may pose unpredictable risks to patients.
The CDSCO's action underscores the critical importance of maintaining uniform drug approval standards nationwide, with public health and safety remaining the top priority in pharmaceutical regulation.
