India's top drug regulator has intensified oversight of legacy combination drugs, issuing a strict three-month deadline for manufacturers to submit crucial post-market surveillance data for two fixed-dose combinations (FDCs) that were previously approved at the state level.
Dr. Rajeev Singh Raghuvanshi, Drug Controller General of India (DCGI), addressed state and Union Territory drug controllers in a February 24 communication, highlighting widespread non-compliance with previous regulatory requirements. The directive specifically targets manufacturers holding pre-October 2012 licenses who have failed to submit required safety and efficacy data.
Clinical Implications for Approved FDCs
The regulatory committee's evaluation has identified two rational FDCs among 19 reviewed combinations. The Imipramine Hydrochloride-Diazepam combination (25mg + 2mg and 25mg + 5mg tablets) received continued approval with specific clinical parameters:
- Indicated exclusively for co-morbid anxiety conditions
- Treatment duration restricted to 6-8 weeks
- Requires strict adherence to safety monitoring protocols
For the triple combination of Chlorpheniramine Maleate, Ammonium Chloride, and Sodium Citrate (available in two strength formulations: 2mg + 100mg + 50mg/5ml and 2.5mg + 125mg + 55mg/5ml), manufacturers must implement revised labeling requirements:
- Clear specification of adult and pediatric dosing schedules
- Updated prescribing information to ensure proper usage
- Modified product labeling for enhanced safety
Regulatory Context and Compliance Requirements
The current directive stems from a 2013 DCGI mandate requiring pharmaceutical companies to demonstrate the safety and efficacy of FDCs. Despite the establishment of a dedicated committee in 2021 to examine these combinations, many manufacturers have failed to submit the required documentation.
Post-market surveillance data, which provides critical information about drug safety and efficacy after market authorization, has become a key focus of regulatory oversight. Companies failing to comply with the three-month submission deadline may face appropriate regulatory action, potentially affecting their manufacturing and marketing authorizations.
Impact on Pharmaceutical Industry
This regulatory intervention represents a significant step in strengthening drug safety monitoring in India. Manufacturers must now:
- Submit comprehensive post-market surveillance protocols
- Provide detailed safety and efficacy data
- Ensure compliance with central licensing requirements
- Implement required labeling modifications
The DCGI's action underscores the growing emphasis on evidence-based regulation of pharmaceutical products, particularly those approved before the establishment of current regulatory frameworks.
