The US FDA has issued a Warning Letter to Indian OTC medication manufacturer Dabur, following an FDA inspection of the firm's OTC drug manufacturing facility in Dadra and Nagar Haveli, India.
The letter follows a Form 483, made public in May of this year, in which the FDA detailed deliberate falsification of equipment usage logs, no cleaning validation and a live bird in the raw material warehouse after the inspection in January.
The regulatory agency said Dabur's response to the Form 483 did not adequately address the deficiencies, noting that the problems it identified reflected broader failures in quality culture, data integrity and manufacturing control.
"Systemic" data-integrity failures
The FDA said the deficiencies went beyond isolated documentation errors, describing them as evidence of a “systemic breakdown” in quality unit (QU) oversight and a deficient quality culture.
During the inspection, investigators had found that a second equipment logbook provided to them had been falsified, with entries for several US-marketed OTC products deliberately omitted from the version initially supplied.
While the discrepancies did not involve out-of-specification results, the FDA said the QU had approved the records without ensuring their accuracy and completeness.
The agency has requested a comprehensive investigation into the extent of Dabur's data-integrity failures, including an assessment of omissions, alterations, deletions, record destruction and non-contemporaneous record completion.
It also recommended that Dabur use an independent third-party consultant and assess whether employees implicated in data-integrity failures remain able to influence cGMP or drug-application data.
Cleaning and process validation concerns
The Warning Letter also expands on concerns around manufacturing controls at the facility.
During its facility inspection, the FDA found that cleaning validation for a non-dedicated production line relied exclusively on visual examination, without scientifically established maximum allowable carryover limits, quantitative residue testing or direct surface sampling of difficult-to-clean areas.
Dabur had also not performed cleaning validation on another line despite using it to manufacture multiple OTC drug products.
The FDA said the company's proposed retrospective testing was insufficient to assess potential cross-contamination across products already released to the US market.
Separately, Dabur acknowledged that it had not performed process validation for most of the drug products manufactured on the relevant production lines.
The FDA has requested a timeline for process performance qualification for each marketed drug product, alongside ongoing monitoring of intra- and inter-batch variation.
Recall and import restrictions
Dabur India issued a voluntary recall of some of its products on 2 June, following an FDA teleconference on 13 May in which the agency recommended that the company remove certain products from the US market.
The specific product names were not disclosed in the Warning Letter, but subsequent FDA enforcement records show that 14 separate OTC products from Dabur were subject to recalls.
All were classified as Class II recalls and had been distributed across the US.
The recalls covered a sizeable range of private-label OTC creams and antibiotic ointments, including private-label antifungal, hydrocortisone, bacitracin zinc and triple-antibiotic products.
FDA also placed drugs and drug products from the Dabur facility on Import Alert 66-40 on 5 June, meaning products can be subject to detention without physical examination where the agency determines that manufacturing controls do not appear to conform to cGMP requirements.
The agency may also withhold approval of new applications/supplements naming the facility.
The agency has recommended that Dabur engage a qualified cGMP consultant to conduct a comprehensive six-system audit and assess the effectiveness of its corrective and preventive actions before seeking resolution of its compliance status.
