The agency has seen an increase in preapproval inspections of generics manufacturers by 60% between 2011 and 2013, though the FDA seems to be having particular difficulties in inspecting foreign generic drugmakers. For example, 24% of preapproval inspections requested in 2011 were outstanding by the end of 2013, and all of those requests were for foreign manufacturer inspections.
And of the 155 outstanding preapproval requests for inspections in 2013, 98% of those were for foreign manufacturers.
FDA staff attributed the gap to a lack of resources and said that they expect the percentage of inspections conducted to increase with additional funding from generic manufacturers’ user fees.
The findings from the OIG come as several recalls of generic drugs in recent years have raised concerns about FDA’s oversight of manufacturers. Those recalls and violations include Ranbaxy’s pleading guilty to federal charges that it failed to follow requirements in the manufacturing process and made false statements to FDA.
Risk-Based Inspections
In contrast to the preapproval inspections, the US agency seems to be faring much better with risk-based inspections. For instance, in the first year of risk-based inspections —FY 2013— FDA prioritized at least 283 manufacturers of generic drugs for routine surveillance inspections and conducted inspections at all of them, including 185 foreign sites.
Of the 20 manufacturers against which FDA took action, there were four against which it took multiple enforcement actions and all four were in India, including
- Sentiss Pharma: FDA issued an import alert and a warning letter;
- RPG Life Sciences Limited: FDA issued a warning letter and an import alert that applied to two separate manufacturers owned by this company;
- Hospira Healthcare India: FDA issued one import alert and a warning letter; and
- Wockhardt: FDA issued two warning letters to two different manufacturers owned by this company, as well as two import alerts
The risk-based model incorporates the outcomes of previous surveillance inspections, the type of establishment, and the type of product manufactured, among other factors. And although the FDA has created ways to request manufacturer records in lieu of, or in advance of, an inspection, the OIG found that the agency has not yet used these procedures to request records.
As far as recommendations for the FDA, the OIG calls on the agency to conduct outstanding preapproval inspections; ensure compliance with the requirement for manufacturers of generic drugs to register with FDA; and use its authority to request records in lieu or in advance of an inspection, which could free up staff time during the onsite portion of the inspection. FDA concurred with all three recommendations.