The GAO issued a 30-page report describing progress made by FDA in the inspection of generic drug firms. This report was prepared at the request of Congress based on concerns about the “safety and quality of generic drugs produced by foreign manufacturers.” The data in this report cover the period 2011 – 2013. The purpose of the report is to determine: 1) the extent to which FDA conducts preapproval inspections of domestic and generic firms and 2) progress FDA has made in implementation of FDASIA requirements to “achieve parity” in the inspection of foreign and domestic generic drug manufacturers (section 705), register manufacturers of generic drugs (section 701 and 702) and utilize their ability to request documents in advance or in lieu of an on-site inspection (section 706).
The report states that “FDA did not begin collecting until FY2013 the data as to which drug manufacturers are involved in producing generic drugs.” This limits the scope of the data available for analysis. Tables 1 through 4 provide specific data regarding inspections of generic manufacturers between FY2011 and FY2013. As FDA continues to collect data on this topic this will allow a better understanding of the progress that appears to have been made in the inspection of foreign generic drug manufacturers. Appendix A identifies the sources of data used to prepare the report. Appendix B provides FDA’s response to the report.
- In 2013 FDA reports they conducted inspections of all generic manufacturers that it identified as high risk.
- FDA has made progress in ensuring parity between domestic inspections and those conducted OUS. This is particularly important because only 27% of generic drug manufacturers are located in the US. Most are located in Asia (41%) and Europe (26%). FDA inspected 43% of generic manufacturers located in the US, 21% of those located in Europe and 31% of those located in Asia during FY2013. (see table 4 in the report)
- Many PAIs of foreign manufacturers were coupled with a general GMP inspection for other products. This minimizes travel cost and permits more efficient use of limited inspection resources. Twenty-six routine surveillance inspections were classified as Official Action Indicated (OAI) and FDA look official action against 20 of these manufacturers. Four of the manufacturers, all located in India, received multiple actions including warning letters, and import alerts. The four located in India include Sentiss Pharma, RPG Life Sciences Limited, Hospira Healthcare India and Wockhardt Limited (HERE and HERE). Import alerts were also put in place for each of these firms.
- Although FDA has developed policies and guidance, they have not yet implemented requests for documents either in advance of or in lieu of inspections according to this report. The draft guidance on submission of “Quality Metrics” is planned to publish this year, with implementation to be phased in after the guidance is finalized. FDA has co-chaired several public meetings with stakeholders. This guidance will specify the metrics that all firms must submit periodically to FDA. MHRA is also requesting quality system information prior to pharmaceutical inspections as a way to risk-rank and prioritize inspections. In both cases, the information will be provided by all pharmaceutical manufacturers, not just generic drug firms.
- Conduct Pre-Approval inspections that are outstanding. These were backlogged at the end of FY2013. While it is important to ensure that the supply of generic drugs to the US is safe and effective, it is also import to ensure timely approvals which require both review of applications and successful PAIs. FDASIA provides additional funds to ensure timely completion of both activities.
- Continue to work to ensure that generic firms are compliant with the requirements to register with FDA. Warning letters have been issued in the past two years for “failure to register” and the GAO report endorses continued compliance actions. FDA should ensure that all firms are identified and registered, and that FDA has a complete picture of the location of all generic drug manufacturers for inspection planning. GAO suggests that FDA cross check the manufacturers identified in ANDAs and those identified in “other lists of known generic manufacturers” to ensure completeness.
- FDA should work to implement the policies and procedures that permit them to request information in advance or in lieu of an inspection “as a potential way of reducing costs and enhancing flexibility in conducting inspections.” This authority was granted in section 706 of FDASIA.
Note that these data include only FY2011 – FY2013 with the exception of one of the warning letters issued to Wockhardt Limited that was issued in early FY2014. After that time, FDA continued to increase the number of compliance actions taken against manufacturers outside the US. A previous blog entry, HERE, addresses warning letter enforcement actions taken in FY2014 and at the halfway point in FY2015, including the number of actions taken against firms in the US and outside the US. For those who want a more broad picture of compliance actions, the blog entry HERE addresses the period between 2009 and 2014, though this blog does not separate actions regarding the countries in which the sites were located.
2015 COPYRIGHT Unger Consulting Inc., All Rights Reserved. A version of this article was published in the subscription based GMP Regulatory Intelligence Newsletter for which I write content. See HERE.