T 51: A Comparison of CDRH Review Times of Original PMA Applications for Products Classified as Combination versus Non-Combination
Global Regulatory Affairs Fellow
Rutgers, The State University of New Jersey United States
The objective of this study is to determine if there is a difference in review time and predictability of the CDRH review of combination products versus non-combination products.
The data collected for this study was from publically available information. Sources used included the FDA’s PMA database as well as the FDA’s compiled list of approved devices by year.
Average review time for combination and non-combination products was sorted by each submission fiscal year (FY) and analyzed based on data collected from original PMAs approved between 2011 and 2015. Product outliers with atypically extensive review times were removed from the data sets along with FYs without any combination product submissions (2005 – 2008 FY) as no correlations could be made. Although a downward trend in review time was observed between 2009 and 2011 FYs for combination and non-combination products, combination products took on average ˜109 days longer to review in 2009 (1001 days for combination products versus 892 days for non-combination products). In 2012 FY, average review time for combination products sharply increased relative to non-combination products with ˜999 days and ˜375 days respectively (624 day difference). Despite a slight increase in the average review time of non-combination products in 2013 FY, the review time for these products continued to trend downward between 2013 and 2015 FYs, unlike combination products that illustrated no consistent trend. Upon further analysis of the variability of the overall data between 2009 and 2015 FYs, greater variation in average review time was established for combination products (SD 449.61) in comparison to non-combination products (SD 320.82).
One noteworthy limitation of the study includes the limited number of combination products studied. Since only original PMAs approved between 2011 and 2015 were reviewed, there were a number of products submitted during the 2009 to 2015 FYs that were not incorporated into the data.
*FY=fiscal year (e.g. 2015 FY=October 1st 2014 – September 30th 2015)
The trending decrease in review time of original PMA approvals for non-combination products can partly be explained by the Food and Drug Administration Safety and Innovation Act (FDASIA), which was signed into law on July 9, 2015. FDASIA reauthorized the Medical Device User Fee Act of 2012 (MDUFA III) that took effect on October 1, 2012.The intent of MDUFA III was to increase the user fees collected by FDA in order to decrease the review time of products reviewed by Center of Devices and Radiological Health (CDRH). This legislation authorized FDA to collect $595 million in User Fees over five years leading to an additional 200 FTEs in CDRH. The commitment letter provided several process improvements for PMA review, including an improved pre-submission process, submission acceptance criteria, interactive review and guidance document development.
Meanwhile, the unpredictability of combination product review as demonstrated by the larger standard deviation compared to non-combination products as well as the non-linear average review time by submission FY, can be attributed to MDUFA shortcomings. In MDUFA III, no additional goals were added specifically for combination products, only an analysis of the impact of combination products on the review process was added. Moreover, the cross-center review of combination products is complicated and the process is not clearly defined. Based upon this data, it can be concluded that by adding combination product-specific goals in the next MDUFA authorization, average review time of combination products will likely decrease and action dates will become more predictable.
Additional author: Jake Rogala, Operations Manager, US Regulatory Affairs, Bayer HealthCare Pharmaceuticals