One of the closing sessions at the recent Association for Accessible Medicine’s GRx + Biosimilars conference covered Post-Approval Changes to Complex Generic Drugs.  The session included presentations from multiple individuals from FDA, as well as from industry, to provide a breadth of perspective on this subject. As one would expect, the session did offer both success stories and areas for improvement.

The statistics presented by FDA for the five years of GDUFA II showed that a little over 74% of Prior Approval Supplements (PAS) and almost 94% of Changes-Being-Effected (CBE)-30 supplements were approved in the first cycle.  Even though I suspect that most of these statistics are for non-complex products, these statistics are still rather remarkable, considering the fact that, not that many years prior, one of the primary pain points for industry was predictable actions for supplements, especially PASs.   This does show that, when properly resourced and oriented to concerns from Industry, FDA is able to make appropriate changes to review processes and dedicate resources where they are most needed.

However, this session was meant to cover post-approval changes to complex generic drugs and the panelists from industry made a compelling argument that there is a desperate need for multiple new guidance documents as well as updates to older guidances for non-complex products. One slide pointed out that four of the eight guidances related to Post-Approval Changes date from the 1990’s and need to be refreshed, while another observation from an industry panelist pointed to contradictions between the existing guidances. In addition, despite transdermal delivery systems being a relatively mature dosage form that has been in use for decades, there is no guidance on post-approval changes for this dosage form, leaving Industry to potentially take a more conservative approach than necessary for supplemental changes.  This theme, that lack of guidance leads to overly conservative filings for post-approval changes, was one that each of the industry participants embraced. Moreover, a compelling case was made that the existing methods employed by FDA to seek feedback are not adequate to address changes that may need to be implemented on an urgent basis and that lack of clear guidance can and does lead to manufacturing delays, increased cost, and even drug shortages.

According to FDA’s webpage “Search for FDA Guidance Documents”, just in 2022, FDA published 20 guidances specific to Generics and 10 guidances related to Pharmaceutical Quality.  As one of the FDA panelists pointed out during the session, FDA provides a mechanism for input into guidance development which can be found here. Based on the number of guidances that FDA publishes nowadays, it is clear that FDA has the infrastructure and resources to both update and develop guidance at a fair pace. I think that the FDA participants at this session clearly heard the call from industry, namely that guidance development is necessary for complex generics and updates to existing guidances for non-complex products would also be useful.  If industry truly wants these guidances to be developed and updated, efforts should be coordinated to provide input via FDA’s established procedures to formally orient FDA to industry’s concerns.  After all, industry is funding these efforts, so you might as well get what you want!