On the second day of the first annual 2018 GRx+Biosims Meeting in Baltimore, MD held from September 5-7, 2018, Kurt Karst, JD and Mark Schwartz, JD (Directors, Hyman, Phelps & McNamara, P.C) provided a very informative overview of cGMP trends and emerging legal issues concerning GDUFA and FDARA. The on-going modernization of the generic drug approval process has presented industry with new legal considerations. The session examined the recent statutory change under GDUFA II and FDARA as well as the legal issues that may arise during FDA inspections, specifically concerning data integrity issues.
Mark Schwartz discussed FDA’s main-focus areas for inspections: data integrity, rudimentary cGMPs, supply chain and sterility assurance. These issues not only affect manufacturers but present challenges for the entire supply chain. As industry knows, Warning Letters are at a historic high and the expectation is when the final 2018 tally is in, the number of Warning Letters issue will exceed those for 2017. FDA’s “regulatory spring board” is the basics, such as Part 11, Part 210, Part 211 and FDA’s 2016 draft guidance on data integrity. The bottom line is this – companies need to foster a culture of compliance and keep in mind that if it’s not documented, it didn’t happen!
Kurt Karst continued the discussion with an overview of priority vs. expedited review, Competitive Generic Therapy (CGT) designations and the current administration’s plans to change the 180-day exclusivity provisions. The priority review, as described in MaPP 5240.3 and FDARA, specifies a shorter goal date from the standard review. This constitutes an 8 month review for priority review with Pre-Facility Correspondence (PFC). Expedited review, if granted, does not afford an applicant a shorter goal date; this date is aspirational. FDA’s MaPP 5240.3 pulls these provisions together and should be followed when considering a regulatory filing strategy for a product.
Competitive Generic Therapy (CGT) designation is a new provision under FDARA that added section 506h to the FD&C Act. Firms must remember to request a CGT designation prior to or concurrently with an ANDA submission. If requested subsequently to ANDA submission, FDA will deny the request. However, there is one exception. A CGT designation can be requested upon a re-submission of an ANDA resulting from a refuse to file action. In addition, ANDA sponsors need to keep in mind that a CGT designation can be withdrawn by FDA if the approval landscape changes, particularly if you submit your CGT request too early.
Further, the 180-day CGT exclusivity works differently than the exclusivity granted to PIV first filers. The CGT exclusivity only triggers when the first approved CGT applicant initiates commercial marketing. CGT exclusivity is prospective and will not block approvals until it is triggered. It is highly recommended to commence marketing a CGT product as soon as possible after approval and notify FDA immediately of first commercial marketing to reap the full benefits of the 180-day exclusivity. Firms must remember that CGT exclusivity can be forfeited if the product is not marketed within 75 days of ANDA approval.
The final point of discussion was the Administration’s current plans to change the current PIV 180-day exclusivity. The currently proposed Fiscal Year 2019 budget includes language to prevent “parked exclusivity” to increase generic competition. While there is currently no legislative language, it is proposed that if a First-to-File ANDA cannot be approved due to deficiencies in the application, a Tentative Approval of a subsequent applicant would trigger the First Applicant’s 180-day exclusivity.
The take home message from this session was that even with the passage of FDARA, implementation of GUDFA II, and FDA’s issuance of several related guidance documents, it is clear there are still legal and regulatory challenges that loom large for industry.