Only about 2 years after its last revision (which was only 5 months after its previous revision), FDA decided this week that MAPP 5240.3, Prioritization of Original ANDAs, Amendments, and Supplements, just wasn’t working. With too many ANDA submissions designated as priority, and thereby entitled to 8 month review, FDA released version 5 of MAPP 5240.3 to try to more efficiently allocate its resources “to areas where priority review is most likely to meaningfully increase generic drug access and ensure fairness to applicants.” As Dr. Choe shared in her statement announcing the revised MAPP:
Under the previous prioritization policy, roughly half of all ANDA submissions were designated as priority submissions, including many products that could not be marketed for several years as a result of blocking patents or exclusivities.
This practice strained the agency’s limited resources and did not support the agency’s goal of ensuring that ANDAs for those drugs with the greatest potential impact on public health are prioritized.
It seems that, despite FDA’s best efforts, the June and November 2017 versions created much more work for the Agency than anticipated. For that reason, FDA has reconfigured its “prioritization factors and procedures.”
While the prioritization factors, generally speaking, have remained largely the same, the approach to granting Priority Review and prioritizing applications containing Paragraph IV certifications has changed a bit. Firstly—and importantly—FDA will no longer prioritize review of an ANDA unless there is “an explicit request from the applicant at the time of submission” that includes the prioritization factors under which the applicant qualifies for priority review. The only products that FDA will consider for priority review without such a request are products on FDA’s Drug Shortage list and products for which there are not more than 3 approved drug products in the Orange Book and for which there are no blocking patents or exclusivities listed for the RLD. Any other type of drug product needs to explicitly state “Priority Review Requested,” include the basis for the request, and provide sufficient supporting documentation for the request. Priority review applies to the entire application—not just an indication or strength that meets the priority review criteria.
Further, while FDA may still grant priority review after an ANDA has been submitted and received, it will not adjust a goal date for a submission even if the product later becomes eligible for priority review. If, for example, an already-submitted ANDA wouldn’t otherwise qualify for priority review but becomes subject to a drug shortage under section 506E of the FDCA at some time during the review process, FDA may still grant priority review, but it will not change the GDUFA goal date to reflect that priority status. This means that once an ANDA receives a goal date, priority review basically just becomes expedited review, in which FDA will try to act on the ANDA as soon as possible but makes no actual commitment.
With respect to prioritization itself, FDA ditched the numerically-ranked Prioritization of Review in favor of “Prioritization Factors” that don’t appear to have a hierarchy. The same categories as version 4 are still subject to priority review:
- Submissions with inadequate generic competition and no blocking patents or expired exclusivities listed in the Orange Book;
- Submissions with paragraph IV certifications and exclusivity considerations;
- Submissions related to drug shortages;
- Submissions subject to special review programs (like the President’s Emergency Plan for AIDS Relief);
- Submissions related to public health emergencies;
- Submissions related to certain government purchasing programs (like the Government-Wide Quality Assurance Program);
- Submissions subject to statutory mandates or other legal requirements;
- Supplements for public health reasons or supplements in which a delay would impose extraordinary hardship on the applicant (essentially resulting from catastrophic events); and
- Sole source products.
Only the considerations for Paragraph IV filers and ANDAs blocked by exclusivity appear to have actually changed.
Previously, FDA prioritized ANDAs containing paragraph IV certifications even if the ANDA would be blocked from marketing for years due to patents, 30-month stays, or exclusivity. The revised ANDA limits priority review only to submissions ‘that will be ready for final approval at or before the goal date for that submission” and are from first-filers, from applicants blocked by a first-filer whose 180-day exclusivity has been triggered, or seek approval of a drug with limited competition (fewer than four therapeutically equivalent drug products listed in the Orange Book at the time of submission). When approval for a noncomplex generic with limited competition is dependent on expiration of a patent or NDA exclusivity, the application will receive priority review if submitted between 24 and 36 months prior to expiration of the last applicable patent or exclusivity period; for complex products, priority is given to these applications submitted between 36 and 48 months prior to expiration of the last-expiring patent or exclusivity.
Importantly, FDA is now requiring documentation that the application will be eligible for final approval at or before the goal date for that submission. For some of these factors, like a drug shortage, submitting this documentation is theoretically easy. Or if you have tentative approval but are blocked by a first-filer’s 180-day exclusivity, documentation that the 180-day exclusivity period has started to run can be submitted without much challenge. But for others—particularly paragraph IV filers—it presents a procedural challenge to get a priority review goal date. Paragraph IV filers must wait to provide notice to the RLD sponsor until FDA receives its ANDA. Once the ANDA filer provides its notice, the RLD sponsor has 45 days to sue the ANDA sponsor. If the RLD sponsor doesn’t sue, then it will be easy to provide documentation that the product will be eligible for approval at goal date, but that can’t happen until at least 100 days after ANDA submission (60 days for FDA to “receive” the ANDA and 45 days to wait to see if the RLD holder will sue). But FDA won’t assign a priority review goal date without that documentation. So, presumably, FDA will have already assigned a non-priority review date to that ANDA upon receipt. And even though it now meets the criteria for priority review, FDA won’t amend an already-assigned goal date and will only promise its best efforts to review quickly (expedited review). And what about ANDAs for products with limited competition but will be blocked by unapproved first-filers. How do those applicants show that they’ll be ready for approval at goal date? Especially when FDA won’t make a determination about 180-day exclusivity forfeiture until another ANDA applicant is ready for approval. And if you’re a first-filer subject to a 30-month stay, the revised MAPP means that you cannot get a priority review goal date because you won’t’ become eligible for priority review until the relevant litigation has been settled, dismissed, or completed. For some, especially those going through an entire trial, it may not matter, but for those who settle quickly, ineligibility for a priority review date could delay market entry because the ANDA sponsor couldn’t provide documentation of a settlement before litigation even commenced.
Additionally, even though it’s implicit that the documentation FDA now requires to demonstrate that an application will be ready for final approval at the goal date is specific to applications subject to blocking patents or exclusivities, the MAPP could be interpreted to require documentation that the ANDA itself is robust enough for approval at the goal date. If FDA decides for some reason that such documentation is needed, priority review assignment could become very subjective. And even if FDA does not apply the policy this way, it is policy that FDA will not accelerate a goal date once an initial date is granted means that a lot of applicants are only entitled to vague promises of expedited review even if the ANDA meets the requirements for priority review. Obviously, FDA is still working out some kinks in its priority review process. Hopefully, the fifth time is the charm, but it remains to be seen how well this new documentation requirement will be enforced.