FDA issued a draft guidance on March 14, 2016 explaining how the agency proposes to implement the provisions under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) for moving protein products currently approved under the drug statute (section 505 of the Food, Drug and Cosmetic Act) to the biologics system (section 351 of the Public Health Service Act). Essentially, the BPCIA requires that as of March 23, 2020, all new drug applications (NDAs) and abbreviated new drug applications (ANDAs) for protein products will be “deemed to be a license” under section 351 of the Public Health Service Act (PHS Act). The draft guidance is the first time FDA has issued an interpretation of the “deemed to be a license” provision.

The most significant aspect of the draft guidance is the position FDA takes on exclusivity and patents for this group of products (which we refer to as “transition products”). The draft guidance also addresses the situation in which a drug application for a transition product may be pending at FDA as of the March 23, 2020, “deemed to be a license” date. Examples of protein products that FDA notes as being subject to the transition provisions are: insulin, hyaluronidase, human growth hormone or somatropin, desirudin, pancrelipase, pegvisomant and thyrotropin alfa products.

The key to FDA’s interpretation of the provision is that as of the March 23, 2020, transition date, any approved drug applications for products that meet the definition of a biological product “will no longer exist” as NDAs or ANDAs. Draft Guidance at 5. Instead, they will immediately be replaced by approved biologics license applications (BLAs). Importantly, FDA does not take a position in the draft guidance on how it will determine whether an approved NDA will be deemed to be a 351(a) biologic or a 351(k) biosimilar, which has significant implications for protein products approved under 505(b)(2) NDAs. Similarly, it might be presumed that ANDA products would be deemed to be 351(k) biosimilars, but the draft guidance is silent on that issue as well.

Second, FDA emphasizes that the statutory transition provision only accounts for approved drug applications. FDA reads this to mean that any NDA or ANDA for a biological product that is either pending or tentatively approved as of March 23, 2020, will effectively be deemed withdrawn. Draft Guidance at 5-6. The sponsor would have to resubmit the application under 351(a) or 351(k), potentially imposing a disruption for the sponsor. Draft Guidance at 8-9. Again, this may be quite significant for 505(b)(2) NDAs or ANDAs that are submitted about one to two years before the transition date, and which do not receive final approval before the March 23, 2020, deadline (e.g., because the review is still pending or because final approval is blocked by another sponsor’s exclusivity or by a 30-month litigation stay).

FDA notes that one way around this problem for 505(b)(2) sponsors is to submit an application for a product as a 351(a) application during the transition period, which is permitted under the statute. However, it would require a 505(b)(2) applicant to modify its development program to meet the requirements of a full BLA, something which FDA suggests in the draft guidance but which may in fact not be practical for most sponsors. See Draft Guidance at 8. Alternatively, the 505(b)(2) applicant could defer its application until after the transition date, and file it as a 351(k) application, provided it includes the data FDA would expect to see in a 351(k) application. Draft Guidance at 9 Note that unlike a 351(a) application, a 351(k) application could not be submitted prior to the transition date because such applications must reference an approved BLA.

With respect to Orange Book listings – including patents and exclusivities for these products – the listings and the exclusivities will be terminated as of the transition date, except for orphan drug exclusivity. Draft Guidance at 6. This means that any existing Hatch-Waxman exclusivity (3 year new use exclusivity or 5 year new chemical entity exclusivity), and any remaining 30-month stay time, will immediately be extinguished and, in FDA’s view, forever lost. The only exclusivity that will survive is 7-year orphan drug exclusivity (plus any pediatric exclusivity that attaches to the orphan exclusivity), because that exclusivity is by law capable of blocking approval of BLAs as well as NDAs and ANDAs.

Even more, FDA makes clear in the draft guidance that it does not believe a “deemed licensed” transition product is entitled to receive any amount of the 12-year exclusivity period allowed under section 351 for reference biological products. Draft Guidance at 6. FDA bases this conclusion on two points. First, the agency notes that 12-year exclusivity is only available for a product that is “first licensed” under section 351(a). The agency states – as if it were self-evident – that an application “deemed” to be licensed under section 351(a) for the first time is not “first licensed” under 351(a). Second, the agency claims that there is nothing in the BPCIA to suggest that Congress intended to award 12-year exclusivity to biological products previously approved as drugs, “some of which were approved decades ago.” Draft Guidance at 7. However, there is also nothing apparent in the statute indicating that Congress intended to deny exclusivity to such products. Moreover, if a new sponsor of a previously approved transition product were to obtain approval of its own version of the product under section 351(a), that product would be protected by 12-year exclusivity, even if a prior version of the product had been approved “decades ago.”

Comments to draft guidances are generally submitted within 60 days of publication of the guidance, or May 13, 2016, in this instance. See Docket FDA-2015-D-4750.