With just days remaining until the “Deemed to Be a License” transition takes effect, the FDA issued an unexpected sweeping change to compounding practice. In the FDA’s words:

This transition affects compounding under sections 503A and 503B of the [Federal Food, Drug, and Cosmetic Act] FD&C Act because, beginning on March 23, these transitioning biological products will not be eligible for the exemptions for compounded drugs under sections 503A and 503B of the FD&C Act.

Despite receiving more than 400 public comments from various stakeholders including trade associations, pharmacists, physicians and patients, many urging the FDA to continue to allow this practice, the FDA decided contrarily. In one fell swoop, the FDA has presumably eliminated the compounding of certain drugs that prescribers and patients have relied on for decades.

Takeaways

• According to the FDA, 503A compounding pharmacies and 503B outsourcing facilities will no longer be able to compound drug products approved as new drug applications (NDAs) that the FDA is administratively converting to biologic license applications (BLAs), including human chorionic gonadotropin, hyaluronidase, follicle stimulating hormone (or urofollitropin) and menotropins.
• On March 23, the FDA is removing hyaluronidase from category 1 of the list of substances under FDA’s 503B bulks interim policy.
• 503A compounding pharmacies and 503B outsourcing facilities may be able to mix, dilute or repackage such products under the Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (January 2018) guidance.

Background

The Deemed to Be a License transition has been 10 years in the making, but until today, the FDA has never explained the impact to the compounding industry. The Biologics Price Competition and Innovation (BPCI) Act of 2009 created an abbreviated licensure pathway in the Public Health Service (PHS) Act for biological products demonstrated to be biosimilar to or interchangeable with the FDA-licensed biological reference products. It also amended the definition of biological product, which was again amended on Dec. 20, 2019. In effect, the BPCI Act deemed certain products that meet the definition of biological product to be BLAs, even though the products were approved as NDAs under the FDA drug approval pathway.

The BPCI Act provided a 10-year transition period so that sponsors of biological products could prepare for this administrative conversion of NDAs to BLAs. In assisting sponsors in this transition, the FDA issued numerous guidance documents explaining to sponsors the statutory and regulatory requirements for BLAs that are different from the requirements for NDAs. FDA is even providing enforcement discretion to sponsors for certain BLA requirements, such as labeling, until March 23, 2025. Interestingly, not once in 10 years did the FDA provide any guidance on the applicability or effect of this transition on compounders – until just days before the transition.

The FDA maintains that the BPCI Act established the abbreviated licensure pathway to provide more treatment options, increase access to lifesaving medications and potentially lower healthcare costs through competition. With the unexpected notice to compounders, the FDA will do the opposite: provide fewer treatment options and decrease access to lifesaving medications.

Outsourcing facilities play an important role in mitigating drug shortages. Congress intended this when it passed the Drug Quality and Security Act in 2013. The FDA’s notice to compounders effectively prohibits outsourcing facilities from doing so if any of the transitioned Deemed to Be a License products go on shortage.

Compounders and Outsourcing Facilities

The FDA will use enforcement discretion when certain biological products are mixed, diluted or repackaged in a manner not described in their approved labeling. Beginning on March 23, 2020, biological products subject to licensure under Section 351 of the PHS Act will include deemed BLAs and according to the FDA, deemed BLAs will not be eligible for the exemptions for compounded drugs under section 503A and 503B of the FD&C Act. Deemed BLAs may be mixed, diluted or repackaged following the Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (January 2018) guidance which provides the situations in which the FDA will use enforcement discretion.

Look for an updated 503B bulk category list. The FDA will update category 1 of the list of substances under the FDA’s 503B bulks interim policy when it removes hyaluronidase on March 23. A general update has been long awaited, as the last update was on Oct. 31, 2019.