Limited Enforcement

This week, KV Pharmaceuticals filed a lawsuit against FDA to force the agency to stop compounded versions of their synthetic progesterone drug, Makena (hydroxyprogesterone caproate), from being produced. Makena was granted approval in February 2011 to reduce the risk of premature birth, and was granted seven years of market exclusivity under the Orphan Drug Act. At approval, KV set the price of Makena at $1500 per dose, but before Makena was approved, physicians had been able to prescribe synthetic progesterone prepared by compounding pharmacies at a cost of $10–$20 per dose. The resulting outcry over the huge price tag prompted KV to drop the price to $690 per dose and implement a patient assistance plan, but apparently the company is still encountering difficulty in persuading prescribers and payers that the GMP product is worth the considerable upcharge.

When the price of $1500 per dose was originally set, FDA took the unusual position of declining to specifically enforce Makena’s exclusivity. In a press release issued in March 2011 the agency stated, “In order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products.”

KV’s response was to try to convince FDA that compounded versions of the drug presented a safety risk, but without success. FDA acquired 16 samples of hydroxyprogesterone caproate API and 13 compounded versions of hydroxyprogesterone caproate and tested them for purity and potency. Although some deviations from the purity and potency standards specified in the Makena NDA were found, no major safety issues were identified. After the analysis, FDA clarified that it makes its enforcement decisions about compounded products on a case-by-case basis after considering the particular facts at issue, and that compounding of any product, including hydroxyprogesterone caproate should not exceed the scope of traditional pharmacy compounding. In other words, the agency declined to issue a blanket ban on compounding, but also left the door open for enforcement if warranted by safety concerns or if pharmacies were found to be producing drugs in bulk.

Risk-based, limited enforcement makes sense in a resource-constrained environment. Chasing down pharmacies compounding hydroxyprogesterone caproate requires resources that could be better spent investigating more serious safety breaches. This type of reality is not to KV Pharma’s liking, hence the lawsuit. If KV Pharma wins its suit, one company, in essence, would be dictating enforcement priorities for the agency.