FDA approved Makena (hydroxyprogesterone caproate) in February 2011 for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth. For many years before Makena was approved, a version of the active ingredient of Makena has been available to patients whose physicians requested the drug from a pharmacist who compounded the drug. In March 2011, after learning that the owner of Makena, K-V Pharmaceuticals, had sent letters to pharmacists indicating that FDA will no longer exercise enforcement discretion with regard to compounded versions of Makena, FDA issued a statement about compounded hydroxyprogesterone caproate to clarify the agency's enforcement priorities. In the March 2011 statement, FDA explained that the agency prioritizes enforcement actions related to compounded drugs using a risk-based approach, giving the highest enforcement priority to pharmacies that compound products that are causing harm or that amount to health fraud. The agency also 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. As always, FDA may at any time revisit a decision to exercise enforcement discretion.
In October 2011, FDA received information from K-V Pharmaceuticals regarding the potency and purity of samples of bulk hydroxyprogesterone caproate active pharmaceutical ingredients (APIs) and compounded hydroxyprogesterone caproate products. According to the analysis of this information provided by K-V, there is variability in the purity and potency of both the bulk APIs and compounded hydroxyprogesterone caproate products that were tested. Although FDA has not validated or otherwise confirmed the analyses provided by K-V, FDA has carefully reviewed the data and will conduct an on-site review of the laboratory analyses.
FDA has begun its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk APIs used to make them. That process is ongoing. In the meantime, we remind physicians and patients that before approving the Makena new drug application, FDA reviewed manufacturing information, such as the source of the API used by its manufacturer, proposed manufacturing processes, and the firm's adherence to current good manufacturing practice. Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product.