The Food and Drug Administration is reviewing the results of tests conducted by the manufacturer of Makena, the approved version of a compounded product for preventing preterm births, which the company said has identified some problems with other compounded versions.
Makena, a compounded formulation of 17-alpha hydroxyprogesterone caproate (17P), was approved by the FDA in February 2011, providing for the first time an approved version of product that had previously been compounded in local pharmacies and used to reduce the risk of certain preterm births in patients who had already experienced a prior preterm birth.
The Nov. 8 FDA statement says that Makena manufacturer K-V Pharmaceutical provided information about tests that identified “variability” in the purity and potency of bulk hydroxyprogesterone caproate and compounded products that use it as the active ingredient. The FDA “has not validated or otherwise confirmed” these results, but “has carefully reviewed the data and will conduct an onsite review of the laboratory analyses.” In addition, the FDA has begun “its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk [active pharmaceutical ingredients] used to make them,” a process that is ongoing, according to the statement.
“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 [active pharmaceutical ingredients] used by its manufacturer, proposed manufacturing processes, and the firm's adherence to current good manufacturing practice,” the statement said, adding: “Therefore, as with other approved drugs, greater assurance of safety and effectiveness is generally provided by the approved product than by a compounded product.”
Soon after Makena was approved, the initial enthusiasm over the availability of a more reliable product was tempered once it became clear that Makena would cost much more than the previously available products, eliciting concerns that this would affect access to the product among poor women, who are considered at greatest risk of preterm labor.
Despite the availability of an approved product, the FDA released a statement in March that said, “in order to support access to this important drug,” the agency had no plans to take enforcement actions against pharmacies when there was a valid prescription for hydroxyprogesterone caproate for an individual patient, unless there were problems with the quality or safety of the product, or they were not being compounded in accordance with the appropriate standards for compounding sterile products. The FDA issued that statement after learning that the company had sent letters to pharmacists saying that the agency would no longer exercise such discretion, according to the current statement.