Quality investigation of hydroxyprogesterone caproate active pharmaceutical ingredient and injection

Abstract

The purpose of this study was to investigate the quality of hydroxyprogesterone caproate (HPC) active pharmaceutical ingredient (API) sources that may be used by compounding pharmacies, compared to the FDA-approved source of the API; and to investigate the quality of HPC injection samples obtained from compounding pharmacies in the US, compared to the FDA-approved product (Makena®). Samples of API were obtained from every source confirmed to be an original manufacturer of the drug for human use, which were all companies in China that were not registered with FDA. Eight of the ten API samples (80%) did not meet the impurity specifications required by FDA for the API used in the approved product. One API sample was found to not be HPC at all; additional laboratory testing showed that it was glucose. Thirty samples of HPC injection obtained from com pounding pharmacies throughout the US were also tested, and eight of these samples (27%) failed to meet the potency requirement listed in the USP monograph for HPC injection and/or the HPLC assay. Sixteen of the thirty injection samples (53%) exceeded the impurity limit setforthe FDA-approved drug product. These results confirm the inconsistency of compounded HPC Injections and suggest that the risk-benefit ratio of using an unapproved compounded preparation, when an FDA-approved drug product is available, is not favorable.

Pharmacy Compounding Primer for Physicians

“…[7,12–17] Because federal surveillance requirements do not exist for compounded drugs, the extent of quality and safety problems is unknown. [18]…”

“…One additional sample of API labelled as hydroxyprogesterone caproate did not contain any active ingredient and was subsequently found to contain only glucose. [17]…”

Quality assessment of compounded 17-hydroxyprogesterone caproate

“…A recent report by Chollet and Jozwiakowski from the Ther-Rx Corporation which markets Makena suggested that compounded 17-OHPC poses a risk as many unspecified impurities were identified in the active pharmaceutical ingredients (APIs) used to compound 17-OHPC and that the concentration of the compounded product was commonly not in the range of accepted potency 7 . The FDA conducted their own investigation and could not identify any major safety problems for compounded 17-OHPC.…”

“…7,8 Our purpose was to obtain compounded 17-OHPC formulations from compounding pharmacies throughout the United States and to analyze the product for potency (concentration), impurities, sterility and pyrogen status. Sterility and pyrogen status assessments of compounded 17-OHPC were not provided in the reports of the FDA or of Chollet and Jozwiakowski.…”

Stability of hydroxyprogesterone caproate alone and in a compounded pharmaceutical product

“…2 These investigators suggested that both the active pharmaceutical ingredient and compounded hydroxyprogesterone caproate products contained impurities that exceeded the bounds defined in the new drug application (NDA) submitted to FDA for hydroxyprogesterone caproate and claimed that 16% of analyzed samples of the compounded products containing hydroxyprogesterone caproate had impurities out of the NDA-specified range. However, it is unclear if deterioration of hydroxyprogesterone caproate contributed to these observations.…”