Rozenberg and colleagues reported that 17-hydroxyprogesterone caproate (17Pc) (500 mg twice/wk) did not significantly increase time to delivery or improve neonatal outcome when used as maintenance therapy after an episode of preterm labor. We would ask the authors to disclose the source of the drug and to clarify whether there was any testing to assure its quality. This is critical because of questions about the purity and potency of some 17Pc preparations available on the global market.

In a recent report, chemical analysis was performed on 40 samples of 17Pc obtained from various sources throughout the United States, including 10 samples of active pharmaceutical ingredient (API) (the powdered raw ingredient) and 30 samples of compounded drug (API mixed with oil by compounding pharmacies). Of the API samples, 7 were traced to manufacturers in Asia that are not registered with or regulated by the US Food and Drug Administration (FDA); in other cases, the drug had been repackaged by distributors and the manufacturer could not be positively identified. One of the 10 API samples contained only glucose and no progesterone of any kind. Two thirds of the compounded samples failed analytical testing, either because of subpotency or superpotency exceeding US Pharmacopeia standards and/or unknown contaminants exceeding FDA standards.

These findings cast doubt on the results of any studies that used compounded 17Pc unless there was testing of purity and potency, especially studies that found no significant differences between 17Pc and control groups.

For the record, we would like to clarify that the 17Pc used in our recent trials of twin and triplet pregnancies was not a compounded drug but was manufactured according to current Good Manufacturing Practices. The API was made by an FDA-regulated manufacturer with an active FDA Drug Master File and prepared by another FDA-regulated manufacturer as specified in an FDA Investigational New Drug approval. An aliquot from each lot of prepared drug was sent to an independent laboratory to test for potency, purity, and sterility. Concentration was retested annually to assure stability. All 17Pc used for these trials met FDA specifications. Thus, we are confident in our conclusion that prophylactic 17Pc (250 mg weekly) is not effective for prolonging unselected twin and triplet pregnancies.