We appreciate the important clinical contributions Caritis et al have made in prematurity research. Their article regarding the quality and stability of compounded formulations of 17-alpha hydroxyprogesterone caproate (HPC) addresses an important and timely issue, as pharmacy compounding is currently a topic of active debate among health care professionals and government regulators. We believe the perspective of pharmaceutical researchers may also be relevant to American Journal of Obstetrics and Gynecology readers.

The testing of 6 formulations specially prepared by a single pharmacy for 1 research study is not representative of HPC compounding in general, due to differences in processes, facilities, and personnel training. Recalls of numerous pharmacy-compounded sterile preparations, including HPC, have recently occurred when quality issues such as microbial contamination or unidentified particulate matter were found in some compounded drugs. These occurrences demonstrate that compounding sterile drugs in the absence of Good Manufacturing Practice controls and Food and Drug Administration (FDA) oversight may pose significant risk to patients.

The primary conclusion of this study was that these compounded HPC formulations were stable over the 19-week study period. However, the test procedure used to obtain the data was only capable of detecting relatively large (eg, >10%) changes in potency. By contrast, the precision and accuracy requirements for stability-indicating test procedures used for FDA-approved products are considerably more stringent; such methods must be capable of distinguishing smaller (eg, 2%) potency changes. FDA-approved drugs must also be tested for impurities, which are more sensitive indicators of stability than potency, and essential to confirm that harmful contaminants are not present in the formulation; yet no purity results were reported for the compounded preparations. Endotoxins were found in some vials of compounded product at concentrations the authors characterized as below the pyrogenic level thought to be indicative of contamination. The presence of detectable endotoxins at any level is an issue of concern for all sterile injectable drugs, given the recent contamination issues in improperly compounded drugs.

The FDA statement referenced in the article, which said that the FDA would not take enforcement action against pharmacies compounding HPC, was issued in March 2011. FDA superseded that statement in June 2012, announcing the agency’s return to normal enforcement policies regarding compounding of HPC, and specifying that the FDA-approved drug (Makena; Ther-Rx Corporation, Chesterfield, MO) should used if it is medically appropriate for the patient. The long-standing position of the FDA is that FDA-approved drugs provide a greater assurance of safety and efficacy.