Note: The opinions expressed in this blog are those of the author and should not be interpreted as the positions or policies of USP or any other organization.
The compendial Sterility Test first appeared in recognizable form in the British Pharmacopeia in 1932 and then in the USP in 1935 as a direct response to a clear need for a recognized test to check for pharmaceutical product sterility. Since this time, the design of the test has remained fundamentally unchanged although there has been refinements in the actual test design ending with its international harmonization in 2003. What we call the “Sterility Test” is more appropriate titled “Sterility Tests” in the compendia as the chapter includes two distinct types of testing, one utilizing membrane filtration and the second a direct transfer of the medicine into recovery media for recovery. The concerns discussed below apply to both test designs. Read more
Scott Sutton, Ph.D.
The Microbiology Network, Inc.
The current fungal meningitis crisis is a tragedy, but one that could have been avoided if clear warning signs had been heeded. To understand the risks we have been running, we need to understand clearly the differences in controls and intents between GMP pharmaceutical manufacture of sterile products and a pharmacy compounding “sterile” products. These differences are reflected in the regulation of pharmaceutical manufacturing by 21 CFR 211 (GMP) vs the regulation of compounding pharmacies by individual states relying on USP <797> “Pharmaceutical Compounding – Sterile Preparations” as the source document. The fundamentally different approaches to preparation of sterile product taken reflects the different purposes – the GMP is designed to ensure a reproducible, stable drug product suitable for interstate commerce and storage, the pharmacist’s preparation is meant for for immediate use, made in small amounts for a specific patient in response to a doctor’s script. This basic difference in intent has led, predictably, to this situation as externally sourced “compounding pharmacies” have begun to manufacture in batch sizes up in the thousands of units for national distribution.
Scott Sutton, Ph.D.
Microbiology Network, Inc.
A compounding pharmacy, New England Compounding Center’s (NECC), released over 13,000 vials of methylprednisolone acetate injection from the Framingham, Massachusetts site. These were distributed across 23 states. As of October 18, 2012, 257 cases of meningitis (and 20 fatalities) have been traced to this medication, and several other compounded mixtures (with enormous batch sizes) have also raised concerns (UPI 2012). Amazingly, this manufacturing operation, or rather, “compounding pharmacy”, existed outside the authority of FDA as it exploited a provision in the law meant to protect hospital pharmacies manufacturing small numbers of specific medications under a doctor’s direct instruction.
Clearly something has gone awry.