Improving the Quality of Compounded Sterile Drug Products: A Historical Perspective

Abstract

The term compounding generally refers to the practice of combining, mixing, or altering ingredients of a drug product to create a medication tailored to the needs of an individual patient. Compounding has long been a common activity within the practice of pharmacy. The scope of pharmacy compounding includes the compounding of sterile products, a practice that is especially prevalent within hospitals, home infusion pharmacies, and, more recently, outsourced compounding facilities. Reports of patient morbidity and mortality associated with compounded products have led many over the years, including the US Food and Drug Administration (FDA), to call for more stringent federal oversight of pharmacy compounding to ensure patient safety. A tipping point was reached in 2012 with the emergence of a multistate outbreak of fungal meningitis and other infections in patients who received contaminated steroid injections compounded by the New England Compounding Center in Framingham, Massachusetts. This article describes the history of the practice and regulation of pharmacy compounding, culminating in the passage by Congress of the Compounding Quality Act of 2014.

Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors

“…Interestingly, there was a concurrent increase in the need for hospital pharmacy compounding during the same period; largely due to the advent of chemotherapy, TPN, and cardiac surgery which necessitated the administration of complex cardioplegic regimens. By the 1980s, these advanced therapeutics began to spill into the outpatient setting, generating a novel home infusion industry for treatments such as TPN, antibiotics, and chemotherapeutics [ 29 ]. As a result, the 1990s and 2000s yielded further diversification within the compounding industry as pharmacies began to compound in bulk.…”

“…The inspiration for this article is a well-documented history of medication errors attributable to pharmaceutical compounding, for which a lack of regulatory oversight persists as a common thread [ 3 , 29 , 32 , 33 ]. The most lethal and infamous of these cases occurred in 2012, when an outbreak of fungal meningitis occurred amongst patients who had received epidural spinal injections.…”

“…However, because compounders traditionally produced drugs in response to individual prescriptions and on a much smaller scale than conventional drug manufacturers, pharmaceutical compounding developed and remained under the regulatory purview of individual state boards of pharmacy [ 32 , 40 ]. Towards the end of the twentieth century, pharmacies began bulk compounding in response to (1) the home infusion industry and (2) hospitals’ financial interest in outsourcing compounding from their inpatient pharmacies to the outpatient setting [ 29 ]. Concerned that bulk compounders were self-classifying as pharmacies to avoid the rigorous federal oversight required of drug manufacturers under the FDCA, Congress passed the 1997 Food and Drug Administration Modernization Act (FDAMA) [ 40 ].…”

“…This development was brought about by expanding home infusion programs, the more frequent outsourcing of hospital compounding to the outpatient setting, and the rise of hormone replacement therapy. Large volume compounding blurs the line between traditional compounding which has state-based regulatory oversight, and the mass manufacture of pharmaceuticals which falls under wellestablished federal FDA regulations [29][30][31].…”

“…In 2002, a narrowly divided US Supreme Court ruled in Thompson v. Western States Medical Center that the FDAMA advertising prohibition was unconstitutional on First Amendment free speech grounds [42]. The ensuing regulatory confusion is well described in the literature, and the details are beyond the scope of this review [3,28,29,31,32,40]. For reference, a summary of the relevant legislation and litigation is provided in Fig.…”