US Rep. Edward Markey readies justification for expanded FDA regulation of compounding pharmacies

News reports over the past month fill in a grim picture of the poor manufacturing practices at New England Compounding Center (NECC; Framingham, MA), the pharmacy at the center of the expanding scandal over contaminated dosages of a steroid, methylprednisolone acetate, that has now caused 25 deaths and 314 cases of fungal meningitis, among over 17,000 units of the drug that have been shipped nationally during the past half-year. While FDA and Massachusetts authorities continue to investigate the now-shuttered plant, Rep. Edward Markey (D-MA) has issued a report on FDA efforts, the constraints it operates under in litigation with pharmacy associations, and the “lax” enforcement of most state boards of pharmacy. Earlier in the month, Markey indicated his intent to propose new legislation to address this regulatory impasse, although the bill has not yet been introduced.

The Markey report, “Compounding Pharmacies, Compounding Risks,” documents 23 deaths and at least 86 serious illnesses since June 2001 involving compounding pharmacies nationally (these do not include the recent NECC case). A 1997 federal law was overturned, partially, in subsequent litigation that had carried through to 2008, after which FDA conceded most enforcement responsibility to state boards of pharmacy. But, based on a search of publicly available documents at these boards, Markey’s investigators found that they “do not, as a general rule, appear to undertake enforcement actions that relate to the safety or scopy of compounding pharmacies,” and that “it is impossible to conclude … that the safety of pharmacy compounding activities has been or can be sufficiently assured” through the boards. While FDA has issued warning letters to more than 50 compounding facilities in 34 states between 2003 and March 2012, only six states have taken enforcement actions over that time period.

Coincidentally, an industry publication, Pharmacy Purchasing and Products (www.ppmag.com; registration required) published in its October issue a second annual survey of compliance practices with the USP General Chapter <797>, which is the usual reference to proper procedures for compounding sterile preparations (CSPs). <797> is up for revision in 2013 under the USP guidance development process. The survey, which solicited voluntary responses (which ultimately came mostly from hospital pharmacies), paints a picture of gradual improvement in compliance practices—but one that is far from universally adhered. Overall, respondents reported an average 77.7% level of compliance. The most common shortcomings were in performing environmental sampling programs (within the working space of the compounding area) and then developing corrective actions when deficiencies were found. Respondents also noted that “financial/budgetary restrictions” were the most common reason for less-than-complete compliance.

It’s hard to say how that 77.7% figure matches up with actual performance industry-wide, since the survey is not a representative one. Still, a sense that compliance is achieved in roughly only three out of four instances—especially at hospital pharmacies where a higher level of oversight might be expected&mdash;is a shockingly low expectation. Not only are compounding pharmacies regulated by different means than manufacturers, but they also appear to be held to a lower standard of performance.