The Food and Drug Administration (FDA) is slowly issuing multiple guidances for state-licensed community, hospital, and federally licensed outsourcing compounding pharmacies—and raising hackles in doing so. The agency issued three final “interim” guidances in June,1–3 which followed its three draft guidances in April.4–6Those guidances cover issues such as central compounding pharmacies in health systems, ingredients that can be used in compounded drugs, and whether community pharmacies can sell small amounts to physicians without getting individual prescriptions for each dose.
Congress, too, is unhappy with some aspects of the FDA’s regulatory program, which is supposed to be based on the language of the Drug Quality and Security Act (DQSA),7 passed in 2013 in good part because of compromised product sold by the New England Compounding Center that caused a fungal meningitis outbreak resulting in more than 60 deaths and more than 750 cases of infection.8 In response, Congress passed the DQSA, which set up a dual regulatory program called 503A and 503B. The former includes community and hospital pharmacies and limits in some ways who they can sell product to, including within health systems. The 503B program regulates bulk compounders that sell mostly sterile drugs to hospitals in bulk, where no individual prescriptions are required.
The International Association of Compounding Pharmacists (IACP) was in Washington in mid-June for a “fly-in”—where congressional lobbying is done—and convention. Its top officials, in an interview with P&T, made clear their concern particularly with three ongoing trouble spots in the FDA’s regulatory program. The IACP represents mostly community pharmacists, many of them compounding only, but does have some 503B and hospital pharmacists sprinkled among its membership.
The IACP and a broader coalition of stakeholders, including groups such as the American Medical Association, have been heartened by legislation moving through the House that pressures the FDA to explain why it refuses to allow community pharmacies operating under 503A to sell small amounts of bulk doses to physician offices. Cynthia Blankenship, the outside general counsel for the IACP, argues that in House and Senate floor statements made during passage of the DQSA, congressmen and senators made it clear that “office use” was legal. The FDA countered that a physician has to send a patient to the pharmacy with a prescription, and then the patient has to bring the drug back for the doctor to administer it.
The IACP leaders pointed out why, in many instances, that was impossible, particularly when a physician needs to administer the drug while the patient is in his office. The physician could get a bulk supply from a 503B pharmacy. But one bulk manufacturer explained that because of the high cost of meeting the FDA’s 503B safety and manufacturing requirements, it doesn’t pay for him to manufacture many of the dental, pediatric, and ophthalmological drugs that would otherwise be supplied by 503A pharmacies for office use.
Hospitals have a different problem related to draft guidance in April that limits compounding pharmacies in health systems to distributing compounded drugs to facilities within the system only within one mile from the location of that pharmacy. The FDA reasoned that a central pharmacy sending compounded drugs beyond the one-mile limit would, for all intents and purposes, be operating like a 503B pharmacy, but without the federal regulation. The 503B pharmacies are inspected by the FDA based on current good manufacturing practices (cGMPs), which are the same inspection standards used for companies such as Pfizer and Lilly. The DQSA requires the FDA to establish separate inspection standards, less than the cGMPs, for 503B pharmacies. But the agency has not done so.
H. Waid Ray, Associate Corporate Counsel of Baptist Memorial Health Care Corporation, which has locations in Tennessee, Arkansas, and Mississippi, says 10 of its 14 hospitals serve patients in a rural setting, all outside a one-mile radius. “If the guidance is implemented as drafted, Baptist will most likely cease offering oncology and other hazardous medication infusions in its rural hospitals. The patients will then either have to find another care provider, which usually does not exist within the rural community, or travel a significant distance to obtain the infusion at a larger hospital, which may not be a participant in the patient’s health plan.”
Linda McElhiney, PharmD, Compounding Pharmacy Operations Coordinator at Indiana University Health (IUH), which has 16 hospitals, says that her central compounding pharmacy tests all compounded sterile preparations from sterile and nonsterile ingredients, regardless of the batch size. They are all tested by an FDA-registered analytical laboratory for sterility (bacterial and fungal) according to United States Pharmacopeial Convention Test 71 (USP <71>), endotoxins according to USP <85>, and potency (usually high-performance liquid chromatography method) as needed. “IUH has never had a contamination issue with compounded sterile preparations by the compounding pharmacy, and this is a direct result of strict adherence to the USP standards,” she points out. “Compounded sterile products from 503B outsourcing facilities do not guarantee that they are completely safe or sterile either. There are hundreds of recalls every year of FDA-approved products that are contaminated, adulterated, or do not meet the specifications of the drug monograph.”
Given those recalls and the apparent need for more authoritative guidance documents that take into account real-world situations, one hopes the FDA will make some significant changes in its guidance documents when it publishes final versions, which with any luck will happen sooner than later.