In December 2018, the FDA released a Draft Guidance entitled, “Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act.”
According to the document, the FDA intends to promulgate new regulations pertaining to compounding pharmacies that register as “outsourcing facilities” under Section 503B of the FD&C Act. Since 503B pharmacies are currently subject to standard pharmaceutical cGMPs codified in 21 CFR Parts 210 and 211, this guidance attempts to clarify what sections of 210 and 211 the FDA will apply to outsourcing facilities prior to implementing the new regulations.
Outsourcing facilities are permitted under law to compound and distribute certain drugs without receiving patient-specific prescriptions. They often produce large batches of pharmaceutical products for use in healthcare facilities when a medical professional is initially treating a patient.
Subsequent to the release of the Guidance, FDA Commissioner Scott Gottlieb, M.D. along with Deputy Commissioner Anna Abram, issued a statement outlining efforts to assure the quality of compounded drugs, including, but not limited to, the new regulations for 503Bs.
The statement reads, “access to compounded products made under appropriate production standards is key to helping mitigate risk and assure quality for patients. In implementing the new law, we’re seeking to strike a balance that helps ensure compounded products are accessible to patients that need them and that they meet appropriate quality standards.” Adding, “we’ll advance other new efforts to promote our oversight in this sector, to make it more feasible for compounding pharmacies to become outsourcing facilities, and for outsourcing facilities to meet provider requests.”
This statement comes on the heels of the FDA’s alliterative, “2018 Compounding Policy Priorities Plan” released in January 2018 outlining the Agency’s intention to increase scrutiny and inspection of compounding pharmacies in response to several recent contamination issues originating at these facilities. The FDA website introduces the Priorities Plan as “an overview of the key priorities (the FDA) will pursue to implement the federal law on compounding and to advance the FDA’s public health mission. (The FDA) must continue to recognize the importance of compounders’ role in providing quality drugs so that patients have access to the medicines they need. We will clarify and appropriately tailor the policies for traditional compounding pharmacies and the outsourcing facilities that may supply a broader market.” The Guidance document is a revision of one released in 2014 and provides clarification on utilizing cGMPs for outsourcing facilities when compounding both sterile and non-sterile drug products.
Areas of focus in the Guidance include:
- Environmental Monitoring – “operations and appropriate written procedures designed to prevent microbial contamination include a well-defined and documented program for environmental monitoring that evaluates the potential routes of microbial contamination of the human drug that could arise from the air, surfaces, process, operation, and personnel practices;“
- Water Quality – “the quality of water produced on-site and used as an ingredient or processing aid must be tested regularly, using validated methods, at the point of use to verify acceptable microbial quality, chemical quality, and endotoxin limits;”
- Quality of Raw Materials – “components (raw materials) that are not approved finished drug products (both active pharmaceutical ingredients (APIs) and inactive ingredients) must be tested to verify identity and evaluated for conformity with appropriate specifications (e.g., USP) and, if necessary and depending on intended use, tested for endotoxin level and bioburden before use in compounding;”
Current regulations require 503B firms to designate a separate quality control unit that provides internal oversight for pharmacy operations and assures compliance with cGMPs. The QC Unit’s responsibilities include qualifying any outside laboratory providing services to the pharmacy.
Coincidently, on February 6, 2019, the FDA issued a consent decree of a permanent injunction banning a Pennsylvania-based compounding pharmacy from operating. Commissioner Gottlieb commented on the injunction, “we continue to see concerning activity when it comes to some compounded drugs, including problems related to the conditions under which compounded sterile medicines are made, which can raise significant risks to patients. (Compounding pharmacies are) an area of intense focus for the FDA. We’re committed to making sure that compounded drugs are made under appropriate production standards.”
FDA oversight of compounding pharmacies increased in 2013 with passage of the Drug Quality and Security Act (DQSA) which brought compounders under the auspices of the Food, Drug and Cosmetic Act (FD&C). After a significant contamination issue at an East Coast compounding pharmacy, the FDA acted to garner more authority over these organizations. DQSA also established the distinction between compounding pharmacies and outsourcing facilities.
It is clear the FDA is serious about continuing to ramp up enforcement of compounding pharmacies and outsourcing facilities. As new regulations become available compounders and their laboratory partners will need to work together to interpret and implement the new requirements.
Link to Draft Guidance here
Link to FDA Announcement here