Summary of Proceedings
The U.S. Food and Drug Administration convened its eleventh intergovernmental working meeting on drug compounding with state government officials on November 1 and 2, 2022. Attendees included officials from state boards of pharmacy and state health departments, representatives from the National Association of Boards of Pharmacy (NABP), and representatives from FDA. The meeting was held virtually.
The purpose of the meeting was to continue discussions about compounding oversight, efforts to support the implementation of the Compounding Quality Act (CQA), and opportunities to protect the public health through federal-state collaboration and regulatory discussions.
Officials from 39 states and the District of Columbia attended the 2022 intergovernmental working meeting on compounding.
FDA previously held intergovernmental working meetings on compounding with state officials and their designated representatives in December 2012, March 2014, March 2015, November 2015, September 2016, September 2017, September 2018, October 2019, October 2020, and October 2021. FDA initiated these meetings after the 2012 fungal meningitis outbreak associated with contaminated compounded drugs, which led to deaths and serious illnesses across the country.
State & FDA Policy Updates
The intergovernmental meeting began with a discussion of FDA’s recent policy and rulemaking updates, including
- List of Bulk Drug Substances for Which There is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act (January 2022)
- June 2022 Pharmacy Compounding Advisory Committee Meeting
- Compounding Memorandum of Understanding Under Section 503A
FDA described in detail the process for identifying and adding bulk drug substances for which there is a clinical need to the list contemplated in section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA). FDA reviewed a recent Federal Register Notice, which proposes to include on the list quinacrine hydrochloride, and proposes not to include on the list bromfenac sodium, mitomycin-C, nepafenac, and hydroxychloroquine sulfate. FDA also provided an overview of the June 2022 Pharmacy Compounding Advisory Committee meeting, as well as an update on the current status of the Compounding Memorandum of Understanding Under Section 503A, and an overview of the recently finalized guidance Compounding Animal Drugs from Bulk Drug Substances (GFI #256).
FDA presented an overview of Section 105 of the Drug Quality and Security Act (DQSA), which addresses enhanced communication between FDA and the State Boards of Pharmacy. Pursuant to section 105 FDA may receive submissions from states concerning actions taken against compounding pharmacies or state concerns that a compounding pharmacy may be acting contrary to section 503A of the FDCA, and FDA subsequently notifies state boards when receiving certain submissions or when making a determination that a compounding pharmacy is acting contrary to section 503A. Submissions should be sent to StateCompounding@fda.hhs.gov.
In a separate session, two states presented on their recent legislative and regulatory updates related to drug compounding. Both states provided background about their respective histories of regulating drug compounding, including their adoption of USP standards. One of the states also shared 2021 legislative updates, which included adding a provision to state code that any complaints, data, or investigative information pertaining to compounded human drug products may be disclosed to FDA to comply with any memorandum of understanding, and a provision that outsourcing facilities must submit evidence of a satisfactory inspection every two years.
Inspection Updates with Panel Discussion
FDA presented inspection and regulatory action updates, including a 53.3% reduction in the number of days from inspection closeout to regulatory action over a four-year period. FDA conducted 72 compounding inspections in fiscal year 2022, up from 63 in fiscal year 2021. The majority of these inspections were follow-ups.
Following the presentation, a panel of representatives from FDA and state boards of pharmacy discussed compounding inspections. The state regulators shared that the main challenges they face when conducting compounding inspections are lack of resources, inadequate training, and lack of jurisdiction over physician compounders. They also said that relying on other states for information about non-resident compounding pharmacies is challenging.
FDA presented on the topic of drug adulteration. FDA reminded states that even firms that meet the conditions of section 503A and may be eligible for exemption from the adulteration provision in section 501(a)(2)(B) concerning current good manufacturing practice are not exempt from other adulteration provisions in federal law, including those concerning the presence of filth, insanitary conditions, and difference from stated strengths. FDA reminded the audience that sterility testing a sample of products within a batch cannot prove that all units within a batch are sterile, so it is important that sterility assurance is built into the compounding process rather than simply tested for. In September 2020, FDA issued pertinent guidance for industry, Insanitary Conditions at Compounding Facilities—Guidance for Industry. However, the guidance should not be considered exhaustive. FDA reviewed the New England Compounding Center case as an example of the risks posed by insanitary conditions and other drug adulteration.
Compounding Outside the Pharmacy Setting
Representatives from FDA, the Federal Trade Commission (FTC), NABP, and state boards of medicine, nursing, pharmacy, and naturopathic medicine shared their perspectives on and experiences with drug compounding that occurs outside of a pharmacy.
FDA presented about the Compounding Risk Alert issued in October 2021 highlighting concerns with the compounding of drugs by medical offices and clinics under insanitary conditions, and awareness of an emerging business model of intravenous (IV) hydration clinics and mobile spas. FDA is aware of various approaches to these practices. The establishments involved may be owned by physicians or nurse practitioners, may be brick and mortar or mobile, may employ nurses or others such as pharmacy technicians, and may mix and administer IV drugs. The quality standards used by these establishments are unclear.
FDA economists presented data about the scope of IV hydration clinic businesses. They gathered data for the 200 most populous U.S. cities and identified more than 3400 facilities offering on-demand IV hydration or similar services. These facilities include, among others, stand-alone clinics, med spas, ketamine and cryotherapy centers, and holistic or naturopathic medicine providers.
FTC presented about its enforcement actions for advertising of these practices and products. FTC noted that it receives many complaints about such businesses and takes legal action as appropriate.
Following these presentations, FDA staff, NABP staff, and members of several state regulatory boards engaged in a panel discussion. Participants expressed concerns about patients seeking and choosing their own IV infusions, and about who is being targeted with the opportunity to own IV hydration businesses. According to panelists, oversight of these practices is often limited, and they do not fall clearly under the authority of many states’ regulatory boards. Oversight, if any, they said, is largely complaint-driven rather than proactive. State boards of pharmacy expressed desire to take more action to determine which healthcare providers, if any, prescribe these IV infusions, how these facilities obtain the drugs they administer, and the conditions under which these drugs are compounded or otherwise prepared.
State Licensing & Oversight of Outsourcing Facilities
The Outsourcing Facility Association (OFA) joined as a guest presenter for a discrete special session on state licensing and oversight of outsourcing facilities. OFA presented an overview of their perspectives on compounding regulatory issues including the prohibition on wholesaling under section 503B, variation in state approaches to licensing outsourcing facilities, the inspection of outsourcing facilities, pharmacist supervision, and the difference in standards for compounding according to USP and CGMP. OFA said that varying state regulatory approaches can pose difficulties to outsourcing facilities and suggested that outsourcing facilities be inspected according to CGMP standards rather than USP standards, as some states continue to do. Following their presentation, OFA left the virtual meeting.
Following OFA’s presentation, FDA moderated a panel of state board of pharmacy representatives discussing state regulation of outsourcing facilities. The representatives shared that a lack of resources, training, and/or expertise leaves some states (especially smaller states) reliant on FDA to conduct inspections. Some states have a separate licensure category for outsourcing facilities, including non-resident outsourcing facilities, but many do not. According to the panelists, the discrepancies in how states license outsourcing facilities can cause confusion for both outsourcing facilities and states, especially as few, if any, states have mechanisms for license reciprocity.
Drug Supply Chain Security Act Updates
FDA provided an update on the implementation of the Drug Supply Chain Security Act, including the 2023 Enhanced Drug Distribution Security provisions which go into effect on November 27, 2023. FDA also provided an overview of Proposed Regulation 21 CFR 205, which would establish national standards for the licensure of wholesale drug distributors and third-party logistics providers.
Adverse Event Reporting
Following a presentation about FDA’s Compounding Incidents Program, representatives from FDA and several state boards of pharmacy joined in a panel discussion about adverse event reporting. The states discussed their approaches to reporting and responding to adverse events and product quality issues associated with compounded drugs, as well as what an ideal adverse event reporting system might look like.
Next, FDA provided a forum for states to discuss adverse event reporting in smaller groups. Some states have mandatory reporting processes for adverse events related to compounded drugs, but many do not even have a mechanism for reporting. States have different thresholds to report adverse drug events to FDA; most would like a rapid response from the agency when they do so. Some states shared that they believe that fear of retribution prohibits some compounders from reporting adverse events. A “just culture” approach was suggested to help ease these concerns and increase reporting.
The Future of Compounding Oversight
In the last panel of the meeting, representatives from FDA, NABP, and state boards of pharmacy reflected on the past ten years of compounding regulation and the future regulation of the industry. Participants reported observing a marked improvement in the overall sector, especially in hospital compounding. Adverse event reporting and communication between state and federal regulators are potential areas for improvement moving forward. New trends causing concern among state regulators are the rise of compounders making biological products, and “compounding kits” being issued to patients, who are then expected to prepare their own drugs with supplied ingredients and instructions, sometimes even for injection.
November 1-2, 2022, Intergovernmental Working Meeting Action Items
- FDA will continue to work on streamlining its inspection and compliance process to reduce timeframes and improve information availability to states concerning inspections of compounding facilities within their states and subsequent regulatory actions. FDA will also continue to work to provide timely state notification about adverse events and complaints.
- FDA will continue to work with states and NABP to identify, understand, and enhance pathways for information sharing about adverse events, complaints, and product quality issues related to compounded drugs.
- FDA will explore pathways to facilitate additional collaboration and dialogue between federal and state regulators on non-pharmacist compounding and IV hydration facilities.
- FDA will consider providing additional training for state regulators and inspectors on FDA guidance documents.