There have been numerous legal and regulatory developments over the past year that pertain to 503A pharmacy compounding. In Part 1 of this two-part series, we explore the revisions to the United States Pharmacopeia’s (“USP”) <797> and <795> guidelines for sterile and nonsterile compounding and veterinary compounding, as well as the future of interstate distribution following Wellness Pharmacy v. FDA. In Part 2, we will review the current state of compounding certain drugs on the shortage list, as well as peptides, DTE, semaglutide, and bHRT, and proposed legislation to fill regulatory gaps.
USP 797 and 795 Revisions
On November 1, 2022, the long-awaited revisions to USP <797> for sterile compounding and <795> for non-sterile compounding became official. Implementation and enforcement does not begin until November 2023, and appeals have already been filed regarding the beyond use date (“BUD”) and batch size provisions. Despite that, it is important to be proactive and develop best practices as it is unlikely that USP will undertake significant further revisions. Batch size limitations of 250 units have been imposed on the basis that larger batch sizes increase risk of contamination, although some would argue that smaller, more frequent batches increase risks of error and contamination.
Additionally, the revisions to USP <797> present a new paradigm for personnel competency and assessment, surface sampling, and standalone hand hygiene and garb testing and validation (separate from aseptic technique testing). A best practice is to conduct a gap analysis regarding the revised chapters initially and at least once annually thereafter to include development of a robust environmental monitoring program and policies and procedures (“P&P”) reflective of the changes. USP has received many questions regarding stability studies to extend BUDs, including multi-dose non-preserved ophthalmic requirements. Revisions to <795> exclude repackaging, but include introduction of water activity, indicative of potential for degradation due to hydrolysis and forming the basis for BUDs. The revision clarifies that bulk APIs must be obtained from an FDA-registered facility. It is important for compounders to recognize that USP chapters are minimal standards and state regulations (e.g. California requires 503As to report Adverse drug events) and FDA Guidances, such as the guidance on Insanitary Conditions,[1] may be more stringent.
Veterinary Compounding
In April 2022, FDA issued a Final Guidance on compounding animal drugs from bulk substances that set up a system quite similar to the framework for 503A/503B compounding.[2] Over 2,000 comments were received on the 2019 draft. In particular, the Guidance establishes a policy for enforcement discretion for compounding patient-specific prescriptions for animal drugs from bulk drug substances and permits compounding for office use when the substance appears on FDA’s bulk drug substances list. The criteria to be included on that list includes (1) that there is no human or animal drug that could be used to treat the condition, and (2) treatment with a compounded drug is necessary to avoid animal suffering or death. Notably missing, however, are any specifics around the process to nominate ingredients for review and possible inclusion on bulks list. The Guidance also explains FDA’s policy on animal drugs compounded from bulk drug substances that are copies (same active ingredient and route of administration) of marketed FDA-approved drugs. There has been widespread industry pushback on this Guidance. While FDA has indicated that it will exercise enforcement discretion until April 2023 and focus instead on education, Congress may need to legislate a specific animal compounding law to resolve the controversy.
Interstate Distribution Post Wellness Pharmacy v. FDA
On October 26, 2020, FDA issued a Memorandum of Understanding (“MOU”) describing the conditions under which certain drugs compounded by 503A pharmacies could be shipped interstate. States that signed the MOU would have committed to investigating and reporting to FDA any time a pharmacy shipped more than 50% of its compounded drugs to out-of-state patients. Pharmacies located in states that did not sign would have been subject to a 5% limit, which would have had a chilling effect on patient access.
In Wellness Pharmacy v. FDA,[3] numerous compounding pharmacies sued the FDA, asserting various claims including bypassing of the Notice and Comment provisions of the Administrative Procedures Act. One contentious issue pertained to the conflating of the terms “distribution” and “dispensing.” The FDA has now suspended implementation of the MOU until the effective date of a Final Rule. It is anticipated that the formal process may take years to complete. In the meanwhile, FDA has also indicated enforcement discretion regarding the 5% Rule which is the statutory 5-percent limit on distribution of compounded human drug products outside of the State in which they are compounded.[4]
How Frier Levitt Can Help
Frier Levitt counsels compounding pharmacy clients regularly on Section 503A and state-specific compounding requirements. We can conduct a comprehensive assessment of your compounding practices for state and federal regulatory compliance, including medical necessity documentation, reimbursement issues, and infrastructure, and prepare compounding P&Ps that provide clear guidelines, standards, and training for staff. For more information or a review of your current compounding practices, contact us to speak with an experienced life sciences attorney.
[1] FDA Guidance for Industry. Insanitary Conditions at Compounding Facilities. Center for Drug Evaluation & Research, Office of Compliance, Food and Drug Administration. Nov 2020.
[2] FDA Guidance for Industry. Compounding Animal Drugs from Bulk Drug Substances. Center for Veterinary Medicine, Food & Drug Administration, April 13, 2022.
[3] Wellness Pharmacy, Inc. v. Becerra (D.D.C. Sep. 21, 2021)).
[4] Extension of the Period Before the Food and Drug Administration Intends to Begin Enforcing the Statutory 5 Percent Limit on Out-of-Sate Distribution of Compounded Human Drug Products 87 Fed Reg 63947, Oct 21, 2022.
