On January 7, 2025, FDA released Guidances on compounding using bulk drug substances for both 503A pharmacies and 503B outsourcing facilities. These Guidances provide support and protection for pharmacies and outsourcing facilities utilizing certain types of bulk drug substances while the FDA continues its process of reviewing products for inclusion on lists of products that can be used in drug compounding.
For a 503A pharmacy to be able to compound a drug using a bulk active pharmaceutical ingredient (API), the API must either be a component of an FDA approved drug or have a USP/NF monograph.[1] If it has neither, the law requires that it must be listed on a list developed by the FDA of drug products that can nevertheless be used in pharmacy compounding. Because this list is not yet complete, FDA Guidances have indicated that the API must be on the FDA 503A Bulks List in its current form, or be listed as Category 1 on the Interim Bulks List.[2] Category 1 products are substances that may ultimately be eligible for inclusion on the 503A Bulks List, and were nominated with sufficient supporting information for FDA to evaluate them, but do appear on any other list. The Category 1 list is available at https://www.fda.gov/media/94155/download. For 503B outsourcing facilities to compound, the drug must appear on FDA’s 506e shortage list, or appear on the 503B Bulks List.
FDA’s efforts to develop the 503A and 503B Bulks List have been very drawn out and consequently, since 2017, FDA has followed its Interim Policy for the use of bulk drug substances. Under the Interim Policy, FDA has indicated that while the bulk list is being developed, FDA does not intend to take enforcement action against a State-licensed pharmacy for compounding a drug that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, if the substance is eligible and was nominated for inclusion (but not yet included) on the Bulks Drug List and does not present significant safety risks, meaning it was placed in Category 1.[3] Similarly, under the Interim Policy for 503B outsourcing facilities, FDA stated it does not intend to take enforcement action against a 503B facility for compounding a drug listed in Category 1 of the 503B Bulks List.
What Has Changed?
After January 7, 2025, pursuant to the two Guidances, FDA will no longer categorize any nominated bulk drug. An important consequence of this for 503A and 503B compounders is that FDA has now cut-off “interim” compounding for new nominated substances. Drugs currently listed in Category 1 will continue to be able to be compounded until FDA either removes them from Category 1 by placing (or declining to place them) on the final Bulks Drug list. Any new drug proposed for, but not yet approved for, FDA’s lists of bulk drug substances, may NOT be compounded until the FDA makes a full and final review of the product, and ultimately chooses to include it on a list (a process which could take several years).
Compounders and other interested parties may continue to nominate substances for inclusion on the lists. Newly nominated substances will need to undergo the FDA evaluation process whereby FDA consults with its own Pharmacy Compounding Advisory Committee (PCAC) and USP, obtains public comment via Notice and Comment in the Federal Register, and makes a determination as to whether the substance meets the statutory and regulatory standard for placement on the Bulks Lists. FDA has indicated that it will continue to prepare the Bulks Lists on a rolling basis. However, there is no way of knowing when a nominated substance will be considered other than by keeping abreast of the PCAC agendas.
How Frier Levitt Can Help
In light of this FDA update, some challenges may arise in navigating FDA regulations for compounding when a drug is being considered for nomination on the Bulks Lists or when a drug is removed from the FDA shortage list. However, Frier Levitt has experience in representing both 503A compounding pharmacies and 503B outsourcing facilities in these matters. We regularly counsel clients on Section 503A and state-specific compounding requirements, assess compounding practices for state and federal regulatory compliance, including USP 797/795/800, medical necessity documentation, advertising, promotion, reimbursement issues, infrastructure, and preparing compounding policies and procedures that provide clear guidelines, standards and training for staff. We assist in all aspects of setting up 503Bs. Contact us to discuss your specific needs.
[1] FDCA §503A(b)(1)(A)(i).
[2] Category I includes substances nominated for the Bulks List Currently Under Evaluation. Bulk drug substances listed in Category 2 are those substances that, in the FDA’s view, were nominated with sufficient supporting information but raise significant safety concerns, and while the FDA continues to evaluate those substances for inclusion in the regulation, it will not permit compounders to use such substances in preparing drugs. Finally, Category 3 reflects those substances that have been nominated without sufficient support. Neither Category 2 nor 3 can be compounded.
[3] FDA Guidance. Interim Policy on Compounding Using Bulk Drug Substances Under § 503(a) of the Federal Food Drug and Cosmetic Act. June 9, 2018.
