Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act

State-licensed physicians and pharmacists that compound under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) may only compound drug products using bulk drug substances that:

1. Comply with an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph if one exists, and the USP chapter on pharmacy compounding;
2. Are components of FDA-approved drug products if an applicable USP or NF monograph does not exist; or
3. Appear on FDA’s list of bulk drug substances that can be used in compounding (the 503A bulks list) if such a monograph does not exist and the substance is not a component of an FDA-approved drug product.

In addition, bulk drug substances must be accompanied by a valid certificate of analysis and must have been manufactured by an establishment registered with FDA under section 510 of the FD&C Act. The agency urges compounders to know your bulks supplier.

Developing the 503A Bulks List

FDA solicited nominations for bulk drug substances in 2015 to include on the 503A bulks list and is consulting with the Pharmacy Compounding Advisory Committee for and the U.S. Pharmacopeia Convention for input as it evaluates them.

FDA regulations:

• A final regulation was issued in February 2019, List of Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance with Section 503A of the FD&C Act, in which FDA placed six substances on the list, identified and did not place four other substances on the list, and established the criteria to evaluate substances for inclusion on the list.
• A proposed regulation was issued in September 2019, Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance with Section 503A of the FD&C Act, in which the agency proposed to place five substances on the list and not to place 26 other substances on the list. After considering public comments, the agency will issue a final regulation. The agency also will continue to evaluate bulk drug substances that have been nominated with sufficient supporting information and address those substances on a rolling basis through notice-and-comment rulemaking.

Interim Policy on Compounding Drugs Using Bulk Drug Substances

FDA developed an interim policy describing conditions under which the agency does not intend to take action against state-licensed pharmacies, federal facilities and licensed physicians for compounding drug products from certain bulk drug substances that cannot otherwise be used under section 503A. The agency issued this interim policy to avoid unnecessary disruption to patient treatment while FDA evaluates the bulk drug substances nominated for inclusion on the 503A bulks list. 

The interim policy describes three categories of bulk drug substances nominated for use in compounding. The categories are:

• Category 1 – These substances may be eligible for inclusion on the 503A bulks list, were nominated with sufficient supporting information for FDA to evaluate them, and do not appear on any other list.

  FDA does not intend to take action against a compounder for compounding drugs using bulk drug substances listed in category 1, provided that the conditions described in the guidance document are met.

• Category 2 – These substances were nominated with sufficient supporting information to permit FDA to evaluate them, and they may be eligible for inclusion on the 503A bulks list. However, FDA has identified significant safety risks relating to the use of these substances in compounding pending further evaluation and, therefore, does not intend to adopt the policy described for the substances in category 1.

  If FDA adds a substance to category 2, we will publish the safety information describing the risks on FDA.gov and advise that the substance has been added to category 2 and is not within the scope of the policies regarding substances in category 1.

  FDA would consider taking action against a compounder for compounding drug products with this bulk drug substance under its general enforcement policies. Visit Safety Risks Associated with Certain Bulk Drug Substances Nominated for Use in Compounding for the substances and a summary of the identified safety risks.

• Category 3 – These substances may be eligible for inclusion on the 503A bulks list but were nominated with insufficient supporting information for FDA to evaluate them. These substances can be re-nominated with sufficient supporting information through Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance with Section 503A of the Federal Food, Drug, and Cosmetic Act; Establishment of a Public Docket.

  These substances are not eligible for the policy that applies to substances in category 1. FDA would consider taking action against a compounder for compounding drug products with this bulk drug substance under its general enforcement policies.

FDA issued a guidance document to revise the application of this policy. This guidance document states the agency does not intend to place bulk drug substances nominated on or after January 7, 2025, into these categories.  

Bulk drug substances that appear in category 1 may continue to be within the scope of the interim enforcement policy described in FDA’s guidance until the agency decides on inclusion of these substances on the 503A bulks list or unless the agency removes the substances from category 1 based on, for example, information about safety risks.

Compounders and other interested parties may continue to nominate substances for inclusion on the 503A bulks list. We will continue to evaluate sufficiently supported nominations for inclusion on the 503A bulks list in accordance with the process and criteria described in the FD&C Act.