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  3. Guidance, Compliance, & Regulatory Information
  4. Human Drug Compounding
  5. Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act
  1. Human Drug Compounding

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

Outsourcing facilities, which operate under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), may not compound a drug product that includes a bulk drug substance unless:

  1. The bulk drug substance appears on a list identifying bulk drug substances for which there is a clinical need (the 503B bulks list), or
  2. The drug product compounded from such bulk drug substance appears on FDA’s drug shortage list at the time of compounding, distribution and dispensing.

Visit the compounding and drug shortages webpage for more information. 

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. In addition, if an applicable United States Pharmacopeia (USP) or National Formulary monograph exists, bulk drug substances must comply with the monograph.

The agency urges compounders to know your bulks supplier.

Developing the 503B Bulks List

The agency solicited nominations for bulk drug substances for inclusion on the 503B bulks list and is evaluating them.

FDA issued a guidance document in March 2019 that describes FDA’s interpretation of the statutory term, “bulk drug substance for which there is a clinical need,” and factors FDA intends to consider when determining whether to include a bulk drug substance on the 503B bulks list.

Visit the 503B bulks list, which will continue to be updated as other bulk drug substances are added to or excluded from the list.

Interim Policy on Compounding Drugs Using Bulk Drug Substance

FDA developed an interim policy describing conditions under which the agency does not intend to take action against outsourcing facilities that compound drug products from certain bulk drug substances that cannot otherwise be used in compounding under section 503B. The agency issued this interim policy to avoid unnecessary disruption to patient treatment while FDA evaluates the bulk drug substances nominated for use in compounding under section 503B of the FD&C Act. 

The guidance documents describe three categories of bulk drug substances nominated by the public for use in compounding. The categories are:

  • Category 1 – These substances may be eligible for inclusion on the 503B 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 an outsourcing facility for compounding drugs using bulk drug substances identified 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 503B 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, it will publish 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 an outsourcing facility 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 503B bulks list but were nominated with insufficient supporting information for FDA to evaluate them. These bulk drug 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 503B of the Federal Food, Drug, and Cosmetic Act; Establishment of a Public Docket.

    The substances are not eligible for the policy that applies to substances in category 1. FDA would consider taking action against an outsourcing facility 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 503B 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 503B bulks list. We will continue to evaluate sufficiently supported nominations for inclusion on the 503B bulks list in accordance with the processes and criteria described in the FD&C Act.

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