U.S. flag An official website of the United States government

On Oct. 1, 2024, the FDA began implementing a reorganization impacting many parts of the agency. We are in the process of updating FDA.gov content to reflect these changes.

U.S. Food and Drug Administration
  1. Home
  2. Drugs
  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 final guidance in March 2019, Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act, 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.

Collaborative Agreements to Help Inform FDA’s Development of the 503B Bulks List

FDA is engaging in two cooperative agreements with research partners to help inform the agency’s evaluation of bulk drug substances nominated for use in compounding under section 503B.

FDA is working with the University of Maryland Center of Excellence in Regulatory Science and Innovation (CERSI) on a project entitled, “Clinical Use of Drugs Including Bulk Drug Substances Nominated for Use in Compounding by Outsourcing Facilities.” This project involves research related to certain bulk drug substances nominated for use in compounding under section 503B, including how drugs compounded with the substances have currently and historically been used in clinical practice. FDA expects that this project will provide valuable information for it to consider when assessing whether there is a clinical need to compound using bulk drug substances that have been nominated for the 503B bulks list, and generally help information agency decision-making, stakeholders, and the public.

FDA is working with the Johns Hopkins University CERSI on a project entitled, “Bulk Drug Substances Used to Compound Drugs for Patients with Autism Spectrum Disorder (ASD).” This project involves researching information about certain bulk drug substances that are used to compound drug products for patients with ASD. Information from the project will help FDA evaluate whether there is a clinical need for use of a bulk drug substance in compounding under section 503B, and help to promote public input as well as stakeholder understanding and discussion.

Back to Top

Interim Policy on Compounding Drugs Using Bulk Drug Substance

FDA issued a revised final guidance in January 2017, Guidance for Industry, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act, which is in place while the FDA develops the 503B bulks list. The guidance describes conditions under which the agency does not intend to take action against outsourcing facilities that compound drug products from bulk drug substances that cannot otherwise be used in compounding under section 503B. FDA issued this guidance document 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 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 are bulk drug substances that were nominated with sufficient supporting information for FDA to evaluate them, but FDA has identified significant safety risks relating to the use of these substances in compounding pending further evaluation. Drug products compounded using these substances are not eligible for the policy described for the 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. 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. 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.

FDA intends to update these categories to reflect any new nominations or other changes on a periodic basis.

New Draft Guidance: Interim Policy on Compounding Using Bulk Drug Substances

FDA issued a new draft guidance in December 2023 describing the agency’s interim policy regarding compounding using certain bulk drug substances that have been nominated for use in compounding under section 503B of the FD&C Act. If the guidance document is finalized in its current form, a substance nominated on or after the date the agency issues the final guidance document would not be categorized, as described in the guidance, and would not be within the scope of the interim enforcement policy described in FDA’s guidance.

Bulk drug substances that appear in category 1, as described in the draft guidance document, before the guidance is finalized would not be affected by this change. These bulk drug substances may continue to be within the scope of the interim enforcement policy until the agency decides on inclusion of these substances on the 503B list or unless the agency removes the substances from category 1 based on, for example, information about safety risks.

FDA continues to evaluate sufficiently supported nominations for the 503B bulks lists in accordance with the processes and criteria described in the FD&C Act.

Sign up to receive email updates on compounding.

Back to Top