Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

The U.S. Food and Drug Administration issued a final guidance for industry, Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act. This guidance addresses the FDA’s policies for developing a list of bulk drug substances that can be used in compounding under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), also known as the 503B bulks list, including the agency’s interpretation of “bulk drug substance for which there is a clinical need,” which is the statutory standard for compounding from bulk drug substances. The guidance also highlights criteria the agency generally intends to use to evaluate whether a bulk drug substance should be used by outsourcing facilities to compound drugs. While compounded drugs can serve an important role for patients whose medical needs cannot be met by an FDA-approved drug product, compounded drug products are not approved by the FDA and therefore present greater risks to patients. Because of these risks, and to help protect the integrity of the drug approval process, section 503B of the FD&C Act limits the bulk drug substances that outsourcing facilities can use in compounding to substances that are used to compound drugs in shortage or that appear on a list developed by the FDA of bulk drug substances for which there is a clinical need. The FDA also issued a Federal Register notice announcing that it has evaluated two bulk drug substances that were nominated for the 503B bulks list, nicardipine hydrochloride and vasopressin, and decided not to include them on the list. Because these bulk drug substances are not on the 503B bulks list and there are no products containing these substances on the FDA’s drug shortage list, outsourcing facilities may not use either substance in compounding under section 503B of the FD&C Act. This is the first time since the passage of the Drug Quality and Security Act that the FDA has made a final decision regarding whether to include bulk drug substances on the 503B bulks list. Each of these substances is an ingredient of one or more FDA-approved drug products. The nominations did not provide a reason to conclude that the FDA-approved drug products containing these substances were medically unsuitable for certain patients, and also did not provide a reason the FDA-approved drugs could not be adapted to compound the drugs that the nominators proposed to compound using bulk drug substances. Accordingly, the FDA did not find clinical need for an outsourcing facility to use these bulk drug substances to compound finished drug products, which is the statutory standard for adding a bulk drug substance to the 503B bulks list. Therefore, the FDA is not including these substances on the 503B bulks list. For more information, please visit: 503B bulks list FDA in Brief.