FDA In Brief: FDA finalizes guidance on evaluating the clinical need for outsourcing facilities to compound drugs with bulk drug substances; provides final decision on two substances

March 1, 2019

Media Inquiries

“Balancing patient needs for compounded products with patient safety is a top priority for the agency. We’re concerned that patients still face too many risks when it comes to compounded drugs. Patients should not be put at risk of receiving a drug compounded from a bulk drug substance when an FDA-approved drug can be used to meet patient medical needs. That’s why today we’re issuing guidance that outlines a careful framework the agency intends to use to determine when there is a clinical need for outsourcing facilities to make drugs using bulk drug substances and advancing our list of bulk drug substances that can be used by outsourcing facilities,” said FDA Commissioner Scott Gottlieb, M.D. “To advance these goals, today, we’re also issuing public notification on two bulk drug substances, nicardipine hydrochloride and vasopressin, that cannot be used in compounding by outsourcing facilities. This is the first decision the FDA is announcing on substances nominated for the list, but others will follow as the FDA continues to develop this list. We’re excluding these substances from the list because the nominator did not provide any medical reason that FDA-approved drug products containing these substances could not be used or adapted to treat patients instead of drugs compounded from bulk substances. For this reason, the agency doesn’t see a clinical need for outsourcing facilities to compound from these substances. The law directs the FDA to limit compounding from bulk substances to situations where there’s a clinical need for such products or in situations where the drugs are judged by the FDA to be in shortage. These limits protect patients from unnecessary exposure to the risks associated with drugs compounded from bulk drug substances, while also protecting the integrity of the drug approval process. Continuing to develop the bulks list for compounding by outsourcing facilities remains a priority and we’ll continue this work in 2019.”

Today, 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.

Recently, the FDA issued a final rule under section 503A of the FD&C Act, describing the criteria used to evaluate bulk drug substances under that provision and placing, for the first time, six bulk drug substances on the list of substances that compounders not registered as outsourcing facilities can use to compound drugs, known as the 503A bulks list.

Related Information

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.