August 27, 2018
“Compounded drug products can serve an important medical need for patients, but they don’t meet the same standards as FDA-approved drugs,” said FDA Commissioner Scott Gottlieb, M.D. “Today, we’ve taken a first-of-its kind action to protect the public health and advance the FDA’s implementation of the Drug Quality and Security Act. We evaluated three bulk drug substances that were nominated for outsourcing facilities to use in compounding. Our preliminary assessment is that the FDA-approved drug products containing these substances can either be used or adapted to treat patients instead of compounding new drugs from bulk drug substances as proposed by the nominations. So, at this point, we don’t see a clinical need for outsourcing facilities to compound from these bulk substances. Consistent with the DQSA, we’re issuing a Federal Register notice outlining our proposal and to seeking comments from the public before making a final decision. As we’ve said in guidance, once we make a final decision, the interim enforcement policy currently in place will no longer apply to these substances.”
Today, the FDA issued a Federal Register notice proposing not to include three bulk drug substances, bumetanide, nicardipine hydrochloride, and vasopressin, on the list of bulk drug substances (or active pharmaceutical ingredients) that outsourcing facilities may use in compounding under section 503B of the Federal Food, Drug & Cosmetic Act (503B bulks list).
This is the first time since the passage of the DQSA that the FDA has issued a proposal regarding whether to include bulk drug substances to the 503B bulks list. Each of these substances is an ingredient of one or more FDA-approved drug products. The nominations did not give any reason why the FDA-approved drug products containing these substances could not be either used or adapted instead of compounding new drug products using bulk drug substances. As stated in the proposal, at this time we do not find clinical need for an outsourcing facility to use these bulk drug substances to compound finished products, which is the statutory standard for adding a bulk drug substance to the 503B bulks list. Therefore, the FDA is proposing to exclude these substances from the 503B bulks list and we are seeking public comment before finalizing our decision.
This action is part of a series of steps that the FDA will take between now and the end of 2018 to continue its implementation of the DQSA. For example, the agency will also be issuing a revised draft Memorandum of Understanding with states that will describe a more flexible approach to addressing certain distributions of compounded products by 503A compounders; a revised draft guidance on insanitary conditions at compounding facilities that will, among other things, address concerns that were raised by providers around the potential implications of the agency’s prior draft guidance; and a revised guidance on current good manufacturing practice (CGMP) requirements for outsourcing facilities that, we believe, will take a more tailored approach to make it more feasible for more 503A pharmacies to become 503B outsourcing facilities.
Compounded drug products are not reviewed by the FDA for safety, effectiveness, or quality, or labeled with adequate directions for use. Federal law provides limited exceptions to the requirements for premarket approval, labeling with adequate directions for use, and drug supply chain security when a drug product compounded by an outsourcing facility meets conditions in section 503B. Among the conditions is a limitation on the use of bulk drug substances by outsourcing facilities to compound drug products. Specifically, an outsourcing facility may only compound using a bulk drug substance if a drug appears on the FDA’s drug shortage list or on a list established by FDA identifying bulk drug substances for which there is a clinical need. Compounded drugs should only be administered when an FDA-approved drug is not available to meet a patient’s needs, and compounding drug products starting from bulk drug substances generally presents greater risks for patients than compounding from FDA-approved drug products.
- Federal Register Notice: List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503B of the Federal Food, Drug, and Cosmetic Act
- Draft Guidance: Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
- Final Guidance: Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act
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.