FDA continues taking key actions on bulk drug substances used for compounding to advance the regulatory framework governing compounded drugs and to protect patients

FDA News Release

• For Immediate Release: July 23, 2018

As part of its ongoing implementation of the Drug Quality and Security Act and to advance the goals of its 2018 Compounding Policy Priorities Plan, the U.S. Food and Drug Administration is announcing several actions to protect public health related to the compounding of human drug products.

“We continue to implement the compounding provisions of federal law and advance a modern framework for the development of compounded drugs,” said FDA Commissioner Scott Gottlieb, M.D. “Our actions underscore our focus on protecting patients while making sure we have an enduring framework for better compounding that is well informed by input from the clinical community. Our aim is to be responsive to the medical needs of patients who require compounded medicines, while making sure that these products are compounded under appropriate standards. We recognize that there continues to be great interest in our work in this important policy area and we’re committed to providing updates as we take a continuing series of actions to implement the comprehensive plan that we outlined earlier this year.”

Today, the FDA is issuing an alert warning about a bulk drug substance (active pharmaceutical ingredient) used in compounding that carries significant safety risks for patients. The FDA is also taking steps regarding its approach to bulk drug substances that are used to make compounded drugs.

“Addressing bulk drug substances used in compounding is an important priority for the agency,” said Anna Abram, Deputy Commissioner for Policy, Planning, Legislation and Analysis. “The FDA seeks to implement the statutory requirements for bulk drug substances that can be used in compounding in a way that strikes a balance between preserving access to compounded drugs for patients who have a medical need for them while reducing the safety risks and protecting the FDA drug approval process. Input from stakeholders, including health care professionals, is critical to achieving this balance.”

Cesium chloride compounding risk alert and citizen petition

Today, the FDA issued a compounding risk alert to warn health care providers, compounders and patients of the dangers of using the bulk drug substance cesium chloride. Cesium chloride is sometimes used by cancer patients despite never having been proven safe and effective for any use. Serious adverse events associated with the use of cesium chloride and other cesium salts include abnormal heart rhythms (arrhythmias), low potassium (hypokalemia), seizures, fainting (syncope), cardiac arrest and death.

Today, the FDA is also announcing that it intends to move cesium chloride to category 2 under the FDA’s interim policy on compounding with bulk drug substances under section 503A. Under the interim policy, a bulk drug substance placed in category 2 raises significant safety risks in compounding and is not subject to the FDA’s enforcement policy on compounding with the bulk drug substance while the FDA is formally evaluating that substance for use in compounding through the rulemaking process. If the FDA encounters a compounder using a substance in category 2, the FDA intends to take regulatory action, such as issuing a warning letter or seizing product. Along with this action, the agency responded to a citizen petition filed by Public Citizen, related to this substance, granting the petition in part.

Collaborations with universities on bulks list projects

Today, the FDA is announcing two new research collaborations to support its goal of developing the list of bulk drug substances that can be compounded under section 503B and to help inform public understanding of the use of bulk drug substances in compounding. The FDA is collaborating with the University of Maryland and Johns Hopkins University, two of the agency’s Center of Excellence in Regulatory Science and Innovation (CERSI) partners, to gather and analyze information important for developing the list of bulk drug substances that may be used in compounding.

The University of Maryland will be working closely with medical specialty groups and researching information about the use of drug products including certain bulk drug substances historically and in current clinical practice.

The Johns Hopkins University will systematically study available safety and effectiveness information on certain bulk drug substances for use in compounding drug products for patients with autism spectrum disorder.

These projects will help inform the FDA’s regulatory decision-making, including whether to place the evaluated substances on the list of bulk drug substances that outsourcing facilities can use in compounding under section 503B, and help promote public awareness and understanding.

Bulks category updates

The FDA has developed interim policies on the use of bulk drug substances in compounding while the 503A and 503B bulks lists are being developed through procedures involving notice and comment. Under these interim policies, the FDA does not intend to object to compounding with a bulk drug substance if it meets certain conditions including being nominated with adequate supporting information for the FDA to evaluate it and it not having been identified by the agency as a substance that presents significant safety risks.

The FDA is currently updating the categories of substances that are subject to its interim policies on compounding with bulk drug substances. The update includes, but is not limited to, placing substances that have been newly nominated or re-nominated with adequate support and do not present significant safety risks in compounding in category 1, those substances eligible for the interim policies. The FDA will place substances that were nominated without adequate support into a category that is not eligible for the interim policies, category 3.

The FDA designed its interim policies to avoid unnecessary disruption to patient treatment. During this interim period, the FDA will continue to restrict compounding of essentially copies of FDA-approved products. If the FDA encounters such compounding during an inspection or otherwise, the agency intends to take action, such as issuing a warning letter or pursuing an injunction.

Pharmacy Compounding Advisory Committee Meeting

To continue to seek public input on its policies around compounding, the ninth Pharmacy Compounding Advisory Committee meeting is scheduled for September 12, 2018. The committee will discuss six bulk drug substances that were nominated for use in compounding by 503A facilities: alpha lipoic acid, coenzyme Q10, creatine monohydrate, pyridoxal 5 phosphate, choline chloride and quercetin dihydrate. The FDA is dedicated toward developing the framework for evaluating bulk drug substances and will continue to update the public on the progress being made in the coming months.

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.

Agency responds to citizen petition, announces agreements with universities, updates bulks categories and schedules advisory committee meeting