Boosting the safety of bulk drug substances is aim of FDA measures

Boosting the safety of bulk drug substances used in compounding is the FDA's aim.

Boosting the safety of bulk drug substances is the aim of new measures from the US Food and Drug Administration (FDA), which include: two research partnerships devoted to bulk lists, revised bulk drug substance categories and a warning about a bulk drug substance used in compounding.

“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.”

As part of its 2018 Compounding Policy Priorities Plan, the FDA will collaborate with University of Maryland and Johns Hopkins University to develop the list of bulk drug substances that can be compounded under the relevant legislation and to help inform public understanding of the use of bulk drug substances in compounding.

The FDA is collaborating with both universities – two of the agency’s Center of Excellence in Regulatory Science and Innovation (CERSI) partners – to collect and analyse information important for developing the list of bulk drug substances that may be used in compounding.

Bulk drug substances

Staff at the University of Maryland will work closely with medical speciality groups to research information about the use of drug products – including certain bulk drug substances used historically and in current clinical practice.

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

Both projects will help inform the FDA’s regulatory decision-making. That will include whether to place the evaluated substances on the list of bulk drug substances that outsourcing facilities can use in compounding, under section 503B of the Food, Drug, and Cosmetic Act (FD&C), and help promote public awareness and understanding.

Meanwhile, the FDA has issued a compounding risk alert to warn health care providers, compounders and patients about 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,” said the FDA in a statement.

Compounding risk alert

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, according to the agency.

Cesium chloride is to move to a Category 2 listing under the FDA’s interim policy on compounding with bulk drug substances under section 503A. As part of the interim policy, a bulk drug substance placed in Category 2 raises significant safety risks in compounding. Also, it is not subject to the FDA’s enforcement policy on compounding with the bulk drug substance while the administration is formally evaluating that substance for use in compounding through its rule-making 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,” it said.