503A and 503B COMPOUNDING ALERT: FDA Issues a Series of Compounding Updates

In keeping in line with its 2018 Compounding Policy Priorities Plan, the Federal Food and Drug Administration (FDA) released four compounding updates on Monday, July 23rd, including:

  • Compounding risk alert regarding the bulk drug substance, cesium chloride
  • Two new research collaborations with the FDA and the University of Maryland and John Hopkins University in order for the FDA to gather information to help construct the list of bulk drug substances that 503B outsourcing facilities may use in compounding
  • Updates to the current 503A and 503B Bulks Lists, which contain bulk drug substances placed into certain categories that are subject to the FDA’s interim policies on compounding with bulk drug substances
  • PCAC meeting scheduled for September 12, 2018, to discuss i.) compounding in relation to dietary supplements and ii.) six bulk drug substances that were nominated for the 503A Bulks List

The four updates offer details compounding pharmacies and outsourcing facilities should be aware of, including: 

Compounding Risk Alert regarding bulk drug substance, Cesium Chloride

First, the FDA issued a compounding risk alert regarding bulk drug substance, cesium chloride, which the FDA believes carries significant safety risks for patients. Specifically, the FDA stated, “Cesium chloride is sometimes used by cancer patients despite never having been proven safe and effective for any use. Serious adverse events associate with the cesium chloride and other cesium salts include abnormal heart rhythms (arrhythmias), low potassium (hypokalemia), seizures, fainting (syncope), cardiac arrest, and death.” Presumably due to these noted risks by the FDA, the FDA announced that it intends to move cesium chloride to category 2 on the 503A Bulks List under the FDA’s interim policy, and reiterated that the FDA intends to take regulatory action, such as issuing a warning letter or seizing product if the FDA encounters a compounder using a substance in category.

FDA enters into two new research collaborations in order to support its goal of developing the 503B Bulks List

Second, the FDA announced two new research collaborations in order to support its goal of developing the list of bulk drug substances that can be compounded under section 503B and also to help inform public understanding of the use of bulk drug substances in compounding. To those ends, the FDA is collaborating with the University of Maryland and John Hopkins University. The University of Maryland will work closely with medical specialty groups and research information about the historical and current use of certain bulk drug substances. John Hopkins University will study available safety and effectiveness information on certain bulk drug substances for use in compounding drug products for patients with autism spectrum disorder. Both groups will work with the aim of gather scientific information to help inform the FDA’s regulatory decision-making, surrounding decisions, such as whether to place the evaluated substances on the list of bulk drug substances that 503B outsourcing facilities can utilize for compounding drug substances. 

FDA updates its 503A and 503B Bulks Lists

Third, the FDA made note that it is in the process of updating the categories of substances that are subject to its interim policies on compounding with bulk drug substances (i.e., the current 503A and 503B bulk drug substances lists). Both the 503A and 503B bulks lists have been updated with annotated recategorizations of certain bulk drug substances. Additionally, the updates include, but are 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. Also, in keeping in accordance with its interim policies, the FDA has placed substances that were nominated without adequate support into a category that is not eligible for the interim policies, category 3. Category 2 includes those bulk drug substances that raise significant safety risks, i.e., the category cesium chloride was moved into. These interim lists and FDA’s associated policies will continue to be in effect, until the FDA develops the “actual” bulk drug substances lists in order to avoid unnecessary disruption to patient care. The FDA reiterates that it will continue to restrict compounding of essentially copies of FDA approved products and intends to take action, such as warning letters or injunctions if encountered by the FDA.

PCAC Meeting to be held September 12th in order to discuss compounding as it relates to dietary supplements and six bulk drug substances nominated to the 503A List

Fourth, the FDA announced a public advisory committee meeting of the Pharmacy Compounding Advisory Committee (PCAC) in order to continue to seek public input on its policies surrounding compounding. The meeting, which will be open to the public, will be held on September 12, 2018 from 8 a.m. to 4:30 p.m. The committee will receive information on balancing the criteria for the 503A bulk drug substance evaluation and compounding as it relates to dietary supplements. In addition, the agenda will include discussion of 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 also establishing a docket for public comment, which will close on September 11, 2018. Comments must be received on or before August 28, 2018, in order to be provided to the committee. Comments received after August 28, 2018, will be taken into consideration by the FDA. If you would like assistance with submitting a comment to the public docket, contact Frier Levitt today.

If you are a compounding pharmacy or an outsourcing facility in need of assistance regarding these recent FDA updates or issues related to the Federal Drug Quality and Security Act (DQSA), including state laws and/or regulations surrounding compounding, contact Frier Levitt today.