Monday was a big day for those monitoring whether and when FDA will add certain previously nominated bulk substances to its various “Bulks Lists” for Section 503A pharmacies and Section 503B outsourcing facilities. As previously blogged about here, back on March 23, 2018, FDA announced it was “revisiting” the Section 503B Bulks List nomination process, discussing clinical need and “medical justification” for those substances, in particular those that include components of approved drugs. FDA provided a 60-day comment period on its new process as well. Notwithstanding the conclusion of the comment period, and no FDA action yet on the nomination process itself, FDA announced yesterday that it was revising the 503A and 503B lists to add substances to the lists, move substances among the lists, and remove others from the lists altogether. While we roundly applaud FDA’s long-awaited efforts to act on nominations for bulk substances that were the subject of submissions and in the “queue” for review for a year or more (as this surely enables greater patient access to certain substances), we remain confused as to why FDA has not made a final determination concerning exactly what its nomination and review process will be for Section 503B Bulks prior to taking this next step (especially considering the draft guidance the Agency just issued in March 2018, and given that the industry comment period just ended).
Bulks List Changes
FDA’s revised interim Bulks Lists for Section 503A and Section 503B are here and here. FDA summarizes the July 2018 changes on the final pages of those lists – definite reads for any compounder.
PCAC Meeting
FDA also announced that will hold a meeting of its Pharmacy Compounding Advisory Committee on September 12, 2018, and address six 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.
Collaboration Efforts with Two Universities
The Agency also announced two new research collaborations (with University of Maryland and Johns Hopkins University) to support development of the Bulks List for Section 503B, and to “help inform public understanding of the use of bulk drug substances in compounding.” The press release can be viewed here. These institutions are two of FDA’s Center of Excellence in Regulatory Science and Innovation (CERSI) partners. Specifically, FDA stated:
- 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.
Cesium Chloride Risk Alert and Move to List 2
FDA also addressed in its press release a “compounding risk alert” that it issued for cesium chloride and its response to a citizen petition filed by Public Citizen. FDA issued the compounding risk alert to warn health care providers, compounders and patients of certain dangers compounding using the bulk substance cesium chloride. FDA noted that cesium chloride is sometimes used by cancer patients notwithstanding a lack of evidence of its safety and efficacy for that or any use. The Agency also cited serious adverse events associated with use of the substances and other cesium salts that include abnormal heart rhythms (arrhythmias), low potassium (hypokalemia), seizures, fainting (syncope), cardiac arrest and death. Relatedly, FDA stated 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 because it raises “significant safety risks in compounding.” If the Agency encounters a compounder using a substance in category 2, it “intends to take action, such as issu[ing] a warning letter or. . .seiz[ing]. . . product.”
Lastly, FDA noted that it responded to a citizen petition filed by Public Citizen related to cesium chloride, and that it granted the petition in part, but it did not mention that it responded after Public Citizen filed a lawsuit against FDA for failing to take action on that petition since 2016 and after FDA found that the substance presented “serious safety concerns.” Public Citizen’s press releases are here and here.