The U.S. Food and Drug Administration (FDA) recently issued a guidance document that intends to “help small businesses better understand and comply” with the Agency’s Section 503A bulk substances final rule, issued February 19, 2019. The final rule establishes FDA’s criteria for evaluating nominated bulk substances, places six substances on FDA’s bulks list and identifies four other substances that FDA determined to not include on FDA’s bulks list.
The May 2019 guidance document for Section 503A pharmacies (dubbed a “Small Entity Compliance Guide”) provides some “questions and answers” concerning FDA’s evolving Section 503A bulks nomination process.
Regular readers of this blog are likely aware of the bumpy, years’ long road on which FDA has traveled to solicit nominations for bulk substances for use in compounding pursuant to FDCA Section 503A. FDA commenced the nomination process within days after passage of the 2013 Drug Quality and Security Act, Title I (The Compounding Quality Act), blogged about here, and here. After fits and starts, and establishing an interim policy for use of bulk substances by Section 503A pharmacies, FDA published a proposed rule in 2016 for six of the hundreds of nominated substances, and rejecting the nominations of four other substances. Note that Section 503A requires that FDA promulgate the list of bulk substances used in compounding via notice and comment rulemaking after consultation with the Pharmacy Compounding Advisory Committee. Section 503A(d)(1).
The straightforward “Q&A” guidance provides no surprises for pharmacies, but not any new information either. The one issue to which the guidance does not directly speak is whether the “interim policy” that FDA published in 2017, and permits pharmacies to compound from the bulks list pending the completion of the rulemaking process, is still FDA’s “policy.” FDA plainly did not “revoke” that policy, but it also did not address it in the Q&A. Note that FDA’s interim policy states that it will use enforcement discretion for those compounders that compound using substances that are listed on FDA’s “Bulks List 1.” FDA’s new Q&A guidance asks the question: “Can substances that have been considered and not placed on the 503A Bulks List through a final rule be used in compounding under 503A?” FDA’s answer: “No.” FDA does not explain, as it easily could have, that the interim policy, featuring FDA’s “List 1” (i.e., nominated substances that FDA considers still under evaluation), remains in effect.
The Q&A does list the ten substances that are the subject of FDA’s final rule. Those substances that “made the cut” and can be used in compounding include the following: (1) Brilliant Blue G, also known as Coomassie Brilliant Blue G-250; (2) cantharidin (for topical use only); (3) diphenylcyclopropenone (for topical use only); (4) N-acetyl-D-glucosamine (NAG) (for topical use only); (5) squaric acid dibutyl ester (for topical use only); and (6) thymol iodide (for topical use only). The four substances that did not make the cut are: (1) oxitriptan; (2) piracetam; (3) silver protein mild; and (4) tranilast.
FDA states that if a compounder wants to use one of the four substances that did not make the list, then the compounder should file a citizen petition under 21 C.F.R. §10.30, and request that FDA consider revisiting the rule to include the bulk substance. Lastly, FDA’s Q&A lists the criteria it uses to evaluate bulk substances, which criteria are also listed in FDA’s final rule. These criteria include the following:
- The physical and chemical characteristics of the substance
- The safety of the substance in compounded drug products
- Evidence of effectiveness, and
- Historical use of the substance in compounded drug products.