The FDA issued a Proposed Rule (here) that announced the first additional 6 bulk drug substances for inclusion on the listing of bulk drug substances acceptable for pharmacy compounding, although they are neither the subject of an applicable United States Pharmacopoeia (USP), nor National Formulary (NF) monograph, nor components of FDA-approved drugs. Specifically, the Agency proposes to place six bulk drug substances on the list. The FDA also made an announcement relative to this action on the CDER web site, which can be found here.
Remember that 503A compounders are basically pharmacy compounders that receive individual patient-specific prescriptions for the compounded product, as opposed to 503B outsourcing facilities that must meet strict cGMP requirements and may compound product in bulk.
503A pharmacies may compound prescriptions, if the drug substance is either a component of an FDA approved product or a drug substance that complies with, and is subject to, a monograph in the USP or NF or, if none of those conditions apply, that the drug substance appears on the list of bulk drug substances that are permitted for use in compounding. The 6 bulk drug substances in the Proposed Rule are the first to populate this list.
The 6 bulk substances that appear on the list are:
- Brilliant Blue G, also known as Coomassie Brilliant Blue G-250 [for topical use only]
- cantharidin (for topical use only)
- diphenylcyclopropenone (for topical use only)
- N-acetyl-D-glucosamine (for topical use only)
- squaric acid dibutyl ester (for topical use only)
- thymol iodide (for topical use only)
It is quite interesting that all of the first 6 bulk drug substances appearing on the list are for topical use only.
In addition, the Proposed Rule declined to include these four nominated bulk drug substances:
- silver protein mild
If and when the Proposed Rule is finalized, 503A compounders will be permitted to utilize the 6 bulk substances in compounded products and will still qualify for an exemption from certain sections of the FD&C Act. There are other bulk drug substances under consideration by the FDA for inclusion on this list and will be the subject of a future rulemaking.
The Proposed Rule provides FDA reasoning for permitting the 6 bulk drug substances and also the reasons for denial for inclusion on the list of the other 4 products.
“With regard to the substances nominated with sufficient supporting information for FDA to evaluate them, including the 10 nominated substances discussed in this proposed rule, FDA generally does not intend to take regulatory action against a State-licensed pharmacy, Federal facility, or licensed physician for compounding a drug product using a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug product, provided that the other conditions in section 503A and the FD&C Act are met, until the substance is addressed in a final rule.” However, the FDA reserves the right to take regulatory action, if there is evidence of a safety issue, or if the nomination is found to have inadequate support.