As the compounding Industry awaits the next round of Guidances from FDA on using bulk drug substances, one point of controversy appears to be the fairness of compounding for 503A and 503B entities. The most recent Guidances for Compounding from Bulk Drug Substances are:
Of note for 503A compounding is a quote from the Federal Register Notice announcing the revised request for nominations and found in the interim Guidance (see Appendix: Summary of Policy):
“Additionally, many of the nominated substances are already eligible for use in compounded drug products, namely, those that are components of approved products or are the subject of a USP or NF monograph. Substances that are in one of those two categories need not appear on the list of bulk drug substances to be used in compounded drug products” and the bulk drug substance is a component of an FDA-approved drug and/or the subject of an applicable USP or NF monograph. The bulk drug substance can be used in compounding under section 503A of the FD&C Act, provided it complies with the standards of the monograph (if one exists) and is compounded in compliance with the other conditions of section 503A. “
However, for 503B Compounding, the following wording is included in the interim policy (see Interim Policy above (January 2017).
“One of the conditions that must be met for a drug product compounded by an outsourcing facility to qualify for these exemptions is that the outsourcing facility does not compound drug products using a bulk drug substance unless (a) it appears on a list established by the Secretary identifying bulk drug substances for which there is a clinical need, or (b) the drug compounded from such bulk drug substances appears on the drug shortage list in effect under section 506E of the FD&C Act at the time of compounding, distribution, and dispensing. Section 503B(a)(2)(A) of the FD&C Act.”
This certainly does seem to be a discrepancy in language for the different classes of compounders. The question is, does this establish an unfair hurdle for 503B Outsourcers? While there may be some good reason for this, it is not clearly articulated in the policy. Thus, for 503B Outsourcers, bulk Drug Substances should be nominated with supporting information and a scientific/clinical explanation of why compounding from the bulk drug substance is desired/required/justifiable instead of just being from a commercially available product.
FDA has stated that it will review the nominations and update their website the first business day of each month.
At this time, it is up to the compounding Industry to expand the Category 1 List by nominations and sound scientific and clinical need supporting arguments for inclusion of the Bulk Drug Substances.
We strongly recommend reading all applicable regulations and Guidances for Compounding on the FDA.gov website and participating in the appropriate trade associations to have a fruitful dialogue with FDA sooner than later.