The FDA recently issued an Interim Policy on compounding using bulk drug substances under Section 503A and 503B of the Food Drug and Cosmetic Act (FD&C Act) offering important guidance for compounding pharmacies.
503A
Section 503A sets forth the conditions that must be satisfied for drug products compounded by a traditional pharmacy in order to be exempt from certain requirements of the FD&C Act (i.e., new drug registration requirements, CGMPs, etc.). Under Section 503A, traditional compounding pharmacies can only use bulk ingredients that are: (i) subject to USP or NF monographs, (ii) components of FDA approved drugs; or (iii) appear on a list of bulk drug substances developed by FDA through regulation.
In December 2013, the FDA invited interested parties to nominate bulk drug substances for inclusion on the FDA’s list. The process was reopened in July 2014, with the FDA offering additional guidance, due to inadequate nominations in the first round. At the same time, the FDA issued guidance reinforcing that human drug products should only be compounded using substances that are components of FDA approved drugs or subject to a valid USP or NF monograph until the bulk substance list is published as a final rule.
In the recently published Interim Policy, FDA acknowledges that this limitation may be causing unnecessary disruptions in care for patients seeking drugs compounded with bulk substances that may ultimately be included on the still unpublished 503A bulks list. While the FDA continues to evaluate the bulk drug substances, which will eventually be codified as the 503A bulks list, the FDA has stated that it does not intend to take action against traditional pharmacies compounding a drug product using a bulk drug substance that appears on the “503A List 1” found on the FDA’s website. Notably, this list includes common products such as Cetyl Myristoleate Oil, Oxitriptan, and Resveratrol. However, Domperidone, another common agent, was included on the FDA’s list of “Bulk Drug Substances that Raise Safety Concerns”. While the FDA has not issued final judgment on this product, the inclusion of Domperidone on this list signals future challenges for compounders seeking to continue to use the product in the absence of a USP or NF monograph.
503B
Section 503B describes the conditions that must be satisfied for drug products compounded by an outsourcing facility to be exempt from certain requirements of the FD&C Act (e.g., new drug registration and adequate labeling, but not CGMPs). Section 503B prohibits drug products compounded by an outsourcing facility from being compounded with bulk substances, unless such bulk substance (i) appears on a list established by the Secretary identifying bulk drug substances for which there is a clinical need, or (ii) the drug product compounded from such bulk drug substances appears on the FDA drug shortage list. The bulk substances must also meet additional quality/safety requirements.
In December 2013, the FDA published a notice inviting interested persons to nominate bulk drug substances for inclusion on the list of bulk drug substances that could be used for compounding under Section 503B and reopened the nomination in July 2014 due to inadequate nominations in the first round. The FDA continues to evaluate all the bulk drug substances nominated for the 503B bulks list and will publish its determinations on a rolling basis. The FDA had not previously issued any guidance which created a grey area for outsourcing facilities because the letter of the law required them to use bulk substances appearing on the “list”, but the list had not yet been published.
In its recent Interim Policy, the FDA has created an interim “list” and an interim solution to avoid disruption to patient treatment. The FDA has stated that it does not intend to take action for compounding drug products under Section 503B using bulk drug substances that are not the FDA drug shortage list if, among other conditions, the bulk substance appears on the 503B List 1 found on the FDA’s website. This List includes approximately 193 ingredients many of which are commonly used by compounders. While useful, the interim guide leaves unanswered questions as to whether or not there will be enforcement against outsourcing facilities that use ingredients not included in List 1.
FDA inspections and enforcement action of compounding pharmacies and outsourcing facilities are on the rise. Compounders who do not ensure their practices are fully compliant with changing regulations will be facing FDA enforcement action. Contact Frier Levitt for assistance guiding your pharmacy or outsourcing facility through the nuanced and ever changing regulations governing compounding.
