To Compound or Not to Compound? That is the Question!

To Compound or Not to Compound? That is the Question!

FDA has issued two guidance documents today (here) and (here) that outline the FDA’s interim enforcement policy relative to the use of bulk drug substances in outsourcing facilities and/or pharmacy compounding. The Agency identifies the historical evolution of the list of bulk drug substances acceptable for use in the compounding of drug products and has described its interim enforcement policy regarding drugs compounded under Section 505 A (dealing with pharmacy compounding) and Section 503 B (dealing with outsourcing facilities) of the Federal Food Drug and Cosmetic Act.

503 A and 503 B bulk drug substances must either be found in an FDA approved drug product or in an applicable USP of NF monograph. If not, the bulk drug substance must appear on a specified list. In the case of the 503 A drugs, a pharmacy compounding advisory committee must also weigh in on the bulk drug’s acceptability for inclusion on the list.

FDA has asked for nominations for drugs to be included on the bulk API lists for both drugs subject to compounding under both sections of the Act and has broken down the drugs nominated for inclusion in those lists (with the exception of bulk drug substances currently contained in FDA approved drug products or for which there is an applicable USP or NF monograph) into four categories.

List 1 – bulk drug substances for which there is adequate information submitted to the Agency for evaluation as to whether the drug may be compounded (criteria outlined in the guidance documents)

List 2 – bulk drug substances which raise safety concerns

List 3 – bulk drug substances nominated without adequate support

List 4 – bulk drug substances for which the FDA has already made a determination that may not be used in compounding.

The FDA has not yet finalized these lists, so an interim policy is being used to prevent disruption to patient access to needed products.

The bottom line is that in addition to compounded drugs that contain bulk drug substances that are already contained in FDA approved products or that have an appropriate USP or NF monograph, FDA will exercise enforcement discretion if the drugs appear on List 1 of the 503 A or 503 B nominated bulk drug substances prior to FDA’s final determinations. In addition, all bulk drug substances must be originally manufactured in a facility that is registered under 510 of the Act and is accompanied by a valid Certificate of Analysis (COA). The compounded product using the bulk drug substance must also meet all other application requirements for Section 503 A or Section 503 B of the Act, respectively.

FDA expects that no bulk drug substance on lists 2-4 may be used in compounding at this time. The FDA lists may be found here for section 503 A  and here for section 503 B.

With this guidance, compounding pharmacies and outsourcing facilities may now have a better picture of what bulk drug substances they can use in their compounding operations without FDA enforcement action – at least for now!