This week, we will review the DQSA and the requirements for a drug to be compounded in the U.S. As described in the DQSA, specific sections of 503A of the FD&C Act require rulemaking or other action by the FDA. These actions include the development of the following:

1. Withdrawn or Removed List
FDA promulgated a final rule which lists drug products that may not be compounded because they have been withdrawn or removed from the market because the drug products or components of the drug products have been found to be unsafe or not effective. FDA intends to update this list periodically, and expects compounders to comply with the list as it currently exists and with any updates.

We will look at this next week.

2. Bulk Drug Substances List
Section 503A provides that a drug product may be compounded using bulk drug substances that do not have an applicable USP or NF monograph and are not components of FDA-approved drugs if the bulk drug substances appear on a list developed by FDA and issued through regulation. Until a bulk drug substances list is published in the Federal Register as a final rule, human drug products should be compounded only using bulk drug substances that are components of drugs approved under section 505 of the FD&C Act, or are the subject of USP or NF monographs.

NOTE: Here is the following update as of April 23, 2021 as published in the Electronic Code of Federal Regulations (E-CFR).

Title 21

SECTION 216.23
     CFR Title 21 Volume 4 Chapter I Subchapter C Part 216 Subpart B › Section 216.23

216.23 Bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act.

(a) The following bulk drug substances can be used in compounding under section 503A(b)(1)(A)(i)(III) of the Federal Food, Drug, and Cosmetic Act.

(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 (for topical use only).

(5) Squaric acid dibutyl ester (for topical use only).

(6) Thymol iodide (for topical use only).

(b) After balancing the criteria set forth in paragraph (c) of this section, FDA has determined that the following bulk drug substances will not be included on the list of substances that can be used in compounding set forth in paragraph (a) of this section:

(1) Oxitriptan

(2) Piracetam

(3) Silver Protein Mild

(4) Tranilast

(c) FDA will use the following criteria in evaluating substances considered for inclusion on the list set forth in paragraph (a) of this section:

(1) The physical and chemical characterization of the substance;

(2) Any safety issues raised by the use of the substance in compounded drug products;

(3) The available evidence of the effectiveness or lack of effectiveness of a drug product compounded with the substance, if any such evidence exists; and

(4) Historical use of the substance in compounded drug products, including information about the medical condition(s) the substance has been used to treat and any references in peer-reviewed medical literature.

(d) Based on evidence currently available, there are inadequate data to demonstrate the safety or efficacy of any drug product compounded using any of the drug substances listed in paragraph (a) of this section, or to establish general recognition of the safety or effectiveness of any such drug product. Any person who represents that a compounded drug made with a bulk drug substance that appears on this list is FDA approved, or otherwise endorsed by FDA generally or for a particular indication, will cause the drug to be misbranded under section 502(a) and/or 502(bb) of the Federal Food, Drug, and Cosmetic Act.

[84 FR 4710, Feb. 19, 2019]

In subsequent issues of this Newsletter, we will look at the following two actions required of the FDA:

3. "Demonstrable Difficulties" for Compounding
4. Memorandum of Understanding Between FDA and the States

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
IJPC
Remington: The Science and Practice of Pharmacy Twenty-second edition