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by Matt Martin, PharmD, BCSCP, PCCA Director of Clinical Services
Section 503A of the FD&C Act prohibits the compounding of copies of human drug products that are essentially copies of a commercially available drug product when compounded “regularly or in inordinate amounts (as defined by the Secretary).”5
In an industry guidance issued by the FDA in January 2018 titled Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act, the FDA states that a compounded medication would be considered a copy of a commercially available drug product if it has the same active pharmaceutical ingredient (API), same, similar or easily substitutable strength (within 10%), and if the commercially available drug can be used by the same route of administration.6
Regarding the route of administration, the guidance notes that if any FDA-approved product can be used by the same route of administration (regardless of how it is labeled), the compound would still be considered a copy.
Health Canada expects the compounded product to provide a customized therapeutic solution to improve patient care without duplicating an approved drug product.7
You may be wondering how you would ever be able to help patients when a drug product is in shortage.
The FDA notes in their guidance that a drug product listed as “currently in shortage” on the FDA’s Drug Shortages List is not considered to be a commercially available product related to copies of drug products. The FDA also notes in the guidance that they do not plan to take action against those compounders that produce up to four copies per month of a commercially available drug product.
It is important to note that each time a copy of a commercially available product is dispensed counts as one of the four copies. In addition, the four copies count in all drug products and is not limited to four copies of a specific drug.
Health Canada notes that compounding should only be done if there is a therapeutic need or lack of product availability and should not be done solely for economic reasons for healthcare professionals.7
As previously mentioned, a high profile shortage of amoxicillin oral suspension and fever reducing ibuprofen and acetaminophen occurred in over-the-counter (OTC) suspension products.
Amoxicillin is classified in a group of antibiotics known as beta lactams. The FDA made note of risk mitigation strategies that need to be in place for working with beta lactam antibiotics through their Insanitary Conditions at Compounding Facilities guidance document.
Due to the points raised in that guidance document and the concern for potential regulatory scrutiny of pharmacies preparing these medications during the shortage, the Alliance for Pharmacy Compounding (APC) reached out to the FDA. APC’s outreach resulted in the FDA issuing a guidance document in November 2022 — a relatively short amount of time — on how compounding pharmacies should pursue compounding beta lactam preparations during the shortage. FDA stated within the guidance, titled Compounding Certain Beta-Lactam Products in Shortage Under Section 503A of the Federal Food Drug and Cosmetic Act, “One of the conditions in section 503A of the FD&C Act is that each drug product must be compounded for an identified individual patient based on the receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient.”8
In the case of the ibuprofen and acetaminophen shortages, those products never made it onto the FDA Drug Shortage List. Additional outreach on these shortages occurred from the American Pharmacists Association (APhA), APC and the National Community Pharmacists Association (NCPA).
The FDA’s response was issuing a guidance document, Compounding Certain Ibuprofen Oral Suspension Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act, that specifically allowed 503B outsourcing facilities to compound ibuprofen suspension (not acetaminophen) for hospitals and health systems. The FDA later updated that guidance document to also allow 503B outsourcing facilities to distribute their compounded ibuprofen suspension to 503A community pharmacies, where 503A pharmacies were allowed to dispense compounded ibuprofen suspension by prescription.9
Health Canada took a different approach as early as November 4, 2022, when they stated that they did not object to allowing compounding of these products without a prescription, but within a patient-healthcare professional relationship, until this shortage resolves.10Compounders in Canada served the needs of their patients within the provided framework and in accordance with any additional requirements of their college.
It is unclear as to why the FDA did not allow 503A pharmacies the ability to regularly compound ibuprofen suspensions for patients — typically young children — who did not have access to these pain and fever medications.
In an FAQ on the 503B outsourcing facility guidance, the agency did note that 503A pharmacies could compound copies of these medications as long as they did not do this regularly or in inordinate amounts under Section 503A of the FD&C Act.11
As previously mentioned, the FDA’s view qualifies only four copies per month per pharmacy, irrespective of patient or community need.
We know compounders serve the unmet needs of patients every day. Many times, this may be related to an allergy of a component of a manufactured drug product, a dose that’s not commercially available or the need for an alternate route of administration.
Each of you working in a compounding pharmacy has the ability to serve as a bridge between a drug shortage and when the manufactured drug product returns to pharmacy shelves. Patients may otherwise go without their medication or may need to switch to an alternate therapy. Prescribers need to know that you can help in drug shortage situations. The FDA and Health Canada have repeatedly recognized the ability of compounders to fill unmet patient needs and that compounders can address shortages.
It is also necessary to be mindful of the regulatory framework, including how the FDA or Health Canada defines a shortage, what the FDA or Health Canada considers duplicating manufactured drug products, and FDA guidance documents related to specific drugs or insanitary conditions. As we have seen with recent shortages, it is also necessary to be a member of and actively involved with professional organizations that are working to ensure that patients have access to needed medications through compounding when shortages happen. The FDA and Health Canada have a plethora of topics to address; having input from professional organizations on the emerging needs of patients, based on feedback from pharmacy professionals like yourself, can help steer future guidance and regulatory acts.
A version of this article originally appeared entirely in PCCA’s members-only magazine, the Apothagram.
21 USC 353a: Pharmacy Compounding, from Title 21-Food and Drugs, Chapter 9-Federal Food, Drug and Cosmetic Act, Subchapter V-Drugs and Devices, Part A-Drugs and Devices (amended Pub.L. 113-54, title I, (§)106(a), 2013 11.27). Accessed 02.27.2023 at https://uscode.house.gov/view.xhtml?req= granuleid:USC-prelim-title21-section353a&num=0&edition=prelim
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Office of Compliance. (2018 January). Accessed 02.276.2023 at https://www.fda.gov/files/drugs/published/ Compounded-Drug-Products-That-Are-Essentially-Copies-of-a-Commercially- Available-Drug-Product-Under-Section-503A-of-the-Federal-Food--Drug-- and-Cosmetic-Act-Guidance-for-Industry.pdf
Policy on Manufacturing and Compounding Drug Products in Canada (POL-0051) Accessed 3.15.2023 at https://www.canada.ca/en/health-canada/services/ drugs-health-products/compliance-enforcement/good-manufacturing-practices/guidance-documents/policy-manufacturing-compounding-drug-products.html
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Office of Compliance. (2022 November) Compounding Certain Beta-Lactam Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act. Accessed 04.06.2023 at https://www. fda.gov/media/163367/download
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Office of Compliance. (2023 February) Compounding Certain Ibuprofen Oral Suspension Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act. Accessed 04.06.2023 at https://www.fda.gov/media/164693/download
Health Canada. Letter. (2022) https://files.constantcontact.com/637dcb92701/ b3fd1b5f-b78f-47ba-ab60-55822821816e.pdf?rdr=true
FDA. (content current as of 02.09.2023) Questions and Answers on Compounded Oral Suspension Medications for Pain and Fever. Accessed 03.06.2023 at https:// www.fda.gov/drugs/human-drug-compounding/questions-and-answers-compounded-oral-suspension-medications-pain-and-fever