In an APhA2023 education session titled “Back to the Basics: Nonsterile Compounding 101,” Matt Martin, PharmD, BCSCP, explained the FDA’s role in 503A compounding, when to utilize certificate of analysis for active ingredients in compounds, how to assign beyond-use dates (BUDs) to nonsterile preparations, and how to calculate the Minimum Accurately Weighable Quantity for balances as defined by the FDA.
Dr. Martin began by explaining the differences between 503A and 503B pharmacies. He stated that 503A pharmacies do not have to comply with federal laws on new drugs, directions for labeling, or current good manufacturing practice (cGMP). In contrast, 503B pharmacies are FDA-registered, can ship across the country, must produce sterile preparations, must comply with cGMP, and may compound patient-specific prescriptions.
Dr. Martin also described insanitary conditions that may occur at compounding facilities. Insanitary conditions are conditions that could cause a drug to become contaminated with filth or rendered injurious to health. He explained that “The drug itself need not actually be contaminated.” Other conditions, he noted, can also cause insanitary conditions:
• Vermin (e.g., insects, rodents) or other animals (e.g., dogs) or evidence of their presence (e.g., urine, feces) in the production area or adjacent areas
• Visible microbial contamination (e.g., bacteria, mold) in the production area or adjacent areas
• Foreign matter in the production area (e.g., rust, glass shavings, hairs, paint chips).
Dr. Martin also discussed interim policy on compounding using bulk drug substances under Section 503A of the Federal Food, Drug, and Cosmetic Act. He explained that a compounded drug product has the same active pharmaceutical ingredient(s) (APIs) as the commercially available drug product; the APIs have the same, similar, or an easily substitutable dosage strength; and the commercially available drug product can be used by the same route of administration as prescribed for the compounded drug.
According to the Unites States Pharmacopoeia 795 Revisions on extending BUDs, if there is a stability study using a stability-indicating analytical method for the API(s), compounded nonsterile preparation (NSP) formulation, and material of composition of the container closure that will be used, then the BUD indicated by the study may be used in lieu of the BUDs for aqueous and nonaqueous dosage forms for up to a maximum of 180 days, and any CNSP that is extended beyond that date would need to be tested for antimicrobial effectiveness.
Dr. Martin ended the session by discussing minimum accurately weighable quantity, also known as MAWQ. MAWQ is the smallest weight or mass that will produce no greater than a predetermined fraction of error on a properly calibrated, situated, and operated balance. He explained, “The compounder should use professional judgment when assigning the acceptable error for each process.”
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Published April 17, 2023