Compounding warning letters to 503A facilities between 2017 and 2021

Abstract

Background: The growing population demand and the epidemic lead of coronavirus disease 2019 have highlighted the critical importance of patient access to compounded formulations, including for special purposes such as pediatrics, geriatrics, and other uses. However, there are many potential risks, including quality issues and 503A facilities have not received valid prescriptions for individually-identified patients for a portion of the drug products they produce.

Objective: The aim is to analyze the (503A facilities) warning letters and identify the problem of compounding medicines not meeting the United States Pharmacopoeia specifications.

Methods: Content analysis and descriptive statistics methods were used to analyze the violations of compounding warning letters from 2017 to 2021. The content of warning letter violations was analyzed in terms of both the compounding environment and 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced.

Results: A total of 113 compounding warning letters (503A facilities, N = 112) from 2017 to 2021 were analyzed in this study. The percentage of 503A facilities involved in sterile compounding environmental issues was 79.46%, with facility design and environmental controls (73/89, 82.02%), cleaning and disinfecting the compounding area (59/89, 66.29%), and personnel cleansing and garbing (44/89, 49.44%) being the top 3 issues. Seventy-two (72/112, 64.29%) 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced. Fifty-one (51/72, 70.83%) of these warning letters were related to sterile environment issues, and 28 warning letters identified specific drugs that did not qualify for Section 503A exemptions.

Conclusion: The warning letter of compounding drugs issued by Food and Drug Administration can be used as a learning tool for compounders. Compounders can learn from the experience and lessons, improve compounding operations and reduce mistakes.