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| 2 minutes read

FDA Warning Letter focuses on GMP failures at 503B compounding outsourcing facility

After a brief hiatus from the string of Warning Letters sent to 503B outsourcing facilities in mid- to late 2021, on June 7, 2022, FDA issued a Warning Letter to Hybrid Pharma, LLC based on an inspection ending in September 2021. FDA appears to be coming back with a vengeance, as the same Hybrid Pharma facility received a previous Warning Letter in November 2018. 

While the November 2018 Warning Letter to Hybrid focused solely on failures to meet the conditions of Section 503B, the June 2022 Warning Letter appears more focused on compliance with cGMPs.  The November 2018 Warning Letter, much like the majority of the Warning Letters sent to 503B outsourcing facilities in mid- to late 2021, outlined Hybrid’s shortcomings in complying with the statutory provisions of 503B, including 1) compounding drug substances not eligible for exemptions under 503B; 2) insufficient labeling; 3) failure to meet registration and bi-annual drug product reporting requirements; and 4) insufficient adverse event reporting procedures. 

It appears as though Hybrid corrected many of these failures prior to the 2021 inspection, as the only 503B statutory condition noted in the most recent Warning Letter is Hybrid’s failure to submit a complete report to FDA in December 2020 and June 2021 identifying all of the products compounded by the facility during the previous 6-month period. 

The remaining observations in the Warning Letter focus on failure to comply with cGMPs, which largely track the recent trends seen in cGMP observations in 483s and Warning Letters issued to 503B outsourcing facilities.  The cGMP violations listed in the Warning Letter include 1) failure to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed; 2) failure to establish the accuracy, sensitivity, specificity, and reproducibility of test methods; and 3) failure to establish an adequate system for monitoring environmental conditions in aseptic processing areas. 

Signed into law on November 27, 2013, the Drug Quality and Security Act created a new section 503B in the Federal Food, Drug, and Cosmetic Act. Section 503B governs compounders that are outsourcing facilities engaged in the compounding of sterile drugs.  Drugs that are compounded by an outsourcing facility can qualify for exemptions from FDA-approval requirements and the requirement to label products with adequate directions for use, but must comply with current good manufacturing practice (CGMP) requirements and reporting of adverse events, among other registration-related conditions.

FDA’s list of registered outsourcing facilities, which tracks recent enforcement actions, shows that many inspections of 503B outsourcing facilities from late 2021 and early 2022 remain open, so we will continue monitoring for trends in Warning Letters issued as a result of these inspections. 

Learn more about the implications of this development by contacting any of the authors.


north america, regulation, health research, pharmaceuticals, regulation-pharma

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