FDA 483 Observations in 503B Outsourcing Facilities

In this issue, we will continue our review of FDA 483 observations in 503B outsourcing facilities; specifically, we will look at the category involving "Compounded Product Quality."

COMPOUNDED PRODUCT QUALITY

• Your firm does not have any process validations for the aseptic production of your firm's suspension products, including but not limited to.....
• In a batch failure due to nonsterility, your firm's investigation documents only half of this lot was destroyed and does not provide any scientifically sound justification as to why the entire lot was not destroyed.
• The written stability program for drug products does not include reliable, meaningful, and specific test methods.
• Your firm does not maintain documentation of the start, stop, or elapsed time for the incubation of rapid sterility tests. The firm only temporarily records start and end times on a piece of tape on the box holding the sample, and this tape is discarded following testing.
• Your firm is using preservatives for sterile products produced as "multi-dose." However, there is no data to establish products using said preservatives have been tested to demonstrate efficacy.
• There is no testing of the preservative content in the injectable drug products at the time of release or during beyond-use dating studies.
• Your firm failed to test preservative content at the end of the expiration period to verify the preservative system is effective and protects the product over the shelf life under expected conditions of use.
• Not every batch of drug product purporting to be pyrogen-free is laboratory tested to determine conformance to such requirements.
• Your firm does not conduct potency testing for any finished drug products prior to distribution.
• Your firm has not established alert levels or initiated investigations into repeated microbial incursions into the ISO-5 classified zone.
• Failure to review any unexplained discrepancy and the failure of a batch of any of its components to meet any of its specifications whether or not the batch has already been distributed.
• Your firm had an action level environmental monitoring excursion on the surface of the table in ISO-7....too numerous to count CFUs were found. The isolates were not sent out for identification and no investigation was conducted.
• No investigations were conducted for rapid sterility tests when "background too high" result was obtained. This happened repeatedly over the past 3 months. There is no written definition of "background too high" in the firm's procedures.
• There are no instructions for the firm's practice of discarding samples deemed to have "background too high."
• The firm does not have procedures requiring eye exams for individuals that conduct review of rapid-sterility-test sample results.
• Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not followed.

More next week.

The FDA announced that effective December 31, 2021, it was withdrawing the March 2020 temporary guidance that, among other things, allowed "manufacturers that were not drug manufacturers" to produce alcohol-based hand sanitizers.

Effective Dec. 31, 2021, companies manufacturing alcohol-based hand sanitizers under the temporary policies must cease production of these products. After that date, manufacturers wishing to continue producing hand sanitizer can do so provided they comply with the tentative final monograph for over-the-counter topical antiseptics and other applicable requirements, including the FDA's Current Good Manufacturing Practice requirements.

Among the temporary guidance documents being withdrawn December 31 are those allowing 503As and 503Bs to compound hand sanitizer during the pandemic.