FDA Warning Letter due to Inadequate Storage Conditions and Repacking/Relabeling Operations

Recommendation

20-22 June 2023
Barcelona, Spain

GMP & GDP Forum 2023
Day 1, 2 and 3

End of December 2022, the U.S. Food and Drug Administration (FDA) has published a Warning Letter dated 22 November 2022. The letter goes back to an inspection from 25 April to 09 May 2022 at a drug repackaging and relabeling facility located in Pennsylvania. The document summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for Active Pharmaceutical Ingredients (APIs). It also addresses Good Distribution Practice (GDP) aspects.

Customer Complaints for Returned APIs

The FDA says that the company did not adequately investigate customer complaints for returned APIs. In the Warning Letter, some examples are described:

• An API lot was returned to the company's facility because of quality issues. Nevertheless, the company redistributed the same lot of API to a different customer. An investigation to assess the drug quality was not performed.
• The company received a COA from one of the suppliers with an expiration date of 19 April 2024 for an API lot. This lot was distributed. Later, the supplier provided a COA with a different expiration date of 19 April 2023 for the same lot. No investigation was performed to assess whether the change in the expiration date was accurate and appropriate. Thus, it was unclear whether it was scientifically justified to distribute the API lot with a year longer expiration date.

The FDA points out, that it is the company's responsibility to ensure that API returned to the "inventory and redistributed has the identity, strength, quality, and purity that it is purported to have."

Storage Conditions

According to the FDA, the firm did not adequately monitor the API storage conditions:

• The temperature probes to monitor the controlled substances storage area and refrigerator were not operational at the time of FDA inspection.
• The firm could not provide records for temperature and humidity monitoring to demonstrate that the facility held the APIs under appropriate storage conditions.
• There were no documents available showing that the probe locations to monitor temperature and humidly were representative of the worst-case environmental conditions.

The FDA requested the company to provide, beside others, "a comprehensive assessment of [the] storage, holding, and environmental monitoring controls."

Repacking and Relabeling Operations

The FDA investigators observed that repacking and relabeling operations of APIs were performed in "an uncontrolled and open environment without adequate controls to prevent mix-ups and cross-contamination": The following example is given:

• Repackaging and relabeling was performed without line clearance procedures and appropriate documentation. This concerned in particular a highly potent and toxic agent and another API classified as an immunosuppressive agent.

The FDA points out that those operations require appropriate handling and controls to prevent cross-contamination into other drugs. Even if the company has already committed to no longer perform repacking and relabeling operations, the FDA is concerned that mix-ups or cross-contamination could have occurred in the past.

For more details, please see the complete FDA Warning Letter to MD Pharmaceutical Supply, LLC.