Sterile Product Manufacturing Process: Warning Letter to Texas Longhorn

During an FDA inspection in the fall of 2021 at Texas Longhorn RX, LLC, the inspector had identified a number of serious deficiencies in the sterile product manufacturing processes used there. According to the FDA, these deficiencies could result in patient harm. Accordingly, the agency responded by issuing a 483 er form.

The regulatory background in this case is Section 503A of the FDCA (Food, Drug, and Cosmetic Act), which deals with the manufacturing conditions for human drugs in the state-licensed pharmacy. Any exceptions and their requirements are also described there.

Content

In their Warning Letter, the FDA describes a number of deficiencies with regard to the requirements of FDCA:

• The design of the facility allows the flow of unclean air into cleaner areas
  a. The separation between ISO5 and ISO7 cleanroom classes were not adequately sealed
  b. There were visible cracks between ISO7 and ISO8 areas
• Cross-contamination between high-risk and lower-risk drugs could not be ruled out, as both were manufactured in the same premises
• There was visible contamination and unknown foreign substances on surfaces in the ISO classified areas
• Transfer disinfections were absent
• No smoke studies had been conducted
• Conditions during APS (media fills) were not suitable to simulate manufacturing conditions under worst case conditions

Reactions

Subsequently, the company sent the FDA a list of corrective actions. However, the authority commented as follows:
"We have reviewed your company's response to the FDA 483 form. Although one of your proposed remedies appears appropriate, others are deficient."

For example, the measure to improve sealing between ISO5 and ISO 7 was not convincing because it lacked a detailed description of the corrective actions. Similarly, there was no assessment of whether reclassification might be necessary as a consequence. The same applies to the cracks found in the wall. Furthermore, although measures of spatial separation to prevent cross-contamination were announced, there was no time frame and no indication that production would not continue in its previous form for such a long time.

The foreign substance found was removed by the company, but without clarification of what it was, let alone finding out what the source was.

Feedback on the other defects found was in similar form, leading to the Warning Letter that is now available.

For a more detailed description, please read the Warning Letter to Texas Longhorn on the FDA website.