FDA Warning Letter to US Manufacturer of non-sterile Drugs

On 23 July, the FDA published a Warning Letter to the company Omega Tech Labs LLC in Boise, USA. In this Warning Letter, the FDA summarised 5 deficiencies covering various areas, from microbiological control and the handling of microbiological deviations, to the control of the water used and the stability tests. The contents of the Warning Letter are summarised below.

Written Procedures

1. Omega had not implemented appropriate written procedures to prevent the contamination of unauthorised microorganisms in its non-sterile medicinal products. Although the microbiological limits were exceeded in several batches, the products were released after a longer waiting period in order to reduce the contamination by means of the preservatives and then released after repeated testing. There was also no clear investigation of the source.

Accordingly, the FDA demands the following reactions and information:

• A comprehensive assessment of production processes and microbiological risks.
• A risk assessment of potential contamination and the impact on unexpired batches.
• A complete investigation of all potentially contaminated batches.
• A definition of microbiological release specifications and test methods for the products
• A summary of test results from retained samples and an explanation of corrective actions for OOS results.

Production and Process Control

2. In addition, the company had failed to implement and validate adequate production and process control procedures. Process validation and equipment qualification data was missing, as was validation of the water system used for manufacturing and cleaning. The water was also suspected as the source of the contamination under point 1. Therefore, the FDA requires::

• An assessment and remediation of the water system.
• A plan to monitor and validate the manufacturing processes.
• A schedule for process qualification and written procedures for equipment qualification.
• Improvements to the cleaning validation programme to address worst-case conditions.

Testing of incoming raw materials

3. thirdly, the FDA criticised the lack of or inadequate testing of incoming raw materials, including active pharmaceutical ingredients. Glycerine in particular was released without validation of the analysis, which poses a risk of DEG or EC contamination.

As a result, the following actions are expected::

• A review of the material system and supplier qualifications.
• A description of the tests used to approve each incoming batch.
• Test results to assess the reliability of certificates of analysis.
• A risk assessment for all potentially contaminated batches and appropriate corrective actions.

Stability Data

4. fourthly, the FDA noted that adequate stability data were not provided to ensure the quality of the products throughout their shelf life. Accordingly, the FDA expects an evaluation and improvement of the stability programme, including methods for stability determination and studies and procedures to ensure shelf life.

Quality Control Department

5 Finally, the FDA clarified that the quality control department failed to ensure that products met CGMP standards. Deviations and microbiological test results were not adequately investigated and documented. Therefore, the FDA expects an assessment and remediation plan and that the quality control department is also given the necessary authority and resources.

More detailed information can be found directly in the FDA Warning Letter.