FDA Warning Letter to US Drug Maker

Recommendation

24/25 April 2024

QC Compliance Manager - Live Online Training

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter to Blaine Labs Inc, a US-based drug maker. In the Warning Letter dated May 5, 2020, significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals are summarized.

During an inspection from September 25 to 30, 2019 at the company's drug manufacturing facility in Santa Fe Springs, California, the FDA  observed specific violations.

Inadequate OOS-investigations

The Warning Letter mentions that several investigations into out-of-specification (OOS) test results, for both finished products and raw materials, were inadequate. Although the company's "Quality Unit (QU) was aware of the drug quality failure, no investigation of manufacturing was performed and the lot was approved for release to customers."

According to the FDA, the response to Form FDA 483 was inadequate, as Blaine Labs Inc lacked adequate improvements to investigation programme and did not adequately evaluate the manufacturing processes to ensure that failures are properly remediated. Among other things, the FDA is now demanding a retrospective, independent review of all invalidated OOS results.

Failture to validate the drug product manufacturing processes

In the field of validation, the FDA accuses the company of numerous violations:

• lack of process validation for a topical antifungal solution and cream
• failure to qualify the equipment used to manufacture the products
• failure to qualify the extensive hold times
• failure to validate the equipment cleaning processes

In the Warning Letter, the FDA requests a detailed summary of the validation programme as well as a timeline for performing process performance qualification (PPQ) for each of the marketed drug products and improvements to the cleaning validation programme. Also, the company was requested to prepare a plan for initiating testing on the reserve samples and to communicate the results of all testing to the FDA.

No adequate water monitoring

The FDA criticized that the company did not adequately monitor the pharmaceutical water to make sure that it is suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.

No adequate quality unit established

As a further point, the FDA criticizes that the Quality Unit (QU) did not ensure that adequate procedures and oversight of the manufacturing activities were established. The FDA gives multiple examples:

• the company lacked written or approved procedures describing process validation equipment qualification, OOS investigations, stability programme, and change control
• multiple versions of a bulk material test report template were in circulation
• laboratory personnel signed off on their own test reports without secondary verification

In conclusion, the FDA requests the company to correct the violations cited in the Warning Letter promptly. " Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction."

For further information please see the complete FDA Warning Letter to Blaine Labs Inc.