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Regulatory Focus™ > News Articles > 2020 > 7 > FDA warns California-based CDMO, Mexican drugmaker

FDA warns California-based CDMO, Mexican drugmaker

Posted 22 July 2020 | By Michael Mezher 

FDA warns California-based CDMO, Mexican drugmaker

The US Food and Drug Administration (FDA) earlier this month warned two companies, contract development and manufacturing organization (CDMO) Stason Pharmaceuticals and Mexican drugmaker Signa SA de CV.
 
Stason Pharmaceuticals, Inc.
 
In its warning letter to Irvine, CA-based CDMO Stason Pharmaceuticals, FDA cites the company for product testing and data integrity issues uncovered during a three-week inspection last October.
 
According to FDA, the company was not able to assure that temozolomide capsules it produced met dissolution attributes throughout their shelf life. After obtaining out-of-specification (OOS) results for multiple lots of the drug, the company investigated some of the OOS results and had a relaxed dissolution specification for the drug approved by FDA.
 
However, FDA says Stason’s “response was inadequate because [it] did not determine a clear root cause of the dissolution failure found in a lot after the specification was revised.” The agency notes that the company is continuing to perform studies to identify an alternate desiccant but adds that the company has not shown that the dissolution failures were related to over-drying of the capsules.
 
FDA also says the company “lacked adequate interim measures to address cleaning issues, including a verification failure, following the manufacture of methotrexate tablets.”
 
Additionally, FDA says Stason did not have sufficient controls in place to ensure the integrity of electronic test data: “Notably, a demonstration performed during the inspection revealed that the computer operating the [Redacted] spectrophotometer (ID: L-563) was not secured such that data files could be deleted without the knowledge of your quality unit. The instrument was used for finished product release and stability testing for several drug products.”
 
Signa SA de CV
 
After inspecting Signa SA de CV’s Toluca, Mexico facility in December, FDA is warning the company for failing to adequately investigate OOS results and not putting in place appropriate corrective actions to address the issues.
 
In one instance dating back to January 2018, FDA says the company received an OOS result for a batch of its product, but “ultimately concluded, without adequate supporting evidence,” a root cause. The company later found the root cause to be unsupported.
 
After another instance in October 2018, FDA says the company failed to conduct “a meaningful or formal Phase 2 manufacturing investigation,” following an OOS result.
 
Signa is part of the Apotex group, which FDA says has been cited for similar deviations at other facilities in its network.
 
“FDA cited similar CGMP deviations at other facilities in your company’s network. These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate,” FDA writes.

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