Warning Letter for inadequate OOS Investigations and Complaint Handling

Recommendation

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The U.S. Food and Drug Administration (FDA) recently warned Teligent Pharma, Inc. for different significant violations of current good manufacturing practice (CGMP) at the company's facility in Buena, New Jersey - among others, for failing to thoroughly investigate out-of-specification (OOS) test results.

OOS Investigations and Stability Testing

According to the FDA, out-of-specification (OOS) investigations were inadequate. In this context, the following aspects were criticized:

• Timeline: OOS results were not investigated in a timely manner.
• Root causes: OOS investigations were concluded, without adequately assigning definite root causes or without adequate supporting evidence.
• Impurities: Despite a specific lot Clobetasol propionate failing for impurities at release testing and at two different stability intervals, Teligent Pharma, Inc. took no market action.
• CAPAs: Investigations were closed without the implementation of CAPAs such as revising the expiration date.

In addition, according to the FDA, Teligent Pharma, Inc. failed to test stability samples within the timeframes stipulated in the company's corresponding SOPs. In some cases, the internal targets were exceeded by several months. As an example, the FDA mentions two stability studies: The results were generated six months from the test date in one case and nine months in the other. On both occasions, the results were failing. Due to the delay in generating and reviewing the results, the company was unable to investigate the OOS results in a timely manner.

Complaint Handling, Changes, Field Alert Reporting Violations

In the warning letter it is also stated that the company's quality unit failed to follow their complaint procedures. Product quality complaints were not adequately reviewed, approved, and closed within the time limits specified in the corresponding SOP. More than half of the complaints received during 2018/2019 remained open for more than 30 days. At least six complaint investigations were even open for more than 150 days.

Furthermore, it is stated that Teligent Pharma, Inc., failed to evaluate changes in the manufacturing process prior to implementation to assess impact to the product and ensure consistent manufacturing operations and drug quality.

The last point mentioned in the warning letter concerns the failure to report FAR (Field Alert Reporting) related events within three days of becoming aware of a problem.

Conclusion

As in a previous inspection in 2017 similar CGMP observations were made, the FDA comes to the conclusion that executive management oversight and control over the manufacture of drugs are inadequate. The company was requested to promptly correct the violations cited in warning letter.

For more detailed information please read the FDA's Warning Letter to Teligent Pharma, Inc.