Warning Letter on Data Integrity Issues in the Microbiological Laboratory

An FDA inspection of the Pfizer subsidiary Hospira in India resulted in a FDA Warning Letter which was published in March 2019. The FDA inspectors identified serious GMP violations which resulted in a Warning Letter. Warning Letters of the US-American FDA always refer to corresponding Chapters of 21 CFR Part 211.

With regard to GMP violations in the microbiological laboratory, reference was made to Chapter 21 CFR 211.194(a): "Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards"

Observations during the inspection

The following GMP violation was criticized. During a walk-through of the laboratory, the inspector observed microbial growth on personnel/environmental monitoring media plates associated with aseptic processing line. During the evaluation of the laboratory records, it was found that the employees had each recorded a "Nil" growth of these plates. On the same day, it was also observed on 3 samples that the microbiologist had recorded significantly lower values. During the inspection, the employees also confirmed that the current laboratory records did not reflect the microbiological results.

Reaction of the company

The company confirmed these deficiencies in its reply and also confirmed that after "extra readings" in environmental monitoring and especially in personnel monitoring, significantly higher values were found. From the FDA's point of view, these findings cast doubt on the validity of all QC results.

Already during the inspection, the company suspended the release of the products until the data integrity problems had been resolved. In a subsequent meeting with the FDA, the company management confirmed the issue and discussed a plan to find the cause. In a more detailed response, several corrective actions were presented, including additional company and third party controls of the microbiological tests and data evaluations. These measures were not sufficient for the FDA because neither the extent of the inadequate reports nor the share of management and employees in the data manipulation was addressed.

Expectations of the FDA

The FDA expects the following actions in response to the Warning Letter relating to these violations:

• A final report on the CAPA measures implemented to ensure that aseptic activities are fully under control. The personnel involved in these activities should also be fully requalified.
• A final report on changes implemented in the QC laboratories to improve the inadequate procedures, training and cGMP documentation observed during the inspection.
• A retrospective assessment of the reliability of all microbiological laboratory data including water system and environmental monitoring. This evaluation should refer to all batches that were delivered to the USA and have not yet exceeded the expiration date.

Source: Warning Letter for Hospira Healthcare India Pvt. Ltd. dated March, 4 2019