CSV FDA Warning Letter : Periodic Review

Date: 21 May 2010
Link: FDA Warning Letter (New Window)

Observation

6. Your firm failed to check the accuracy of the input to and output from the computer or related systems of formulas or other records or data and establish the degree and frequency of input/output verifications [21 CFR § 211.68(b)].

For example, the performance qualification of your (b)(4) system software (Validation No. 4000-03-PQ-0002) failed to include verification of the expiration date calculations in the (b)(4) system. In addition, there is no established degree and frequency of performing the verification. Discrepancy reports have documented that product labeling with incorrect expiration dates have been created and issued for use.

Your response states that you opened Investigation T-139 and you provide a January 29, 2010 through February 26, 2010 completion timeline. You have not provided a response to correct this violation and establish a corrective action plan to assure that computer systems are properly qualified.

Comment

This observation by the FDA relates to both the inadequacy in the initial validation of the computerised system and the failure to perform requalification.

With respects to the initial qualification of the computer system a risk assessment should have identified the potential risk of the failure to calculate the expiry date (a significant failure) and performed validation. However the challenges put on the software may not have generated the circumstances that the failure occurs, but would have provided a level of quality assurance that the function would operate correctly. The risk assessment may have also determined that due to the potential risk further detection methods should be in place to ensure that the incorrect expiry dated product did not move forward in to the supply chain.

Periodic Review of the computer system should have identified trends in failures of the control system to meet its requirements via trending incidents and deviations relating to the system. Where major failures are detected, then a process of redesign and process improvement should be implemented, to remove the risk of failure.

A Periodic Review of critical computer systems provides the most efficient method of assuring that the system is operating within its validated state and determining the level of revalidation required.

The Periodic Review should identify trends in system failure incidents or deviations are detected then a Corrective Action Preventative Action (CAPA) should be put in place to resolve the issue.

The Periodic Review should consider a number of things which I will add to a future article.