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Case Study O3 deals with validation, a relatively new concept to hospitaltransfusion services. Although TS have always evaluated new methods and equipment, the need for formal, documented validation has arisen out of the adoption of quality systems and the requirements of new standards and regulations targetted at TS.
This format is different from typical serologic cases (which focus on a patient's laboratory and clinical data and the resulting serologic investigation). Instead, various issues related to the case are discussed, along with links to external resources.
This case takes a topic- validation - and covers different aspects similar to a self-study module.The aim is to introduce validation concepts and to gather resources to use as tools and for further study when faced with validating a process. The case can act as a primer on validation or as just-in-time learning.
Upon completion of this exercise, participants should be able to
This case was motivated by the many citations for validation deficiencies found in the audit literature.
Validation of equipment is one of the most frequently cited deficiencies on the College of American Pathologists (CAP) transfusion medicine checklist:
1. Failure to have in place written validation protocols, maintenance of complete and accurate documentation of the performance of the validation protocols, and an analysis of the results by the blood bank computer system [21 CFR 211.68(a) & (b)] in that:
Observation 1: The response is inadequate, in that the "validation" data lacks specific details regarding the steps taken to qualify the equipment. For example, your response indicated that the incubation of the [redacted] instruments was performed for [redacted] minutes. However, there was no data or information regarding the assessment of the incubation temperature for the intended use of the equipment. Additionally, how were the times for the incubator assessed? Also, your response noted ?target? and "actual" times for the incubator and [redacted] shaker. However, there was no indication as to how the measurements were taken.
Failure to perform adequate process validation with a high degree of assurance. [21 CFR 820.75(a)] For example: The antibiotic disinfection process validation approved 9/25/93, Antibiotic Challenge, was not adequate. A worst case multiple microbe challenge was not performed, organisms were individually tested in the disinfection solution. A two log reduction was not achieved for Candida albicans. Additionally, the rationale for the organisms selected for the study could not be explained. [21 CFR 820.75 (a)]
We took this action because of the firm?s long-standing failure to comply with FDA?s Good Manufacturing Practices (GMP) regulation, now called the Quality System regulation, and its failure to fulfill commitments to correct deficiencies in its manufacturing operations.
These failures go back to 1993, when our inspection of the facilities where Abbott Diagnostics Division manufactures diagnostic products showed non-compliance with the GMP requirements. Areas of non-compliance included process validation, corrective and preventive action and production and process controls. The company?s failure to comply with these requirements increases the likelihood that the diagnostic products produced at these facilities may not perform as intended.
Because some provincial Colleges of Physicians and Surgeons are now going to accredit Canadian TS using CSTM Standards for Hospital Transfusion Services, v 1 and CSA Standard Z902-04, and because the UK is implementing legislation based on the EU blood directive, a case study on how and when to validate methods, equipment, etc., seems timely.
To test your knowledge and as an advance organizer for the discussion section, read and consider these questions:
Why do methods, equipment, etc., need to be validated?
What is a validation master plan and what is typical content?
Proceed to Discussion (includes interactive questions with feedback):
This case study has examined formal, documented validation as a quality system requirement of new standards and regulations for TS, with an emphasis on method validation. Many resources are available to help with validating processes. However, the task remains difficult due to its newness and the relative lack of exemplary validation protocol modelsthat can be adapted to the needs of individual TS.
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