Quality Management Systems - Process Validation Guidance

Front page:
This document was originally intended "to provide non-binding guidance to regulatory authorities for use in the regulation of medical devices..." and as of now I still believe many auditors hold this in high regard.

0 - Introduction:
Process validation is a term used in the medical device industry to indicate that a process has been subject to such scrutiny that the result of the process (a product, a service or other outcome) can be practically guaranteed.

0 - Introduction:
Validation of a process entails demonstrating that, when a process is operated within specified limits, it will consistently produce product complying with predetermined (design and development) requirements.

0 - Introduction:
In general, the validation of a process is the mechanism or system used by the manufacturer to plan, obtain data, record data, and interpret data. These activities may be considered to fall into three phases: 1) an initial qualification of the equipment used and provision of necessary services – also know as installation qualification (IQ); 2) a demonstration that the process will produce acceptable results and establishment of limits (worst case) of the process parameters – also known as operational qualification (OQ); and 3) and establishment of long term process stability – also known as performance qualification (PQ).

2 - Definitions:
2.4 Process validation: establishing by objective evidence that a process consistently produces a result or product meeting its predetermined requirements.

3 - Process validation within the quality management system:
While the output of a process may be verifiable, application of software used in that process should be validated for its intended use.

5 - Conduct of a validation:
5.1 Getting started
Members of the validation team could include representatives from or personnel with expertise in:
· Quality Assurance
· Engineering
· Manufacturing
· Others depending on company organization and product types:
· Laboratory
· Technical Services
· Research & Development
· Regulatory Affairs
· Clinical Engineering
· Purchasing/Planning
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Many manufacturers develop what is referred to as a master validation plan which identifies those processes to be validated, the schedule for validations, interrelationships between processes requiring validation and timing for revalidations.
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Following is a list of activities which may be used as a checklist to review validation activity:
· Form multi-functional team for validation
· Plan the approach and define the requirements
· Identify and describe the processes
· Specify process parameters and desired output
· Decide on verification and/or validation
· Create a master validation plan
· Select methods and tools for validation
· Create validation protocols
· Perform IQ, OQ, PQ and document results
· Determine continuous process controls
· Control the process continuously

5.3 - Installation Qualification (IQ):
Simply put, IQ means is it installed correctly?
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Copies of the suppliers’ qualification studies should be used as guides, to obtain basic data, and to supplement installation qualification. However, it is usually insufficient to rely solely upon the validation results of the equipment supplier. Each medical device manufacturer is ultimately responsible for evaluating, challenging, and testing the equipment and deciding whether the equipment is suitable for use in the manufacture of a specific device(s). The evaluations may result in changes to the equipment or process.

5.4 - Operational Qualification (OQ):
The use of statistically valid techniques such as screening experiments to establish key process parameters and statistically designed experiments to optimize the process can be used during this phase.

5.5 - Performance Qualification (PQ):
In this phase the key objective is to demonstrate the process will consistently produce acceptable product under normal operating conditions.

5.6 - Final Report:
At the conclusion of validation activities, a final report should be prepared. This report should summarize and reference all protocols and results. It should derive conclusions regarding the validation status of the process. The final report should be reviewed and approved by the validation team and appropriate management.

6.1 - Monitor and control:
Trends in the process should be monitored to ensure the process remains within the established parameters. When monitoring data on quality characteristics demonstrates a negative trend, the cause should be investigated, corrective action may be taken and revalidation considered.

6.2 - Changes in processes and/or product:
Any changes in the process and /or product including changes in procedures, equipment, personnel, etc. should be evaluated to determine the affects of those changes and the extent of revalidation considered.

6.3 - Continued state of control:
Various changes may occur in raw materials and/or processes, which are undetected, or considered at the time to be inconsequencial. (An example of this type of process is sterilization.) These changes may cumulatively affect the validation status of the proc ess. Periodic revalidation should be considered for these types of processes.

7 - Use of historical data for validation:
A complete validation based onhistorical data is not feasible if all the appropriate data was not collected, or appropriate data was not collected in a manner which allows adequate analysis. Historical manufacturing data of a pass/fail nature is usually not adequate.