GMP Primer: Validation, Qualification and Documentation

In last week’s issue, we outlined a training session for introducing the basic principles of validation. This week, we continue our discussion with a focus on stages and levels of validation, the qualification process and validation reporting.

Part One: Qualification Stages

The four qualification stages of validation are:

1. Design Qualification (DQ) – In this stage, the design of the system or equipment to be validated is examined. The aim of DQ is to determine if the design serves user requirements and functional specifications adequately.
2. Installation Qualification (IQ) – IQ verifies that the equipment and its ancillary systems or sub-systems have been installed in accordance with installation drawings and/or specifications. It further details a list of all the cGMP requirements that are applicable to this particular installation qualification. These requirements must all be satisfied before the IQ can be completed and the qualification process is allowed to progress to the next stage.
3. Operational Qualification (OQ) – OQ aims to establish confidence that process equipment and sub-systems are capable of consistently operating within established limits and tolerances. OQ focuses on demonstrating that equipment (or facilities, services or systems) functions as expected; that all parts and components operate correctly; that all controls perform their intended function; and that all gauges and indicators are calibrated and display the correct values.
4. Performance Qualification (PQ) -- The purpose of PQ is to demonstrate compliance with all user requirements. PQ should be carried out using real process materials and tests and should simulate actual production conditions.

Part Two: Levels of Validation

• Prospective Validation is conducted prior to the distribution of either a new product, or product made under a revised manufacturing process, where the revisions may affect the product's characteristics. The process is broken down into individual steps which are then evaluated on the basis of past experience to determine whether they might lead to critical situations.
• Concurrent Validation is a subset of prospective validation and is conducted with the intention of ultimately distributing product manufactured during the validation study. Concurrent validation may be conducted on a previously validated process to confirm that the process is still valid.
• Retrospective Validation is the validation of a process based on accumulated historical production, testing, control and other information for a product already in production and distribution.
• Revalidation must be performed when changes affecting a manufacturing and/or standard procedure may have a bearing on the established product performance characteristics.

Part Three: Documentation

A validation master plan drives all validation efforts within a facility, outlining the principles involved in the qualification of a facility, defining the areas and systems to be validated and providing a written program for achieving and maintaining a qualified facility with validated processes. The plan should include protocols for each validation stage describing how each validation activity will be conducted:

• The DQ protocol defines the functional and operational specifications of the instrument and details the conscious decisions in the selection of the instrument and supplier.
• The IQ protocol provides for a systematic method of checking the static attributes of the equipment before it is used. It describes what the system is intended to do and all major components of the system.
• The aim of the OQ protocol is to enable reviewers to verify that all functional testing of quality-critical equipment and components has been performed and the verification data have been collected and attached to the OQ report.
• The PQ protocol defines all performance requirements, including critical quality attributes and critical process parameters in user requirements specifications.

Once each protocol is completed, a validation report summarizes all validation activities and results, gives recommendations for fixing errors and/or improving the overall quality and lists failures/anomalies and actions taken to resolve them.

• A validation report should have the following structure:
• Objectives of the validation;
• Description of the instrument or system validated;
• The scope of the effort, and all activities conducted;
• Rationale for the validation;
• A report on each stage of qualification;
• Conclusions; and
• Supporting documents and list of follow-up actions.

The complete Validation Overview training package, including slides, leader’s script and knowledge assessment, is available as part of the FDAnews Customizable Training Series for drug manufacturers and devicemakers.

Contact Information:
Dave Gallup
GMPTraining.com, Inc.
18585 Coastal Highway
Unit 10, #149
Rehoboth, DE  19971
215-870-5665
dagallup@gmptraining.com
www.gmptraining.com