VAL-080 Validation Master Plan

5.1   Validation Life Cycle

Validation is establishing documented evidence that provides a high degree of assurance a specific method, process or system will consistently perform as intended.  All operations at the GMP facilities which have a direct impact on product quality will be validated in accordance with the code of GMP and in compliance with site policy.

Manufacturing at GMP site, aims for total quality commitment; i.e. quality is built into the product.  The building of quality is assured through the process of validation by embracing the Life Cycle concept of validation which begins with identification of the requirements for a system or process and continues through design, installation, commissioning, qualification, operation and maintenance and retirement.  This document is intended to outline the life cycle approach to validation.

5.2    Validation Overview

A brief summary of each validation type is detailed below.  A more detailed description of the scope of each type of validation is described in their respective procedures as detailed below.

5.2.1 Process Validation

Process validation refers to testing related to the performance of the product formulation under pre-determined processing conditions.  Process validation encompasses all aspects of manufacturing and packaging that directly impact product manufacture and packaging.  Refer to SOP VAL-085Process Validation Guideline.

5.2.2 Cleaning Validation

Cleaning validation provides documented evidence that a cleaning procedure is effective in reducing chemical, microbiological and cleaning agent contamination to pre-defined maximum allowable limits that ensures that there is a minimum risk of product contamination.  Refer to SOP VAL-020 Procedure for Cleaning Validation.

5.2.3 Equipment Qualification

Equipment qualification provides documented evidence that the equipment consistently and without detriment achieves and maintains parameters that could directly or indirectly affect, product quality.  Refer to SOP VAL-090Equipment Validation Guideline.

5.2.4 Computer Validation

Computer validation ensures that all computerised systems (including hardware and software) that have a direct impact on product quality, operates as per the required specifications and principles of GxP.  Refer to SOP VAL-040 Computer System Validation.

5.2.5 Utility Validation

Utility validation provides documented evidence that the utility systems that have a direct impact on product quality, operate as per requirements and consistently and without detriment achieves and maintains parameters that directly impacts product quality.  Refer to SOP VAL-095Facility and Utility Validation Guideline.

5.2.6 Analytical Method Validation

Analytical method validation provides documented evidence that test methods are effective, reproducible and repeatable.  Refer to SOP LAB-135 Validation of Analytical Test Procedures.

5.3 Validation Documentation Overview

All validation activities are conducted according to local validation procedures as defined in Section 5.2.

Validation Documentation shall be organized and retained to allow for easy retrieval.  Each document shall be assigned a unique document code as per site procedure and shall be retained in accordance with the site document retention procedures.

5.3.1 Validation Master Plan

This Validation Master Plan (VMP) documents the general approach to validation at Site, Site. The requirements for specific validation activities will be defined in guidelines and procedures.

5.3.2 Validation Project Plans

A Validation Project Plan or Project Commissioning and Qualification Plan shall be used for the validation of complex projects.  Simple projects may be managed by the use of protocols or through the change control system together with supportive documentation.

5.3.3 Validation Protocols

Protocols outline the scope of work and the specific activities and tests that are required to complete the validation.  They also contain the predetermined acceptance criteria for the validation.

5.3.4 Validation Reports

A Final Validation Report is used to summarize and document a completed validation study.  The report serves as a certification of completion of validation.

An Interim Validation Report shall be used when additional studies are to be executed, but a review of the current results and validation status is required (e.g. for batch release during a concurrent validation study).

5.3.5 Validation Status

The validation status lists all systems requiring validation and contains details on the current validation status of the system.  The validation status will be updated on a quarterly basis by the Validation Committee and presented to the Site Quality Review Team as a detailed status and gap analysis report on the validation state of the plant.

Other documents that are required to support the validation life cycle will be detailed in the applicable procedures or Validation Project Plans.

5.4 Validation Approaches

Validation Approaches include:

5.4.1 Prospective Validation

Prospective validation establishes documented evidence that a process does what it purports to do prior to release of product for commercial distribution, or release of the system for use.

5.4.2 Concurrent Validation

Concurrent validation establishes documented evidence on a batch-to-batch basis that the equipment, system, or process does what it purports to do; allows under certain conditions (e.g. predetermined acceptance criteria) batch-to-batch release of product for commercial distribution prior to completion of the validation study.

5.4.3 Retrospective Validation

Retrospective validation establishes documented evidence using historical process data, such as batch records and trend analyses, that a process or system does what it purports to do.

5.4.4 Risk Based Validation

Science and risk-based validation approaches may be used to narrow the scope of the validation to focus on those areas of potential risk to product quality or regulatory compliance.

Prospective validation approaches are required for new systems or processes, and for systems or existing processes that undergo significant changes that require validation.  An exception to this requirement is new processes that are run infrequently, as described in the concurrent validation section below.

Concurrent validation may be used for well-understood and documented systems and processes under the following circumstances:

a. For a legacy systems or process that may not have been previously validated, provided that there are no proposed major changes to the system or process;

b. When the process is run infrequently;

c. For validation of rework procedures;

d. For minor changes to an existing validated system or process; and

e. When there are no significant process or product failures attributable to process-related causes (i.e. failures have assignable causes such as operator error or equipment failure)

Retrospective validation approaches may be used for legacy systems or processes, provided that:

a. The system or process is well understood and documented through full-scale commercial manufacturing experience;

b. There are no major historical changes to the system or process;

c. Representative historical data are available for all Critical Process Parameters and Critical Quality Attributes; and

d. There are no significant process or product failures attributable to process-related causes (i.e. failures have assignable causes such as operator error or equipment failure).

The use of prospective, concurrent, or retrospective validation approaches shall be documented in a VMP, VPP, PCQP, or protocol, and approved by the VC.  Concurrent and retrospective validation approaches must have documented justification.

5.5 Validation Methodology

5.5.1 When to Validate

The need for validation of new or modified systems or processed will be determined though change control and impact assessment.  The need for validation of legacy systems or process will be determined though the validation master plan and impact assessment.

5.5.2 Design Review

For New Direct Impact Systems, a Design Review shall be conducted, to ensure the system meets site requirements, product and process quality and regulatory requirements and is considered fit for its intended use.

5.5.3 Standard Operating Procedures

Standard Operating Procedures (SOP) used in the execution of protocols shall be approved prior to the commencement of Performance Qualification / Process Validation.  If draft procedures are used, they shall be attached and approved as part of the protocol.

5.5.4 Commissioning

Commissioning Testing may be used to verify critical functions and components, if the commissioning tests successfully meet all approved predetermined acceptance criteria and the tests meet documentation requirements.

5.5.5 Test Equipment Qualification and Calibration

All Test Equipment used in the execution of validation protocols shall be verified to be within their calibration status prior to use.  Calibration status shall be documented in the validation protocol.  If required test equipment qualification shall be verified as complete prior to use and documented in the validation protocol.

5.5.6 System Description and Operation

Documentation (e.g. User Requirement Specifications, Vendor Operation and Maintenance Manuals) must be available that describes the system including what the system does, and how the system performs its functions.  The documentation will be used to perform the Impact Assessment and will serve as the basis for defining validation acceptance criteria.

5.5.7 Validation Deviations

Deviations that occur during validation shall be documented and investigated in accordance with site procedures.

5.5.8 Validation Acceptance and Approval

Each validation event will be reviewed and approved by authorised individuals as detailed in the relevant guideline documents.  Where applicable, a minimum of three consecutive events conducted on a fixed process with the same predetermined acceptance criteria will be required before the validation event is considered complete.  Specific acceptance criteria for validation projects will be detailed in validation project plans and protocols.

5.5.9 Maintaining the Validated State

All processes and systems once validated will be maintained in a validated state through the life cycle of the process / system.  Following completion of validation testing, all planned and unplanned changes with potential impact on validated systems and/or processes shall be addressed by established change management procedures (e.g. change control, deviation, investigations).  These changes shall be assessed against prior validation studies and an impact assessment performed as per site procedure.  Re-qualification and revalidation requirements are identified by the following mechanisms:

a. Change Control System

b. Product Audits (includes review of Deviations and Cross Functional Investigations)

c. Periodic Review

Validated Systems and Processes are subject to Periodic Review.  The results of the periodic review shall be documented, reviewed, and approved by the VC.  The review may result in the need for additional studies.  The periodic review frequency shall be based on the results of risk assessment and regulatory requirements.  Periodic reviews shall be conducted within the time interval not to exceed five (5) years.  Periodic review of process validation may be combined with the Annual Product Records Review.  Where no significant changes have been made to the validated status, a review with evidence that facilities, systems, equipment and processes meet the prescribed requirements fulfils the need for revalidation.