GMP Requirements for Process Validation
The expectations placed upon the manufacturer regarding GMP compliant execution of process validations can be categorized into three levels:
- The quality assurance system must include GMP compliant requirements for process validation.
- Process validations must be executed according to the general requirements of the QS system.
- The product and process-specific validation design must be appropriate for the specific risks to the patient health and be scientifically justified.
The expectations which GMP inspectors should place on process validations are presented in the following.
If not noted otherwise, the expectations apply regardless of the validation approach used (e.g. traditional or continuous process verification).
Quality Handbook and Process Validation
The Quality Handbook should include a voluntary commitment declaration by the general management to perform process validations in accordance with the EU GMP Guidelines requirements, to provide the necessary organisational framework and the necessary personnel and material resources permanently.
The commitment to process validation applies also for manufacturers which produce medicinal products on behalf of third parties. Responsibility for the validity of manufacturing processes in production cannot be delegated.
Should only a portion of the medicinal product manufacturing steps be performed at a manufacturing site, then the limitation of responsibility for process validations should be regulated in a quality agreement between contract giver and contract acceptor.
Contract giver must be obligated to provide all the necessary information which a manufacturer requires to fulfil his responsibility.
Standard Operating Procedures for Process Validation
The fundamental approach to process validations used at a manufacturing site and the general work procedures should be described in a standard operating procedure (SOP). It is at the discretion of the company whether this SOP be an individual document or be integrated in the validation master plan.
The following aspects should be addressed in the SOP at a minimum:
- Definition of the scope:
- Areas for which this SOP applies
- Types of products for which the manufacturing processes are to be validated
- Responsibilities of personnel for process validation
- Listing of manufacturing processes subject to validation and their validation status in the validation master plan (VMP)
- Initiation procedure for initial process validations (events, role of the VMP)
- Organisation of and procedures involved in process validation, approved validation approaches
- Required documents for the planning, execution and reporting of process validations (approval process, minimum content)
- Assurance that the prerequisites for the execution of process validations (qualification of the equipment to be used, validation of test methods, …) are fulfilled
- Performance of risk assessments to determine the validation scope
- Accepted validation approaches for the initial process validation (traditional, continuous process verification, or potentially hybrid approach) as required, including information regarding prerequisites to allow implementation of concurrent validation instead of prospective validation
- Planning of initial validations; generation of validation protocols
- Assurance of marketing authorisation conformity of the validation design
- Execution, evaluation and documentation of the validation runs
- Handling of unexpected deviations from the manufacturing instructions, test instructions or validation requirements
- Management of the generated validation data (ensuring data integrity, traceability of reports back to the raw data)
- Reporting for process validations
- Release of a validated process
- Conditions for the release of validation batches for market use prior to completion of the initial validation
- Establishment and execution of ongoing process verification
- Execution of re-validations in instances of process changes or transfer of a validated process from another production site
Process Validations as Part of the Validation Master Plan
In the validation master plan all the manufacturing processes subject to validation should be listed (e.g. also including the processes for the production of the media used in manufacturing).
The procedure for identifying the processes must be quality assurance controlled to ensure that all relevant processes are actually listed in the VMP.
For every manufacturing process the following information should be listed in the VMP:
- Unique name of the manufactured product, or manufacturing stage, as applicable
- Document no. of the master batch record used
- Validation status of the process (released for commercial production yes/no)
- incl. date of release or declaration of the phase which the validation is currently in, scheduled date for completion of the validation
- Validation approach (traditional or continuous process verification)
- Type of validation (prospective or concurrent)
- Whether the process has previously been validated using the bracketing approach (see following section)
- If this specific process has not been validated: indication of the reference process used to deduce the validity of the process
This text is an excerpt from the new GMP Series Download Inspection of Process Validation
- What should validation documentation contain?
- How does one implement continued process verification?
- What is the role of risk management?
- What receives particular attention during an inspection?
In this GMP Series Download you will be given specific answers to these and other frequently asked questions.
The validation of processes is a primary requirement in the pharmaceutical industry. This Aide-Mémoire of ZLG is a structured guide for the planning and execution of process validation. New concepts for modern process validation are introduced and known facts are summarised.
Due to its importance for the pharmaceutical industry, the directive document was translated into English by the Maas & Peither AG, GMP-Publishing. With this volume, you receive a bilingual comparison with excellent practical applicability, also in an international context.