4A. 444 42 4241 43 43.4 VALIDATION MASTER PLAN Principle Validation in general requires a meticulous preparation and careful planning of the various steps in the process. In addition, all work involved should be carried out in a structured way according to formally authorised standardised working and administrative procedures. In addition validation is characterised by: — Multidisciplinary approach: A specific characteristic of validation work is that it requires the collaboration of exoerts of various disciplines such as pharmacists, technologists, metrologists, chemical analysts. microbiologists, engineers. experts on Q.A. validation ete. r Time constraints: Generally validation work is submitted to rigorous time schedules. These studies are always the last stage prior to taking new processes, facilties into routine operation Costs: Validation studies are costly as they require time of highly specialised personnel and expensive technology The above factors require a well organised and structured approach that should be adequately described in a Validation Master Plan (VMP) Purpose The VMP should present an overview of the entire validation operation, its organisational structure, its content and planning. The core of the VMP being the list / inventory of the items to be validated and the planning schedule. A\VMP helps management - to know what the validation programme involves with respect to time people and money, and to - understand the necessity for the programme; ‘A VMP helps all members of the validation team - to know their tasks and responsibilities. A VMP helps GMP inspectors: - to understand the firm's approach to validation end the set up an organisation of all validation activities Definition A Validation Master Plan is a document that summarises the firm's overall philosophy, intentions and approach to be used for establishing performance adequacy PI 006-3 Page 5 of 26 25 September 200744 444 442 443 45 4.5.4 452 4.5.2.1 45.2.2 45.2.3 Scope All validation activities relating to critical technical operations, relevant to product and process controls within a firm should be included in a VMP. This includes qualification of critical manufacturing and control equipment. |t should comprise all Prospective, Concurrent, Retrospective Validations as well as Re-validations In case of large projects like the construction of a new facility, often the best approach is to create a separate VMP. (In such situations the VMP should be part of the total project management.) Format and Content The VMP should be a summary document and shoud therefore be brief, concise and clear. It should not repeat information documented elsewhere but refer to existing documents such as Policy Documents, SOP’s and Validation Protocols/Reports The VMP should be agreed by management. ‘A VMP should contain data on the following subjects / proposed chapters Introduction Firm's validation policy, general description of the scope of these operations covered by the VMP, location and schedule (including priorities) Organisational Structure of All Validation Activities Personnel responsibility for - the VP, = protocols of individual validation projects, - validation work, = report and document preparation and control, - approval / authorisation of validation protocols and reports in all stages of validation processes, - tracking system for reference and review, - training needs in support of validation. Plant / Process / Product Description Provides @ cross reference to other documents. A rationale for the inclusion ‘or exclusion of validations, for the validation approach and the extent of validation should be included, Note: A common principle in validation studies is to chalenge processes, systems etc, The rationale behind any challenge and or ‘worst case PI 006-3 Page 6 of 26 25 September 200745.2.4 45.2.5 45.26 45.2.7 45.2.8 45.2.9 situation should be explained. Consideration can be given to the grouping of products / processes for the purpose of validating "worst case" situations. Where "worst case" situations cannot be simulated, the rationale for the groupings made should be defined. Specific Process Considerations Under this heading specific characteristics / requirements of the plant / process etc, that are enitical for yielding a quality product and need extra attention may be briefly outlined here List of Products / Processes / Systems to be Validated All validation activities comprised in the VMP should be summarised and compiled in a matrix format, Such matrix should provide an overview and contain all items covered by the VMP that are subject to validation describing the extent of validation required fie. IQ, OQ and/or PQ). It should include validation of analytical techniques which are to be used in determining the validation status of other processes or systems, the validation approach, ie. Prospective, Retrospective or Concurrent, the Re-validation activities actual status and future planning Key Acceptance Criteria General statement on key acceptance criteria for the items listed under (4.5.2.5) above Documentation Format The format to be used for protocols and reports should be described or referred to. Required SOP's List of relevant SOP's should be presented Planning & Scheduling An estimate of staffing (including training needs), equipment and other specific requirements to complete the validation effort should be described in the VMP. A time plan of the project with detailed planning of subprojects. This time plan could be included in the above mentioned matrix (4.5.2.5). A VMP requires regular updating PI 006-3 Page 7 of 26 25 September 2007Change Control 45.2.1 A statement of the company's commitment to controlling critical changes to 54 544 materials, facilities, equipment or processes (including analytical techniques). should be included, INSTALLATION AND OPERATIONAL QUALIFICATION Recommendations for the Installation Qualification and Operational Qualification of equipment involved in the manufacture of pharmaceutical products. Principle Installation and Operational Qualification exercises assure through appropriate performance tests and related documentation and records that equipment and ancillary systems or sub-systems have been commissioned correctly and that all future operations will be reliable and within prescribed or specified operating limits. These Recommendations outline the principles and basic requirements for the Installation and Operational Qualification of systems or subsystems (equipment) including support systems used in the manufacture of all pharmaceutical products, (including active pharmaceutical ingredients) (APIs) ‘The Recommendations are intended to cover installaton and operation of new or modified systems or sub-systems. The detail and scope of a qualification exercise is in many respects related to the complexity of the equipment involved and the critical nature of that equipment with respect to the quality of the final product. Nevertheless, the basic principles should be adhered to whether itis the installation and operation of a simple piece of equipment or an autoclave The basic principles are as follows (a) The equipment should be correctly installed in accordance with an installation plan, as per supplier and any special (purchaser) requirements, (b) The requirements for calibration, maintenance end cleaning developed as draft procedures should be reviewed and finally issued as authorised standard operating procedures (SOPs) as part of the SOP programme of the company, (c) Operating requirements should be established and tests conducted to assure equipment is operating correctly, under normal and ‘worst case" conditions, (d) Operator training requirements pertaining to the new equipment should be finalised and documented ‘At various stages in a validation exercise there is need for protocols, documentation, procedures, equipment, specifications, acceptance criteria for test results to be reviewed, checked and authorised. It would be expected that PI 006-3 Page 8 of 26 25 September 2007