WHO’s Draft Guidelines on Validation May 2016

Hello good people of the world! On May 15, 2016, the World Health Organization released its draft Guidelines on Validation. It is available on the WHO website for download here.

This post covers my review of the guidance.

The document is a revision to the existing WHO guideline: Supplementary Guidelines on Good Manufacturing Practices (GMP): Validation from 2005, which can be found here. I won’t compare the revision to that document explicitly, instead noting anything interesting from the revision as a stand-alone document.

1. Introduction
   • The guidance explicitly states that validation is part of GMP and GCP (Good Clinical Practices).
   • Validation incorporates qualification
   • Validation should be applied over the lifecycle of the applicable product, process, system, equipment, or utility.
   • There are 7 appendices planned, covering in order, validation of: HVAC, water systems, cleaning methods, analytical methods, computer systems, systems and equipment qualification, and non-sterile processes.
   • “quality, safety, and efficacy must be designed and built into the product”
   • quality risk management principles should be applied
2. Scope
   • The guidance covers overall concept of validation and is not prescriptive in specific validation requirements
3. Glossary
   • computer validation = computerized system validation
   • process validation = the collection and evaluation of data, throughout the product life cycle, which provides documented scientific evidence that a process is capable of consistently delivering quality products
   • worst case = a condition or set of conditions encompassing the upper and lower processing limits for operating parameters and circumstances, within SOPs, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily include product or process failure.
4. Relationship Between Validation and Qualification
   • Qualification and validation are essentially the same. The term qualification is normally used for equipment and utilities, and validation for systems and processes.
5. Validation
   • Statistical calculations should be applied, where appropriate…
   • There should be a specific programme or schedule to support planning and execution of validation activities
6. Documentation
   • Include: valdiation master plan, standard operating procedures, specifications, protocols and reports, risk assessment outcomes, process flow charts, operator manuals, training records, calibration procedures and records, sampling plans, testing plans and methods, statistical methods and results, history of qualification or validation, plan for ensuring review of validation status, plan for ensuring maintainence of validated state
7. Validation Master Plan
   • Include: signature page, table of contents, abbreviations and glossary, validation policy, philosophy, intention, and approach to validation, roles and responsibilities of relevant personnel, resources to ensure validation is done, outsourced services, deviation management, change control, risk management, training, scope of validation, documentation requirements, premises qualification, utilities qualification, equipment qualification, process validation, cleaning validation, personnel qualification, analytical method validation, computerized system validation, establishing acceptance criteria, life-cycle management including retirement, requalification and revalidation, relationship to other quality system elements, validation matrix (what is this specifically?), and references
8. Qualification and Validation Protocols
   • Protocols should include: objectives, site, responsibilities, SOPs to be followed, equipment and/or instruments to be used, standards and criteria, stage of qualification or validation, process and/or parameters, sampling, testing, and/or monitoring requirements, stress testing where appropriate, calibration requirements, predetermined acceptance criteria, review and interpretation of results, change control, deviations, archiving and retention.
9. Qualification and Validation Reports
10. Qualification
    • All relevant SOPs for operation, maintenance, and calibration should be prepared during qualification – ?
    • Normally, qualification should be completed before process validation is performed
    • Computer system testing should include stress, load, volume, and other performance verification tests that mimic the live production environment. It also includes user acceptance testing according to draft SOPs and training as well as end-to-end business processes for indented use.
    • It is recommended that manufacturers implement the new approach in process validation. See Guidelines on process validation.
11. Change Management
12. Deviation Management
13. Calibration and Verification

Really nothing very new or controversial in this guidance document – it seems pretty much inline with current industry practices. I like how they include a list of topics for VMP and protocols. That should improve consistency in these documents between organizations.

Anything catch your eye in this draft? What would you comment to the WHO?