Module 7. Primary (API) process validation

Aims

The aims of this module are:

• to provide an awareness of chemical and fermentation process development through to full scale manufacturing.
• to provide an understanding of the validation lifecycle and the Good Manufacturing Practice process envelope as it applies to primary manufacture.
• to understand the role of quality critical attributes and identification of quality critical parameters and ranges.
• to describe the role of process utilities such as water, nitrogen, vacuum, air and solvent recovery in full scale manufacturing.
• to understand the equipment qualification process.
• to understand cleaning and analytical validation as they apply to primary manufacturing processes.
• to describe the differences between prospective, concurrent and retrospective validation approaches.
• to provide an understanding of the relationship between validation and Good Engineering Practice and the impact on Project Execution of Manufacturing Processes.
• to describe the deliverables associated with a primary process validation.
• to provide an understanding of how validation relies upon pre-determined specifications, traceability of requirements through design to testing, and maintenance of validation under change control
• to provide an understanding of how primary process validation protocols are developed, integrated, managed, executed and reported. Options for organizing for validation will be described.
• to provide an understanding of how automated control systems validation fits into the overall validation programme.

Learning outcomes

On completion of this module the student should be able to:

• describe the development of chemical and fermentation primary processes and associated utilities.
• describe the similarities and differences between prospective, concurrent and retrospective validation approaches and their application.
• describe the principles and practices of equipment qualification, process validation, the GMP envelope and how they relate to Good Engineering Practice.
• describe how these principles and practices apply to full scale manufacturing process control including an understanding of chemical and fermentation process similarities and differences.
• identify cleaning validation processes.
• describe how the Validation (Master) Plan, the system definition and boundaries, and impact assessment affect the validation activities
• list the type of in-house and vendor documents required to support primary process validation.
• describe how to organise for validation.
• develop a validation policy for primary processes incorporating the concepts of quality critical attributes and parameter ranges and the GMP process envelope.
• develop validation documents.
• describe the role of training, suppliers and contractors in the validation process.
• describe the activities needed to maintain the validated status of primary processes and the role of the Annual Product Review.
• describe the role of authors, reviewers, approvers, witnesses for documentation
• describe the role of plans and summary reports in the validation process and how these can be integrated into process/equipment validation deliverables.
• describe how statistical techniques can be used to support primary process validation.

Tutor information

Hugh Butcher

Hugh is part of the senior management of SciTech Engineering as their Validation & Regulatory Compliance Director.

He has over 25 years Regulatory Affairs and Project Management experience in pharmaceuticals. Qualified in Industrial Pharmaceutical Studies, he has been retained by many pharmaceutical organisations as a consultant. Since joining the Engineering and Contracting Sector 15 years ago, Mr. Butcher has managed teams of technical specialists on major pharmaceutical and biotechnology projects worldwide. A regular contributor to the advancement of this profession, Hugh presents papers at European ISPE events and has played a significant role in advising the European Commission.

Prior to joining SciTech Engineering Ltd., Hugh held a similar position with SembCorp Simon Carves and Fluor Daniel making a major contribution to pharmaceutical projects in the UK, Ireland and in mainland Europe. His activities included writing Validation Master Plans, GMP Audits and DQ, IQ, OQ Protocols as well as Project Management of the start-up of an aseptic clinical trials facility, GMP Consulting, qualification of revamped facilities etc.
With Beecham Pharmaceuticals (later GSK), he accumulated over 10 years experience of Penicillin and Cephalosporin manufacturing. This extended to all aspects of sensitizing antibiotic manufacture, from routine operating to taking part in regulatory compliance audits from the FDA and the UK MHRA regulatory bodies.