Dr Rainer Gnibl, GMP Inspector for EMA
Timur Güvercinci, Merck KGaA, Germany
Dr Bettina Knapp, Boehringer Ingelheim, Germany
Gert Moelgaard, Head of ECA´s Validation Group, Denmark
Dr Thomas Schneppe, Bayer Bitterfeld GmbH, Germany
Dr Chris Watts, VoPal, USA, Formerly with FDA
With the Guidance for Industry “Process Validation:
General Principles and Practices”, the FDA requires a
new direction. Validation is now a „Life Cycle Process” with 3 stages:
- Process Design
- Process Qualification
- Continued Process Verification
The stage 3 “Continued Process Verification” is a new step in validation. Also legacy process should be (re)validated regarding this life cycle. The start is stage 3 “Continued Process Verification”. The goal of the third validation stage is continual assurance that the process remains in a state of control (the validated state) during commercial manufacture. A system or systems for detecting unplanned departures from the process as designed is essential to accomplish this goal, says the Guidance. Now, also the EU requires Ongoing Process Verification as part of a validation lifecycle.
But how to implement Continued/Ongoing Process Verification in the routine production – beginning from the definition of the control strategy to the Product Quality Review /Annual Product Review?
- What is state of the art regarding systems for detecting unplanned departures from the process?
- How to handle the monitoring at Stage 3 (Continued/Ongoing Process Verification)?
- What are the differences between Continued Process Verification (FDA), Continuous Process Verification
- (ICH Q8) and Ongoing Process Verification (EU) ?
- Are there parallels regarding Medical Devices?
- What statistic parameters could help?
- Is a statistician necessary?
- How is OPV/CPV linked to PQR/APR?
- What are the expectations of an EU Inspector?
These questions are discussed, and the possibilities for implementation are covered.
Since 1987 the FDA Guideline on Process Validation has been the basis for qualification and validation. Within the new FDA programme “Pharmaceutical cGMPs for the 21st Century” there was an announcement for a revision of the guideline. A new FDA Policy Guide of 2004 gives some hints as to the new validation approach.
In January 2011 the new “Guidance for Industry Process Validation: General Principles and Practices” was published as final guidance. That is now FDA’s „current thinking“. EMA´s new Process Validation Guidance also mentions a Life Cycle Approach for Process Validation. And with the citation of ICH Q8, the possibility to do Continuous Process Verification is also mentioned. In the new Annex 15 revision document also a Continued Process Verification, Ongoing Process Verification called, is mentioned.
In the Annex 15 revision document, valid from 1 October 2015, also a Continued Process Verification, called Ongoing Process Verification, is mentioned.
The addressees of the event are qualified staff charged with or responsible for validation activities, especially regarding stage 3 (Continued/Ongoing Process Verification) of the process validation life cycle. We mean commissioners for validation, heads of quality assurance, department heads, etc. It also addresses members of validation teams (e.g. chemists, pharmacists, microbiologists) as well as staff who is involved in process monitoring activities and consultants.
Overview: The new process validation guides from FDA and EMA and the new industry guides from ISPE, PDA and ECA: content and principles
Ongoing Process Verification – View of an EU Inspector
- How the concept of Process Validation is about to change
- Ongoing changes in the Quality Management philosophy
- Comparision of Annex 15 revision with FDA Process Validation Guidance
- Real-life examples
Case Study: From Control Strategy to Statistical Process Control
- EU process validation lifecycle approach (overview)
- EU GMP requirements on EU-OPV
- Authorities' expectations regarding PQR
- Interaction and linking with EU-PQR
- Comparison of EU and US requirements to maintain status of control
Case Study: Large Molecules - Process Validation and Statistical Trending in Biopharmaceutical Manufacturing
- Introduction in Biopharmaceutical Processes
- Process development and definition of parameters
- Parameters and control
- Control Strategy
- Process Performance Validation Approach
- Statistical Process Control
Recent trends in FDA inspections, observations and warning letters
- Basic Statistics
- Content of CPV protocol/report
- Trending programme and related procedures
- Evaluation of Trends and CAPAs
- Link to APR/PQR
Case Study: How to implement CPV of a legacy process
- Examples of expectations and enforcement
- Regulatory enforcement trends related to observations and Warning Letters
The bridge between the traditional and a new life cycle validation approach - the way to continuous process verification
- Lessons learnt
The future role of PAT, industrial IT and automation in continued process verification: Implementing a control strategy
- Hybrid Validation approach as a interim solution
- Technology upgrade
- Case study: OPV program for small business: A concept for the definition of the critical parameters/attributes and the documentation strategy in consideration of the data integrity
Workshop Continued Process Verification – Process Data Evaluation and Conclusions
- Control strategy and implications for automation solutions
- Bridging islands of information systems in manufacturing
- From data to information to knowledge: getting gold out of data
- Continued process verification: monitoring challenges
- Window to the Quality: The future role of automation and IT systems in manufacturing?
The delegates analyse in small groups process data regarding the validity of a legacy process.