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Challenges in Bio Process Validation

Gretchen A. Allison
Maurice B. Parlane, B Tech MIT
Article - ISPE Pharmaceutical Engineering
Challenges in Bio Process Validation

We are in a period of unprecedented change – some would even say disruption in the types of medicines and technologies adopted. This comes in an environment with ever increasing demands to improve time to market and manage resources. Process validation is a significant program within our pharmaceutical quality system as it is central to the demonstration of successful process performance and product monitoring systems.

On June 20-21, ISPE will host the 2019 ISPE Process Validation Workshop at the Boston Renaissance Waterfront. This workshop will focus on:

Challenges in Process Validation for Today’s and Tomorrow’s Next Generation Bio Products

Maurice Parlane and Gretchen Allison are the chairs of this workshop and are excited to share this year’s agenda with you. The planning committee has worked hard to put together an agenda that includes regulatory (e.g. FDA) insights as well as industry speakers.

Presentations at this event will range from case studies to approaches used for bio process development/design through to continued process verification. Some of the newer areas of bio process validation that will be covered include:

  • Continuous manufacturing
  • Validation for Gene therapy products
  • Validation of breakthrough therapies

From our own experience these areas raise a number of questions and potential changes to historical process validation approaches. For example, continuous manufacturing often relies heavily on real time monitoring of critical attributes and/or parameters. Real time monitoring and control of the process such as diversion of product that does not meet critical attributes typically involves building of models to perform the monitoring and take action when necessary. How much batch data are required to build the model and at what point must it be demonstrated to be accurate before process validation can be initiated? These are some of the common questions encountered during preparation for process validation of a continuous manufacturing process. Others may include how many ‘batches’ (however defined) maybe required, and should the shortest, longest, or standard run times/speeds be validated?

Accelerated development and validation of breakthrough therapy products also raises its own set of many questions such as at what point must critical attributes and their ranges be established – can it be during or after process validation? How much development is required prior to process validation – e.g. is it the same as or less than for non-breakthrough therapy products? What has been the experience of other firms that have explored these topics? For example, is there any allowance by regulators for some uncertainty and ambiguity of critical attributes and parameters at time of initial validation (i.e. PPQ)?

Beyond the conduct of process validation (PPQ) runs we will also explore how process development; clinical and engineering runs can be fully leveraged during process validation.

The adoption of science and risk-based approaches to process validation brings with it a need to demonstrate improved process understanding, control strategy and process robustness. The traditional tool-sets (e.g. inferential statistics applied to smaller sample populations) used for process validation are sometimes found inadequate and increasingly new techniques (e.g. predictive models, continuous data) are required to effectively meet these needs. Astute application of risk management and statistical prediction or monitoring practices are required to ensure efforts are truly delivering quality, safety and value to patients.

The extent of change in process validation approaches is evident in the level of interest and body of work coming out of ISPE’s Process Validation Team in recent years. This is the fifth edition of a specifically themed Process Validation Conference ISPE has run in the past six years; and is the result of industry demands to understand and develop practical approaches to implementation of lifecycle process validation to an ever increasingly complex group of products and manufacturing platforms.

This workshop intends to explore these challenges and the ways in which process validation practices must and can adapt; adopting science and risk-based techniques and tools.

We will explore emerging challenges and proven process validation techniques in more depth and learn what experience others in the industry have had in these and other areas of this type of manufacturing. We are fortunate to once again have a high level of enthusiasm and support from the regulatory community for this conference. At this event you will have the opportunity to hear the views of regulators on challenges and the current trends they see in process validation for these new products, technologies and validation approaches.

We hope you are able to join us for this informative workshop to both gain insights to regulatory and industry views, and also to contribute to group discussion to identify areas which are still challenging. With this dialog, industry can collaborate to improve knowledge, understanding and in turn improve product quality.

The early registration deadline ends on 1 April 2019 - register today to receive the best rates.  See you in Boston in June! 

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