The PPQ challenges for gene therapies – a master plan

29 November 2023
Advanced Therapy Medicinal Products
Kathleen O’Hagan
Global Change Facilitator

For the most part, process performance qualification (PPQ) methodologies established for protein biologics can be leveraged for in vivo gene therapy processes and they often require similar validation support studies. There are, however, differences that are specific to gene therapy products and production processes that need to be addressed.

PPQs typically require extensive non-routine in-process sampling and testing. This can be challenging for gene therapy modalities, where process scale and step yields are typically low. In addition, the relative immaturity of gene therapy process platforms can cause a higher level of process performance variability.

Our new paper, Process performance qualification master plan: considerations for gene therapies, addresses these PPQ challenges. It outlines a general strategy for drug substance and/or drug product manufacturing processes that are expected to undergo PPQ with unique gene therapy considerations.

It looks at process validation acceptance criteria and a validation strategy and approach that includes:

  • PPQ prerequisites
  • PPQ strategy
  • PPQ approach
  • Drug substance process description
  • Drug product process description
  • Reprocessing
  • Analytical methods
  • PPQ supporting studies.

“This publication is the result of mindful collaboration among process validation professionals experienced in the commercial manufacture of viral vector-based products, and the recommendations may serve as a resource to strengthen an organization’s approach to validating gene therapy processes,” said Patrick Bartlow, Senior Scientist at Janssen. “I appreciated the forum provided by BioPhorum to collaborate with fellow scientists and engineers across the industry to shape the still-evolving conversation on issues about gene therapy commercialization.”

For sponsors with established quality systems and process validation experience, this paper may help identify gaps or additional considerations when modifying existing validation templates for gene therapy products. For companies with limited validation experience, it is intended to be a resource to help develop plans related to initial PPQ campaigns.

Activities may be added or removed based on the specific program, facility or product history, or regulatory feedback for that program. The latter may come in the form of planned interactions with various regulatory agencies or through information requests from them.

The paper’s recommendations were developed through focused input from process validation professionals across 18 companies in the gene therapy industry. These considerations provide a framework for activities outlined in a process performance qualification master plan in the gene therapy industry.

The validation requirements were developed based on an interpretation of published guidance from the FDA and EMA. An extensive list of this guidance can be found in BioPhorum’s Cell and gene therapy validation challenges. For more information, download the paper here and contact Kathleen O’Hagan, Global Change Facilitator, at

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