It is necessary to consider the unique nature of CGT products to maintain the potency of the viral vector while removing or inactivating adventitious and/or helper viruses. The need and extent of virus clearance studies depend on several factors, such as the stage of clinical trial phase and the risks associated with the manufacturing process. This paper proposes an approach to viral clearance for adeno-associated viral (AAV) vectors that, ultimately, would result in the harmonization of a general methodology.
Viewing related articles
This paper evaluates the applicability of the current understanding of viral clearance to the products and processes employed in CGT manufacture to assure the viral safety of these therapies. Unique considerations for preventing contamination through raw material risk mitigation are highlighted. Guidance on viral clearance strategies for inactivation and removal are also provided. This guidance focuses on adeno-associated viral vectors but may also apply to other viral vectors.
For the last three years, the BioPhorum Viral Clearance team have completed a short survey on their published papers to understand how they have been used and the response of regulators if used to support filings. This is the report for 2022
Viral clearance studies are mandated as part of the viral safety evaluation of products derived from human or other mammalian cell lines. When acceptable ranges of process parameters are known, the ICH and EMA recommend that scale-down models are evaluated under worst-case conditions for viral clearance. To identify operating parameters that are commonly considered to present worst-case conditions for viral clearance, our Development Group...
A BioPhorum member only survey to understand viral purification and clearance practices member companies are undertaking in CGT.
This member only resource developed by the BioPhorum Development Group Viral Clearance team is based on their analysis of the worst-case conditions benchmarking survey and was presented at the PDA Viral Clearance conference in Brussels in June 2022.
A benchmarking survey on the experiences in applying prior knowledge and modular claims to health authority regulatory submission for clinical programs and licensure applications.
Poster presentation at BPI East based on analysis of the Viral Clearance worst-case conditions benchmarking survey.
A benchmarking survey looking at worse-case conditions, which is contributing to a paper that the team are currently writing.
Small-scale models (SSMs) are widely used in the biopharmaceutical industry. These models are used for process development and optimization, scale-up, technology transfer, process characterization, process validation, virus clearance studies, and resolution of deviations encountered during manufacturing throughout a product’s lifecycle. SSMs are also referred to as ‘scale-down models’ or ‘scaled-down models’. Demonstration that an SSM is representative of the large-scale manufacturing system is called ‘small-scale model qualification’ (SSMQ), which is sometimes also referred to as ‘assessment’, ‘evaluation’, or ‘verification’. The demonstration is an important task that supports process validation and is required by regulatory authorities. However, design, execution and analysis of SSMQ studies can be challenging due to the lack of clear guidance on current best practices. This white paper provides options and tools for design, execution, and data analysis of SSMQs together with illustrative case studies.