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Proceedings of the 2019 Viral Clearance Symposium, Session 1: Viral Clearance Strategies and Case Studies

Simon Reitz1, Astrid Schwantes2

  • 1Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach an der Riss, Germany; and.

PDA Journal of Pharmaceutical Science and Technology
|December 16, 2021
PubMed

Insights

Strategies for demonstrating robust viral clearance of recombinant proteins and recombinant adeno-associated virus (rAAV) vectors were discussed. Methods for virus reduction and improved log reduction value calculations were proposed for regulatory compliance.

Area of Science:

  • Biotechnology
  • Virology
  • Process Engineering

Background:

  • Demonstrating viral clearance is critical for biotechnologically produced biologics and viral vectors.
  • Current methods for viral clearance and log reduction value (LRV) calculation are subject to refinement.
  • Recombinant adeno-associated virus (rAAV) vectors require specific strategies for adventitious virus reduction.

Purpose of the Study:

  • To propose strategies for robust viral clearance using prior knowledge for recombinant proteins.
  • To introduce methods for virus reduction applicable to rAAV vectors.
  • To discuss proposals for generic viral clearance claims and refine LRV calculation methods.

Main Methods:

  • Discussion of generic viral clearance claims for detergent inactivation (Triton CG-110), low pH, anion-exchange chromatography, and virus filtration.
  • Presentation of ASTM standard development for retrovirus removal by small virus filters.
  • Demonstration of methods for rAAV vector adventitious virus reduction including 35nm filtration, detergent/heat inactivation, and chromatography.

Main Results:

  • Proposed strategies for demonstrating viral clearance and virus reduction for biologics and rAAV vectors.
  • Identified areas for updating and refining conditions for retrovirus removal filters.
  • Questioned current LRV calculation and proposed a modified concept.
  • Demonstrated feasibility of multiple methods for rAAV adventitious virus reduction.

Conclusions:

  • Prior knowledge and proposed methods can support robust viral clearance claims for recombinant proteins.
  • Specific methods are feasible for reducing adventitious viruses in rAAV vectors, meeting ICH Q5A principles.
  • Refinement of viral clearance strategies, filter standards, and LRV calculations is warranted.

Keywords:
Biologic License ApplicationDownstream processingGeneric/modular claimRecombinant Adeno-Associated virus (rAAV) vectorsViral clearanceViral clearance symposium

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