Viral Safety Evaluation

  • Date: February 18, 2011
  • Source: Admin
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Standards in controlling viral contamination of biotechnology products:

  • Selection and testing of starting materials (cell banks, raw materials etc.)
  • Product testing at various stages of production
  • Assessing the capacity of the production processes to clear infectious viruses and incorporating viral inactivation and removal steps.

 Strategies to evaluate risk of viral contamination and removal of virus:


  • Thorough characterization/screening of cell substrate starting material in order to identify which, if any, viral contaminants are present
  • Assessment of risk by determination of the human tropism of the contaminants
  • Establishment of an appropriate program of testing for adventitious viruses in unprocessed bulk
  • Careful design of viral clearance studies using different methods of virus inactivation or removal in the same production process in order to achieve maximum viral clearance
  • Performance of studies which assess virus inactivation and removal

Virus Safety Principles

ICH: Q5A or CPMP/ICH/295/95: Note for guidance on quality of biotechnological products: viral safety evaluation of biotechnology products derived from cell lines of human or animal origin.

-         Cell line qualification: testing of viruses

-         Testing for viruses in unprocessed bulk

-         Evaluation and characterization of viral clearance studies

 Regulatory guidelines



1.       Viral Safety Evaluation of Biotechnology Products Derived from Cell lines of Human or Animal origin 1, (1997)

·         Requires manufacturer to demonstrate the capability of the manufacturing process to remove or inactivate known contaminants.



1.       Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use 2 (1997)

2.       Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals 3 (1993)

·         Similar guidelines as ICH Q5A guideline


·         Further viral safety evaluation methods

EMEA - CPMP guidelines:

The 2008 EMEA – CHMP guidelines on viral validation

1.       Guideline on Virus Safety Evaluation of Biotechnological Investigational Medicinal Products 4

1996 EMEA - CPMP guidelines

2.       Note for Guidance on Virus Validation Studies: The Design, Contribution and Interpretation of Studies Validating the Inactivation and Removal of Viruses 5

3.       CPMP’s Note for Guidance on Plasma Derived Medicinal Products 6 provides detailed recommendations for the manufacturers of biopharmaceutical products to follow when performing viral validations.

·         Recommendations for manufacturers to follow when performing viral validations

·         Set specific values for virus clearance levels that had to be attained


EU Clinical Trials Directive 2001/20/EC 7


The International Standard ISO 22442-3: Medical devices utilizing animal tissues and their derivatives – Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents 8

·         All EU Member States now require submission of an Investigational Medicinal Product Dossier (IMPD) starting at phase 1


·         Requirements on viral clearance for the medical devices




Q5A Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin

Describes approaches risk evaluation of viral contamination and potential of the

production process to remove viruses.



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