- Date: February 18, 2011
- Source: Admin
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
|
ICH Q5A:
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.
|
|
FDA:
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
|
Guidance
|
FDA
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.
|
Source
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073454.pdf
http://www.microbac.com/technical_articles/news_detail.php?news_ID=64
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM129101.pdf
