Design Finalization
for Virus Safety

Step 6

Once the virus clearance step has been optimized and virus retention studies completed, your next challenge is designing a strategy that enables you to increase your flow volumes within the constraints of your physical plant, without violating the safety margins you have established for your project.

A key decision is finding a filter configuration that will support a large-scale implementation. When multiple filters are required to process the batch volume you have set, look for a filtration solution that can be installed to meet your process time requirements and to meet the physical constraints of your plant. Merck can help increase your probability of success with Procedural reviews, Operator Training, Equipment Qualification and our knowledge in standard approaches and expertise in downstream processing.

Plant Related Considerations:

• Sanitization
• Hardware requirements
• Disposable flow path opportunities

Operating Procedure Related Considerations:

• SOP feasibility
• Equipment and operator qualification
• Automated and or Manual Integrity testing

Design Constraints:

• Ability for increased batch size
• Safety Factors
• Tolerance for process excursions

Other virus filter-related considerations include:

• Operating sequence
  A typical sequence of operations in a virus filtration process includes the following steps:
  • Filter installation, flushing, and water permeability measurement (optional)
  • Sterilization and sanitization (optional)
  • Pre-use integrity testing
  • Buffer pre-conditioning and permeability measurement
  • Processing and product recovery (optional)
  • Post-production integrity testing
    
    
• Sanitization and sterilization
  In a typical downstream purification process, virus clearance filters are used downstream of a chromatography column and upstream of an ultrafiltration/diafiltration step, neither of which is considered an aseptic operation. However, there appears to be an industry trend to sanitize or sterilize the virus filter to reduce the bioburden. Some virus filters are available pre-sterilized, thus eliminating the sterilization step. It is important that the filters you select are compatible with the sanitization or sterilization method you plan on implementing at manufacturing scale, and that the process steps used during large scale processing are also carried out during your scaled down virus retention studies.
  
  
• Integrity testing
  To ensure virus clearance is consistent with results obtained during virus retention studies, end users can perform filter integrity pre- and/or post-test use.
  • The virus removal filter is properly installed
  • The filter is free of gross defects and damage
    
    
• Process
  Make sure that the conditions used during processing are within the parameters used during the scaled-down virus retention assessment studies.