Biomedical Engineering Reference
In-Depth Information
.
What is the starting load and identity of virus?
.
Are there specific patient
risk issues (e.g.,
immunocompromised patient
population)?
.
What will the cumulative dose be (e.g., in chronic disease states)?
.
What are the regulatory implications to not achieving a “high” level of viral
clearance?
8.5.2 Define Viral Load
It is important to understand the potential viral load to apply QbD to virus clearance.
Several scenarios illustrate this point. Consider a cell line with an unknown history of
exposure to adventitious virus (e.g., a university source). With little understanding of the
virus risk (virus type and number) that this cell line represents, one would be forced to set
a very stringent process CQA (i.e., a “high” LRV) for virus clearance. Extensive testing
of that cell line may characterize the risk and counter the need to achieve an excessive
level of viral clearance. Even more favorable is the use of a well-characterized cell line
that has a good history of use in one's company.When using awell-characterized cell line
in a new biopharmaceutical process, the viral load may be approximated through one's
historical understanding of the cell line as that cell line has been used to express similar
products. Even with this platform manufacturing strategy, however, it is necessary to
confirm the virus load and that viral clearance targets are met.
Define product
virus safety-
related COAs
1
Construct a virus
clearance
knowledge base
3
2
Define viral load
Select a manufacturing
strategy that will
achieve viral clearance
4
Perform characterization
and robustness studies
5
Create a
design space
proposal
6
Figure
8.1. Six elements to creating a virus clearance design space.
