Biomedical Engineering Reference
In-Depth Information
X
Severity
Figure
4.30.
Criticality of deamidation. (See the insert for color representation of this figure.)
would be recommended for lot release and stability testing. By using this, the range of
prior product knowledge is defined by the lower boundary of the development
experience (0.50 OD ratio). The upper OD ratio boundary is not relevant because
higher OD ratios indicate lower deamidation levels. Because the prior product
knowledge (0.50 OD ratio) is broader than the process capability (
1.4 OD ratio),
the data support a native IEF OD ratio specification less than 1.4 and greater than
0.50. The native IEF sample bands must remain within the pI range of prior product
knowledge (pI
>
>
8.65).
4.3 CONCLUSION
We describe here a risk assessment process to evaluate product quality attributes and
categorize the attributes as being of low, medium, or high risk to product quality. The
categorization of risk and the information obtained during the risk assessment process for
an attribute provide the basis for determining the appropriate testing plan, including the
test(s) performed, frequency of testing, and specifications.
In this chapter, we have illustrated the use of a risk assessment process with two
examples of the glycosylation and deamidation quality attributes. The information was
obtained during the development of two anti-RSV monoclonal antibodies (palivizumab
and motavizumab). We show here that glycosylation is a noncritical (low-risk) attribute
and deamidation is a key (moderate-risk) attribute. It should be noted that the assess-
ments presented here are limited to these monoclonal antibodies. For other monoclonal
antibodies, the outcome of the assessment might be different.
A risk assessment process for evaluating product quality attributes requires an
accumulation of considerable information to achieve a meaningful outcome. The
criticality determination necessitates a comparison of the prior product knowledge with
the process capability. Some relevant information for prior product knowledge might be
sourced from literature, but in many cases the data comes from nonclinical and clinical
