Biomedical Engineering Reference
In-Depth Information
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What are the consequences?
Severity
Figure
4.2.
Example of criticality determination. (See the insert for color representation of this
figure.)
relevant data from similar molecules and literature references. This combined knowledge
provides rationale for relating the attribute to product safety and efficacy. Process
capability is the demonstrated range of product attribute data on the basis of laboratory
studies, manufacturing experience, and process control gathered during nonclinical and
clinical development. Therefore, the capability of the process to deliver a product attribute
within the range of prior product knowledge provides information on the probability of
occurrence of harm. The risk assessment rationale together with data supporting the
choice of the criticality of the attribute can be used to define a testing plan. The testing
plan will be used to determine whether routine monitoring or characterization testing is
conducted.
The first step in criticality determination gauges the severity of what might gowrong
as the potential for the product quality attribute to impact safety (such as toxicity and
immunogenicity) and efficacy (biological activity and pharmacokinetics (PK)). An
“unknown” risk is considered equivalent to a “high” risk. The second step gauges the
probability of an adverse impact, which is measured by the extent of the prior product
knowledge compared to the process capability. The risk associated with the severity and
the probability is a continuum. The method of assessment described here classifies the
attributes as noncritical, key, and critical based on the following risk categories:
.
Low Risk: In the case where the combination of severity and probability results in
low risk, the attribute is considered “noncritical” and routine monitoring is not
required. Testing for this attribute may be used to provide additional information
on product characterization.
.
Moderate Risk: In the case where the combination of severity and probability
results inmoderate risk, the attribute is considered “key.” Depending on the extent
of prior product knowledge (i.e., laboratory, nonclinical, and clinical data)
compared to process capability, the attribute may be tested by (1) routine
