Biomedical Engineering Reference
In-Depth Information
On the basis of the authors' experience and interpretation of the current regulatory
guidances, some definitions are provided. Other relevant definitions can be found in ICH
Q6B, Q8, and Q9.
Prior Product Knowledge: the accumulated laboratory, nonclinical, and clinical
experiences for a specific product quality attribute. This knowledge may also
include relevant data from other similar molecules or from scientific literature.
Process Capability: the demonstrated range of product attribute data on the basis of
laboratory studies, manufacturing experience, and process control.
Noncritical Product Quality Attribute: an attribute for which the combination of
severity and probability results in a low risk of impact on safety or efficacy.
Key Product Quality Attribute: an attribute for which the combination of severity
and probability results in a moderate risk of impact on safety or efficacy.
Typically, for this type of attribute, the range of prior product knowledge is
broader than the process capability.
Critical Product Quality Attribute: an attribute for which the combination of
severity and probability results in a high or unknown risk of impact on safety
or efficacy. There may be a potential for process capability to exceed the range of
prior product knowledge, in the absence of adequate control.
4.1.1 Quality Attribute Risk Management
A risk assessment process is used to determine which quality attributes are important to
the performance of the product (safety and efficacy) and to justify the acceptable range of
variation for these attributes. The acceptable range or boundary for each quality attribute
in turn provides the operational target designed to robustly control each attribute and
assists in establishing the design space for manufacturing process parameters. All
product quality attributes are considered and assessed for risk to determine the
appropriate testing (e.g., routine monitoring, characterization testing, or no testing)
required as part of the overall product-testing plan. A flowchart for the product quality
attribute risk management is presented in Fig. 4.1 with the following outcomes.
.
Product-related substances can be evaluated by using criticality determination and
do not require routine monitoring.
.
Product-related impurities are also evaluated by using criticality determination.
However, these attributes often require routine monitoring.
.
Risk assessment for process-related impurities is based on either criticality
determination or safety assessment, and routine testing may not be necessary.
.
Attributes already established as regulatory requirements are included in routine
monitoring.
4.1.2 Criticality Determination
As part of the product quality risk assessment, criticality determination is used to identify
the quality attributes that are important to the performance of the product (safety and
