Chemistry Reference
In-Depth Information
TABLE 11 . 2 . Key Terminologies in QbD
Terminology
Definition
Critical quality
attribute
Attribute for which deviations from established limits may result in
decreased assurance of quality, safety, and/or efficacy
Critical and key
parameters
An aspect of the process whose variability has a meaningful impact on a
critical quality attribute and therefore should be monitored or
controlled to ensure that the process produces the desired quality. The
difference between key and critical is determined by a risk assessment
of the potential impact on product quality, which includes factors such
as the magnitude of the effect, closeness of the design space to the
edge of failure, location of the NOR within the design space, and
robustness of the process. If the risk to the critical quality attribute is
high, the aspect of the process is deemed critical; if the risk is
moderate, the aspect is deemed key
Noncritical
A noncritical aspect of the process (i.e., material attribute, process
parameter, and/or in-process control) has no significant potential of
impacting a CQA
Design space
The multidimensional combination and interaction of input variables
(e.g., material attributes) and process parameters that have been
demonstrated to provide assurance of quality. Working within the
design space is not considered as a change
Normal operating
range
The range of material attributes and process parameters that are utilized
during normal manufacturing
Process parameters
Procedures that can be adjusted to control the manufacturing process
(e.g., stoichiometry, temperature, and time)
Proven acceptable
range
A characterized range of a process parameter for which operation within
this range, while keeping other parameters constant, will result in
producing a material meeting relevant quality criteria. The
characterized range is obtained using empirical models, experimental
range examined, scientific fundamentals, and equipment limits
Design space limit
The maximum allowable range for each individual parameter that is part
of a multivariate design space. The design space is described by DSLs
and may include a limiting equation
Knowledge
boundary
The combination of scienti
c fundamentals and experimental ranges for
all parameters that represent the extremes of the variables used to
develop the limits of process understanding and/or equipment limits
QTPP goals to be met. They could be physical, chemical, biological, or microbiological
properties. What makes them critical are the detrimental effects
—
that would be expected if some variation in the product or process causes the CQA to fall
outside its target range. For this purpose, the potential for harm is assessed
before
taking
into account any other measures that might mitigate the risk. Certain properties are
generally considered to be CQAs. For instance, in the case of amorphous dispersions, the
level of residual spray drying solvents is usually a CQA, especially in the likely event that
the solvent is restricted to certain limits for human exposure. Amount of an observed
—
to safety or ef
cacy
