Biomedical Engineering Reference
In-Depth Information
and multivariate or univariate approaches [8]. Residual risk should be assessed
and documented in the RA report.
The risk-based approach uses risk ranking to classify process variables based
on their potential impact to CQAs, process performance, and possible interaction
with other parameters. Process parameters can be divided into three groups:
(i) parameters warranting multivariate evaluation; (ii) parameters whose ranges
could be supported by univariate studies; and (iii) parameters that do not require
new studies, but instead would employ ranges based on knowledge space or
modular claims established from prior knowledge. Each parameter was assigned
two rankings: one based on the potential impact to CQAs or other attributes (main
effect) and the other based on the potential of interactions with other parameters
(interaction effect). Main and interaction effects were multiplied to calculate the
overall severity score. The severity score serves as the basis for identifying study
types: multivariate studies (high scores), univariate studies (medium scores), or
no further study needed (low scores).
The following factors should be considered when performing RA:
• level of existing knowledge on effect magnitudes and potential interactions;
• historical data and scientific rationale that may indicate minimal risk and
justify that no additional studies are required;
• higher risk associated with impact on CQAs;
• potential of an unexpected interaction effect for a parameter with a high
impact main effect.
Table 8.3 shows a template to score main and interaction effects. On the basis
of the severity score (equal to main effect × interaction effect), studies can be
divided into various categories as shown in Table 8.4.
8.7.2 Critical Process Parameters
CPP is defined as a process parameter whose variability has an impact on a CQA
and therefore should be monitored or controlled to ensure the process produces
the desired quality [5]. CQA is a physical, chemical, biological, or microbiolog-
ical property or characteristic that should be within an appropriate limit, range,
or distribution to ensure the desired product quality. A process parameter that
TABLE 8.3 Template for Effects and Risk Scoring
Proposed Range Main
Effect Interaction Severity Process Potential
Process
Rank
Effect
Score Outputs Interaction
Parameter
( M ) Rank ( I )
(MxI) Affected Partners Rationale
Search WWH ::




Custom Search