Biomedical Engineering Reference
In-Depth Information
13.5 IMPLEMENTING QbD AND PAT
If a manufacturer is to implement a QbD business process and reap the full benefits of
consistent product quality, responsive processing and the ability to incorporate im-
provements on a continuous basis within their own quality system, the approach to
developing the process will probably differ from the traditional approach in a number of
ways. The principle of these would be the amount of data that is gathered and the way in
which it is presented. Since the basis for QbD is a well-defined design space, there
will be a greater degree of experimentation required upfront to fully explore the
relationships between input materials and process parameters. Second, since the
focus has shifted from a detailed description of the process to its outcomes and
a demonstration of process understanding, there should be more emphasis on the
knowledge gained during development and an explanation of the purpose behind each
step (or series of steps) and how the desired end points are achieved. It is also necessary
to establish a common basis for what is meant by “process understanding,” see
later. Detailed descriptions of control strategies will replace detailed descriptions of
processes and quality will be managed over the life cycle of the product through
continuous improvement. A comparison between traditional and QbD/PAT processes is
given in Table 13.2.
TABL E 13.2. A Comparison of Traditional and QbD/PAT Processes
Aspects
Traditional
QbD
Product design
Screening, the best candidate
wins
TPP developed though broader
use of prior knowledge,
consideration of
manufacturability
Pharmaceutical
development
Empirical; typically univariate
experiments
Systematic; multivariate
experiments, PAT tools used
Manufacturing
process
Fixed
Adjustable within design space;
opportunities for innovation
(PAT)
Process control
In-process testing for go/no-go;
offline analysis
PAT tools utilized for feedback
and feed-forward controls
Product
specification
Primary means of control;
based on batch data at
time of submission
Part of the overall quality control
strategy; based on desired
product performance (safety and
efficacy)
Control strategy
Mainly by intermediate and
end-product testing
Risk-based; controls shifted
upstream; reducing product
variability; real-time release
Life cycle
management
Reactive to problems and OOS;
postapproval changes
needed
Continual improvement
facilitated
Source: Modified from ICH Q8 R1 and with thanks to Moheb Nasr.
