Knowledge Management and Process Monitoring of Pharmaceutical Processes in the Quality by Design Paradigm - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 239

paper (such as batch records) or in electronic format. However, more
sophisticated forms of data archiving, visualization and analysis may be
reserved for parameters that have been prioritized. An example of such an
approach is illustrated in Fig. 16 .
(b) Create domain-specific visualizations that can help to monitor processes
and serve as a standard way of communication of process data across the
organization. Such visualizations will represent the relationship between
different types of data (e.g. batch performance data, time profiles, batch
events etc.) and would be accessible to all who are associated with the
process and the product.
(c) Perform advanced data capture and statistical analysis to gain deeper
insights into the process for chosen parameters (Fig. 16 ). These advanced
tools should be used (or piloted) by a smaller subset of the organization.

3.2.2 Process Monitoring

As defined earlier, process monitoring involves collection of process data and
statistical evaluation of parameters to serve multiple purposes ranging from
demonstration of process control to identification of opportunities for process
improvements. In the USA, this is a requirement in the Code of Federal Regula-
tions (21CFR Part 211) specifying ''application of suitable statistical procedures
where

appropriate'', with in-process specifications ''derived from previous

acceptable process average and process variability estimates'' [ 16 ].
In the QbD paradigm, process monitoring has gradually evolved from just being a
retrospective analysis of data for the annual product review to a more dynamic
process involving more real-time analysis of data and linkages to the quality systems
of the company [ 11 ]. The latter include systems related to non-conformances, cor-
rective and preventive actions, lot release as well as other key activities associated
with GMP manufacturing of pharmaceuticals. This thinking is also reflected in
recently published documents from the different regulatory agencies and the Inter-
national Conference on Harmonisation (ICH). The ICH Q8 guideline states that
''Collection of process monitoring data during the development of the manufacturing
process can provide useful information to enhance process understanding.'' [ 7 ]. The
PAT guidance further states that ''Process monitoring and control strategies are
intended to monitor the state of a process and actively manipulate it to maintain a
desired state. Strategies should accommodate the attributes of input materials, the
ability and reliability of process analyzers to measure critical attributes, and the
achievement of process end points to ensure consistent quality of the output materials
and the final product.'' (FDA's PAT Guidance). The ICH Q10 guidance identifies
monitoring as a key element of the pharmaceutical quality system and states that
''Pharmaceutical companies should plan and execute a system for the monitoring of
process performance and product quality to ensure a state of control is maintained.
An effective monitoring system provides assurance of the continued capability of