The complexity of biopharmaceutical processes warrants that gathering of knowledge about the product and the process will
continue as the product progresses through the different phases of commercialization, i.e., process and product development,
process and product characterization, and process validation and routine manufacturing. Process monitoring has emerged as
a critical tool for demonstrating that the manufacturing process is in control and identifying future process improvement
Process monitoring is the method for collecting process data and statistical evaluation of parameters to verify and demonstrate
that the process is operating in a state of control, identify possible process changes and shifts, and promote continuous
improvement. Typical process monitoring applications in biopharmaceutical manufacturing incorporate statistical process control.
In the United States, the Code of Federal Regulations (21 CFR Part 211) specifies "application of suitable statistical procedures where appropriate," with in-process specifications "derived
from previous acceptable process average and process variability estimates."1
Process monitoring has been a topic of discussion in recent guidances from the regulatory agencies. The ICH Q8 guidance states
"Collection of process monitoring data during the development of the manufacturing process can provide useful information
to enhance process understanding."
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."
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 processes and controls to meet product quality and to identify areas for continual improvement."
Finally, a presentation on the recently released FDA guidance on process validation highlighted process monitoring as a critical
follow-on to process validation to verify that the process is in control, add assurance of product quality, and reveal the
need or opportunity for improving the process and the control strategy.5
This article is the 16th in the Elements of Biopharmaceutical Production series and reviews some of the commonly used approaches for process monitoring as well as the evolution of process monitoring
in the Quality by Design (QbD) paradigm.