The bio-pharmaceutical industry demands exacting detail in design, development,
operation, quality, and just about every other aspect of the business.
As such, there is a degree of specialty in most every field of endeavor
in this industry. This book was developed to try to accelerate the learning
process for the application of automation in bio-pharmaceuticals. The
authors' hope is that the content of this book will help scientists and engineers
continue to contribute to the manufacture of high-quality medicines
via improving process control and on-line availability of information
while reducing costs, cycle time, and process variability.
Some readers may come into this industry with previous automation
experience. Others may be in the bio-pharmaceutical industry, but have
limited automation knowledge. In either case, the authors strived to bring
the reader to a more thorough understanding of the topics.
This book is supplemented by a wealth of reference materials in the industry.
Each chapter contains a list of recommended reference materials.
TABLE OF CONTENTS Chapter 7 - Advanced Techniques
7.1 Bioprocess Measurement
PAT (Process Analytical Technology)
The U.S. FDA defines PAT as follows:
| Process Analytical Technologies are: systems for analysis and control of manufacturing processes based on timely measurements, during processing, of critical quality parameters and performance attributes of raw and in-process materials and processes to assure acceptable end product quality at the completion of the process. |
PAT is actually a broad-based continuous improvement initiative, encouraging
greater use of new technologies, risk-based management, increased
automation, and data analysis to achieve objectives such as greater understanding
of processes, increased on-line decision making, reduced cycle
time, improved process control, and reduced process variation, while
maintaining product quality [7.14].
PAT measurements are a subset of the overall PAT vision. They range from
traditional on-line measurement sensors (monitoring critical process
parameters) to the moving of more complex off-line or lab-based assays to
the production floor and interfacing them on-line or at-line to the process.
In part, the PAT initiative captures the evolution from the historical
use of "univariate" process measurements (e.g., temperature, pressure) to
ones that better capture the biological, physical, and/or chemical attributes
or state of materials being processed.
However, PAT involves more than appropriate measurements. It includes
use of multivariate tools for design, data acquisition and analysis, process
control tools, knowledge management tools, and continuous process
improvement.
The idea of PAT is that the information generated will be timely (avoiding
unnecessary process delays and holds) and can be used for appropriate
real-time or near-real-time decision making and control of existing process
runs; i.e., the goal is to enhance understanding and control of the
manufacturing process. This may be referred to as "continuous real-time
quality assurance" [7.7].
PAT is believed to be one of several contributors to the ultimate goal of
operating a capable, compliant, robust, in-control, and reproducible process.
For instance, PAT can be an important part of building quality into a
process, as opposed to testing for quality "after the fact."
While the topic of PAT has received much recent attention in the literature
and at technical conferences, primarily due to the FDA's recent endorsement
of it, PAT has actually been a successful part of many commercial
bioprocesses for more than twenty years. Two examples (on-line mass
spectrometry and HPLC) are described that have a long-term track record
for improved understanding and control of many pharmaceutical
processes.
