Since FDA issued its report, Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century—A Risk-Based
Approach (1), and its guidance on process analytical technology (PAT) (2) in 2004, academia and industry have been making
strides in integrating quality-by-design (QbD) principles and PAT into solid-dosage manufacturing processes.
Fotosearch/Eriko Koga/Comstock/Getty Images; Dan Ward
PAT and QbD principles both emphasize the need for process and material understanding as a basis for effective control of
the process. “This emphasis has stimulated the industry to focus on how to get the information it really needs, which is leading
to a productive re-examination of the existing analytical toolkit and an embracing of newer technologies that deliver the
goods,” says Tim Freeman, managing director for Freeman Technology. Progress has also been made in integrating PAT into continuous
manufacturing of finished-drug products, with the eventual goals of closed-loop control and real-time product release.
Online PAT is successfully being used to optimize individual unit operations in solid-dosage manufacturing by monitoring on-line
critical quality attributes (CQAs). Data from PAT give manufacturers better understanding and can be used to control the unit
operation. Moisture content, for example, is used to determine the endpoint of a drying cycle. In tableting, the most common
online measurements are near infrared (NIR) spectroscopy, which measures moisture content and blend uniformity, and laser-diffraction
Bulk-powder characterization techniques, which are performed at-line or in the laboratory, also fulfill the purpose of PAT
by providing crucial information in a timely manner. “Precisely quantifying the flow behavior of powders, either as raw materials
or as a blend, and other characteristics such as the ease with which a powder entrains and releases air, supports the development
of more efficient processes,” explains Freeman. Flow-property measurements are increasingly being recognized as a desirable
online measurement, but this technology is not yet available.