PAT Means Revolution — For FDA, Too

Nov. 24, 2004
PAT demands cultural change, not only within pharmaceutical manufacturing companies but also within FDA. Currently, the skills, training and background of FDA inspectors vary widely. Can they make the leap from the traditional chemistry-based quality approach to a future grounded in analytics and instrumentation?

By Agnes Shanley, Editor in Chief

A small group of visionaries, within the pharmaceutical manufacturing community and FDA, is transforming the concept of drug quality, from the old-fashioned “pass/fail” approach to one grounded in statistical process control, instrumentation and modeling. The new approach promises to facilitate continuous improvement, and Process Analytical Technologies (PAT) will be critical to achieving the level of process knowledge required. At this point, though, PAT still hasn’t reached the day-to-day radar screens of many pharmaceutical manufacturing and quality professionals.

At this early stage of implementation, there are still many questions about PAT: First, what are other drug companies doing with analytics and instrumentation? Which technologies and modeling approaches appear to work best for specific processes? How will PAT work with biopharmaceuticals?

In this first issue of PAT Insider, we bring answers to these questions, and best practices, from a number of sources. We also publish the latest results from an industry benchmarking survey indicating current PAT resource allocation, usage patterns and trends for the future.

While industry grapples with change, another looming question is how FDA will adapt to the new approach to quality, and to the changes that PAT requires. Ajaz Hussain, after all, may have a background in modeling and neural networks to complement his pharmaceutical science background, but what about the inspectors on the ground, who will be examining PAT installations? If PAT comes as a culture shock for the QA chemist at the typical pharma company, accustomed to traditional laboratory testing, it may be even more challenging for some of the more tradition-bound FDA inspectors.

While nobody doubts the skill and integrity of FDA inspectors as a whole, perhaps some of you have experienced inspections that seemed somewhat arbitrary, or met inspectors that seemed to have “blinders” on, or inadequate knowledge of the subject matter at hand. In the U.K., individuals can only be licensed as inspectors after they have worked in industry for a number of years. In the U.S., requirements have been less stringent. As a result, the skill and training levels of individual inspectors may vary widely.

The Agency has launched a major program to improve the professional standing of its inspectors, establish science-based standards and harmonize inspectors’ efforts with those of other global regulatory agencies. Gary German, who oversees the training of FDA’s new Pharmaceutical Inspectorate (PI) as director of ORA’s HR division, says these select few trainees will surely be up to the challenge. “We’re not bringing rookies in here,” he says. “These are already good, qualified investigators. We’re not teaching them how to be inspectors. We’re teaching them how to do inspections at a higher level.”

Still, there are many skeptics. “Instead of training inspectors to understand systems and processes, now they need to be trained in the science of manufacturing processes,” says Roddy Martin, senior consultant for life sciences with AMR Research. “It’s a fundamental cultural shift the FDA has to make. I just don’t see that time is on their side.”

Many Pharmaceutical Manufacturing readers have already weighed in as to whether they believe FDA’s new initiatives will succeed. In our latest web poll, pessimists far outnumber the optimists. (You can view the poll down the left side of this page and give us your opinion.) We’ll wait and see. This newsletter, and Pharmaceutical Manufacturing, will track progress and keep you informed.