By Terry K. McMahon, CONTROL ColumnistTHE FIFTH
meeting of the Pharmaceuticals Process Analytics Roundtable (PPAR-5) was held in late September at Pfizer’s R&D campus in La Jolla, Calif. About 25 individuals attended, representing 13 manufacturers and three supporting organizations. The manufacturers were Amgen, Baxter, Eastman Chemical, Genentech, Invitrogen, Lilly, Merck, NovoNordisk, Pfizer, Talecris (formerly Bayer), 3M Pharma, Vertex and Wyeth. The supporting organizations were the National Institute for Science and Technology (NIST), the University of Washington’s Center for Process Analytical Chemistry (CPAC), and the University of Tennessee’s Measurement and Control Engineering Center (MCEC).
John Loran, science and technology VP at Pfizer’s La Jolla-based R&D Center for Pharmaceutical Sciences, opened the meeting, remarking on Pfizer’s early use of NIR for process development. With federal regulators demanding sharply increased levels of process understanding and process robustness, now is the time to link key business drivers, such as Pfizer’s Right the First Time (RFT), with technological initiatives in pursuit of FDA’s Process Analytical Technology (PAT) guidance.
Early meetings of this PPAR group, as well as its parent, Pharmaceuticals Automation Roundtable, were initiated by corporate attorneys concerned with potentially collusive, non-competitive discussions. Lately, these introductions have stressed using process technology to promote product safety and uniformity, while improving manufacturing efficiency.
"While process understanding (PU) is the real meaning of the Process Analytical Technology (PAT) guidance, ‘PU Initiative’ just didn’t have the proper ring to it.”
Collaboration between FDA’s Center for Drug Evaluation and Research (CDER) and pharmaceutical manufacturers to achieve a deeper scientific understanding of drug manufacturing processes is the PAT Initiative’s objective. This deeper understanding leads to more robust processes, product reliability, and economic benefits.
Several attendees were concerned that FDA’s Center for Biologics Evaluation and Research (CBER), a critical group for biotech manufacturers, was not a part of this effort. However, a telephone conference with CDER’s Ali Afnan assured them that CBER was represented on the PAT Initiative’s steering committee and that CBER inspectors would be included in second-round PAT training late this year and early in 2006.
The name, Process Analytical Technology, has been badly misconstrued in some quarters by limiting it to on-stream analyzers. These analyzers are an important tool in process understanding, but they’re neither a necessary nor a sufficient condition for complying with PAT guidance. Afnan remarked that, while process understanding (PU) is the real meaning of the guidance, “PU Initiative” just didn’t have the proper ring to it.
The current PAT guidance is the final one to be authored by CDER. Future developments and enhancements will derive from ASTM’s E55 Committee, which is charged with providing a consensus platform for definitions, standards and other technical support.
Afnan was co-chair of IFPAC/2005. His colleague, Chris Watts, is co-chair of IFPAC/2006. Scheduled for Feb. 20-23, 2006, in Washington, D.C., conference details are at www.ifpac06.org
. Pharmaceutical professionals were a growing fraction of IFPAC’s attendees in 2003-05.
Anyone seeking to gain a clearer appreciation of the PAT Initiative and related technical activities needs to consider three important venues: ASTM E55 Committee, PPAR and IFPAC. This year’s PPAR host, Andrew Lange, of Pfizer in La Jolla, did an excellent job of organizing and moderating the gathering. Amgen/CPAC, Merck and Talecris have offered to host the 2006 gathering. Location, date and other details will be posted at www.patroundtable.org
Meanwhile, the annual PPAR benchmarking survey included responses from 12 pharmaceuticals manufacturers. One question concerned analytical technologies now used in commercial manufacturing, as well as those used for direct closed-loop control:
The full results of this questionnaire, with more than 40 questions and responses to three earlier benchmarking surveys, also can be viewed at www.patroundtable.org
A roughly two-hour teleconference was held with CDER’s Afnan to review 12 questions that had been formulated by PPAR’s conferees. The session was very informative, and Afnan’s performance was incisive, analytical, authoritative and decisive. This level of interaction between the FDA and pharmaceuticals industry was inconceivable five years ago. The transformation is almost entirely due to Ajaz Hussain and the Patriot Team under his direction. The extent to which the PAT Initiative and the collaborative spirit takes firm root in the culture of FDA will depend on both the industry’s response in funding the necessary investments and the agency’s follow up in pursuing science-based regulatory policies.
Terrence K. McMahon of McMahon Technology Associates, Leonia, NJ is the "Around the Loop" columnist for CONTROL magazine and ControlGlobal.com. He can be reached at Mcmahontec135@aol.com