ave Adler and colleagues at Eli Lilly conceived and organized the first Pharmaceutical Automation Roundtable (PAR) in the Fall of 1994. At the sixth PAR gathering (September 2000), also held in Indianapolis, Rick Cooley of Eli Lilly hosted a parallel gathering of process analyzer professionals (Pharmaceutical Process Analysis Roundtable–PPAR). By PPAR-2 at Pharmacia (Skokie, Ill.) in April 2002, the PAT Initiative was taking form and this roundtable meeting had growing significance. This past summer, in the course of some research, I came upon yet another pharmaceuticals multi-company forum, the Midwest Utilities Group, for WFI/purified water specialists to discuss generic concerns in this vital support function. There are undoubtedly many others but the PAR and PPAR meetings are focused exclusively on measurement and control and are, therefore, of primary interest to process control engineers.
I have attended all but one of the 10 PAR conclaves and all four of the PPAR gatherings. Traditionally, the kick-off speaker at these events was from the host company’s legal staff cautioning participants to stay general and carefully avoid any hint of collusive action. The FDA’s cGMPs for the 21st Century, with its stress on robust, well-understood manufacturing processes, is now firmly in place. Top manufacturing executives including: Sr. director–Biochem Business Unit, John Frenz—Genentech (PPAR) and Sr. vice president, Engineering, Raymond Scherzer—GlaxoSmithKline (PAR) started the latest roundtables in October 2004 urging participants to take away enhanced skills for meeting the cGMP goals.
The fourth PPAR meeting was hosted by Genentech in San Francisco (Oct. 12–14). Twelve manufacturers (split 50-50 between traditional pharma and biotech) as well as the two leading research consortia for process analysis were represented among the 30 attendees. About half of the attendees participated in an extensive tour of a Genentech bioprocess synthesis (fermentation) and separation (process chromatography) facility. Special attention was devoted to the use of on-stream analyzers and analytical data in these operations.
A teleconference was also held with Chris Watts and Ali Afnan of FDA CDER’s PATRIOT Team. CDER’s progress in training inspector’s was reviewed as well as their intention to invite European and Japanese regulators to participate in the next round of PATRIOT training courses.
The results of a benchmarking survey (12 companies participated) were also discussed. The survey covered 13 organizational questions (e.g., the size of PAT effort–number of professionals?), 12 manufacturing questions (e.g., where is PAT currently used?) and nine research questions (e.g., barriers to the use of PAT in R&D?).
A week later (Oct 17–19), 21process automation specialists, representing 13 pharmaceuticals and biotech manufacturers, met at GlaxoSmithKline’s research campus in Research Triangle Park, N.C. This was the tenth Pharmaceuticals Automation Roundtable session in a format that began in 1994. Under Computer Validation, an FDA training course was described that had been developed by Schering Plough and Johnson & Johnson. In March 2004, 50 FDA Inspectors took this course which is directly concerned with computers used for manufacturing automation not LIMS, MES, ERP or similar uses. At least three of the companies represented at the Roundtable had had automation-specific FDA investigations.
The roundtable concluded with a visit to Bayer’s Clayton, N.C. Biological Products site. Important life-saving pharmaceutical products derived from human blood plasma are produced at the facitlity. Roundtable members toured the new immune globulin (Gamunex) facility. Automation is used throughout the process to support highest standards of product safety combined with optimum manufacturing efficiency.
I do not claim to be an authority, and remain a guest at these roundtable proceedings, but my reading of the PAT Initiative is that it is much more than using process analyzers in pharmaceuticals processes. It is about gaining true understanding of the mechanisms that drive the process and their robustness. Will the process tolerate excursions in the principal measured parameters without dire consequences to product quality? Is the operating surface broad and flat, or a pinnacle where small deviations can yield significantly sub-optimal results?
Process analytical instruments, and other automation/data analysis technologies, can be vital tools in this pursuit but, from my perspective, process understanding and applying this knowledge to manufacturing protocols is the over-arching objective of this widely misunderstood Initiative.
Terrence K. McMahon, McMahon Technology Associates, can be reached at Mcmahontec135@aol.com.