PAT Takes Manhattan — and San Juan

By Paul Thomas, Managing Editor“If PAT can make it there, it can make it anywhere. . .” well, you get the idea. PAT was a big hit at April’s Interphex show in New York City at the Jacob Javits center in Manhattan. From session rooms to the exhibition floor, everyone it seemed was using those three letters to grab a little piece of the show spotlight. PAT was also emphasized at Induniv’s fifth annual Forum for Innovation held from April 6-8 in San Juan, Puerto Rico.  Two full days of Induniv’s conference were devoted exclusively to PAT basics and implementation as well as case histories and sharing of “best practices.”On the Interphex exhibition floor, signage advertised PAT for blending, PAT for drying, PAT for tableting, PAT for packaging—anything that’s monitored in real time or has wireless applications got the PAT label.But what truly qualifies as PAT? That was a question being raised in the sparsely attended sessions and workshops away from the show floor. Nancy Mathis, president of thermal effusivity sensor maker Mathis Instruments, led off one workshop by discussing email correspondence she’d had with FDA. She had posed this question to the Agency: Is measuring temperature on a fluid bed dryer in real time PAT? The Agency had concluded that, no, the measurements in themselves are not PAT unless the operator can leverage those measurements to gain a greater understanding of his or her processes.Away from the vendor booths, the point that many were driving home is that PAT is less about monitoring pharmaceutical processes than it is about controlling and understanding those processes. Mathis herself is the first to admit, for instance, that her sensors are only a very small piece of what is becoming an extremely grand and complex PAT pie. Process control specialists, including Emerson Process Management, which has launched a new Operational Excellence program, see PAT as a critical tool for improving manufacturing efficiency.How to make sense of it all? Enter the consultants, who were out in full force at the show, espousing homemade PAT recipes for manufacturing clients. In the Mathis-led session on thermal effusivity as a process analytical technology, Tracy Davis and Normand Dubuc of Invensys Validation Technologies, which now boasts more than 200 PAT consultants worldwide, outlined their firm’s six-stage approach to PAT success.Davis in particular offered a clear perspective. While all firms should be developing PAT strategies for long-term implementation, Davis noted, starting with just one piece of equipment is a step in the right direction. Collaboration and partnering among solutions providers is also key, he said. Invensys has partnered with Mathis, O’Hara Technologies, and Sentry Equipment Corp. on a device for real-time effusivity monitoring of a FBD. The device is now being tested at Confab, a Canadian contract manufacturer.In another session, Dr. Philippe Cini, managing consultant of Tunnell Consulting, discussed his firm’s “flexible and comprehensive” framework for process understanding. Cini showed how firms can begin their pursuit of PAT with qualitative steps such as process maps, move into basic quantitative areas such as control (Cpk) charts and bivariate analysis, and then move into an advanced quantitative stage with the ability to perform regression analyses as a means of controlling processes. While Tunnell’s approach is heavy on statistics, Cini noted that one of the most important features of any PAT strategy is a company’s ability to create high-performing, cross-functional teams.Joseph Vinhais, vice president of regulatory affairs at Camstar Systems, Inc., an execution systems vendor, spoke on the need for manufacturers to align PAT, Lean and Six Sigma. “How effective will PAT be if you’re at 1 Sigma?” he asked.Finally, Swagelok Co.’s David Simko discussed NeSSI (the New Sampling/Sensor Initiative), an effort to drive the next generation of modular product sampling systems through miniaturization, wireless technology, and an open platform. Simko’s conclusion was that modular concepts are aligned with PAT in their promotion of smart microanalytical devices.If Interphex proved one thing, it’s that PAT is gaining broad commercial appeal, driving what might have been considered fringe technologies and solutions into the mainstream of pharmaceutical manufacturing.Induniv’s San Juan conference showed how widespread the use of PAT is among member companies, and how early adopters are sharing best practices with peers and other manufacturers on the island. Induniv, a consortium joining academia and industry, aims to bridge the communication gap between industry and academia to promote pharmaceutical and biopharmaceutical manufacturing and R&D in Puerto Rico. The island is already a manufacturing powerhouse, but is now staking a claim in development -- particularly the back end of process development, and in clinical trials.Speakers included Rebeca Rodriguez from FDA’s PAT team, professors from the University of Puerto Rico’s Mayaguez campus, local engineering providers, and representatives of Wyeth, including Graham Cook, associate director of tech ops for Wyeth Europa, as well as Wyeth Guayama validation specialists Reinaldo Vazquez and Pedro Perez, who discussed a use of light-induced fluorescence (LIF) to determine blend uniformity, and laser diffraction for measuring particle size. Rick Cooley of Dionex Corp. discussed use of process analytics for biotech and online liquid chromatography.PAT is clearly well advanced at Induniv member facilities, but the conference underscored those companies’ endeavors to share best practices with other manufacturers on the island. Similar efforts have already taken place with Six Sigma and other efforts aimed to improve pharmaceutical manufacturing efficiency, says Induniv director Ivan Lugo.The Materials Characterization Center attests to the island’s strength in process analytics. The Center, which was set up 10 years ago at the University of Puerto Rico’s Rio Piedras campus, was originally supported by the government. However, it became independent in 1999 and has been self-supporting since 2002, and now handles some 400 industrial projects each year in NMR, mass spectrometry, chromatography, surface microscopy and spectroscopy, x-ray diffraction and crystallography.If its manufacturers are serious about PAT, Puerto Rico is also serious about moving beyond manufacturing, and developing a “knowledge-based” economy, and Induniv is joining industry and academia to advance that effort. In June, construction will start on a Bioprocess Research and Workforce Development Center, a $12.5-million pilot plant based in Mayaguez that would provide services to biotech companies in Puerto Rico, and train the workers needed for biotech and process development research.Induniv’s Road Map initiative aims to set up life sciences clusters in pharma, biotech, medical devices and healthcare services. Last year, a law was passed granting new tax incentives to companies that carry out clinical studies on the island, and Induniv is now working to develop a clinical investigations center in Puerto Rico. For more information, visit www.induniv.org.