OR WAIT null SECS
From RFID and pedigrees to PAT and process understanding, industry professionals are eying the growing gap between ambitious high-level guidance and current practice, and wondering how they can bridge this new space and keep in compliance with the untested rules.
Here are vignettes from two recent conferences.
At Secure Pharma 2006 (May 23–24 in Philadelphia), we met a ballroom-full of drug makers and wholesalers who were manifestly willing, even eager, to implement any pedigree plan—as long as they could be sure that they were investing in and implementing the right plan. As it was, however, they were paralyzed by the very wealth of possibilities confronting them. Some speakers suggested that pioneers in RFID (radio-frequency identification) tagging may have to replace their systems once or even twice as the technology and standards evolve.
A few weeks later at the first PharmTech Event (June 12–15 in Somerset, NJ), Jon E. Clark, associate director for policy development and good manufacturing practice in the Office of Pharmaceutical Science, said this:
"The process analytical technology guidance is a very ... empowering guidance, though very general and high level. For those of you who are looking for highly detailed, specific guidances that tell you how to do things, you might be disappointed in the coming years, because guidances will look like the PAT guidance." (Emphasis added.)
Uncertainty and anxiety ran high at both meetings.
State of flux. Manufacturing regulation is now in unprecedented flux: FDA can announce a final rule for Phase I manufacturing in January, then withdraw it in May, and then, in June, first sweep away seven manufacturing and stability guidances that don't fit today's emphasis on flexible, science-based regulation and then shake itself out of a six-year torpor and finally schedule implementation of an industry-wide drug pedigree.*
Change is coming to an industry that doesn't like change. Perhaps worse, for an industry that likes its facts concrete and its recommendations specific and in triplicate, the changes are dropping in from a high, almost stratospheric, conceptual level.
Clearly, the industry will have to move ahead, even if it is under the lash of regulations that tell us where we must go, but not how to get there.
How in the world can we bring this high-flying high-mindedness down to earth and the factory floor?
The early 19th Century French observer Alexis de Tocqueville famously noted an American genius for solving problems through private associations. FDA officials have clearly indicated that it will be up to the industries, professional societies, and voluntary standards organizations to fill in the details of the path ahead.
It's going to be a bumpy night. The regulators have been at pains to reassure us they will not penalize companies that continue to follow old or withdrawn guidances—for a while. But real progress will require someone in the industry to stick his or her neck out and actually venture where the guidances appear to lead.
This is not a prospect that our industry particularly relishes.
At the PharmTech event, Joan Materna (the Novartis senior associate director of global regulatory CMC, and a coauthor of PhRMA's July 2005 position paper, "Current Thoughts on Critical Process Parameters and API Synthesis"**) surveyed the upheaval and summed up the next few years with Bette Davis's line from All About Eve: "Fasten your seat belts. It's going to be a bumpy night."
*For more details, see this month's In the Field and last month's "FDA Withdraws Jan.17 Rule Relaxing Phase I GMP Standard," Pharm. Technol. 30 (6), 18 (2006).
**W.P. Ganzer et al., Pharm. Technol. 29 (7), 46–66 (2005).
Douglas McCormick is the editor in chief of Pharmaceutical Technology, firstname.lastname@example.org