More from ISPE Orlando: FDA’s Moheb Nasr Discusses QbD

Nat Ricciardi was not the only keynote speaker at ISPE's meeting in Orlando, at a hotel right within Disneyland,  this week.  Also on the program was a marketing director for Disney. (And now for a brief digression...to avoid reading it, scroll down to the next subhead in bold to read the important part ): I confess that I rolled my eyes when the program change was announced (ISPE had originally planned to have an "imagineer," rather than a marketer, speak at the event),  only to find that he was an excellent speaker who brought up some of the challenges that the company faces (notably, energizing poor performers)  and techniques that the company uses for brainstorming and process improvement, all quite relevant to drug development and manufacturing.  His talk was also full of promos for the company---as a parent of three, I've heard entirely too much from Disney over the years, and, horrifying as this may sound, had never even been anywhere near a Disney theme park --- and (to echo the drug industry's most popular mantra) by design.  In Orlando, one can almost hear the giant sucking sound of money being vacuumed from pockets, and all with a plastic smile and the strains of "It's a small world after all" piping in.   As the speaker put it, Disney's new competitors aren't other theme parks, but home repair and construction contractors and even orthodontists.  (I say, make the repairs on the house and fix the kids' teeth first, although I realize that a trip is warranted)   If one can't help but admire, even if begrudgingly, Disney's ingenuity, one must also credit ISPE for finding crowd-pleasing destinations and organizing its programs so well.  Next year's program will be at another sure-fire hit destination: Las Vegas (which has always ranked high on my must-to-avoid list, but then I'm a contrarian).  OK. Rant over Dr. Moheb Nasr on QbD If "saving the best for last" was the intent, then the leading keynote speaker at the event was FDA's Dr. Moheb Nasr, Director of the Office of New Drug Chemistry, who started his talk by summarizing all the challenges facing drug development and manufacturing.  (For the record, FDA's P.R. staff really needs to have a new publicity photo of Dr. Nasr taken; in the existing one, he appears unfriendly and forbidding, neither of which would describe him in person.) "The industry's supply of drugs is adequate and of sufficient quality," he said, but pharma remains slow to innovate and to embrace new technologies. He also mentioned the Nickerson/Macher study. Dr. Nasr went on to discuss ICH's vision for quality, walking through the goals for Q8 (design space), Q 9 (risk management) and Q 10 (quality systems).  As he put it, the term "quality by design" is still misunderstood within the industry, even though it has been around for so long. Nasr went on to talk about FDA's CMC Pilot Program, which allows applicants to propose a regulatory strategy specific to a product and/or process.  He also discussed needs and gaps, highlighting the need for control, quality control and change control:
  • new manufacturing platforms
  • continuous processing
  • process intensification and increased use of microreactors (we're covering this regularly in the magazine, and adoption is increasing, at least in labs)
  • new control platforms, to facilitate PAT, real-time release, and statistical process control.
Pharma companies must shift from the old mantra of "how can I put as little information as possible into this application," to "how can I facilitate a review based on good science,"  he said. Removing functional silos, but also the budgeting silos within each company, will be critical, as will increased scientific dialogue, which, Nasr suggested, should start at the end of Phase II. Some companies may not "get it" but an increasing number are taking FDA up on its offer for more dialogue: 12 applications were submitted to the CMC Pilot Program, of which 11 applications were accepted ---2 have been approved, 3 are under review, and another 6 remain to be formally submitted. As Dr. Nasr summarized, the FDA's new role should be that of "facilitator" rather than gatekeeper.  And, like Ajaz Hussain before him, Nasr suggested that it remains in the industry's court to accept the challenge to improve and control its processes. Unfortunately, there was no Q&A session after the speeches.  I would have asked Dr. Nasr how FDA planned to communicate its new role to Washington and to the media, given the increasing hostility and concerns about undue ties to the industry and "conflicts of interest." Rep. Waxman's previous report on FDA enforcement reflects a fundamental misunderstanding of the Agency's motives, its reasons for change and the positive impacts that change could have on the industry and the patients who use its products. I would also have asked Ricciardi and ISPE's management, as well as NIPTE, which held a special meeting on Sunday and Monday, whether there will be any concerted effort launched to study the Nickerson and Macher benchmarking data and draw any lessons for pharma.  We're grappling with the 450+-page monster and will summarize whatever can be distilled into four short magazine pages, in our December cover story. Too many concurrent programs, too little time There were a number of interesting panel discussions and workshops competing for attention, on such topics as flu vaccine manufacturing facilities of the future, critical utilities project management, Quality by Design.  I attended one on continuous processing, which included an interactive exercise led by U.K.-based consultant Lynn Bryan, in which participants rated the reasons both for and against moving from batch to continuous--- key to articulating strong proposals to senior management.  She brought a much needed bit of humor to the program. FDA's PAT team's Ali Afnan could not attend, but retired FDA person Joe Phillips (whose son works in the industry and was also in attendance) spoke,  as did FDA's Joe Famulare, who gave a presentation originally made by his colleague, Chris Watts, in which he traced the evolution of the term "validation" and how the "three batch" definition came up.  He also addressed an important problem with continuous processing:  how to define a "batch" (e.g. in case of a product recall), using a time-based paradigm. FDA is putting together a draft guidance to provide more details, and how this would relate to stability. Everyone at the workshop was quite gracious about having a dreaded "member of the media" observe the proceedings. What was clear from the exercise was how relatively unimportant capacity utilization appears to be at many companies. Student posters were all very interesting (the winning one, from Montreal, focused on PAT). Meetings the next day were also quite good, and some vendors, particularly those in the PAT space, had some news to announce---Ometric now has wireless capabilities to facilitate inline process control, while Montana-based PAT Toolkit is releasing some new case histories (one of which will be published in our next edition of PAT Insider).  Caught part of a presentation by Pfizer senior scientist Bradley Diehl on process development, which looked at how Pfizer is applying PAT, using NIR and Focused Beam Reflectance Measurement, to optimize solid dosage processing from blending, wet granulation, fluidized drying and milling.  It offered a clear illustration of the "design space" and how the concepts of PAT are being applied within it.   The winning ISPE journal paper this year, not surprisingly, was the PAT article written by Joydeep Ganguly and his colleagues on Talecris' PAT team. It was also nice to see some of the people within ISPE recognized at its lunch---not only an outgoing VP, but also the designer of its magazines, whose work, along with that of its inhouse editor, remains largely invisible. The organization is linking up with other groups, notably AAPS and biopharma organizations, and this year's conference underscored the importance of joining ISPE for any drug industry professional. -AMS