Contributing editor and PAT/QbD expert Emil Ciurczak is on the ground in Baltimore, covering this week’s IFPAC 2010 show, and will update us daily. Here is his Wednesday installment, followed by Tuesday's and Monday's below:

February 3: There were many sessions today, but the one that captivated me and held me in my seat was on imaging. The session, organized by Carl Anderson (Duquesne University) and Steve Hammond (Pfizer), consisted of nine disparate talks tied together by the theme of imaging. Some of the highlights:

Ralf Marbach (VTT, Finland) used his novel math treatment in conjunction with a new Fabry-Perot filter instrument to analyze the components in a multi-API tablet. Both the instrument and math treatment were novel and worth mentioning.

Benoit Inge (Duquesne) carried on the tradition of excellent graduate students at that school doing incisive work. He shared his work on following the “relaxation” of tablets after production using chemical imaging. There is a common knowledge that compression, followed by relaxation causes tablet properties to change over time, but this is the first in-depth study I have seen that approaches the problem in a planned, scientific manner.

Timo Hyvarinen (SPECIM, Sweden) spoke about and showed a fast, relatively inexpensive imaging system, suitable for process analysis. Their instrument has capabilities of thousands of scans/second. The video showed was of tablets moving down a conveyor belt and instantly being imaged and viewed in real time. The cost is below a simple bench-top NIR system.

Zhenqi Shi (Duquesne) shared some very interesting two-dimensional localization research results. There was some very interesting math used that was a touch above my pay grade.

I also managed to sit and chat with a number of people from both the FDA and industry. There were many, many encouraging comments, but a few discords, too. Several biotech people commented that there were no concrete QbD submission examples. While several good technical papers were presented, no one simply said, “This was done for Widget CR.” The other comments related to the economy: several people were worried that massive layoffs are often indiscriminant and the necessary people for PAT/QbD would be thrown out with the bathwater.

Thursday is the last day, but by no means less important. There are a number of strong speakers I look forward to hearing.

February 2: The talks started in earnest today, with five concurrent sessions. Most were dedicated to pharmaceutical applications, so it was “interesting” to try to cover many of them. One session, in particular, caught my attention: New Directions and Modeling. Since it made numerous references to chemometrics/multivariate modeling, I had to check it out. In the interest of brevity, I will merely highlight a few talks.

Sharmista Chatterjee (FDA) spoke about the value of multivariate models for real-time release testing (RTRT). He pointed out (as is generally know to us NIR-types) that MV models are the heart of design space and understanding the interaction of all parameters and how they affect the “quality” of the final product.

Phil Nethercote (GSK) spoke to using QbD in analytical methods. This has been mentioned at other meetings, but needs to be emphasized. In HPLC, it has been a practice to “stress” the method (miniature variations in flow, temperature) and show that it still gives correct answers. This approach may be spread to all methods: design space for SOPs and operating methods.

Theodora Kourti (GSK) spoke about expanding the MV approach to stability monitoring. GSK’s major thesis is that close monitoring of everything from raw material parameters through operating parameters through final product qualities may be “crunched” into a formula to predict and correct stability of a product.

Bob Mattes from FOSS NIRSystems showed more applications of NIR for bioreactor monitoring. As familiar as I am with NIR, I am always pleasantly surprised at what may be measured in a complex aqueous mixture.

Process Raman was also the topic of several papers. Andrew Whitly (HORIBA) disclosed the company’s new transmission Raman (I will investigate this further).

Ian Lewis (Kaiser Optical Systems) spoke about several newer approaches, including a convertible probe (large area to small area) for various process measurements.

These were the presentations that I felt elaborated on new ideas and technologies. A number of other talks, while good, were similar to those given in the past.

February 1: IFPAC 2010 started with a pre-conference workshop entitled “Implementation of QbD and PAT: A Regulatory Perspective.” Several regulatory agency speakers and industry representatives gave brief presentations, then sat for a Q&A session. Participating were Evdokia Korakianiti (European Medicines Agency), Steven Kozlowski (OPS, CDER, FDA), Frank Holcombe (Office  of Generic Drugs, OPS/CDER/FDA), and Christine Moore (NDQA, OPS/CDER/FDA) from the agencies, as well as Robert Baum (Executive Director, Pfizer) and Jim Cheney (Executive Director, Novartis) from industry.

Just a few of the highlights:

Dr. Moore addressed the scientific challenges facing QbD, particularly understanding multivariate approaches and new instrumentation. She informed us that, over the last two years, there were 12 NDAs, 18 INDs, and 6 sNDAs (supplemental NDAs) submitted with QbD as part of the submission. All were in addition to the pilot study (of a dozen products) previously run by the agency.

An interesting point made by Dr. Kozlowski: the ratio of QbD-based submissions for small molecules compared to biologics has been roughly 15 to 1.

Dr. Korakianiti explained that one impediment to rapid acceptance of QbD in Europe was the diversity: the EU consists of 27 member states, many with semi-autonomous agencies within a single country. She admitted that the submissions for biologics were essentially non-existent yet. She did comment that, after a company made a QbD submission, the second was made quickly thereafter. In all, she acknowledged that there were less than two dozen submissions to date.

Dr. Holcombe discussed a shift in approaching generics and QbD: FDA has generated a questionnaire that steps submitters through the process (since they often have much smaller staffs with less experience than larger companies). It does not replace the submission itself, but is intended to lend support.

Baum and Cheney indicated that their companies continue to be committed to PAT/QbD and were looking forward to more submissions. There were no major announcements in their talks.

In any case, no one seemed willing to actually name the products that they were speaking about. It leaves a bit of unease when they speak about “a solid dosage form” or “a biological product.”

More to come tomorrow, as the show begins in earnest today!