TUESDAY, NOVEMBER 18

8:00am Morning Coffee

Tools for Optimization and Scale-up 

8:30  Chairperson’s Remarks
Neal G. Anderson, Ph.D., Anderson’s Process Solutions

8:40 Innovations in Micro-Flow Reactors for Continuous Processing
Klavs Jensen, Ph.D., Warren K. Lewis Professor and Department Head, Department of Chemical Engineering, Massachusetts Institute of Technology
Microflow reactors promise rapid, continuous discovery, and development of new products with less use of resources and waste generation.  These systems combine microchannels, chemical-synthesis-on-a chip, and microscale separation to enable multiple synthesis and separation steps. Integration of on-line monitoring and control allow automated process optimization and the extraction chemical kinetics. Cases studies are drawn from chemical synthesis relevant to fine chemicals and pharmaceuticals, as well as synthesis of colloidal nanoparticles.

9:10 PAT Applications for Scale-up Synthesis: Comparing On-line HPLC and In-line IR
Andrew Lange, Ph.D., Associate Director, Analytical Development, Vertex Pharmaceuticals, Inc.
Reaction case studies will be considered in order to compare and contrast on-line HPLC with in-line mid-IR for chemical reaction monitoring.  Recently, on-line monitoring via automated microbore HPLC has provided an alternative to in-situ mid-infrared (in-line mid-IR) technology for allowing chemists real-time information about key reaction species. At the same time, in-line mid-IR technology has benefited from advances in software and probe technology, making both techniques important tools for process development. Each technology, of course, has its limitations. For example,  high-viscosity or heterogeneous mixtures may cause sampling difficulties for on-line HPLC, whereas monitoring low-level impurity levels may not be feasible with in situ mid-IR measurements. The strengths and weaknesses of each technique will be more fully explored.

9:40 A Fast and Efficient Way to Measure Drug Form Optimization and Production with Near Infra-Red and Infra-Red-Based Imaging
Weiyong Li, Ph.D., Research Fellow, Johnson & Johnson Pharmaceutical Research and Development
This presentation will focus on fluid-bed wet granulation, a commonly used unit operation in pharmaceutical manufacturing. Case studies will illustrate how NIR and the recently emerged NIR chemical imaging, in combination with fast particle size analysis techniques, enable better understanding and control of the fluid-bed granulation process, thereby enhancing formulation and process optimization. Discussion will also include use of unconventional methods to replace the conventional HPLC blend uniformity and sieve analysis for fast turn-around time and better process and product knowledge.

10:10 Networking Refreshment Break, Poster and Exhibit Viewing

Impact of QbD on Process Development

10:45 Chairperson’s Remarks
Ambarish K. Singh Ph.D., Associate Director, Chemistry Manufacturing and Control, Bristol-Myers Squibb Co.

10:55 Control Strategy in a Quality by Design (QbD) Environment
Stephen Liebowitz, Ph.D., Group Director, Global Regulatory Sciences-CMC, Bristol-Meyers Squibb Co.
Control Strategy is a pivotal element of QbD.  Developing a control strategy within the design space to assure manufacture of quality pharmaceutical APIs and drug products is more than just conformance to specifications.  What is control strategy in QbD and how it may differ from the traditional manufacturing approach will be discussed in this presentation.  How to create an effective control strategy in a risk-based paradigm will also be highlighted.

11:30 Does Your Process Achieve QbD? A Statistical Model Can Predict ‘Critical Quality Attributes’
Bir Gujral, Ph.D., MBA, PAT Coordinator, DSM Pharmaceuticals Inc.
We are developing a mathematical model that will enable us to predict the quality of Pharmaceutical batches based on our choice of control processes, raw materials and formulations. This model will provide a “roadmap” for innovative pharmaceutical manufacturing under various process parameters. This presentation will share the rationale behind how we evaluate ‘critical quality attributes’ (CQA) of processes and materials on which our optimized and validated mathematical model is based. We will also discuss applications of the model.

12:00pm Luncheon Technology Workshop (Sponsorship Available) or Lunch on Your Own

Impact of Genotoxicity Concerns on Process Development

1:30 Chairperson’s Remarks
Ambarish K. Singh Ph.D., Associate Director, Chemistry Manufacturing and Control, Bristol-Myers Squibb Co.

1:35 Genotoxic Impurities in Pharmaceuticals: A Regulatory Perspective
David Ziering, Ph.D., Director, Global Regulatory Sciences-CMC, Bristol-Meyers Squibb Co.
While the ICH guidance are clear about what levels an ordinary impurity needs to be identified and assessed for safety, the guidance have not specified what limits should apply to more onerous impurities, i.e., those with the potential to cause cancer. The EU has issued a final limit of these genotoxic impurities to 1.5 mcg/day total.  For a 150 mg daily dose that corresponds to a limit of 0.001% (10 ppm).  Furthermore, FDA has indicated that 1.5 mcg/day is likely to be the limit specified in their pending guidance.
As there may be multiple potential genotoxic impurities in an API, there now is a dramatic increase in the technical challenges for the analytical and chemical-process development groups, the commercial manufacturing sites, and the in-process and release laboratories. This session will provide a basic understanding of the regulatory considerations for genotoxic impurities, and approaches to successful technical-regulatory genotoxic impurity-control strategies.

2:10 Genotoxic Impurities:  Hazard Identification and Safety Considerations during Drug Development
Krista Dobo, Ph.D., Associate Director, Genetic Toxicology, Pfizer Global R&D
An overview of the application of structure-based assessments for the purposes of identifying known or potentially genotoxic impurities will be presented using practical examples.  In addition, the use of chemistry knowledge and the generation of gentoxicity data to inform decisions on appropriate management of potentially genotoxic impurities will be discussed.  Finally, other considerations that impact the management of gentoxic impurities during drug development will be highlighted, such as clinical population, therapeutic indication, genotoxic profile of the API, and multiple genotoxic impurities.

2:40 Networking Refreshment Break, Poster and Exhibit Viewing

Biocatalysis

3:15 Chairperson’s Remarks

3:20 Integrating Biocatalysis and Process Chemistry: Challenges and Success Stories
Alex Tao, Ph.D., Chief Scientific Officer, BioVerdant
This presentation will help bridge the divide between biocatalysis in theory to biocatalysis in practice. The following practical issues will be covered:

3:50 Reducing the Initial Time Lag from Incorporating Biocatalysis into Process Development
Martin Schuermann, Ph.D., Applied Biocatalysis Scientist, Innovative Synthesis and Catalysis Department, DSM Pharmaceutical Products
By speeding the development of new biocatalytic processes to only a few months, DSM’s biocatalysis applications have become competitive with other established technologies. We will present the methods we implemented. They include: HTP screening of a large diversity of biocatalysts under process conditions, fast process parameter screening and rapid scale-up of enzyme production based on our “pluGBug concept”.

4:20 Engineering Effective Biocatalysts
Romas Kazlauskas, Ph.D., Professor, Department of Biochemistry, Molecular Biology and Biophysics and the Biotechnology Institute, University of Minnesota
Evolution creates new catalysts from existing enzymes by mutagenesis to give them new abilities.  One goal of biocatalysis is to recreate this evolution in the laboratory to produce unnatural enzymes that can solve current synthetic problems. There are three ways to create a new catalytic activity: 1) replace the active site metal ion with a new one, 2) extend the existing catalytic mechanism to analogs, often by changing substrate binding, and 3) create completely new catalytic steps. This lecture will discuss natural and engineered examples of each of these approaches.

4:50  Shared Presentation: Green Manufacturing of Pharmaceuticals Using Custom-Evolved Biocatalyst
The outsourced biocatalysis provider perspective
Jim LaLonde, Ph.D., Vice President, Research and Development, Codexis, Inc.
The customer view
Greg Hughes, Ph.D.,Associate Director, Process Research Department, Merck & Co., Inc.

5:35  End of Day