TUESDAY, OCTOBER 16

8:30 am Interactive Roundtable Discussions: Threats and Opportunities for Process Development

9:30 Chairperson’s Remarks

9:35 Strategic Decisions in Organic Process Development for the Pharmaceutical Industry 
Professor Bertrand Castro, Scientific Director, Industrial Affairs, Sanofi-Aventis
The management of organic process development is mainly founded on the answer given by top management to the question: Is industrial chemical production of APIs a strategic activity for the Company? If the answer is negative, the chemical development activity will be centered on the clinical supply production up to Phase IIa and on the technical transfer of the future NDA route to an external supplier. The answer given to this question by Sanofi-Aventis has been positive. This implies that the chemical development is shared by two different though narrowly connected organizations, an upstream “Chemical Development” dedicated to the determination of the saline form, of the NDA route, essentially focused on the definitively fixed last step, and the production of the toxicological and clinical batches until Phase IIb. At the end of Phase IIa, if proof of therapeutic concept is set up, the technology transfer is directed toward a downstream “Process Development” directly connected with our chemical plants; this entity produces the late Phase IIb and early Phase III clinical batches, sets the industrial process, and transfers it to the chemical plant. This organization allows an earlier preparation of second-generation routes that can be submitted to registration as soon as the final approval is given. This process is nevertheless applied with the highest flexibility and can be modulated project by project. Some examples will be given on irbesartan, clopidogrel, and oligosaccharides projects, showing how the organization and the CMC dossiers have been managed.

10:05 Cost-Efficient Deprotection of PMP: Toward an Industrially Viable Asymmetric Mannich Protocol
Quirinus B. Broxterman, Ph.D., Corporate Scientist – Route Scouting & Selection, DSM Pharmaceutical Products – Advanced Synthesis, Catalysis & Development (DPP-ASC&D)
A number of conceptually very useful asymmetric synthesis technologies, such as asymmetric Mannich reactions, proceed through imine intermediates. In many of these, use of the para-methoxyphenyl (PMP) protecting group is essential. State-of-the-art deprotection technology such as use of ceric ammonium nitrate, however, is not cost effective from an industrial perspective. This slows down the large-scale use of asymmetric Mannich technology for the production of chiral intermediates for the pharmaceutical industry. Therefore, we developed cost-efficient removal technologies: the use of TCCA (trichloroisocyanuric acid) and other oxidants lead to deprotection in high yield. Moreover, laccases (EC 1.10.3.2), especially in the presence of mediators, also proved to be an efficient enzymatic removal method.

10:35 Technology Watch (Sponsorship Available)

10:50 Networking Coffee Break, Poster and Exhibit Viewing

11:35 Case Study of Outsourcing Process Chemistry 
David Mitchell, Ph.D., Research Advisor, Chemical Process R&D, Eli Lilly and Co.
The goal of this presentation is to discuss the process chemistry of a potential pharmaceutical target. As a case study, outsourcing strategies, enabling greener chemistry along with improved synthesis efficiency, will be presented. This talk discloses current trends along with challenges faced in process R&D. Using a central molecule as a theme, several current tools that are available for process development will be demonstrated for solving process chemistry problems.

12:05 pm Process Validation from the Standpoint of an Organic Chemist
Neal G. Anderson, Ph.D., Anderson’s Process Solutions
The benefits of validating processes will be discussed. Proactive validation requires laboratory scouting to determine suitable ranges of parameters for rugged processing. For successful process introduction fail-safe operations must be considered. Organic chemists can provide practical guidelines to validate processes on the manufacturing scale. Points will be illustrated by brief case studies.

12:35 Lunch on Your Own or Luncheon Technology Workshops
(Sponsorships Available)

2:20 Spotlight on Biologics Process Development: Challenges in mAb Production and Application of PAT
Amit Banerjee, Ph.D., Research Fellow, Global Biologics Worldwide Pharmaceutical Sciences, Pfizer, Inc.

3:05 Speaker to Be Announced 

3:35 Networking Refreshment Break, Poster and Exhibit Viewing
(Last Chance for Viewing)

4:05 Isolation of the Drug Substance Impurities at 0.05–0.1% Level Using At-Column Dilution, Mass-Driven Collection, and Comprehensive Automation of the Entire Process
Michael Breslav, Ph.D., Research Fellow, US EC [East Coast] Early Development, Johnson & Johnson Pharmaceutical Research and Development
ICH guidelines suggest identification of the process impurities and/or degradation products present at or over certain levels in new drug substances. For example, if the maximum daily dose is <_ 2g/day, impurities present at > 0.05% should be reported, and impurities present at > 0.1% should be identified. However, if the daily dose exceeds 2g/day, impurities present at > 0.03% should be reported, and impurities present at > 0.05% should be identified. Identified impurity is defined as an impurity for which a structural characterization has been achieved. Identification usually requires isolation of these impurities for structure elucidation by NMR. Our goal was to develop new methods, techniques, and processes in preparative chromatography in order to achieve isolation of the low-level impurities in a short time frame. At-column dilution, mass-driven collection, and extensive automation allowed for the efficient isolation of the impurities in various drug substances, followed by the structure elucidation and subsequent reporting and registration of the impurities and standards within J&J. 

4:35 Anticipation of Scale-Up Issues in Process Development: Scale Up Risk Evaluation (SURE)
Dr. Ir. Frans L. Muller, Associate Principal Scientist, Process Research & Development, AstraZeneca
Scale Up Risk Evaluation (SURE) is a tool developed to anticipate scale-up issues early on in the development of a new compound. The principle of SURE is based on that of a hazard and operability study (HazOp). For each operation in a process recipe, various scale-up/down scenarios are identified. A scenario represents an unplanned change in conditions from those specified in the recipe. The potential impact of a scenario on the process is qualitatively assessed and identified as a "threat" or an "opportunity." The scale-up scenario is then scored on: (i) The likelihood process conditions change with scale; (ii) The likelihood the operation affects the product quality or process operability. A number of examples from SURE studies will illustrate the use of the tool. The output of a SURE study is risk matrix, and a prioritized list of the threats and opportunities that provide development drivers for the development team. We conclude with an analysis of the data generated by SURE studies in AstraZeneca that demonstrates how risk changes as processes move through the stages of development. 

5:05 Close of Day Two