Abstract
The 3rd Annual Symposium on Chemical and Pharmaceutical Structure Analysis was once again held in Shanghai, where a rich history of ‘East meets West’ continued. This meeting is dedicated to bringing together scientists from pharmaceutical companies, academic institutes, CROs and instrument vendors to discuss current challenges and opportunities on the forefront of pharmaceutical research and development. The diversified symposia and roundtables are highly interactive events where scientists share their experiences and visions in a collegial setting. The symposium highlighted speakers and sessions that provided first-hand experiences as well as the latest guidance and industrial/regulatory thinking, which was reflected by the theme of this year’s meeting ‘From Bench to Decision Making – from Basics to Application.’ In addition to the highly successful Young Scientist Excellence Award, new events were featured at this year’s meeting, such as the Executive Roundtable and the inaugural Innovator Award.
Jenny Zheng of Janssen Pharmaceuticals, Inc. (Shanghai, China) served as Chemical and Pharmaceutical Structure Analysis (CPSA) Shanghai 2012 Program Chair. Along with Mike Lee of Milestone Development Services (PA, USA), they both formally opened the meeting by welcoming everyone and passing on special thanks to organizing committee members, session chairs and volunteers. Our distinguished plenary lectures were delivered by Leslie Benet of the University of California at San Francisco (CA, USA) on ‘Predicting Drug Disposition and Drug Dosing Parameters for New Molecular Entities’ and by Thomas Baillie of the University of Washington (WA, USA) on ‘Target Covalent Inhibitors versus Chemically Reactive Drug Metabolites: Considerations for Rational Drug Design and Toxicological Risk Assessment’. Benet and Baillie were introduced to the audiences by Frank Lee of Millennium (MA, USA) and Mingshe Zhu of Bristol-Myers Squibb (NJ, USA), respectively, and their outstanding achievements and contributions to drug development were highlighted. Indeed, their work laid the foundation for many of the contemporary research interests. The conference was well attended (over 400 attendees) by academy, government and industry, from more than ten countries worldwide.
In addition to 72 oral presentations from 22 sessions, approximately 60 posters were presented. Preceding the main conference, three short courses ran on Wednesday 25 April 2012. Lucy Xu of Novartis (Shanghai, China) and Hua Li of Academy of Military Medical Sciences (Beijing, China) organized a full-day short course on ‘The role of Drug Metabolism and Pharmacokinetics (DMPK) in Exploratory Drug Development’ with distinguished instructors such as Francis Tse of Novartis (NJ, USA), Tonika Bohnert of Biogen (MA, USA) and Cindy Xia of Millennium on topics related to drug–drug interactions (DDI) and transporters. The course also included a roundtable discussion with the panelists Lucy Xu, Francis Tse, Lawrence Gan of Biogen, Angela Wong of Merck Serono (Beijing, China) and Jing Lin of Sunovion (MA, USA). Another full-day short course was organized by Wenkui Li of Novartis and Naidong Weng of Janssen (NJ, USA) on ‘Regulated LC–MS Bioanalysis’. Naidong Weng started the short course with the introduction of basic GLP and current regulatory requirement for bioanalytical method validation and sample analysis. Some of the regulatory ‘hot topics’ were highlighted. Robert Coldreck and Fengying Chen of WuXi (Shanghai, China) shared their experiences and perspectives on how to prepare for regulatory and sponsor inspections for a regulated bioanalysis laboratory. In particular, the similarities and differences on inspections among the US FDA, Organization for Economic Cooperation and Development and China’s FDA (SFDA) were highlighted. The short course was continued with basic principles of sample preparation, chromatography and detection. Key potential pitfalls for bioanalysis and their trouble-shootings were also illustrated with case studies. In the course, Wenying Jian of Janssen discussed bioanalytical method development and validation strategies for biomarkers and protein/peptides. Two pivotal points of emphasis were shared with the attendees: a very good understanding of the bioanalytical method development/validation, as well as the overall project goals is essential. A significant involvement of bioanalytical strategy into the preclinical and clinical protocols is also essential to prevent bioanalysis pitfalls, such as pseudostability during sample collection. The third workshop was on ‘Pharmaceutical Sciences – Analytical Science and Technology in Pharmaceuticals’ and was held offsite at the Shanghai Institute of Materia Medica (Shangai, China), led by Dongying Chen of Shanghai Institute of Materia Medica and Yong-Guo ‘Fred’ Li of Roche (Shangai, China). The workshop featured lectures from industry-leading scientists: Jeannine Petrig Schaffland of Roche (Buste, Switzerland); Liu Fang of WuXi; and Shaolian Zhou of Novartis (Shangai, China). This is the first short course at Shanghai CPSA, and was joint with a local research institute, held offsite with the aim of attracting a broader audience, particularly early career researchers and graduate students.
On Wednesday afternoon, the executive Roundtable discussion on Emerging Drug R&D Models in China was led by Todd Gillespie of Eli Lilly (IN, USA) and Jing-Tao Wu of Millennium. The panelists included executives from multinational pharmaceutical companies: Tony Zhang of Eli Lilly (Shangai, China); Richard Connell of Pfizer (Shangai, China); and Frank Lee of Millennium; Connie Sun of Pharmaron, a CRO in China; and Mingxin Qian of Metabomics (a home-grown biotech company in China; Shangai, China). The highly interactive discussion focused on the strengths, opportunities and challenges of conducting drug R&D in China. The audience was treated to diverse yet critical insights into the variety of emerging operational models in this fast growth area in China.
On Thursday morning, after the distinguished plenary lecture given by Benet, the CPSA 2012 Shanghai symposium opened with a current ‘hot topic’ on ‘Current Understanding of Regulatory Requirements of DDI’. This topic is very timely since the US FDA just issued a guidance on DDI in February 2012. This session was lead by Yan Li of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union medical College (Beijing, China), Jenny Zheng of Janssen Pharmaceuticals and Yurong Lai of Pfizer (CT, USA). Jin-Ding Huang of National Cheng Kung University (Tainan City, Taiwan) gave a presentation titled ‘Application of Pharmacogenomic Knowledge in Clinical Pharmacokinetics‘, followed by a presentation on ‘Drug Transporter DDI: Interagency Testing Committee Workshop Report and New Quantitative Structure–Activity Relationship Analysis’ presented by Toshihisa Ishikawa of RIKEN Yokohama Institute (Kanagawa, USA). The third presentation was ‘A Comparison of Current Modeling and Simulation to Predict DDI Using Irinotecan (CPT-11) as a Model Compound’ given by Stephen Wang of Millennium.
Parallel sessions were scheduled on Thursday afternoon. The first focused on discussions on transporters led by Cindy Xia of Millennium and Zack Cheng of GlaxoSmithKline (Shanghai, China). The session featured lectures by Hiroyuki Kusuhara of University of Tokyo (Tokyo, Japan) on ‘Quantitative Investigation of Drug Transport Across the Blood–Brain Barrier‘, Hiroshi Sugimoto of Takeda (Osaka, USA) on ‘Quantitative Investigation of the Impact of Pgp Inhibition on Drug Absorption and Disposition at the Drug-Discovery Stage‘, Yurong Lai of Pfizer on ‘Roadmap of Drug Transporter Evaluation in Pharma’ and Sijie Lu of GlaxoSmithKline on ‘Application of Pgp/BCRP Double-Transduced MDCK Cell Assay for CNS Drug Discovery’. The second parallel session focused on bioanalysis and was led by Naidong Weng of Janssen and Dafang Zhong of Shanghai Institute of Materia Medica. Zheming Gu and XinPing Fang of Xenobiotics (Nanjing, China) presented ‘Critical Aspects in the Quantification of Radioactive Samples Using an LC–MS/MS Assay’. Xiaohui ‘sophia’ Xu of Bristol-Myers Squibb presented ‘The Use of Accelerator MS for Studying Absolute Bioavailability in Humans – Challenges and Benefits’. Wenying Jian of Janssen discussed the strategy of biomarker quantitation using LC–MS/MS assays followed by Qian Ruan of Bristol-Myers Squibb on strategy on analysis and quantitation of intact proteins using high-resolution MS. The third parallel session with the title of ‘Pharmaceutical Sciences – Pharmaceutical Profiling and Formulation Design’ was lead by Fred Li of Roche and Xiaoping Cao of Pfizer. Thorsten Lobert of Roche (Basel, USA) presented ‘Dissolution and Imaging as Powerful Tools in the Formulation Development Process’ followed by Xiaoping Cao on ‘Materials Science: Integrated Active Pharmaceutical Ingredient and Drug Product Design‘, and Chao-Pin Lee of GlaxoSmithKline discussed the design of clinical formulations for the drug development candidates based on the developability profiles. The session was concluded with the last presenter, Chris Zhao of Frontage Laboratories (Beijing, China), who discussed impurity analysis using differential UV detection.
The session on ‘Biotransformation – DDIs and Safety Implications of Drug Biotransformation and Disposition’ was chaired by Ge Lin of the Chinese University of Hong Kong (Hong Kong, USA) and Mingshe Zhu of Bristol-Myers Squibb. Pharmacokientic and pharmacodynamic DDIs and drug toxicities were highlighted by Aiming Yu of University at Buffalo, State University of New York (NY, USA). Ge Lin discussed the ‘Mechanism-Based Biomarker for the Assessment of Biotransformation-Induced Toxicity of Medicinal Herbs’ and Chuan Li of Shanghai Institute of Materia Medica presented ‘Absorption, Disposition, and Pharmacokinetics of Sapanins from Chinese Medicinal Herbs and the Associated Potential Herb–Drug Interactions’. The session on Bioanalysis was led by Daniel Tang of ICON (Shanghai, China). Pei Hu from Peking Union Medical College Hospital (Beijing, China) discussed the current bioanalysis in clinical trials in China and Chengwei Fang of Pharmaron (Beijing, China) highlighted the challenges and opportunities of conducting GLP bioanalysis in China. Philip Timmerman of Janssen (Beerse, Belgium), on behalf of the European Bioanalytical Forum, provided the European Bioanalytical Forum perspective on DBS analysis. As a founding member of the Global Bioanalytical Consortium (GBC), Timmerman and Tang also provided a historic perspective on bioanalytical regulations and a GBC update and impact to regulated bioanalysis in China. GBC members also held an informal discussion at CPSA Shanghai 2012 to discuss the path forward. Kevin Bittorf of Vertex (MA, USA) and Xiaoyi Gong of Merck led the session on ‘Analytical Methodology and Technology’. In this session, Shao-Ping Li of University of Macau (Macau, USA) presented ‘Discovery of Active Components from Chinese Herbs Based on Integration of Sample Preparation and HPLC Analysis’. Todd Gillespie of Eli Lilly lectured on ‘Analytical Technologies for Enabling Continuous Process Development’. Kevin Bittorf of Vertex discussed ‘Analytical Methods for Continuous Drug Product Processing’ and Danny Zhou of WuXi on ‘Reviewed Process Analytical Technology: A Tool for Building Quality into Products’.
On Friday morning, following the distinguished plenary lecture from Thomas Baillie, Jeff Zhang of Novartis (Shanghai, China) chaired the session on ‘Emerging Drug Discovery DMPKT Platform in China’ and featured three highly entertaining presentations from Mingshe Zhu of Bristol-Myers Squibb on ‘The Evolving Face to Drug Metabolism Research and Service in China‘; Jeff Zhang on ‘Emerging Drug-Discovery Models in China: DMPKT Challenges‘; and Chunlin Chen of Medicilon (Shanghai, China) on ‘Difference of SFDA GLP Compliance versus FDA GLP: Medicilon Experience’. The presenters and attendees enjoyed some highly interactive questions and answers sessions after each presentation, which covered a number of challenges and opportunities of emerging drug-discovery models in China.
Similar to the Thursday afternoon sessions, Friday afternoon’s sessions were also packed with high quality presentations on biomarkers and biological metabolites. The biomarker session was led by industry veterans Scott Fountain of Pfizer (CA, USA) and Nathan Yates of University of Pittsburgh (PA, USA). This session featured three distinguished presentations on ‘Biomarker Applications – From Bench to Bedside’ by Scott Fountain, ‘Experimental Designs for Discovery Proteomics by Nathan Yates’ and ‘Verification of Biomarkers with Targeted Proteomics’ by Weixun Wang of Merck (NJ, USA). A panel discussion on the development and application of diagnostic tools was then led by the chairs. The Biologics session, led by Binodh Desilva of Bristol-Myers Squibb (NJ, USA) and Haojing Rong of Pfizer featured three presentations: ‘Ligand Binding Bioanalytical Approaches to Quantify ‘Total’ and ‘Free’ Therapeutic Antibodies and Their Targets’ by Binodh Desilva; ‘Immunogenecity: Concerns, Detection and Perspectives’ by Haifeng Song of the Beijing Institute of Radiation Medicine (Beijing, China); and ‘Using Cerebrospinal Fluid as Surrogate for Assessing Drug Transport into CNS’ by Qin Wang of Biogen (CA, USA). The session on ‘Metabolite Data in Regulatory Submission’ also attracted a full room of scientists. This session was led Andy Ayrton of Scinovo/GlaxoSmithKline (Shanghai, China), Zheming Gu of XenoBiotics and Rong Kong of PTC Therapeutics (NJ, USA). Naidong Weng of Janssen presented practical considerations, challenges and solutions of metabolite measurement in ‘Metabolites in Safety Testing’. Dafang Zhong discussed the drug metabolite profiling and identification in animals and humans in support of regulatory submission to SFDA. Martin J⊘rgensen of Lundback (Valby, Denmark) discussed their strategy on obtaining human metabolism data early in Phase I using accelerator MS combined with a tiered bioanalytical approach in metabolite quantification.
The session ‘Translational Sciences in the 21st Century’ was held on Friday and led by Chris Lepsy of Pfizer (MA, USA) and Wei Lu of Peking University (Beijing, USA). Presentations included ‘Pharmacokinetics/Pharmocodynamics in Drug Discovery for Target Validation and Biomarker Identification’ by Chris Lepsy; ‘Pharmacokinetics/Pharmocodynamics Modeling Application in Preclinical: Case Study’ by Wei Lu; and ‘Apply Modeling and Simulation to Aid Drug Discovery and Development’ by Wen Chyi Shyi of Millennium. The session on Technology, Solutions and Decision-Making was lead by Todd Gillespie of Eli Lilly and Naidong Weng of Janssen. John Mao of QPS (DE, USA) highlighted the candidate selection and preclinical development strategies to reduce development risks. This lecture was followed by a presentation by Weidong Jiang of Henlius Biopharmaceuticals (CA, USA) on ‘Analytical Strategy for Filing a Biologics/Biosimilar IND in China’. The final presenter of this session was Na Pi Parra of Agilent (CA, USA) on ‘An Automated On-Line Card Extraction LC–MS System for the Determination of Clozpaine and its Metabolites in Rat Blood’.
On Saturday morning, CPSA Shanghai 2012 had a joint session with the local bioanalytical and metabolism discussion groups at Shanghai Institute of Materia Medica. The meeting was hosted by Jeff Zhang of Novartis and Dafang Zhong of Shanghai Institute of Materia Medica. Cindy Xia of Mellennium, Wei Tang of ChemPartner (Shangai, China) and Hongjian Zhang of PharmaResources (who recently also joined SuZhou University [SuZhou, China] to become a professor and director of their newly established DMPK center) discussed topics on drug transporters, DMPK in drug discovery and clinical DDI. The interactions with the graduate students at the Shanghai Institute of Materia Medica were excellent. The joint meeting was a great way for students to gain first-hand perspectives with industry practices and interact with leading scientists.
Throughout the entire meeting, high-quality lunch workshops and dinners were held by various companies. Novel technologies and new instruments were introduced and new approaches of dealing with current challenges were presented. These workshops were also well attended by the meeting precipitants and have become an important part of CPSA Shanghai.
The new feature of CPSA 2012 Shanghai was the inaugural Innovator Award session. This session was chaired by Xiaoyi Gong of Merck, Kelly Dong of GlaxoSmithKline (Shanghai, China) and Frances Wang of AstraZeneca (Shanghai, China) and represented a novel extension of the interactive exhibition (CPSA EXPO – Where Technology and Solutions Meet!) that featured 23 exhibitors. This year, the Innovator Award was presented to: Na Pi Parra of Agilent (‘An Automated On-Line Card Extraction LC–MS System for the Determination of Clozpaine and its Metabolites in Rat Blood‘); Martin Steel of McKinley Scientific (‘A Collaborative LC–MS/MS Solution for the Urine Testing for the Detection and Quantification of Drugs-of-Abuse and Pain Management‘; NJ, USA); and Gary Valaskovic of New Objective (‘A Dedicated Ultralow Flow Pump for the Flow Injection Nanospray for the Relative Quantification of the Analytes‘; MA, USA).
A truly unique feature at CPSA Shanghai is the Young Scientist Excellence Awards chaired by Zack Cheng, Xiaoyi Gong, Mingshe Zhu and Dan Li of GlaxoSmithKline (Shanghai, China), which had its second year of success. An expert panel of judges was formed to select the best posters submitted from the participating young scientists. The judges were all impressed by the high scientific quality of the posters at this year’s annual event. The first place award went to Chunying Gao of Shanghai Institute of Materia Medica (Shangai, China) for a poster presentation ‘Mechanistic Study on the Metabolism and Transport of Scutellarin: Selective OATP2B1-Mediated Hepatic Uptake is Responsible for its Unusual Pharmacokinetic Characteristics’. The second place award went to Xiaorong Ran of Agilent Technologies (CA, USA) in a collaboration with Beijing Institute of Pharmacology and Toxicology (Beijing, China) and Bristol-Myers Squibb for a poster on ‘Qualitative and Quantitative Analysis of Metabolites of a Bioactive Component Using Q-TOF LC–MS: A Novel Approach to Studying Absorption, Distribution, Metabolism and Excretion of Chinese Herbal Medicine in Humans’. There were three third place awards. They were won by Cong Xu of the Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University (Hangzhou, China) for a poster ‘Involvement of CAR and PXR in the transcriptional regulation of CYP2B6 Gene Expression by Traditional Chinese Medicines‘, Cai-Sheng Wu of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) on ‘A New Strategy for Discovery and Identification of Metabolites Using High-Performance Liquid Chromatography Coupled With a Hybrid Linear Ion-Trap and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry After Oral Administration of Five Epimedium Flavonoids Monomers and the Herbal Extract of Epimedium to Rats,’ and Houfu Liu of GlaxoSmithKline R&D China (Shangai, China) for a poster ‘Tritans are Substrates of OATP1A2 and can be Transported by this Transporter Across MDCKII Monolayer’.
CPSA Shanghai 2012 was a great success! Plans are now already underway for next year’s annual meeting, CPSA Shanghai 2013. We hope to see you in Shanghai next year!
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.