Dr. San Kiang (Chairman&Session 3 Moderator)

 

SME in continuous processing API, continuous processing DP, particle engineering, pharmaceutical composite material, co-processing and pharmaceutical process scale up in both API and DP. Research Professor at Rutgers University Department of Chemical Engineering. Research projects on continuous manufacturing and material science related to pharmaceuticals. Champion work flow in pharmaceutics development that eliminates DS/DP boundary. Thirty five years of pharmaceutical development and technology transfer experience in Bristol-Myers Squibb covering both Active Pharmaceutical Ingredient (API) and Drug Product (DP) areas. Expertise in crystallization, particle engineering, reaction engineering, continuous processing (both DP and API), pharmaceutical composite material (PCM) and co-processing. Participated in 11 NDA projects that were eventually commercialized. Successfully participated in QbD filing with the inclusion of risk assessment and process modeling to emphasize fundamental approach to process design. Comprehensive knowledge of cGMP, advanced development techniques, strategic sourcing, plant facilities and issues at the API-DP interface. Pioneer in pharmaceutical engineering and the application of PAT. Recognized expert in crystallization and particle engineering issues. Maintains extensive network and at FDA, universities, research centers and technology consortia.

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Dr. Qi Gao(Session 1 Moderator)

Distinguished Research Fellow at J-Star Research

 

Dr. Qi Gao received a B.S. degree in Chemical Engineering and Materials Science from Tsinghua University and a Ph.D. in Crystallography from University of Pittsburgh. After postdoctoral research in Biophysics and Structural Biology at MIT, she joined Bristol-Myers Squibb where she worked for 27 years on many molecules and processes of drug discovery and development. With over 35 years of experience in solid-state chemistry and materials science and 30 years of experience in Pharma R&D, she is an SME in crystallization, characterization, and properties of pharmaceuticals related to molecule, solid form and material, and in development of associated intellectual property and regulatory filings.

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Dr. Jian Wang(Session 2 Moderator)

Vice President, Center for Pharma Crystallization at J-Star Research

 

Dr. Jian Wang received her Ph.D. degree in Chemical Engineering in 1994 from the University of Pittsburg with Prof. Donna Blackmond and Prof. Irving Winder. During her 11-year tenure at Merck afterwards, Jian became a champion in implementing science-based and technology-enabled approaches in API crystallization and reaction engineering. In 2005-2010, she promoted directly the applications of PAT tools in process R&D serving as a consultant at Mettler Toledo AutoChem. During 2011-2013, Jian took the responsibility as VP of Crystallization Development at Crystal Pharmatech, where she served a diverse client base solving challenging crystallization problems. In the beginning of 2014, Jian started up a crystallization group at J-Star Research, which now became the Center for Pharma Crystallization (CfPC). As VP of CfPC at J-Star Research, Inc., Jian has been engaged in growing a comprehensive team of subject matter experts at CfPC to serve drug development programs around the globe with technical rigor, synergy and efficiency.

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Dr. Joanne Johnson(Session 4 Moderator)

Senior Vice President, Business Development, Porton Pharma Solutions Ltd.

 

Dr. Joanne Johnson joined JSTAR Research, Porton USA on Feb.1st 2020 as Senior Vice President, Business Development, with a focus on developing deeper relationships with large pharmaceutical clients in North America and Europe throughout the development cycle. Joanne obtained her B.Sc, Ph.D. postdoctoral experience in the UK working in bio-organic chemistry. A move in 2001 to the USA brought Joanne to AMRI working both in scientific and business roles. Prior to Porton, Joanne was one of the initial US employees at Asymchem spending over 10 years as Vice President and part of the IPO team in 2017.

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Session 1  Smarter Solid State Research by Prediction and Simulation

 

Prof. Tonglei Li

Professor and Allen Chao Endowed Chair in the Department of Industrial & Physical Pharmacy, Purdue Univ.

 

Prof. Tonglei Li received bachelors and master’s degrees in Chemistry and Computational Chemistry, respectively, from Nankai University, China. He obtained Ph.D. in Pharmaceutics, as well as MS in Computer Science, from Purdue University. After staying as a visiting assistant professor at Purdue, he joined the faculty at the University of Kentucky. Dr. Li returned to his alma mater in 2012. His research interests include solid-state chemistry, formulation and drug delivery, and multiscale modeling and simulation. He currently serves as Editor-in-Chief of Pharmaceutical Research.

Title 1: Locality, Strength, and Hierarchy of Intermolecular Interactions in Crystallization 

Abstracts: Self-assembling of molecules in crystallization is collectively driven by intermolecular interactions among the solute and solvent. Better understanding of nucleation mechanism may be perceived in light of the locality, strength, and hierarchy of intermolecular interactions. Primary interactions such as hydrogen bonding decide pre-nucleation dynamics and the secondary such as aromatic stacking and close contacts may affect complementing and competing functions while primary assemblies develop. Additionally, molecular conformation and local preference of a particular interaction can mutually influence the kinetics and structure of self-associates. To demonstrate these principles, several of our recent studies focus on solution chemistry and the interplay between conformation and intermolecular interaction of a series of structurally similar diarylamine compounds.

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Dr. Yuriy Abramov

VP of Scientific Affairs at XtalPi Inc.

 

Computational science leader. Accomplished computational chemist with a proven track record of successful design of novel drugs. Scientific and technical expertise in the broad area of Computational Science in Pharmaceutical Industry. Performed computational support of multiple projects in small molecule drug design through Hit ID, Lead Generation, Lead Optimization, compound selection for clinical testing and drug development. My computational chemistry contributions were reflected in multiple NDA filings of drugs, which are currently on the market.  

Title 2: Pharmaceutical Crystallization Support by Computational Approaches

Abstracts: Given challenges facing the pharmaceutical industry, an accelerated Drug Development greatly benefits from guidance provided by computational methods. This presentation will focus on computational support of the following important tasks related to the pharmaceutical crystallization. That includes derisking of the stable solid form selection of pharmaceutical API; in silico coformer screening for an API or intermediate crystallization; rational solvent selection for solid solvate desolvation; and in silico solvent screening for impurity purge via recrystallization.

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Dr. Shanming Kuang

Head of Center for Pharma Crystallization at Shanghai and Senior Director of Solid Form Studies at J-Star Research

Dr. Shanming Kuang received his PhD in physical chemistry from the Chinese University of Hong Kong. After a postdoc at Purdue University, Dr. Kuang spent approximate 20 years in pharm industry with BMS, Roche, GSK, Crystal Pharmatech and J-Star Research, Inc. His tenure involves managing solid state chemistry groups focusing on solid form screening and selection, crystallization process development and pre-formulation. His teams are integral in understanding drug candidate developability and ensuring projects are minimally impacted by solid state property issues. Shanming has extensive experience in developability assessment for more than 300 small molecule drug candidates and has published more than 50 peered reviewed papers and patent applications.

 

Title 3: Computation Assisted Solvent Selection in Crystal Form Investigation  

Abstracts: Rational selection of solvents plays a critical role in solid form screening and production. On the one hand, a variety of solvents with different properties are chosen in form screening to maximize the screening space of searching for all potential solid forms because some solvents selectively favor the generation of a particular form as a result of crystallization kinetics. On the other hand, some solvents need to be avoided in crystallization process due to formation of solvates that result in issues in residue solvent control and/or form transformation. We will present a lesson learned from a case study in which the wrong solvent was selected, which created huge pain in the commercialization. Efforts including computational approach utilized to address this issue will also be discussed.

 

Session 2 Physical Property Based Crystallization Process Development

 

Prof. Kevin Roberts

Brotherton Professor of Chemical Engineering at the University of Leeds

 

 

Kevin Roberts is currently Brotherton Professor of Chemical Engineering at the University of Leeds in the UK where he is also Director of the EPSRC’s Centre for Doctoral Training in Complex Particulate Products and Processes. Kevin RobertsHis research work encompasses both fundamental and applied research, the latter in collaboration with the pharmaceuticals, specialities, fine chemicals, and nutritional products sectors. He has published more than 450 papers and has led, mentored and developed the research work of more than 90 post-graduate research students.

Title 1: The Crystallisation Structural Pathway of Para Amino Benzoic acid: From Solvated Molecule through Solute Clustering and Nucleation to the Growth of Facetted Crystals  

Abstracts: In solution phase crystallisation processes, understanding and controlling the transition pathway associated with the assembly of molecules from their solvated state, into three-dimensional, ordered crystalline-solids, represents a significant grand challenge for the physical-chemical sciences. Crystallisation can be sub-divided into three-dimensional nucleation and two-dimensional, surface-mediated, crystal growth stages. Understanding and controlling the various physico-chemical aspects associated with these two stages is important mindful of their impact upon the critical quality attributes of the resulting product crystals. In particular, the nucleation stage directs the crystal size distribution, crystallinity and polymorphic form whilst the crystal growth stage directs crystal purity, morphology, surface properties and inter-particle properties.

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Dr. Bing-Shiou Yang

Director of Solid-State Science & API Engineering in Material & Analytical Sciences (MAS), BI

 

Bing-Shiou Yang is a Ph.D. Chemical Engineer with 18+ years of pharmaceutical process development experiences in the areas of API isolation development, solid-state and engineering technologies. He is currently the Director of Solid-State Science & API Engineering in Material & Analytical Sciences (MAS) at BI in Ridgefield, CT, where he leads a multidisciplinary group that broadly impacts BI’s small molecule portfolio through scientific leadership and innovation in areas of crystallization, separation technology, continuous processing, process engineering and process analytical technology (PAT). He also leads multidisciplinary project team to streamline the DS and DP development interfaces based on solid form, API isolation process and material science profiling. Bing-Shiou represents BI in multiple working groups in International Consortium for Innovation and Quality (IQ) and Enabling Technology Consortium (ETC) and serves as Board of Director for the ETC.Prior to BI, Bing-Shiou worked at Process Research and Development at Bristol-Myers Squibb (BMS) where he served as a crystallization and particle engineering specialist and had made significant contribution to portfolio compounds including ELIQUIS® (Apixaban). Bing-Shiou received his B.S. and M.E. degrees from National Taiwan University and Ph.D. in Chemical Engineering from Princeton University. Bing Shiou has co-authored over 60 publications, patents, book chapter and presentations

Title 2: Facilitating DS/DP development through integrated solid-state and crystallization development 

Abstracts: Crystallization is an important and economic unit operation for the purification of pharmaceutical API. It also serves as the key step to define the required quality attribute of the API (e.g. solid form, particle size distribution) that would impact the subsequent processing (e.g. filtration, drying, milling) and drug product performance (e.g. dissolution, content uniformity). To successfully bring a compound into the market, an integrated approach to link the development of API solid form, isolation and dosage form is essential to ensure the robust delivery of the desired drug product quality, throughout the scale. Thorough understanding of the solid form of a compound would significantly facilitate the design of proper crystallization, resolve process challenges, and enhance the control of the API quality attributes. This presentation will use several examples in development or manufacturing to illustrate the concepts, including producing small particle size of API for enhance dissolution, producing the desired form for a compound with complex solid form landscape and identifying root-case of out-of-specification via solid form understanding, etc.

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Mr. Don Kientzler

Process Engineering Head, J-Star Research

 

Mr. Kientzler is a chemical engineer with 25 years of drug substance development & 10 years of drug product development. His experience involved chemical synthesis, pharmaceutical materials science, crystallization, particulate engineering, technology transfer, continuous processing, PAT, facility design, as well extensive expertise with DS & DP unit operations. His current focus lies with drug substance final forms, drug product intermediates and the drug product. Through novel chemical & pharmaceutical processing techniques he is enabling robust drug products with improved performance properties.

Title 3: A Challenging Path to Controlled Nano-API Crystallization and Isolation

Abstracts: Controlled crystallization of an API in submicron size was enabled based on an accurate solubility profile and a growth inhibition property via semi-continuous processing, to meet special formulation requirements. This process was also challenged by isolation of nano-API crystals to meet the low specification of residual salt content. When residual salt becomes too low, crystal growth accelerates. Diafiltration using membranes was applied for salt removal in connection to outstream of a flow-through CSTR for generation of submicron crystals, to deliver product meeting the specifications of both crystal size and the residual salt content.

 

Session 3: Particle Engineering and DS-DP Co-Processing

 

Prof. Rajesh N Davé 

Distinguished Professor, Ph.D.

 

Research areas: Particle Engineering, direct compression formulations, engineered excipients, drug nano-composites, polymer film coating of fine particles, dry coating, thin films for pediatric/geriatric drug delivery

Title 1: Particle Surface Engineering for Predictive Enhancement of API Properties

Abstracts: Particle surface engineering is a cost-effective, promising route to achieve enhancements in the flowability, bulk density and other properties of a variety of cohesive active pharmaceutical ingredients (APIs). This presentation will discuss predictive enhancements after dry coating based particle surface engineering and discuss models and guidelines for the selection of flow aid type and amount, as well as predicting powder bulk properties from their particle-scale properties such as the particle size and distribution, materials density, surface energy, and surface roughness. The use of dry coating in developing direct compression ready blends will be also presented. through dry coating of either API or excipients. Towards those goals, industrially relevant and scalable dry coating devices are used and compared against a material sparing benchmarking device. Mechanistic particle contact models are employed for examining the causes of cohesion reduction and subsequent property enhancements. The bulk property based 2-D processability maps are introduced and used to assess the extent of enhancements in flow and packing as well as the possibility of avoiding wet and/or dry granulation, as well as for moving towards direct compression at high drug loadings. Results are presented to demonstrate that dry coating for particle surface engineering is a powerful technique. Along with our predictive, model-based approach, it can help mitigate problems posed by fine powders, with positive outcomes in flow, and bulk density improvements. Such enhancements enable high drug loaded fine and cohesive API blends through particle engineering. Overall, the bulk property based 2-D processability maps along with dry coating based property enhancements can help make manufacturing decisions regarding the formulation strategy for solid pharmaceutical dosages, presenting a promising platform for commercial applications and cost reduction.

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Dr. Deniz Erdemir

Principal Scientist at Bristol-Myers Squibb

 

Dr. Deniz Erdemir is a Principal Scientist at Bristol-Myers Squibb (BMS). Prior to joining BMS, she received her Ph.D. in Chemical Engineering from the Illinois Institute of Technology. Dr. Erdemir’s research focus lies at the drug substance-drug product interface with emphasis on crystal polymorphism and design of materials via particle engineering to enable robust drug products. She is the author of numerous publications on co-processed materials and crystallization process development, the inventor on two US patents and the co-editor of the 3rd edition of Handbook of Industrial Crystallization.  

Title 2: Co-processing: An Effective Particle Engineering Approach for Drug Substances

Abstracts: N/A

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Dr. Saif A. Khan

Associate Professor of Chemical and Biomolecular Engineering at National University of Singapore

 

Dr. Saif A. Khan obtained a Bachelors degree in Chemical Engineering at the University Department of Chemical Technology (UDCT)，Mumbai. He received his Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology in 2006, where he was a Presidential Fellow. In 2006, he joined the National University of Singapore (NUS), where he is currently a tenured Associate Professor of Chemical and Biomolecular Engineering. His research group at NUS develops new microfluidics-based ‘factories’ for the continuous manufacture of pharmaceuticals and advanced materials in collaboration with several industrial partners worldwide. He has also co-founded two start-up companies focused on advanced materials manufacture and opthalmic drug delivery.

Title 3: Drug Particle Engineering Using Microfluidic Emulsion-based Crystallization

Abstracts: This paper will present an overview of recent progress towards single-step fabrication of pharmaceutical drug-excipient microparticles through microfluidic emulsion-based processing. In the pharmaceutical industry, active pharmaceutical ingredients typically undergo a series of secondary manufacturing operations, such as crystallization and formulation with additives and excipients, to obtain drug products of varying types, such as orally ingestible tablets or injectables. Traditionally, drug substances crystallized in batch vessels allow poor and coarse control over crucial crystal attributes, which tremendously impacts the number of subsequent processing steps required to arrive at the final drug product. We have recently developed microfluidics-based methods which allow for crystallization and formulation of drug substances to be carried out in a single processing step, leading to monodisperse spherical granules with unprecedented control over crystal attributes such as shape, size and polymorphism. These methods couple the usage of microfluidics for emulsion generation and evaporative or anti-solvent crystallization where, by tuning the various process parameters (such as droplet sizes and compositions, solvent removal rates, etc.), we are able to crystallize and formulate a wide range of hydrophilic and hydrophobic model and commercial drugs into monodisperse spherical microparticles with tunable properties. The versatility of emulsion-based processing for formulating drug-excipient composite particles with tunable structures will be showcased in this paper with different drug-excipient systems. Specifically, we will discuss how an interplay of phase separation, drug crystallisation and polymer vitrification in drug and polymer-containing droplets during evaporative or anti-solvent crystallisation leads to a diversity of microparticle structures which exhibit different drug release profiles. We will also discuss the fabrication of composite microparticles containing drug and colloidal excipients with exquisitely tunable crystalline microstructure by co-confinement of a drug and a colloidal excipient dispersion within sub-millimeter droplets. These engineered particles embody the idea of drug product intermediates that lie at the drug substance-drug product interface. In conclusion, microfluidic emulsion-based crystallisation enables novel routes for drug particle engineering, and challenges the conventions of secondary pharmaceutical manufacturing.

 

Session 4 Partnering for Addressing Challenges of Today & the Future

 

Dr. Fang Wang

Head of Chemical Development at Global Blood Therapeutics

 

Dr. Fang Wang is currently the Head of Chemical Development at Global Blood Therapeutics. She is responsible for the chemical process development of all small molecule active pharmaceutical ingredients (API) as well as their manufacturing including clinical manufacturing and commercial manufacturing. Dr. Wang provided API leadership in obtaining FDA’s approval of Oxbryta® NDA three months ahead of schedule in 2019. Most recently, Dr. Wang was the President of Clover Crystallization Consulting for more than two years providing strategic consulting and training to various pharmaceutical companies. Prior to consulting, Dr. Wang was the Head of API Crystallization and Engineering at Gilead Sciences for seven years. She provided strategic and cross-functional leadership to API form selection and API crystallization process development for all Gilead’s development programs ranging from pre-IND through NDA stage programs. Dr. Wang was the key contributor who provided strategic leadership for the crystallization development and commercialization for SOVALDI® and HARVONI®. Prior to Gilead, Dr. Wang started her career at Pharmacia/Pfizer after completing her Ph.D. in Chemical Engineering.

Title 1: Partnering for Addressing API Crystallization Engineering Challenges of Today and the Future

Abstracts: In light of the balancing act among quality, speed, and cost, collaborative partnering between pharmaceutical companies and contract research/manufacturing organizations is becoming increasingly important in meeting our goals of delivering high quality APIs and drug products to patients. This talk will summarize the challenges the pharmaceutical industry is facing today and will continue to face in the future in the area of API crystallization engineering and manufacturing. In addition, various strategies will be discussed to overcome the challenges in order to deliver high quality therapies to patients quickly and cost effectively. Case studies will be provided to illustrate the strategies. Ultimately an effective model of partnering to meet patient’s needs will be presented.

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Dr. William Blauser

Head of Strategy at XtalPi, Inc

 

Dr. William Blauser is the Head of Strategy at XtalPi, Inc., an AI-driven pharmaceutical technology company, where he leverages two decades of experience applying physics-based in silico solutions to critical problems in discovery and development. He is actively involved in forging strategic partnerships, raising capital and creating innovative business models. Prior to that, he was Vice President of Strategic Business at Schrodinger, LLC, a leader in predictive software modeling and drug discovery services. There he created strategic partnerships with major pharmaceutical companies that provided the basis for Schrödinger LLC’s entry and expansion strategies and also led voice of customer campaigns to inform disruptive innovation in new product development. William Blauser held a postdoctoral fellowship at the University of California, Berkeley in theoretical chemistry after earning a Ph.D. from the University of South Florida in computational chemistry. He then earned an MBA in Technology Evaluation and Commercialization from North Carolina State University, where he cofounded an AI-driven company specializing in bioprocessing.

Title 2: Integrative Approaches to Addressing Canonical Problems in Pharmaceutical Crystallization

Abstracts: Problems associated with polymorphic instability and increasingly insoluble drug candidates represent white space to innovate novel forms and processing methods with better properties in the drug product. But the journey from identifying new solid forms to creating engineered particles with optimal formulation properties has often been too inefficient to realize this goal. Industry-wide voice of customer studies have revealed several bottlenecks along the critical pathway and a multicriteria optimization problem similar to that in earlier discovery phases. These studies suggest solutions that enhance the integration of experiment and computation, which itself integrates both physics-based and AI-based approaches. It also requires integrating mechanical and processing considerations earlier into the form discovery/selection stage. This desiloization of effort will require—in many instances—creative partnerships among biopharma, commercial technology providers, and academia to achieve.

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Dr. Jian Wang

Vice President Center for Pharma Crystallization at J-Star Research

 

Dr. Jian Wang received her Ph.D. degree in Chemical Engineering in 1994 from the University of Pittsburg with Prof. Donna Blackmond and Prof. Irving Winder. During her 11-year tenure at Merck afterwards, Jian became a champion in implementing science-based and technology-enabled approaches in API crystallization and reaction engineering. In 2005-2010, she promoted directly the applications of PAT tools in process R&D serving as a consultant at Mettler Toledo AutoChem. During 2011-2013, Jian took the responsibility as VP of Crystallization Development at Crystal Pharmatech, where she served a diverse client base solving challenging crystallization problems. In the beginning of 2014, Jian started up a crystallization group at J-Star Research, which now became the Center for Pharma Crystallization (CfPC). As VP of CfPC at J-Star Research, Inc., Jian has been engaged in growing a comprehensive team of subject matter experts at CfPC to serve drug development programs around the globe with technical rigor, synergy and efficiency.

Title 3: Addressing Bottleneck Problems in Crystallization R&D for New Drug Development

Abstracts: Diverse crystallization challenges encountered by CfPC (Center for Pharma Crystallization) and our clients will be analyzed systematically to provide insights into main bottleneck problems in today’s drug development programs. The general approaches taken at CfPC to address such problems as well as opportunities for improvement will be discussed. Examples will be given to highlight how enabling technologies and synergetic partnerships played a critical role in providing timely solutions to great challenges.

 

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https://crystallization-summit.jstar-research.com/