Challenging Statistical Issues with In Vitro and In Vivo Bioequivalence Studies: Extreme Variability, Special Study Designs and Novel Approaches
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Speakers, Panelists, Moderators
Charlie DiLiberti has over 30 years’ experience in the pharmaceutical industry, the majority of which (17 years) were at Barr Laboratories (later acquired by Teva Pharmaceuticals). Charlie built and oversaw Barr’s cutting-edge bioequivalence and pharmacokinetics program for generic drugs, small molecule proprietary drugs, and biologics. Charlie left his position as Vice President of Biopharmaceutics at Teva Women’s Health Research in 2010 to start his own firm, Montclair Bioequivalence Services, LLC, which provides strategic consulting services around the world in generic, innovative, and biological drug development, biostudy planning/risk management, formulation development guidance, and advanced troubleshooting methods, with a focus on difficult/complex products. Charlie has given numerous public presentations, in the US and internationally, on a wide variety of topics, including pharmacokinetics, bioequivalence, BCS waivers, biosimilars, highly variable drugs, narrow therapeutic index drugs, complex drugs, locally-acting drugs, adaptive sequential bioequivalence designs, analytical chemistry, physicochemical characterization of biological products, generic drug development, etc. In 2018, along with several colleagues, Charlie co-founded Scientists Advancing Affordable Medicines, Inc. (SAAMnow).
Charlie holds a BA in Biochemical Sciences from Princeton University and an MS in Chemistry from Stevens Institute of Technology.
Speaker and Panelist
Diane Potvin has worked in the pharmaceutical industry for 24 years. She has experience in both the generic and the new drug development fields and she has started her consultant business, Excelsus Statistics, in 2012.
Diane has developed a vast experience in Phase 1 to 4 studies and in PK/PD and bioequivalence studies. The main topics of her research included Individual bioequivalence, inclusion of carryover effects in bioequivalence study, ANCOVA in bioequivalence assessment of endogenous compounds, and adaptive sample size sequential designs for bioequivalence assessment.
Dr. Sandell holds a Ph.D. in Mathematical Statistics (1990, U. of Lund, Sweden). He has worked for AstraZeneca, Amgen and Siegfried Pharma Development GmbH in both specialist and management roles and is currently an Adjunct Professor at the Department of Pharmaceutics, University of Florida.
Dr. Sandell is a world leading expert in the area of CMC statistics, especially related to development, registration and commercial manufacture of inhalation products. He has a special interest in and long experience of in-vitro bioequivalence (IVBE) evaluations as well as correlating in-vitro data with results from pharmacokinetic studies (IVIVC). He has deep experiences from of a wide range of innovator and generic DPIs, MDIs, nasal sprays and nebulization products, as well as different respiratory add-on devices.
Dr. Sandell has 90+ publications and frequently presents at international conferences. He has participated in different industry collaborations such as IPAC-RS, EPAG, PQRI and PhRMA and is a member of USP Statistics Expert Committee, chair of the USP Large N Expert Panel and member of the USP Data Analysis subcommittee.
In May 2010 Dr. Sandell started the consulting firm S5 Consulting, providing CMC statistical support, general inhalation development advice, regulatory writing, and due diligence assistance.
Elena earned her PhD in Statistics from American University, Washington DC. She has worked in academia and as a statistical consultant for over 15 years. In 2013, she joined the Office of Biostatistics, in CDER/ FDA. Her work is mainly focused in developing statistical methodology for assessing bioequivalence of topical/dermatological generic products, characterizing outliers in replicate study designs and the detection of data anomalies. She worked towards the development of the scaled bioequivalence test for IVPT data that first appeared in the FDA Acyclovir Guidance in 2016. In 2015 she was honored with the FDA ‘Outstanding Service Award’. Besides her work at FDA, Elena is an adjunct lecturer at Georgetown University. She is the 2019 Chair-Elect of the American Statistical Association- Section on Risk Analysis.
Julie Szirtes leads the Clinical Research & Development function of Apotex Inc. in Toronto, Canada. Apotex is a Canadian pharmaceutical company with global presence, which develops mainly generic products. Over the last 16 years with Apotex, Julie has accumulated expertise covering the planning, design, conduct and interpretation of bioavailability / bioequivalence pharmacokinetic studies in both healthy and patient populations, for products intended to be registered in numerous global markets. She has been involved in clinical studies on products covering a vast array of therapeutic areas, and a wide variety of dosage forms including small molecule oral solids and liquids, transdermal products, inhalation products, nanoparticle medicines, and large molecule biological products. Julie’s main responsibility is to provide scientific expertise and strategic direction in the design and analysis of bioequivalence studies developed by Apotex. She has overseen scientists, statisticians, data managers, technical writers and project managers involved in the planning and analysis of several hundreds of bioequivalence studies. Julie has also had exposure to in vitro population bioequivalence assessments and in vitro permeability studies. Julie received her M.Sc. degree in Pharmaceutical Sciences from the University of Toronto in 2003, where the focus of her research was evaluating alterations in CYP 450 enzymes and P-glycoprotein and the associated impact on drug absorption through the gastrointestinal tract in the presence of inflammatory processes and diseases.
Keith Gallicano, Ph.D. (Chemistry) is Chief Scientific Officer, Novum Pharmaceutical Research Services, where he leads a team of scientists responsible for protocol development, medical writing, clinical trial design, and data analysis of pharmacokinetic, pharmacodynamic and clinical endpoint studies. He has 30 years of diverse experience working in the pharmaceutical field, including various positions in government (Senior Research Scientist, Health Canada), academia (Assistant Professor of Medicine, University of Ottawa; Adjunct Professor of Pharmacology and Therapeutics, University of British Columbia), the pharmaceutical manufacturing industry (Director, Biopharmaceutics, Watson Laboratories, Inc.) and the CRO service industry (Vice President, Research and Development, Axelson Biopharma Research, Inc.; Scientific Director, CroMedica Prime and Prime Trials). Dr. Gallicano has co-authored 78 publications, including research papers, reviews, and book chapters. He was a member of the Editorial Board of the Journal of Chromatography and the British Journal of Clinical Pharmacology. Dr. Gallicano has given numerous invited lectures on bioanalytical, pharmacokinetic, clinical and pharmacostatistical aspects of drug interaction and bioequivalence studies, as well as chaired or co-chaired international meetings on these topics.
Dr. Liang Zhao is currently the Director of Division of Quantitative Methods and Modeling (DQMM), Office of Research and Standards, Office of Generic Drugs, CDER/FDA. Dr. Zhao has a broad spectrum of scientific and management experience from consulting (Pharsight), industrial R&D (Bristol Myers Squibb & Medimmune), and regulatory agency (Office of Clinical Pharmacology & Office of Generic Drugs at FDA). Through his 15-year professional career, he has established himself as an expert in industrial R&D, quantitative methods and modeling, and model based strategic decision makings in regulatory and industrial settings for new and generic drugs. Over his professional career, he critically contributed to the establishment of the Clinical Pharmacology function at MedImmune and DQMM at FDA. Dr. Zhao has authored and coauthored 41 peer reviewed articles, 5 book chapters, and 100+ conference abstracts, and has delivered 50+ talks in FDAS workshops, national and international conferences. Dr. Zhao has a diversified educational credentials including PhD in Pharmaceutical Sciences and Master in Applied Statistics from the Ohio State University, Master in Pharmaceutics from Shanghai Medical University, BS in Pharmaceutics from China Pharmaceutical University, and Executive MBA from University of Cambridge.
Mark Liu was born in northeastern China. He received the B.S. degree in Applied Mathematics from
Northeastern University, Shenyang, China, in 1985, and the M.S. degree in Mathematical Statistics from
Beijing Normal University, Beijing, China, in 1988. He joined the Mathematics Department, Northeastern
University, as a Lecturer, before he moved to US to study in 1992. He received the M.S. degree in
Biometry from The University of Nebraska – Lincoln, Lincoln NE, USA, in 1995. After graduation, Mark
worked for Clinical CRO MDS in Lincoln NE and then Glaxo Wellcome in Raleigh NC as SAS
programmer/Biostatistician for about 3 years in clinical pharmacology data science area. Since May 1998,
he has been with the PK/DM department in Mylan Pharmaceuticals Inc. in Morgantown WV, where he
started as a research scientist in statistics and became a Senior Director in Statistics in 2009. Currently,
He is leading the Clinical Data management and Statistical science function in Mylan for all earlier phase
programs. He has supported hundreds successful ANDAs, NDAs or Biosimilars submissions in US, EU,
Japan, Canada, New Zealand and Australia.
Dr. Zhichuan (Matt) Li is a clinical pharmacologist in the Division of Quantitative Methods and Modeling within the Office of Research and Standards, the Office of Generic Drugs, FDA. Dr. Li focuses on the development and application of quantitative methods to analyze pharmacokinetic, pharmacodynamic and clinical bioequivalence to ensure generic drug equivalence.
Dr. Meng Hu received his B.Eng. in Biomedical Engineering and Ph.D. in Physics from the Zhejiang University, China. He is currently a scientific lead in the Division of Quantitative Methods and Modeling under Office of Research and Standards in Office of Generic Drugs. His main research interests include the data analytics methodology development for in-vitro bioequivalence study, and application/development of advanced data tools to serve the OGD’s needs in data management, big data analysis and generating real world evidence from real world data.
Murray has a B.Pharm and D.P.H. from the University of Montreal, and a post-graduate Pharm.D from Wayne State University in Detroit Michigan. He is President and CEO of Learn and Confirm Inc., a Drug Development Consultancy firm that offers expert consultancy advice to both innovative and generic Pharmaceutical Companies worldwide in Drug Development and complex PK/PD and pharmacometric analyses. He has presented more than 300 seminars and posters internationally and published more than 150 abstracts, manuscripts and book chapters in clinical pharmacology. He has been involved in thousands of Phase I clinical trials as a PI or sub-PI, and has served as an expert consultant in the drug development field for dozens of pharmaceutical companies located in the USA, Europe, Africa, Middle-East, Asia and Canada. He has directed the work of 6 PhD (1 current), 6 post-doctoral fellows, and 11 MSc candidates. Dr. Ducharme is a Fellow of the American College of Clinical Pharmacy and of the American College of Clinical Pharmacology. He is the past-chair of the American Association of Pharmaceutical Scientists (AAPS) Bioequivalence Focus Group, and is a Core Member of Health Canada Scientific Advisory Committee on Pharmaceutical Sciences and Clinical Pharmacology.
Pina has worked in the Pharmaceutical industry for over twenty years, both on the generic as well as the innovator side. She holds a Master’s degree from McGill University in Biostatistics and Epidemiology. She currently acts as the Executive Director of Scientific Affairs at Novum Pharmaceutical Research Services. The main topics of her recent research include patch adhesion/irritation in dermatology studies, scaled average bioequivalence (SABE) and higher order designs in bioequivalence studies. Pina also lectures at various universities in Montreal and Toronto.
Robert Lionberger, Ph.D. serves as Director of the Office of Research and Standards (ORS) in the Office of Generic Drugs (OGD). Dr. Lionberger leads OGD’s implementation of the GDUFA science and research commitments including internal research activities and external research grants and collaborations to ensure the therapeutic equivalence of generic drug products. ORS also provides pre-submission advice on complex generics through pre-ANDA meetings, product specific guidance and correspondence responses.
He received his undergraduate degree from Stanford University in Chemical Engineering, and a PhD from Princeton University in Chemical Engineering. After his Ph.D., he conducted post-doctoral research in Australia in the Department of Mathematics and Statistics at the University of Melbourne. Prior to joining the FDA 15 years ago, he was an Assistant Professor of Chemical Engineering at the University of Michigan.
Robert Lionberger
Panelist
Dr. Sam Raney is a thought leader in topical and transdermal drug products, with over 25 years of experience as an
academic researcher, an adjunct professor, and a principal or sub investigator on over 400 studies. He has authored
numerous research manuscripts, review articles, book chapters and patents related to pharmaceutical product
development, lectured globally, and held senior management roles in industry. He is the Lead for Topical and
Transdermal Drug Products in the FDA Office of Generic Drugs, and is an expert panel member in the U.S. Pharmacopeia. Dr. Raney holds a B.A. in Molecular Biophysics & Biochemistry from Yale University, and a Ph.D. in Biochemistry & Molecular Biology from the University of British Columbia in Canada.
Sam Raney
Moderator
Shein-Chung Chow, Ph.D. is currently an Associate Director at Office of Biostatistics (OB), Office of Translational Science (OTS), Center for Drug Evaluation and Research (CDER), United States Food and Drug Administration (FDA). Dr. Chow is also a Professor at Duke University School of Medicine, Durham, NC. Prior to that, Dr. Chow also held various positions in the pharmaceutical industry such as Vice President at Millennium, Cambridge, MA; Executive Director at Covance, Princeton, NJ, and Director and Department Head at Bristol-Myers Squibb, Plainsboro, NJ. Dr. Chow is the Editor-in-Chief of the Journal of Biopharmaceutical Statistics and the Editor-in-Chief of the Biostatistics Book Series at Chapman and Hall/CRC Press, Taylor & Francis Group. He was elected Fellow of the American Statistical Association and an elected member of the ISI (International Statistical Institute). Dr. Chow is the author or co-author of over 300 methodology papers and 29 books including Design and Analysis of Bioavailability and Bioequivalence Studies, Sample Size Calculations in Clinical Research, Adaptive Design Methods in Clinical Trials, Translational Medicine, Design and Analysis of Clinical Trials, and Quantitative Methods for Traditional Chinese Medicine Development.
Theo Kapanadze, D.Sc., Ph.D., co-founder and Chief Scientific Officer of Diteba Research Laboratories Inc., has more than 30 years of analytical R & D Chemist and pharmaceutical industry experience.
Dr. Kapanadze capitalized on his years of experience evaluating drug product performance at leading analytical organizations to launch Diteba Research Lab, Inc. (now Diteba Laboratories Inc.) with a mission to provide quality analytical services to the Pharmaceutical, Biopharmaceutical and Nutraceutical industries. With the emergence of newer, alternative dosage forms over the last 15 years, he has become a well-recognized global leader in the development of topical drug products, providing expertise in the development and validation of performance tests used to evaluate the In Vitro absorption of drugs across skin and other membranes.
Diteba, under Dr. Kapanadze leadership, has built a strong track record characterizing topically applied products and superior scientific expertise in In Vitro release testing (IVRT), In Vitro permeation testing (IVPT) and skin absorption models using Franz diffusion and immersion cells under cGMP/GLP environments. In Vitro methodologies that are developed at Diteba have been successfully used in numerous generic drug approvals.
Dr. Kapanadze received his Ph.D. and D.Sc. in Chemistry of Biological Active Compounds from Kurnakov Institute General and Inorganic Chemistry, Russian Academy of Sciences, Moscow, and also completed two years post-doctoral research in pharmacokinetics and toxicology studies at Moscow Oncology Hospital center. In addition he worked as Senior Research fellow at York University (Toronto, Canada). Dr. Kapanadze has more than forty-five scientific publications covering topics in Analytical Chemistry of drug candidates (small and large molecules), synthesis, characterization, separations, and pharmacokinetics.
Theo Kapanadze
Panelist
Dr. Hauck received a B.S. in Mathematics and Economics from Carnegie-Mellon University and his M.S. and Ph.D. in Statistics from Harvard University. He has authored or co-authored 236 peer-reviewed papers and has served as a statistical consultant to working groups within FDA’s Office of Pharmaceutical Sciences, US Pharmacopeia (USP), and to pharmaceutical companies. Within the pharmaceutical industry he is best know for his work on bioequivalence and equivalence studies and for work on the USP bioassay chapters.
Most recently, he worked for USP as their statistician. Prior to USP, he worked at Thomas Jefferson University, Philadelphia, where he was Professor and Director, Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics. Dr. Hauck has also worked at the Harvard Medical School, Worcester Polytechnic Institute, Illinois Cancer Council, Northwestern University Cancer Center, and the University of California at San Francisco.
Walter W. Hauck
Panelist
Dr. Wanjie Sun is a senior mathematical statistician at FDA/CDER/Office of Biostatistics/DBVIII reviewing generic drug ANDA review, consult review and grant review. Dr. Sun is active in regulatory research and receives multiple regulatory research excellence awards. Dr. Sun participates in multiple general and product-specific guidance development, including the adhesion guidance for transdermal delivery Systems and topical patches for ANDAs. Prior to joining FDA, Dr. Sun worked at GWU as a lead research scientist and a PI/co-PI for NIH-supported clinical trials and served as a biostatistician for the pharmaceutical industry. Dr. Sun has over forty publications in statistical, medical, and pharmacy journals with 2000+ citations.
