Equivalence of Complex Drug Products: Scientific and Regulatory Challenges

Organizers

Melanie Brickman Borchard, PhD, MSc

The New York Academy of Sciences

Alison Carley, PhD

The New York Academy of Sciences

Daan J.A. Crommelin, PhD

Utrecht University

Wenlei Jiang, PhD

Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration

Scott McNeil, PhD

Nanotechnology Characterization Laboratory

Vinod Shah, PhD

Non Biological Complex Drugs Working Group

Jon de Vlieger, PhD

Lygature

Keynote Speaker

Lawrence Mayer, PhD

Jazz Pharmaceuticals

Dr. Lawrence Mayer, Senior VP Discovery at Jazz Pharmaceuticals, has played a lead role in the discovery and development of a number of oncology drugs, several of which eventually achieved market approval. He held senior management positions at The Canadian Liposome Company and QLT Inc. before joining the BC Cancer Agency, where he established and directed the Health Canada accredited Investigational Drug Program. Celator was formed in 2000 as a spin-out of Dr. Mayer's laboratory at the BC Cancer Agency. Dr. Mayer has authored more than 250 scientific publications and has more than 35 patent families awarded or pending. Dr. Mayer received his BS in both Chemistry and Biology, summa cum laude, from Wartburg College and his PhD in Biochemistry from the University of Minnesota.

Speakers

Daan J.A. Crommelin, PhD

Utrecht University

Prof. Daan Crommelin is professor emeritus at the Department of Pharmaceutics at Utrecht University. Until December 2011 he was scientific director of the Dutch Top Institute Pharma in Leiden. He is adjunct professor at the Department of Pharmaceutics and Pharmaceutical Chemistry at the University of Utah. Crommelin is co-founder of OctoPlus, a Leiden based company specialized in the development of pharmaceutical (mainly protein based) product formulations and advanced drug delivery systems. He published extensively and is on the editorial board of 10 peer reviewed journals in the pharmaceutical sciences. He is Editor-in-Chief of the AAPS book series Advances in the Pharmaceutical Sciences. He advises venture capital groups and acts as consultant. He chairs the UCAB Foundation: the Utrecht Center of Excellence for Affordable Biotherapeutics, a WHO supported initiative. He chaired the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation (F.I.P.), was chair of the organizing committee of the Pharmaceutical Sciences World Conference 2007 in Amsterdam. He is past president of the European Federation of Pharmaceutical Sciences (EUFEPS) and past vice-chair of the scientific advisory board of the European Innovative Medicines Initiative (IMI).

Beat Flühmann, PhD

Vifor Pharma Ltd

Dr. Flühmann is Pharmacist by training and holds a PhD in molecular biology. He was working in various position in the field of pharmaceuticals and functional nutrition. He was Deputy Department Head of a R&D department for 8 years. Dr. Flühmann was leading a global multidisciplinary research and development team at Roche/DSM nutritional products developing novel compounds for the prevention and treatment of diabetes. In his current position Dr. Flühmann is Global Lead Non-Biological Complex Drugs at Vifor Pharma Ltd Switzerland, with a main interest in regulatory aspects of nanomedicines. He is Steering Committee Member of the Non-Biological Complex Drugs Working Group hosted at Lygature, a non for profit organization. The Non-Biological Complex Drugs Working Group has been set up to discuss appropriate and harmonized science-based approval and post-approval standards to ensure patient safety and benefit with Non Biological Complex Drugs. The working group engages in activities to publish and discus the corresponding scientific evidence with authorities, experts, health care providers. Moreover the group is involved in scientific education and training on the above mentioned topics to relevant stakeholders. He is as well advisory board member of the GoNanoBioMat project a multinational research project in the field of nanomedicine.

Joseph Glajch, PhD

Momenta Pharmaceuticals, Inc.

Joseph L. Glajch is Director of Analytical Development at Momenta Pharmaceuticals in Cambridge, MA. He received his AB in Chemistry at Cornell University and PhD in Analytical Chemistry at the University of Georgia under L.B. (Buck) Rogers. He has held technical and R&D management positions at DuPont, Bristol-Myers Squibb, Certus, and Momenta with emphasis on HPLC column and method development and pharmaceutical development and analysis. He has served President and Program Chairman of the Analytical Division of the American Chemical Society and the Chromatography Forum of the Delaware Valley and Program Chairman of the Gordon Conference on Analytical Chemistry. He has served on the editorial advisory boards of Analytical Chemistry, the Journal of Chromatography, and LC/GC. He is a member of the USP Expert Committee on General Chemical Analysis. He has over 40 publications, co-author of three books, and six patents on HPLC column materials and medical imaging agents.

Elwyn Griffiths, PhD, DSc

World Health Organization and Health Canada

Dr. Elwyn Griffiths retired as Director General, Biologics and Genetic Therapies Directorate, Health Canada, in October 2011 and now lives in the UK. He joined Health Canada in 2003 on his retirement from the WHO, Geneva. He has a PhD and a DSc degree from the University of Wales, and following postdoctoral positions in Canada joined the staff of the Medical Research Council, UK, where he worked for over ten years. In 1980 he became a senior member of staff at the National Institute for Biological Standards and Control, UK, and in 1994 was appointed Chief, Biologicals at the WHO. From 1994 until the end of 2002 he was responsible for WHO's programme for providing international written and physical standards for vaccines, blood products and biotherapeutics.

Dr. Griffiths has published widely in the field of microbial pathogenicity, vaccines and the standardization of biologicals and provided scientific and regulatory advice to numerous regulatory agencies, as well as to the WHO. He is currently a consultant in vaccines and biotherapeutics to the WHO and a member of the WHO Expert Committee on Biological Standardization. He is also a member of the Clinical Trials, Biologicals and Vaccines Expert Advisory Group of the UK Commission on Human Medicines and of the Expert Advisory Group on Biological and Biotechnology products of the British Pharmacopoeia Commission.

Iris Grossman, PhD

Teva Pharmaceuticals

Dr. Iris Grossman, VP, global head of the Personalized & Predictive Medicine (PPM) and Big Data Analytics unit for Teva Global R&D, has dedicated her research career, in both industry and academia, to the advancement of the field of personalized medicine. She is currently charged with defining and implementing the global PMP strategy for Teva, a leading global pharmaceutical company, covering both discovery and development R&D programs. Israel's leading financial magazine, Globes Magazine, selected Dr. Grossman as one of the country's top 40 professionals under 40 years of age in 2013.

Prior to joining Teva, Dr. Grossman was CEO and president of the pharmacogenetics management consultancy IsraGene Ltd., providing services to both the pharma and biotech sectors. This followed several years of spearheading pipeline pharmacogenetic programs for industry and academia as director of pharmacogenetics at Cabernet Pharmaceuticals Inc. Dr. Grossman moved into consultancy having been responsible for running large-scale pharmacogenetic programs at GlaxoSmithKline, with an emphasis on infectious and neurological diseases.

In academia, Dr. Grossman was a key member of Professor David Goldstein's team at the Center for Population Genomics and Pharmacogenetics, Institute for Genome Sciences and Policy, at Duke University. Dr. Grossman received her PhD from the Technion–Israel Institute of Technology, where her research project, conducted in collaboration with the Weizmann Institute for Science, investigated pharmacogenetic markers of multiple sclerosis treatment response.

Wenlei Jiang, PhD

Office of Research and Standards, Office of Generic Drugs, US Food and Drug Administration

Dr. Wenlei Jiang is currently a Senior Science Advisor in the Office of Research and Standards (ORS)/Office of Generic Drugs (OGD)/Center for Drug Evaluation and Research (CDER). She is mainly responsible for coordinating post-market generic drug safety investigation, representing ORS on OGD's new international harmonization activities, and developing opportunities for scientific outreach. Previously she served as the Acting Deputy Director of ORS, where she provided oversight on Generic Drug User Fee Act (GDUFA) regulatory science research programs. Her research interest has been focused on bioequivalence standard development for generic complex drug products containing nanomaterials, solid oral modified release drug products, and narrow therapeutic index drugs, as well as post-market surveillance of generic drugs. She used to work in the Division of Chemistry, OGD to review the chemistry and manufacturing control (CMC) sections of ANDAs. Prior to joining FDA, she was at Novartis Pharmaceutical Corporation where her responsibilities included formulation development of conventional liquid and solid dosage forms, as well as advanced parenteral drug delivery systems. She received her PhD in Pharmaceutics and Pharmaceutical Chemistry from The Ohio State University in 2001.

Scott McNeil, PhD

Nanotechnology Characterization Laboratory

Dr. McNeil serves as the Director of the Nanotechnology Characterization Laboratory (NCL) for Leidos Biomedical Research and Frederick National Laboratory for Cancer Research, where he coordinates preclinical characterization of nanotech cancer therapeutics and diagnostics. At the NCL, Dr. McNeil leads a team of scientists responsible for testing candidate nanotech drugs and diagnostics, evaluating safety and efficacy, and assisting with product development—from discovery-level, through scale-up and into clinical trials. NCL has assisted in characterization and evaluation of more than 300 nanotechnology products, several of which are now in human clinical trials. Dr. McNeil is a member of several working groups on nanomedicine, environmental health and safety, and other nanotechnology issues. He is an invited speaker to numerous nanotechnology-related conferences and has several patents pending related to nanotechnology and biotechnology. He is also a Vice President of Leidos Biomedical Research.

Prior to establishing the NCL, he served as a Senior Scientist in the Nanotech Initiatives Division at Leidos where he transitioned basic nanotechnology research to government and commercial markets. He advises industry and State and US Governments on the development of nanotechnology and is a member of several governmental and industrial working groups related to nanotechnology policy, standardization and commercialization. Dr. McNeil's professional career includes tenure as an Army Officer, with tours as Chief of Biochemistry at Tripler Army Medical Center, and as a Combat Arms officer during the Gulf War. He received his bachelor's degree in chemistry from Portland State University and his doctorate in cell biology from Oregon Health Sciences University.

Kouros Motamed, PhD

NantBioScience, Inc.

Dr. Kouros Motamed, PhD has been the Director of Drug Development at NantBioScience, Inc. since April 2016. Prior to that, he has served as VP of Strategic Alliances and Clinical Communications and VP of Clinical Development and Nanomedicine at Sorrento Therapeutics from 2013 to 2016. He has also served as a co-founder and CSO/CTO of Igdrasol, Inc. and Biomiga Diagnostics start-up companies from 2011–2013. Dr. Motamed has also served as the MOA and Molecular Biology Group Head at Celgene Corp. and Abraxis BioScience Inc. from 2007–2011. Dr. Motamed held an Assistant Professorship position in the Department of Pathology and Vascular Biology Center at Georgia Health Sciences University from 2002–2007. He has over 30 original publications in peer-reviewed journals, over 50 conference presentations and has 5 issued patents. He has served on the Editorial Board of Journal of Nanomaterials & Molecular Nanotechnology since 2013. Dr. Motamed received a BS degree in Biology from University of San Francisco and a PhD degree from the University of California, Davis in Microbiology.

Stefan Mühlebach, PhD

Vifor Pharma Ltd

Dr. Stefan Mühlebach, regulatory Science Lead for NBCDs at Vifor Pharma-Fresenius Medical Care Renal Pharma Ltd. in Switzerland chairs since 2010 the Non-Biological Complex Drugs (NBCDs) Working Group c/o Lygature, a non for profit, private-public partnership in the Netherlands (http://lygature.org/nbcd). He is an university professor, Medical Faculty member, and member of the Clinical Pharmacy & Epidemiology unit at the Deptartment of Pharmaceutical Sciences at the Natural Sciences Faculty in Basel, Switzerland. Research activities, graduate and postgraduate teaching cover topics in pharmacology, clinical nutrition, hospital pharmacy, and regulatory sciences. He authored over 100 peer-reviewed papers, more than 60 indexed in Pubmed/EMBASE, and of several book chapters. 1980–2005 he was Chief Hospital Pharmacist in Biel and in Aarau (Switzerland). He is a honour member of the Swiss Association of Public Health Administration and Hospital Pharmacists and a board member of the Swiss Academy of Pharmaceutical Sciences. 2005–2008 when working at Swissmedic, the Swiss Agency for Therapeutic Products, he was Head of the Pharmacopoeia and of the Swiss Delegation at EDQM in Strasbourg. In 2008 he started as Chief Scientific Officer at Vifor Pharma Ltd Switzerland, since 2009 in the international headquarter in Zürich and moved there in 2015 in the joint company ViforFresenius.

Chetan Pujara, PhD

Allergan

Dr. Chetan Pujara is Vice President, Small Molecule Product Development at Allergan plc, Irvine, CA. His organization is responsible for designing and developing pharmaceutical dosage forms intended for clinical trials and commercialization. SMPD develops topical sterile ophthalmic solutions, suspensions and emulsions, sustained-release ocular biodegradable implants, oral tablets/capsules, topical dermal gels & creams and other locally acting dosage forms. Prior to joining Allergan, Chetan was employed by Abbott Laboratories/Abbvie in Illinois, where he held various positions in Global Pharmaceutical R&D gaining experience in development of solid oral dosage forms and pediatric oral suspensions.

Chetan also contributes to the pharmaceutical sciences community as a volunteer for several non-profit organizations. He is a member of the USP Dosage Forms Expert Committee and serves on the USP <771> Ophthalmic Preparation Expert Panel. He is also a Scientific Advisor to the Editors of Journal of Pharmaceutical Sciences and an Adjunct Professor in the Department of Industrial and Physical Pharmacy, Purdue University, IN. Chetan has also contributed to the Physical Properties Working Group of Product Quality Research Institute (PQRI).

Andre Raw, PhD

Center for Drug Evaluation and Research, US Food and Drug Administration

Andre Raw received his BS degree from the Massachusetts Institute of Technology and his Ph.D. degree in chemistry from the University of California at Berkeley. He was a Welch post-doctoral research fellow under Alfred G. Gilman at the University of Texas Southwestern Medical Center. He 2001, he joined the FDA as a reviewer within the Office of Generic Drugs (OGD). In his fourteen year tenure within FDA he has been promoted to FDA Agency Expert and to Chemistry Division Director. Currently he is Acting Senior Scientific and Policy Advisor in the Office of Lifecycle Drug Products (OLDP) in the Office of Pharmaceutical Quality (OPQ). Dr. Raw was involved in the development of several important FDA initiatives, including the Guidance on Pharmaceutical Solid Polymorphism in Abbreviated New Drug Applications (ANDAs), Regulations on Listing of Polymorph Patents in the "Orange Book", and Question Based Review – Quality by Design (QbD) Initiative, QbD Example for Generic Modified Release Products, and Guidance for Industry: Pharmaceutical Solid Co-Crystals. He has also been active in addressing the scientific and regulatory issues raised in citizen petitions, in defining regulatory policy that impact ANDAs. He was instrumental in FDA's recent approval of generic versions of complex active ingredients including Lovenox (enoxaparin sodium), Ferrlecit (sodium ferric gluconate complex in sucrose) and Copaxone (glatiramer acetate). More recently, Dr. Raw has been active in Risk Based Review and Quality Informatics Initiatives.

Stephan Stern, PhD, DABT

Nanotechnology Characterization Laboratory

Dr. Stephan Stern is Acting Deputy Director and Senior Principal Scientist at the National Cancer Institute's Nanotechnology Characterization Laboratory (NCL), located at the Frederick National Laboratory for Cancer Research in Frederick, Maryland. The NCL assists in all phases of the nanomedicine drug development process, from early preclinical to late stage clinical trials, working with academic laboratories and the pharmaceutical industry. At the NCL, Dr. Stern oversees nanomedicine pharmacology and toxicology. Data generated from these studies support formulation optimization, regulatory filings, and environmental risk assessment. Dr. Stern's research interests include novel drug formulation, bioanalytical method development, and pharmacokinetic modeling. Prior experience includes a postdoctoral fellowship at the University of North Carolina–Chapel Hill in the Division of Drug Delivery and Disposition, and Curriculum in Toxicology, and work within regulated areas of the pharmaceutical industry. He received his BS degree in biochemistry from the University of Rochester and his PhD in toxicology from the University of Connecticut at Storrs. Dr. Stern is a Diplomate of the American Board of Toxicology.

Wyatt Vreeland, PhD

The National Institute of Standards and Technology

Dr. Wyatt Earned his PhD degree in chemical engineering from Northwestern University in 2002 where he developed techniques for the electrophoretic separation of natural and synthetic polymers in microfluidic devices. After his PhD studies, Wyatt joined NIST as an National Research Council postdoctoral fellow working with Laurie Locascio on applications of liposomes as functional elements in microfluidic devices. Borrowing nature's motif of using vesicles as nano-packages, Wyatt focused on using liposomes to package chemicals and release those reagents at controlled times and locations in microfluidic systems. Additionally, during his postdoctoral fellowship he undertook the technical development of a field-portable electrophoresis system for forensic DNA analysis for the Department of Justice. During this effort, he maintained an active research program at the interface of colloidal science and microfluidic devices with an emphasis creating and characterizing very monodisperse and size-controlled vesicle-like particles. Most recently Wyatt's research has focused on controlled synthesis and characterization of colloidal protein systems as can be encountered (and usually undesirably) in many of today's complex drug therapeutics. Finally, in the Spring of 2015 Wyatt served as an US State Department Embassy Science Fellow for the US Embassy in Prague, Czech Republic, where he toured the country's burgeoning biotechnology industry.

Gary West, MD

Azaya Therapeutics

Dr. Gary West is a retired radiation oncologist and currently a member of the Board of Directors, Azaya Therapeutics, San Antonio, Texas. He graduated from the University of Colorado Medical School and was a resident in radiation oncology at the University of New Mexico where he was affiliated with the Los Alamos Meson Facility (LAMF), Los Alamos, New Mexico. He completed his residency at the Joint Center for Radiation Oncology (JCRO), Harvard University. He was board certified in in Radiation Oncology in 1975 and thereafter completed a research fellowship at the Harvard (JCRO) in 1979 where he investigated chemotherapy drug delivery in human tumor cells. While in the Air Force he continued his affiliation with the LAMF and was Chief of the Radiation Oncology Department, Wilford Hall USAF Medical Center. From 1992 to 2005 he served on the USAA Life Investment Trust Board of Governors and was chairman of the audit committee. While in private practice he was Chief of Staff University of Texas Health Science Center, Cancer Therapy and Research Center (CTRC), in San Antonio and a member of the CTRC Board of Governors. He is a retired member of the American Society of Clinical Oncologists and the American Society of Therapeutic Radiologists.

Elena Wolff-Holz, MD

Paul Ehrlich Institute

Dr. Elena Wolff-Holz is an MD and medical assessor at the Paul-Ehrlich-Institut and a member of the Biosimilar Working Party (BMWP) of the Committee for Medicinal Products for Human Use (CHMP) and a national expert to the Oncology Working Party (OWP) of the CHMP, where she contributes to scientific advice procedures and the development of guidelines and reflection papers. Overall, Elena has 20 years of professional experience, including 14 years in the biotech industry where she held various positions in clinical development and medical marketing functions at Centocor Inc (now J&J) and Amgen in the US and in Germany before joining the German national regulatory agency. In the area of biotherapeutics, she is responsible for advising companies on drug development issues, reviewing applications for marketing authorization in the EU and assessing clinical trial applications. Her work has resulted in several (co-)authorships in scientific journals and several presentations at (inter-)national conferences. She is also a lecturer at Institutes covering training of experts and executives from academia, regulatory bodies and biopharmaceutical industry. Elena is a physician by training with an MD degree from Heidelberg University and a postdoctoral fellowship at Harvard Medical School.

Gillian Woollett, DPhil, MA

Avalere Health

Dr. Gillian Woollett, SVP at Avalere, leads the FDA Policy and Regulatory Strategy Practice at Avalere, an advisory services firm of over 250 people that supports clients throughout the healthcare system, from patients to biopharma companies and payers/providers. At Avalere she provides the "prequel" of scientific and technical expertise that supports drugs, biologics and devices gaining approval at the FDA in a manner that allows them to be commercially successful in the public and private reimbursement world. She launched the FDA Practice in 2012. Dr. Woollett and her team translate into practical action all aspects of regulatory engagement strategy and policy development relevant to commercial success for multiple multi-national clients. Concurrently, she created the Avalere FDA Fellows Program to enable scientists to transition effectively into the policy environment with over 20 now having used this stepping stone to transition careers. Dr. Woollett earned her BA, MA in the Biochemistry from the University of Cambridge, and her DPhil in Immunology from the University of Oxford in the UK. She was a post-doc in the Department of Molecular Biology at the University of Edinburgh, and at the Biomedical Research Institute, Rockville, MD funded by USAID.

Jon de Vlieger, PhD

Non Biological Complex Drugs Working Group and Lygature

Dr. Jon de Vlieger, obtained his doctoral degree in bio analytical chemistry from the VU University in Amsterdam. In 2011 he joined Top Institute Pharma, an independent not-for-profit organization based in the Netherlands that catalyzes the development of new medical solutions for patients by driving public-private collaboration between academia, industry, and society. Recently a merger between leading Dutch technology institutes Center for Translational Molecular Medicine and Top Institute Pharma formed Lygature. For Lygature, Dr. de Vlieger coordinates several international public private partnerships, including the Non Biological Complex Drugs Working Group, an international network of scientific and clinical experts from academia, industry and regulatory bodies, with expertise in many aspects of the development and evaluation of NBCDs. He is a co-editor of the book on NBCDs in the AAPS Advances in the Pharmaceutical Sciences Series.