Considerations for and Alternatives to Comparative Clinical Endpoint and Pharmacodynamic Bioequivalence Studies for Generic Orally Inhaled Drug Products

Senior Advisor, Inhalation Science, Per Backman Consulting AB, Emmace AB

Dr. Per Bäckman is senior adviser at Per Backman Consulting AB / Emmace AB. In this role, he provides advice to the pharmaceutical industry on biopharmaceutical aspects related to the development of orally inhaled and nasal drug products (OINDP). This includes general aspects related to the planning and execution of clinically relevant test programs as well as the application of physiologically based biopharmaceutical modelling (PBBM) to understand the relation between in vitro drug performance attributes and clinical performance. Per holds a Ph.D. in Physical Chemistry from the University of Lund, Sweden and has 25 years of OINDP industry experience in various roles.

Professor and Associate Dean, Mechanical and Materials Engineering Division of Pulmonology, Allergy, and Critical Care Medicine, University of Alabama at Birmingham

Prof. Banaszak Holl is Professor and Associate Dean for Research in the School of Engineering. He has more than 20 years of experience in polymer and other nanomaterials for drug and gene delivery including detailed characterization studies. His academic path includes 20 years at the University of Michigan including serving as Director of Macromolecular Science and Engineering and 4 years as Head of Chemical and Biological Engineering at Monash University. He received his B.S. from the University of Chicago and Ph.D. from Cornell University.

Senior Pharmacologist, DTP-I, ORS, OGD, CDER, FDA

Dr. Elizabeth Bielski is a Senior Pharmacologist working at Division of Therapeutic Performance-I (DTP-I), Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center of Drug Evaluation and Research (CDER) at the FDA since October 2022. Prior to her role as a Senior Pharmacologist, she served as a Pharmacologist from October 2020 to October 2022 and as a Chemist from January 2020 to October 2020 within DTP-I. Her areas of expertise involve orally inhaled and nasal drug products (OINDPs) and drug-device combination products (DDCPs). She is actively involved in developing general and product-specific guidances, addressing controlled correspondences, pre-ANDA meeting requests, citizen petitions, internal consults, and collaborating on current research projects to promote generic drug development of OINDPs and DDCPs. Prior to joining the FDA, she served as an ORISE Fellow at FDA within DTP from August 2018-December 2019. Elizabeth completed her Ph.D. in Chemical Engineering from Wayne State University (Detroit, MI, USA) in July 2018 encompassing work also conducted at Department of Chemistry at the University of São Paulo (São Paulo, Brazil) and Department of Pharmaceutics at Virginia Commonwealth University (Richmond, VA, USA) related to novel drug delivery strategies for treatment of lung cancer and lung metastases. Prior to receiving her doctorate, she received her Bachelor of Science in Biomedical Physics Honors with University Honors in 2011, and her Master of Science in Biomedical Engineering in 2012 from Wayne State University.

Pharmacokineticist, DTP-1, ORS, OGD, CDER, FDA

Dr. Susan Boc is a pharmacokineticist in the inhalation and nasal drug products team in the Division of Therapeutic Performance-1. She is responsible for the development of product-specific guidances for generic drug development and reviewing and responding to controlled correspondences, consults, and pre-ANDA meeting requests. Dr. Boc is also engaged in regulatory science research initiatives related to inhalation and nasal drug products under the GDUFA regulatory science program. Dr. Boc has a B.S. degree in Biochemistry from the University of California, Los Angeles, and a Ph.D. in Pharmaceutical Sciences from Virginia Commonwealth University. Prior to joining FDA, she spent over 8 years in the pharmaceutical industry working on a variety of inhalation drug products at different stages of development.

Professor, Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida

Dr. Jürgen Bulitta is a Professor in the Department of Pharmacotherapy and Translational Research at the UF College of Pharmacy. He is supported by the University of Florida’s preeminence program in Drug Discovery and Development, and received the Perry E. Foote Eminent Scholar Chair, Endowed Professorship, in 2019.

Dr. Bulitta has 20 years of hands-on experience with population pharmacokinetics and mechanism-based modeling and significantly contributed to 97 Phase I/IV clinical PK studies. Moreover, he has been working on inhaled drug pharmacokinetics together with Dr. Guenther Hochhaus for over 7 years.

CEO, Fluidda

Dr. Jan De Backer graduated from Delft University of Technology, The Netherlands as aerospace engineer. He attained an M.Sc. degree in Aerodynamics and specialized in Applied Biomedical Computational Fluid Dynamics leading to a Ph.D. from the University of Antwerp, Belgium. He is an alumnus of the M.B.A. program at London Business School, London and Columbia Business School, New York. Dr. De Backer has received several awards for his innovative research in the field of airway modeling in respiratory and sleep medicine. His work has been published in international journals. Dr. De Backer founded FLUIDDA in 2005 and he has held the position of Chief Executive Officer since 2007.

Reviewer, OB, DB-II, OGD, CDER, FDA

Dr. Ping Du graduated from Peking University in China with B.S. and M.S. degrees in Pharmaceutical Sciences. She obtained her Ph.D. degree in Pharmaceutics from The University of Texas at Austin working on advanced orally inhaled dry powder inhalers. Ping has five years of experience in the pharmaceutical industry and has worked on different dosage forms (e.g., MDI and DPI) and administration routes. Right now, Ping is a reviewer in Office of Bioequivalence, Division of Bioequivalence II, Office of Generic Drug, at US Food and Drug Administration.

Reviewer, DQMM, ORS, OGD, CDER, FDA

Dr. Kairui (Kevin) Feng, joined Quantitative Clinical Pharmacology team in DQMM/ORS/OGD/CDER/FDA in April 2019 as a reviewer. Prior to joining FDA, he worked in Certara, with 13+ years’ experience in quantitative clinical pharmacology in Pharsight (a Certara company in Cary, NC, USA) and in translational drug development in Simcyp (a Certara company in Sheffield, UK). He has extensive knowledge/experience in application of preclinical drug development and clinical drug development, including but not limited to new and generic drug application submission and regulatory review, managing grant/contract applications, and acting as grant/contract officer for communicating with internal and external stakeholders. Prior to joining Certara, he worked two years in finance modeling on a portfolio optimization project with Smith Institute in Oxford, UK. Dr. Kevin Feng received a Ph.D. in 2004 in Automatic Control and System Engineering at the University of Sheffield, UK.

Head of Computational Pharmaceutics, Nanopharm Ltd., an Aptar Pharma Company

Dr. Will Ganley is the Head of Computational Pharmaceutics at Nanopharm. He holds an M.Chem. from the University in Southampton and Ph.D. from the University of Bristol where he studied the physical characterization of complex fluids and was awarded two Best Thesis Prizes from the Faculty of Science.

Following this, Will took up a postdoc position at the University of Bath in Professor Rob Price’s group where he conducted in vitro characterization of inhaled pharmaceutical products and developed in silico physicochemical, pharmacokinetic, and statistical models to improve the clinical relevance of in vitro tests.

In 2019, Will joined Nanopharm to lead the Computational Pharmaceutics group. His team develops PBPK, CFD-PBPK, and statistical approaches to accelerate and de-risk OINDP development and to support regulatory decision making. He also leads the development of Nanopharm’s in vitro/in silico approaches combining realistic testing with simulations and sees this as a key aspect in the future of complex generic approvals.

Pharmacologist, DQMM, ORS, OGD, CDER, FDA

Dr. Yuqing Gong is currently a Pharmacologist at the Quantitative Clinical Pharmacology Team in the Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, CDER/FDA. Her current role in the division is to utilize quantitative tools such as population pharmacokinetics, modeling, and simulations, to address specific questions related to generic drug development process and/or regulatory decision making. Before joining the FDA, she received comprehensive trainings in pharmaceutical sciences with focuses on drug delivery, pharmacokinetics, and drug-drug interactions. Dr. Gong received her Ph.D. degree in Pharmaceutical Sciences at the University of Tennessee Health Science Center (Memphis, TN, US) in 2020. Her Ph.D. thesis work was to develop a nanoformulation for antiretroviral drugs to suppress the viral load in in the central nervous system across the blood-brain barrier. She also worked on projects that focused on pharmacokinetics and pharmacodynamics of antiretroviral drugs, especially on drug-drug interactions relate to cytochrome P450s.

Chief Scientific Officer and Interim Chief Corporate Development Officer, Transpire Bio

Dr. Abhishek Gupta, ‘Abhi’, is Transpire Bio’s Chief Scientific Officer (CSO) and interim Chief Corporate Development Officer. Dr. Gupta is responsible for the scientific direction of Transpire Bio. As a member of the executive team, Dr. Gupta is responsible for providing the strategic and operational leadership to develop and implement the company’s scientific strategy, overall product portfolio and conceptualization, and introduction of new product opportunities. Dr. Gupta is also responsible for establishing and executing Transpire Bio’s corporate development strategy including evaluation of new product opportunities including M&A to expand existing business and create new business.

Dr. Gupta is a seasoned and accomplished bio-pharmaceutical executive with over 23 years of product development experience across dosage forms with over 20 years focused primarily on inhalation drug-device combination products. Dr. Gupta’s time in industry has included leadership positions at Novartis Pharmaceuticals, Nektar Therapeutics (formerly Inhale), Cardinal Health, Lupin, and his most recent position at Cipla as the SVP & Head of R&D, North America. Dr. Gupta has successfully led the product development and approval of several branded and generic dosage forms including small molecules, polypeptides, proteins, and biologics for registration in the US and EU.

Dr. Gupta is a graduate of Harvard Business School’s Business Analytics program. Dr. Gupta has a Ph.D. in Pharmaceutical Sciences from the University of Arizona, US with a focus on Pharmaceutics, Analytical and Material Sciences. He is a certified project management professional (PMP) through the Project Management Institute (PMI) of America and has a Bachelor’s in Pharmacy (B. Pharm.) from India. Dr. Gupta has over 50 peer reviewed publications and numerous granted and filed patents.

Professor, Pharmaceutics, College of Pharmacy, University of Florida

Dr. Günther Hochhaus received his Ph.D. in 1984 at the Institute of Pharmaceutical Chemistry, Westfälische Wilhelms University (Münster, Germany). He completed a postdoctoral fellowship at the University of California-San Francisco and subsequently joined the University of Florida’s College of Pharmacy as an Assistant Professor in 1987, where he continues to serve today as a Professor of Pharmaceutics. Dr. Hochhaus’ research is interested in evaluating inhalation drugs through in vitro and pharmacokinetic/dynamic approaches. He collaborates with regulatory authorities to improve methodology for drug approval of generic inhalation drugs. Dr. Hochhaus is a Fellow of AAPS and the American College of Clinical Pharmacology (ACCP). In 1998, he was recipient of the young investigator award of the German Airway and Lung Research Society and received ACCP’s Tanabe Young Investigator Award. He was awarded the University of Florida Foundation Research Professorship in 2015-2018; 2019-2022, American College of Clinical Pharmacology’s Bristol-Myers Squibb Mentorship in Clinical Pharmacology Award (2019) and is Honorary Regent of ACCP. In 2022, he received the Charles G. Thiel Award for outstanding research and discovery in respiratory drug delivery. He has published more than 240 research papers.

Chemist, DCDA, OTR, OPQ, CDER, FDA

Dr. Nicholas Holtgrewe has been a Chemist at the FDA Division of Complex Drug Analysis (DCDA) within CDER/OPQ/OTR since April 2019. His research at FDA focuses on inhalation drug characterization, particle sizing, X-ray powder diffraction (XRPD), and spectroscopy and his expertise is in optics, X-ray diffraction, and Raman spectroscopy. He received a B.S. degree in Chemistry from Truman State University in 2008 and a Ph.D. in Chemistry from Washington University in St. Louis in 2013.

Pharmacologist, DB-II, OB, OGD, CDER, FDA

Dr. Paramjeet Kaur is a Senior Reviewer in the Division of Bioequivalence II, Office of Bioequivalence, Office of Generic Drugs, FDA. Since her joining the Division of Bioequivalence II in 2008, she has been involved in the assessment of bioequivalence
reviews, controlled correspondences, and development of several product-specific guidances and general guidances for industry. She received her Bachelor of Pharmacy from the Banaras Hindu University in India, and her Doctorate in Industrial Pharmacy from St. John’s University in NY.

Associate Professor, School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Australia

Dr. Agisilaos Kourmatzis is an Associate Professor in the School of Aerospace, Mechanical and Mechatronic Engineering at the University of Sydney, Australia. His main research focus is on turbulent two-phase flows with a particular interest being the development of optical and laser diagnostic methods for the improved characterization of aerosol dynamics. Relevant to inhalers, he has recently focused on providing more detailed insights into the mechanisms of particle transport within DPIs and physiologically accurate replicas of the human airway. Mechanisms of de-agglomeration, deposition, and particle-gas mixing are of particular interest. Dr. Kourmatzis has a Ph.D. in Fluid Dynamics (2011) from the University of Southampton, UK, an MSc in Advanced Mechanical Engineering (2007) from Imperial College London, UK, and a BEng (Hons) in Mechanical Engineering (2006) from the University of Nottingham, UK. He is a Professional Chartered Engineer. His research has been supported by both industry and government including the Australian Research Council, Mitsubishi Heavy Industries, Proveris Scientific Corporation, the US-FDA, Suzhou Singmed, the Great Barrier Reef Foundation, Venso Labs, and others.

Deputy Director, DTP-I, ORS, OGD, CDER, FDA

Dr. Darby Kozak is the Deputy Division Director for the Division of Therapeutic Performance in the FDA’s Office of Generic Drugs. Dr. Kozak leads a group of interdisciplinary scientists on the development of new analytical methods and equivalence evaluation methodologies for complex drug substances and parenteral, ophthalmic, otic, and inhalation formulations. Prior to joining the FDA, Dr. Kozak was Chief Scientist for Izon Science and Research Fellow at the Australian Institute for Bioengineering and Nanotechnology. Dr. Kozak has a B.Sc. in Chemical Engineering from the University of Washington (Seattle, WA) and Ph.D. in Chemistry from the University of Bristol (United Kingdom).

Chief Medical Officer, Transpire Bio

Dr. Mark Lepore began his career as a physician, board-certified in both General Pediatrics and Allergy, Clinical Immunology. He earned his medical degree from Jefferson Medical College in Philadelphia, trained in Pediatrics at The University of Maryland Hospital in Baltimore, and trained in Allergy/Immunology at Cincinnati Children’s Hospital in Ohio. After a decade in private practice, Dr. Lepore transitioned into drug development with roles at Teva and Lupin. While at Teva, Dr. Lepore worked on multiple projects which led to new drug or supplementary approvals, including Proair HFA MDI, Qvar MDI, Qnasl Nasal MDI, Airduo Respiclick, Proair Respiclick, and Armonair Respiclick. At Lupin, Dr. Lepore led the clinical group which focused on developing inhaled generic products for the US and Europe. One of the first albuterol HFA MDI generics to be sold in the US came out of this work at Lupin.

Dr. Lepore helped form Transpire Bio after a stint with Aquestive Therapeutics as their Chief Medical Officer, advancing the world’s first sublingual treatment for anaphylaxis. He is currently the Chief Medical Officer at Transpire Bio where their programs focus on improving access to important inhalation products as well as developing new inhalation products to address areas of significant unmet medical need. He has authored numerous papers in the respiratory space and has been a co-author for medical textbooks.

Associate Director for Science, OB, OGD, CDER, FDA

Dr. Bing V. Li serves as the Associate Director for Science for Office of Bioequivalence within the Office of Generic Drugs at CDER/FDA. In this role, she provides scientific leadership and expertise for the assessment of the bioequivalence studies submitted by pharmaceutical industry through Abbreviated New Drug Applications (ANDAs) and oversees the scientific programs including guidance development and implementation in Office of Bioequivalence. Dr. Li is an Expert Pharmacologist at the FDA in the area of bioequivalence of aerosolized drug products. Prior to joining FDA in 2004, she was a Research Investigator at Bristol-Myer-Squibb where her responsibilities included formulation identification, development, and optimization for oral solid dosage forms. Dr. Bing V. Li received her Ph.D. in Pharmaceutical Sciences from University of Wisconsin at Madison in 2001, and a Bachelor’s degree in Medicinal Chemistry in 1990 in Beijing University, China.

Edward M. Mielnik and Samuel R. Harding Professor and Department, Executive Officer, Department of Mechanical Engineering, University of Iowa

Dr. Ching-Long Lin is an Edward M. Mielnik and Samuel R. Harding Professor and Departmental Executive Officer of Mechanical Engineering Department at the University of Iowa. Dr. Lin’s research focuses on: (1) developing computed tomography (CT) imaging-based subject-specific lung models, (2) employing machine learning and deep learning of CT lung images to identify imaging clusters and advance a cluster-informed modeling strategy, and (3) conducting CT and single-photon emission computed tomography (SPECT) human subject studies for model validation. Dr. Lin received his M.S. and Ph.D. degrees from Stanford University. He received the NSF CAREER award and is elected Fellow of the American Physical Society (APS), the American Society of Mechanical Engineers (ASME), and the American Institute for Medical and Biological Engineering (AIMBE).

Director, ORS, OGD, CDER, FDA

Dr. Robert Lionberger 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 Generic Drug User Fee Amendments (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-Abbreviated New Drug Application (ANDA) meetings, product-specific guidance, and correspondence responses.
He received his undergraduate degree from Stanford University in Chemical Engineering, and a Ph.D. 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 18 years ago, Dr. Lionberger was an Assistant Professor of Chemical Engineering at the University of Michigan.

Deputy Division Director, OB, OGD, CDER, FDA

Dr. Qing Liu is the Deputy Division Director in the Division of Bioequivalence I, Office of Generic Drugs within the FDA’s Office of Generic Drugs. She has over 10 years of experience in the assessment of bioequivalence for abbreviated new drug applications, controlled correspondences, citizen petitions, product-specific guidance and protocols submitted to the Agency. In the current role, Dr. Liu works with a group of scientists on complex generic drug products, such as nasal/orally inhaled drug products, long acting injectables, topicals, and ophthalmic suspensions.

Director, DTP-I, ORS, OGD, CDER, FDA

Dr. Markham C. Luke serves as FDA Supervisory Physician (Dermatology) and Director of the Division of Therapeutic Performance 1 (DTP- I) in the Office of Research and Standards, Office of Generic Drugs at FDA. DTP- I is responsible for facilitating pre-application development of generic drugs by conducting and promoting regulatory science research to establish standards to ensure therapeutic equivalence of new generic drug products. Markham has an M.D. and a Ph.D. in Pharmacology from Johns Hopkins University and completed his dermatology residency and fellowship at Washington University, St. Louis, MO and the National Institutes of Health, Bethesda, MD. He is an Associate Professor at the Uniformed Services University of the Health Sciences, Bethesda, MD with research interests in dermatopharmacology, clinical pharmacology, clinical study design, and endpoints assessment (including patient-reported outcomes) for medical, surgical, and aesthetic products. Markham has been at FDA since 1998 serving various roles, including as the Lead Medical Officer for Dermatology Drugs, Chief Medical Officer and Deputy Director for the Office of Device Evaluation in the Center for Devices and Radiologic Health, and as Acting Director for Cosmetics in the Center for Food Safety and Applied Nutrition.

Pharmacologist, DB-II, OB, OGD, CDER, FDA

Dr. Rukia M. Mchumo is a bioequivalence assessor in the Division of Bioequivalence II within the Office of Generic Drugs (OGD). Dr. Mchumo has extensive experience in bioequivalence assessment of inhalation drug products including evaluation of alternative in vitro techniques for demonstrating bioequivalence of such complex drug products within the Office of Bioequivalence. Prior to joining the FDA, Dr. Mchumo worked as a Lead Scientist in the Department of Inhalation Drug Products at Catalent Pharma Solutions (Morrisville, NC). Dr. Mchumo has a B.S. degree in Chemistry from Lincoln University of Pennsylvania (Oxford, PA) and a Ph.D. in Pharmaceutical Sciences (Pharmaceutics) with a focus in Inhalation Drug Delivery from Florida A&M University (Tallahassee, FL).

Lead Pharmacologist, DTP-I, ORS, OGD, CDER, FDA

Dr. Bryan Newman is a pharmacologist and team lead for inhalation and nasal drug products in the Division of Therapeutic Performance 1 (DTP-1), Office of Research and Standards (ORS), under the Office of Generic Drugs (OGD). Dr. Newman’s work focuses on developing product-specific guidances, and addressing controlled correspondences, citizen petitions, consults, and pre-ANDA meeting requests. He also serves as a project officer and contracting officer’s representative for regulatory science research initiatives related to inhalation and nasal drug products. Dr. Newman received his B.S. degree from Louisiana State University in Biochemistry and his M.S. and Ph.D. degrees from the University of Michigan in Pharmaceutical Science.

Co-Director of CRCG, Professor of Pharmaceutical Sciences and Ralph F. Shangraw/Noxell, Endowed Professor in Industrial Pharmacy and Pharmaceutics, University of Maryland

Dr. James E. Polli is Professor of Pharmaceutical Sciences and Ralph F. Shangraw/Noxell Endowed Professor in Industrial Pharmacy and Pharmaceutics at University of Maryland. His research interest is oral drug absorption and formulation, involving laboratory and clinical research. He has served as advisor to 24 Ph.D. graduates. Dr. Polli is co-Director of the recently initiated Center for Research on Complex Generics, an FDA-funded collaborative agreement with the Agency. He is Director of the online M.S. in Regulatory Science program.

Deputy Division Director, DB-III, OB, OGD, CDER, FDA

Dr. Ke Ren is the Deputy Division Director for the Division of Bioequivalence III (DB-III) in the Office of Bioequivalence of Office of Generic Drugs, CDER, FDA. In this role, she leads a team of scientists responsible for the assessment of the bioequivalence section of Abbreviated New Drug Applications. During her time in DB-III, Dr. Ke Ren has developed extensive expertise in generic drug development in various therapeutic areas, including orally inhaled and nasal drug products. She has participated in the drafting of numerous Agency guidances pertaining to bioequivalence. Dr. Ren received her Ph.D. in Pharmaceutical Science from the University of Florida in 2005 and then undertook post-doctoral training at the University of Florida before joining OGD in 2008.

Co-Director of CRCG, William I Higuchi Collegiate Professor of Pharmacy, Professor of Pharmaceutical Sciences, Biointerfaces Institute, College of Pharmacy, University of Michigan

Vice President of Science and Technology, Nanopharm Ltd., an Aptar Pharma Company

Dr. Jag Shur is an academic and entrepreneur having over 100 published scientific papers and was CEO of Nanopharm Ltd, which he led to a successful exit in 2019. Jag’s main area of research and commercial endeavor is in the complex topical pharmaceutical drug products area. A key theme of his research and commercial enterprises have been to develop patient-centric drug development platforms. He began his career with Profile Drug Delivery (now Philips Respironics) where he developed liquid dose drug delivery systems for cystic fibrosis patients, and later went on to work for GlaxoSmithKline. Jag holds a BSc (Hons) in Chemistry and completed his Ph.D., entitled ‘Formulated Muco-Regulatory Agents in the Airways of Patients with Cystic Fibrosis’. Following this, he was a postdoctoral fellow at the London School of Pharmacy, investigating the fabrication of microparticles for vaccine delivery using supercritical fluid technology.

Jag remains a part-time member of Nanopharm Ltd, an Aptar Pharma Company as Vice President of Science and Technology.