Drug-Device Combination Products: Updates and Challenges with Demonstrating Generic Substitutability

Head, Device Development Center, Sandoz

As Head of the Sandoz Device Development Centre in Cambridge, UK, Mr. Ahern has global responsibility for the development of all medical devices and drug/device combination products in biosimilar and complex generics across all routes of delivery including parenteral, respiratory, nasal, and ophthalmic. Previously, Mr. Ahern was the CEO and one of the founders in 2009 of Coalesce Product Development, a UK-based medical device development company that was acquired by Sandoz in 2022.

He has been developing medical and drug delivery technology since graduating in 1993 from Munster Technological University, Ireland with a diploma in Mechanical and Electrical Engineering Design and a diploma in Manufacturing Engineering from the Society of Manufacturing Engineers (SME).

Medical Officer on Team D, DTP-I, ORS, OGD, CDER, FDA

Dr. Betsy Ballard is a Medical Officer on the Device Team in the Division of Therapeutic Performance in the FDA’s Office of Generic Drugs responsible for reviewing complex combination products in the pre ANDA space. Dr. Ballard is a board-certified general surgeon with more than twenty years of clinical practice experience and more than ten years’ experience in regulatory science including time in the FDA’s Center for Radiologic Health and CDER’s Office of New Drugs and Generic Drugs.

Regulatory Council, DPD, OGDP, OGD, CDER, FDA

Lisa Bercu is a regulatory counsel in the Office of Generic Drug Policy, Office of Generic Drugs (OGD), where she focuses on issues related to combination products. Before joining OGD in October 2016, Ms. Bercu worked at a medical society providing strategic advice on issues including pain medicine, drugs, and devices. She holds a JD degree from Georgetown University Law Center and a BA from the University of Michigan.

Director, DCSS, OSCE, OGD, CDER, FDA

Dr. Howard Chazin is Director of the Division of Clinical Safety and Surveillance (DCSS) in the Office of Safety and Clinical Evaluation within the Office of Generic Drugs (OGD) in CDER. For over 20 years during his career at FDA, he has worked to promote improvements in reviewer templates and Guidances to Industry along with facilitating post marketing safety processes related to new drugs, biologics, and generic drugs. From 2002 through 2011, he filled several roles in CDER’s Office of New Drugs. From 2011-2016, Dr. Chazin was the Deputy Director and then Acting Director of the Division of Hematology Clinical Review in FDA’s Center for Biologic Evaluation and Research. Since 2016, he has led the DCSS, which consists of several teams of physicians, nurses, pharmacists, and data analysts tasked with identifying, assessing, and addressing safety signals related to potentially inferior generic drug product quality, therapeutic equivalence, or adverse reactions. Dr. Chazin received his medical degree from the Rutgers-Robert Wood Johnson Medical School, completed an Internal Medicine internship and Neurology residency at the George Washington University Medical Center, and obtained his MBA in Health Services Management from the Johns Hopkins University School of Medicine and Carey Business School.

Biomedical Engineer and Lead Reviewer, OHT III, DHT IIIC, OPEQ, CDRH, FDA

Kyran Gibson is a Biomedical Engineer and Lead Reviewer within the Division of Drug Delivery and General Hospital Devices and Human Factors, Office of Reproductive, Gastro‐Renal, Urological, General Hospital Device & Human Factors at the FDA. Miss Gibson received a Bachelor of Science in Bioengineering from University of Maryland College Park. She reviews both premarket and post market submissions for medical devices submitted as 510(k)s, De Novos, Premarket Approvals (PMAs) as well as combination products submitted as New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), and Investigational New Drug Applications (INDs). In addition, Miss Gibson serves as a focal point for Digital Health and cybersecurity for her division.

Director, DB VIII, OB, OTS, CDER, FDA

Dr. Stella Grosser is Director of the Division of Biometrics 8 in the Office of Biostatistics and the Office of Translational Sciences (OTS), CDER, FDA.  This division provides statistical support in review and research to the Office of Generic Drugs.  She has been at the FDA for over 20 years, beginning as a statistical reviewer for new drug products and serving as a team leader before assuming her current position.  Dr. Grosser received her Ph.D. in biostatistics from UCLA and spent several years there afterwards as an assistant professor in the School of Public Health.

Independent Statistical Consultant and Founder, T Gwise Consulting LLC

Dr. Thomas Gwise is an independent statistical consultant and founder of T Gwise Consulting LLC. Dr. Gwise has more than 17 years’ experience in drug and medical device review with the U.S. Food and Drug Administration. Most recently, he was the director of the Division of Biometrics IX in FDA’s Center for Drug Evaluation and Research (CDER) where he oversaw statistical review of all applications and INDs for hematological indications including cancers. Prior to his role as Director, Dr. Gwise was Deputy Director of CDER’s Division of Biometrics V which at that time reviewed applications for cancer and imaging drug indications. Before transferring to CDER in 2011, he was a statistical reviewer and team leader in FDA’s Center for Devices and Radiological Health (CDRH) where he reviewed marketing applications for both therapeutic and diagnostic devices. During his time with CDER, Dr. Gwise was a member of FDA’s Biosimilar Review Committee and was involved in writing guidance documents for interchangeability and generic drug comparative human factors studies.

OPEQ Device Shortages Lead, CSPS, OPEQ, CDRH, FDA

Michael (Mike) Hoffmann currently oversees the Office of Product Evaluation and Quality’s (OPEQ’s) Shortages Team in the Center for Devices and Radiological Health (CDRH), including responsibilities related to shortages and EUA and PEUAs.  He works with stakeholders across CDRH, who are collectively focused on developing tools, processes, and policies for identifying and mitigating device shortages in the future. Mike has worked at CDRH since 2007 primarily in the area of neurological and rehabilitation devices, serving in various leadership roles within the Office of Neurological and Physical Medicine Devices, which includes oversight and policy recommendations on activities for a wide variety of devices associated with neurology, psychiatry, and rehabilitation. Michael received his B.S. in Electrical Engineering from the University of Illinois in Urbana-Champaign and his M.S. in Biomedical Engineering from Marquette University.

Associate Director for Stakeholder and Global Engagement, OGD, CDER, FDA

Dr. Sarah Ibrahim is the Associate Director for Stakeholder and Global Engagement in the Office of Generic Drugs (OGD)/Center of Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA). Dr. Ibrahim develops OGD strategies to address identified and emerging regulatory challenges in relation to the international nature of the generic drug industry. She established OGD’s current global affairs program, the FDA global generic drug cluster which is the first generic drug forum that involves the word leading regulatory agencies. Dr. Ibrahim also created OGD’s patient engagement program and pioneered OGD’s first patient listening session series. In collaboration with other CDER and FDA offices, she supports stakeholder engagement concerning issues related to globalization of the generic pharmaceutical supply and harmonization of regulatory approaches for generic drugs. Dr. Ibrahim received her Ph.D. in Biopharmaceutics/Pharmaceutics from the School of Pharmacy, University of Cincinnati and a B.S. in Pharmacy and Pharmaceutical Sciences from Cairo University, Egypt. Dr. Ibrahim started her career at the FDA in 2014 as a scientific reviewer in the Office of Pharmaceutical Quality. Prior to her FDA career, she has years of experience in the U.S. pharmaceutical industry in the area of pharmaceutical development.  As an assistant professor, along with the founding faculty, Dr. Ibrahim established the pharmaceutical sciences department for the second school of pharmacy in the state of New Jersey.

Regulatory Devices Portfolio Head, Sandoz

Dr. Johannes Keuschnigg leads a Regulatory Device team at Sandoz. He has >10 years of experience in developing drug device combination products. His current remit includes complex generics and biosimilars from early development through initial submissions into life cycle management. Johannes holds a M.Sc. in Molecular Biology from the Leopold-Franzen’s University Innsbruck, Austria and a Ph.D. in Medical Microbiology and Immunology from the University of Turku, Finland.

Consultant V, DTP I, ORS, OGD, CDER, FDA

Dr. Shinae Kim is a contractor working in the device evaluation team in the Division of Therapeutic Performance I. She is responsible for the development of product-specific guidances for generic drug-device combination product development, reviewing and responding to controlled correspondences, pre-ANDA meeting requests, and internal consults. Prior to joining the FDA, she participated in the development of medical diagnostic devices and related new technologies for real-time oral disease diagnosis at research institutions and academia for more than nine years. She received her B.S. in Electrical Engineering from Korea University and her M.S. and Ph.D. in Electrical Engineering and Computer Science from Seoul National University, Korea. After graduation, she trained as a postdoctoral researcher in the chemical and biomedical engineering laboratory at the Georgia Institute of Technology.

Senior Pharmaceutical Quality Assessor (SPQA), DPQA I, OPQA I, OPQ, CDER, FDA

Dr. Kai Kwok is a Senior Pharmaceutical Quality Assessor (SPQA) in the Division of Product Quality Assessment I (DPQA I), Office of Product Quality Assessment I (OPQA I), Office of Pharmaceutical Quality (OPQ), CDER at FDA. In this role, he acts as the application technical lead for integrated quality assessment of generic parenteral, ophthalmic, topical, nasal, and oral solid/solution drug products. For the past 10 years, he has been reviewing ANDA, Bio-IND, and Pre-ANDA meeting packages involving complex drug products. Also, he served as an FDA liaison in the USP Packaging and Distribution Expert Committee for developing USP packaging chapters and standards and as a member for development of FDA guidance for drug delivery performance of drug-device combination products. Prior to FDA, he spent over 10 years as a formulation scientist for drug product/process development and technology transfer in pharmaceutical companies. He received his B.S. in Pharmacy from Temple University and Ph.D. in Pharmaceutical Sciences from University of Michigan.

President, P/L Biomedical

Mr. Lee Leichter has close to 50 years’ experience in the health care industry, providing direct, hands-on assistance to domestic and international Pharmaceutical, Biotechnology and Medical Device companies for the last 30 years. Projects have encompassed a multitude of business, technical, regulatory, and quality issues, primarily related to drug delivery and combination products for marketing in the USA, Europe, and Canada. He has worked with large multi-national companies, as well as start-ups, successfully navigating the challenges posed during the development, testing, and marketing approval of products that merge pharmaceutical substances with high-tech device systems.

Serving as an independent expert on ISO technical committees for injection and respiratory products, infusion pumps, needles and catheters, and AAMI Injection and Infusion Devices and Human Factors committees, he assists in establishing international standards for safety and performance of these products. He initiated and leads the ISO Workgroup developing a standard for On Body Delivery Systems (OBDS).

Over his career, he has directly interacted with the FDA and other Health Authorities on specific projects and has proposed and responded to FDA positions and proposals covering combination products, most recently as a consultant to the Combination Products Coalition and as the Chairman of the PDA Combination Product Interest Group.

Lee has helped organize and chair several conferences dedicated to Combination products and Human Factors and has trained and presented on a multitude of related topics.  His education includes a Bachelor’s degree from the State University of New York at Stony Brook and an MBA with Honors from Florida Gulf Coast University. Lee is currently certified in USA and EU Regulatory Affairs from RAPS and was certified as a Quality Engineer from ASQ.

CEO and Founder, HFUX Research, R&D Medical Device & Combination Product Development, HFUX Research, LLC

Heidi Manijeh Mehrzad is the founder and CEO of the medical human factors and usability consultancy HFUX Research, LLC, specializing in medical device, technology, and combination product development. With a wide-ranging background as a trained pilot, emergency medical technician, software analyst, and human factors and usability expert within the (medical) product development industry, her motivation for the past 25 years has been directed towards enhancing human-product performance by optimizing user interface design, information architecture, and user and product workflow, through the application of human factors science and usability practices.

Her focus has been on promoting the early integration of human factors into the medical device R&D process. She actively advocates for collaborative methodologies, conducting hybrid human factors and clinical studies, as well as risk assessments, with the aim of advancing study design and statistical modeling for usability evaluations, and expanding capabilities for human factors data collection in alignment with regulatory standards.

Her portfolio includes medical devices spanning drug delivery and reconstitution, ophthalmic, respiratory, and endoscopy equipment, as well as various implantable and injection devices, computer-aided systems, 3D EP mapping, ultrasound-guided, and fluid management technologies, radiological diagnostic equipment, cardiac monitoring devices, and surgical systems. She holds patents in GUI design for medical imaging and surgical navigation software systems and earned a B.S. in Aeronautics and an M.S. in Human Factors and Systems with a concentration in Physiology from Embry–Riddle Aeronautical University (ERAU), in addition to technical degrees in IT Management and Emergency Medical Services from Sacred Heart University (SHU) and Daytona State College (DSC), respectively.

Staff Fellow, Device Evaluation Team (Team D), DTP I, ORS, OGD, CDER, FDA

Dr. Karthika Natarajan is a Staff Fellow on the Device Evaluation Team in the Division of Therapeutic Performance I (DTP I), Office of Research and Standards (ORS), under the Office of Generic Drugs (OGD). Dr. Natarajan’s work focuses on developing product-specific guidances, and addressing controlled correspondences, consults, and pre-ANDA meeting requests. She also serves as a contracting officer’s representative and provides human subject research oversight for regulatory science research initiated by DTP I. Dr. Natarajan has a Bachelor of Pharmacy degree and received her M.S. in Pharmaceutical Sciences from South Dakota State University and her M.S. in Pharmacometrics and Ph.D. in Pharmaceutical Sciences from the University of Maryland, Baltimore.

Principal Device Engineer, Combination Product & Device R&D, Teva Pharmaceuticals

Ms. Carrie O’Donel began her career in industry over a decade ago. Holding degrees in Physics and Mechanical Engineering, she began her career in Forensic Engineering, providing scientific investigations in the areas of Injury Biomechanics, Material Failure, Medical Device Failure, and Amusement Park Ride Design and Operation, to name a few. During her time at Teva Pharmaceuticals, she has worked as both a Quality Engineer and Device Engineer, on programs at every stage of the design process – from Discovery to Commercial and Life-Cycle Management. Her current focus is new and evolving technologies within the Injectable Drug-Delivery System space.

Mechanical Engineer, Cambridge Design Partnership

Fran Penrose is a mechanical engineer, specializing in the early-stage design of drug delivery devices. She has experience in device design from concept generation to design verification testing and manufacturing scale-up spanning many medical devices, including electromechanical injection devices. She has a keen interest in the intersection between sustainability and medical device design. Fran forms part of Cambridge Design Partnership’s core sustainability group, where she is responsible for identifying opportunities for sustainable innovation within the drug delivery sector.

Co-Chair & Faculty, Association for the Advancement of Medical Instrumentation Human Engineering Committee, Professor, Department of Biomedical Engineering, University of Cincinnati

Dr. Mary Beth Privitera, M.Design, FIDSA, is internationally known as an expert in medical product design, specifically in the area of applied human factors.  She is a Professor at the University of Cincinnati’s Department of Biomedical Engineering and works collaboratively among the Colleges of Medicine, Engineering, and Design. She is a consultant to the medical device industry with expertise in user interaction design and human factors. Additionally, she serves as faculty and co-chair of the Association for the Advancement of Medical Instrumentation’s Human Engineering Committee.

She is a Co-Founder of the Medical Device Innovation and Entrepreneurship Program at the University of Cincinnati, bringing the Colleges of Engineering, Medicine, Design and Business together.  Her previous academic appointments include College of Design, industrial design, and the Department of Emergency Medicine.

She has worked professionally as a consultant to the medical device industry for over 25 years on devices which are intended for use across the practice of medicine and intended for home use. Her current research focuses on applied ergonomics and design interpretation. She has conducted contextual inquiry studies internationally with results intended to inform the design of devices. She has been involved in the development of surgical tools, diagnostic equipment, combination products, software as medical device, clinical decision support software, as well as intraprocedural augmented reality.  In addition, she has had research funding supported by the Gates Foundation and US FDA CDER Division. She is a Fulbright Scholar in collaboration with the University of Nottingham.

She has authored several peer reviewed articles and books titled “Contextual Inquiry for Medical Device Design,” promoting best practices for phase zero medical device development.  Her 2nd book, edited and written in collaboration with AAMI Human Factors faculty is titled “Applied Human Factors in Medical Device Design.” This book aims at bringing all references and best practices together in one resource compendium.

Chemist, DPQR II, OPQR, OPQ, CDER, FDA

Dr. Nathan Reed, Ph.D. is a chemist working in the Division of Pharmaceutical Quality Research Branch II (DPQR II), Office of Pharmaceutical Quality Research (OPQR), Office of Pharmaceutical Quality (OPQ), Center of Drug Evaluation and Research (CDER) at the FDA since July 2021. He was an ORISE Fellow at the FDA within DCDA from September 2019 to July 2021. His expertise is primarily in the physiochemical characterization, aerosol dynamics, and dissolution of orally inhaled and nasal drug products (OINDPs). Nathan completed his B.S. in Integrative Biology from the University of Illinois-Urbana Champaign in 2009 and Ph.D. in Chemical Engineering from Washington University in St. Louis in 2019.

Senior Consultant Program Manager, Cambridge Design Partnership

Ms. Carol Stillman is a healthcare program manager with more than 20 years of experience in medical and consumer product development. Her undergraduate degree is in mechanical engineering, with focus areas including biomedical engineering and design for environmental sustainability. Her technical experience has primarily focused on development of drug delivery device and has also included surgical equipment, biological detection systems, diagnostic testing equipment, and other medical device related research including generic combination device substitutability. As a technical lead and program manager she has led projects across all phases of development from insights, strategy, ethnographic research, and feasibility assessment through detailed design, formative user research, design verification, and human factors validation. Sustainability has been a key area of focus throughout her career, including conducting research, developing tools and templates, providing training, and implementing design for environmental sustainability practices within device development programs.

Director, Regulatory Affairs, Gx Steriles, Teva Pharmaceuticals USA, Inc.

Brandon Wood, B.S. is a Director, Regulatory Affairs, Gx Steriles, for Teva Pharmaceuticals USA, Inc. In this role, Brandon leads a group of regulatory professionals and oversees the filing of applications for generic parenteral products. He specializes in the development of generic applications for complex products such as peptides, iron colloids, long-acting injectables, and drug-device combination products. Brandon has been a regulatory professional for over ten years and prior to joining Teva in 2018 served various regulatory and quality assurance R&D positions for CorePharma and Impax Laboratories working on both sterile and non-sterile products. Before starting his regulatory career, Brandon worked as a chemist for West-Ward Pharmaceuticals supporting raw material and bulk release activities, analytical research projects, data review, and investigative writing. Brandon has a B.S. in Chemistry from Monmouth University (West Long Branch, NJ) with a specific concentration in Organic Chemistry.

Senior Fellow, Center on Health Policy, The Brookings Institution

Dr. Marta E. Wosińska is a Senior Fellow at the Center on Health Policy at the Brookings Institution. She is a healthcare economist specializing in prescription drug markets. She has experience spanning top academic institutions, prominent think tanks, and federal agencies including FTC, FDA, and HHS Office of Inspector General. She holds a Ph.D. in Economics from University of California, Berkeley. Dr. Wosińska has extensive experience studying drug supply chains and drug shortages. Her work was cited in the June 2021 White House report on supply chains, and she also served on the Ad Hoc NASEM Committee on Security of America’s Medical Product Supply Chain.

Director, Regulatory Policy, Becton Dickinson (BD)

Rumi Young, M.Eng., RAC is the Director of Regulatory Policy at Becton Dickinson (BD). In this role, she leads a team that advances policies and regulatory science to promote innovation for medical devices, diagnostics, and combination products. Rumi joined BD from FDA where she spent four years in CDRH’s Division of Drug Delivery, General Hospital and Human Factors. As Assistant Director for Injection Devices, her team was responsible for the approval of drug delivery injection devices and combination products such as syringes, auto injectors, pen injectors, on-body injectors, and smart connected devices. Prior to FDA, Rumi worked at Genentech and AstraZeneca for eight years in combination product development.  She has both a Bachelor’s in Chemistry and Chemical Biology and Master’s in Engineering in Material Science from Cornell University.

Director, DQMM, ORS, OGD, CDER, FDA

Dr. Liang Zhao has been serving as the Director of Division of Quantitative Methods and Modeling (DQMM), Office of Research and Standards, Office of Generic Drugs, CDER/FDA since 2015. He has demonstrated excellence and leadership in drug development and regulatory science in regulatory and industrial settings for new and generic drugs during his 18+ professional tenue including in Pharsight as an associate consultant, BMS as a research investigator, Medimmune as an Associate Director, FDA as Clinical Pharmacology reviewer and Pharmacometrics team leader. Dr. Zhao has introduced a broad array of innovative tools in the realm of drug deliveries and bioequivalence assessment, as well as big data tools including machine learning to pharmacometrics. He received the 2023 Gary Neil Prize for Innovation in Drug Development from ASCPT as a recognition to his contribution to clinical pharmacology and pharmacometrics.