Fundamentals of Biologicals Regulation

This second edition of Fundamentals of Biologicals Regulation: Vaccines and Biotechnology Medicines serves as an introduction to the international regulatory arena in which biologicals are developed and offers an overview of the processes and insight into the scientific concepts underpinning global regulations. In this new edition the book provides more in-depth coverage of Quality by Design, Combination Products, Quality Target Product Profiles, Risk Management Plans and REMS, and switching from reliance on in vivo to in vitro analytical methods. This new edition also reflects the new developments and processes accelerated by the COVID-19 vaccine experience, including emergency use authorizations and conditional marking authorizations. New pedagogic elements and case studies have been added to improve learning outcomes for students. This book provides multiple levels of readership with guidance on basic concepts, a detailed look at regulatory challenges, and practical insight into how regulators consider regulatory science and regulatory process issues across various regions with emphasis on the European Medicines Agency and the U.S. Food and Drug Administration. Graduate students will benefit from the new pedagogic features. Regulatory professionals will have in Fundamentals of Biologicals Regulation: Vaccines and Biotechnology Medicines a complete guide to navigate through the approval process. . New chapters on Advanced Therapy Medicinal Products (including cell and gene therapies), Combination Products, and Pharmacovigilance. Presents new and updated case studies, including lessons learned from the development of COVID Vaccines. More in-depth coverage on Quality by Design, Quality Target Product Profiles, and Pharmacovigilance. Chapters focusing on the principles in regulating Biosimilars, In Vitro Diagnostics, Advanced Therapy Medicinal Products, and Combination Products. Covers general biologicals development and authorization regulatory processes as well as scientific principles for CMC, preclinical and clinical development. Also covers ethical considerations for use of laboratory animals and human subjects protections, as well as genetically modified organisms used in or as medicines

Dr. Rebecca Sheets is currently the Vice President for the International Alliance of Biologicals Standardization, North American affiliate. She is the former Vaccine Scientific and Regulatory Specialist at the National Institute of Allergy and Infectious Diseases. Dr. Sheets served 9 years as a Scientific Reviewer in the Viral Vaccines branch of the Division of Vaccines and Related Products Applications at the Center for Biologics Evaluation and Research at the FDA. From 2006-2014, she served as Co-Chair of the World Health Organization's Study Group on Cell Substrates and as Chair of the Adventitious Agents Sub-committee, as well as authoring several WHO guidelines and publications over the past two decades. She also taught for a decade at the Catholic University of America. Before retirement, she was the Principal Consultant at Grimalkin Partners from 2013-2021.Christopher Hamlin is Senior Manager of Regulatory Affairs - CMC at PCI Pharma Services, where he leads a Regulatory Affairs team supporting manufacturing sites across the United States and in Europe. Prior to joining PCI, he was an employee at Division of AIDS at the National Institute of Allergy and Infectious Disease with the U.S. National Institute of Health (DAIDS/NIAID/NIH) where he contributed to the development and translation of HIV vaccine candidates into clinical trials. He was with the Walter Reed Army Institute of Research (WRAIR) and participated in the U.S. Military's HIV Research Program in the Laboratory of Antigen and Adjuvant Research where his protein characterization work contributed to multiple scientific publications. He holds a Master of Science degree in Biotechnology from the Catholic University of America in Washington, DC and Bachelor of Science in Biochemistry Marietta College in Marietta, OH.Dr. Susan Neadle is a recognized international Combination Products, Medical Device, and Digital Health expert with over 35 years industry experience. She is well networked, published, and highly active in numerous industry groups with links to teaching institutions. Neadle's leadership, innovation, and best practices have been recognized with multiple awards, including the Johnson Medal, Johnson & Johnson's highest honor for excellence in Research & Development, and most recently, as a Finalist in TOPRA's 2021 Awards for Regulatory Affairs Excellence. Neadle retired from a distinguished and impactful 26-year career at Johnson & Johnson. She is now Principal Consultant at Combination Products Consulting Services LLC, providing international Q&C, regulatory and design excellence services, to the pharm, biotech and device industries. Neadle serves as Chair of the ISPE Combination Products CoP, and Lead Author in Combination Products Working Groups through ASTM International, AAMI and PQRI. She teaches curricula in Combination Products through UMBC and AAMI, as well as customized training upon request.Dr. Ivana Knezevic, MD, PhD Scientist, Technologies, Standards and Norms Team, Group Lead, Norms and Standards for Biologicals, Department of Essential Medicines and Health Products (EMP), Health Systems and Innovation (HIS) Cluster, World Health Organization (WHO), Switzerland. She is a specialist in medical microbiology and parasitology. She received her MD from the University of Novi Sad, MSc in medicine (microbiology) and PhD in medicine (virology) from the University of Belgrade, Republic of Serbia. Ivana Knezevic has 24 years of professional experience in standardization, scientific and regulatory overview of biologicals. Dr. Knezevic is the author of many publications that made broad audience aware of WHO initiative in the development, establishment, and implementation of standards for vaccines and biotherapeutic products. She is also contributing to the peer-review scientific journals with the international reputation.

About the authorsForewordPrefaceHow to obtain documents from ICH and US SECTION I: Regulatory process 1 Introduction to the regulatory process for biologicals and to international regulatory convergence2 Discovery and development3 Communications and formal meetings with regulators4 Clinical trial authorization and investigational new drug applications5 Marketing authorization6 Alternative regulatory pathways and special programs7 Variations or changes to an approved application8 Good "X" Practices9 Audits and regulatory compliance inspectionsWritten assignments exerciseAssignment Scenarios SECTION II: Regulatory science 10 Preclinical safety and toxicology11 Preclinical pharmacology, proof-of-principle12 Institutional biosafety committees and regulation of genetically modified organisms13 Risk assessments14 Quality by design and product design, construction, development, manufacture, and process validation15 Lot release, analytics, and analytical validation16 Regulatory aspects of clinical trials17 Pharmacovigilance, safety reporting, and risk minimization18 Clinical trial ethics, human subjects protections, and the informed consent process19 Independent ethics committees and institutional review boards SECTION III: Specific product types 20 Biosimilars21 Cell and gene therapies22 In vitro diagnostics and biotech medical devices23 Combination productsGlossaryIndex