Combination Products

Drug delivery systems represent a vast area of research and development within biomaterials and medicine and the demand for sophisticated drug delivery devices continues to drive novel product development. Advanced drug delivery devices can offer significant advantages over conventional drugs and devices alone, such as increased efficiency, improved performance and convenience. The purpose of this book is to illustrate how effective drug delivery can be achieved by means other than tablets. The book will provide a thorough analysis of the fundamentals, applications and new technologies of drug-device combination products for use throughout the human body. Part one provides readers with an introduction and background to the field. Chapters in Part two discuss areas of application such as catheter based products, drug eluting stents and beads and anti-biotic loaded cements. Part three covers the development of drug device combination products with chapters on such topics as pre-clinical testing, sterilisation, patent issues and regulation of drug device combination products. With its distinguished editor and team of international contributors, Drug-device combination products: delivery technologies and applications is an invaluable reference for product development specialists, materials scientists and engineers in the biomedical industry and academia as well as those concerned with drug delivery. Illustrates how effective drug delivery can be achieved by means other than tablets providing readers with a comprehensive introduction and background to the field Provides a thorough analysis of the fundamentals, applications and new technologies of drug device combination products Discusses areas of application such as catheter based products and reviews the development of drug device combination products including pre-clinical testing and sterilisation

The field of combination product development (products born of the integration of medical devices, biologics, and drugs) is so new that, while literature abounds on each part individually, there are very few publications, including FDA documents, available concerning the unique challenges posed by this nascent but fast-growing area. Providing

Assurance of Sterility for Sensitive Combination Products and Materials: New Paradigms for the Next Generation of Medical Devices and Pharmaceuticals discusses the medical device industry and existing challenges regarding the exciting new world of sensitive combination products (SCPs) and their terminal sterilization. This book reassesses the current assumptions to assure the patient's best interests are met in the development of increasingly rigorous sterilization methods used to counteract MRSA and other 'super-bugs'. In addition, the book discusses the special challenges faced with implantable medical devices, sterilization requirements and further methods needed for material selection and the design process. This book is unique in taking a holistic, end-to-end approach to sterilization, with a particular focus on materials selection and product design. Introduces sterilization principles at the material selection and design stages Addresses the industry need for new sterilization processes for new medical devices and biomaterials Provides guidance to select the appropriate sterilization technique for newly developed sensitive combination products Examines forward thinking tactics for matching new developments in material compatibility with possible regulatory and QSR strategies

The field of combination product development (products born of the integration of medical devices, biologics, and drugs) is so new that, while literature abounds on each part individually, there are very few publications, including FDA documents, available concerning the unique challenges posed by this nascent but fast-growing area. Providing the first in-depth look at this breakthrough field, Combination Products includes practical guidelines and a detailed step-by-step process for the development of these novel technologies. It addresses the technical, scientific, regulatory, and quality issues that arise when combining drugs, biologics, and medical devices into a single product. It takes a practical, readily applicable approach to discussing the challenges, victories, and pitfalls associated with merging technologies and systems and how to implement these products into the market successfully and in a timely manner. Specifically, this text explores the process from start to finish, establishing a workable design and development plan complete with relevant definitions. It reviews FDA and other regulatory expectations and covers resource requirements, manufacturing pitfalls, post-launch compliance requirements, and agency audits and challenges. Drawing on the experience and expertise of two leaders in their respective fields, Combination Products boasts the credentials of Dr. Smita Gopalaswamy, a 20 year veteran of technical consulting responsibilities in medical device, biologics, and pharmaceutical industries as well as combination products, along with the support of Dr. Venky Gopalaswamy, an expert in business improvement methodologies such as six sigma, lean, and change management, to provide a comprehensive assessment of the field and an efficient and effective approach to the creation and implementation of combination products.

While the safety assessment (“biocompatibility”) of medical devices has been focused on issues of local tissue tolerance (irritation, sensitization, cytotoxicity) and selected quantal effects (genotoxicity and acute lethality) since first being regulated in the late 1950s, this has changed as devices assumed a much more important role in healthcare and became more complex in both composition and in their design and operation. Add to this that devices now frequently serve as delivery systems for drugs, and that drugs may be combined with devices to improve device performance, and the problems of ensuring patient safety with devices has become significantly more complex. A part of this, requirements for ensuring safety (once based on use of previously acceptable materials – largely polymers and metals) have come to requiring determining which chemical entities are potentially released from a device into patients (and how much is released). Then an appropriate and relevant (yet also conservative) risk assessment must be performed for each identified chemical structure. The challenges inherent in meeting the current requirements are multifold, and this text seeks to identify, understand, and solve all of them. • Identify and verify the most appropriate available data. • As in most cases such data is for a different route of exposure, transform it for use in assessing exposure by the route of interest. • As the duration (and rate) of exposure to moieties released from a device are most frequently different (longer) than what available data speaks to, transformation across tissue is required. • As innate and adaptive immune responses are a central part of device/patient interaction, assessing potential risks on this basis are required. • Incorporating assessments for special populations such as neonates. • Use of (Q)SAR (Quantitative Structure Activity Relationships) modeling in assessments. • Performance and presentation of integrative assessments covering all potential biologic risks. Appendices will contain summarized available biocompatibility data for commonly used device materials (polymers and metals) and safety assessments on the frequently seen moieties in extractions from devices.

Biomaterials, Medical Devices, and Combination Products is a single-volume guide for those responsible for-or concerned with-developing and ensuring patient safety in the use and manufacture of medical devices.The book provides a clear presentation of the global regulatory requirements and challenges in evaluating the biocompatibility and clinical

Combination products are therapeutic and diagnostic products that combine drugs, devices, and/or biological products. According to the US Food and Drug Administration (FDA), “a combination product is one composed of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device and a biological product.” Examples include prefilled syringes, pen injectors, autoinjectors, inhalers, transdermal delivery systems, drug-eluting stents, and kits containing drug administration devices co-packaged with drugs and/or biological products. This handbook provides the most up-to-date information on the development of combination products, from the technology involved to successful delivery to market. The authors present important and up-to-the-minute pre- and post-market reviews of international combination product regulations, guidance, considerations, and best practices. This handbook: Brings clarity of understanding for global combination products guidance and regulations Reviews the current state-of-the-art considerations and best practices spanning the combination product lifecycle, pre-market through post-market Reviews medical product classification and assignment issues faced by global regulatory authorities and industry The editor is a recognized international Combination Products and Medical Device expert with over 35 years of industry experience and has an outstanding team of contributors. Endorsed by AAMI – Association for the Advancement of Medical Instrumentation.

Assurance of Sterility for Sensitive Combination Products and Materials: New Paradigms for the Next Generation of Medical Devices and Pharmaceuticals discusses the medical device industry and existing challenges regarding the exciting new world of sensitive combination products (SCPs) and their terminal sterilization. This book reassesses the current assumptions to assure the patient’s best interests are met in the development of increasingly rigorous sterilization methods used to counteract MRSA and other 'super-bugs'. In addition, the book discusses the special challenges faced with implantable medical devices, sterilization requirements and further methods needed for material selection and the design process. This book is unique in taking a holistic, end-to-end approach to sterilization, with a particular focus on materials selection and product design. Introduces sterilization principles at the material selection and design stages Addresses the industry need for new sterilization processes for new medical devices and biomaterials Provides guidance to select the appropriate sterilization technique for newly developed sensitive combination products Examines forward thinking tactics for matching new developments in material compatibility with possible regulatory and QSR strategies