SECTION III.2
Voluntary Standards, Regulatory Compliance, and Non-Technical Issues
Chapter III.2.1 Introduction: Voluntary Standards, Regulatory Compliance, and Other Non-Technical Issues
Frederick J. Schoen1 and Jack E. Lemons2
This section highlights some of the key non-technical considerations in the development of medical devices that depend so importantly on biomaterials. Several principles underlie the approach presented in this section. The major driving force to technological innovation in biomaterials, implants, and medical devices is to improve the quality of life and survival of patients. The early phase of the process includes these steps: (1) identification of a clinical problem that needs solving (“clinical pull”); (2) determination that a viable market exists for it; and (3) the judicious and sophisticated application of existing, or development of, novel technology to solve this problem. In this sense, hospitals and clinics provide a “problem-rich” environment, and a laboratory for testing and translating the latest technologies and materials into clinical successes. An invention, by itself, is of little value; the value of the idea represented by an invention is through innovation, i.e., the validation and implementation of that idea or embodiment thereof to affect individuals and populations through its utilization and acceptance by others.
In addition, it is important to recognize that the future of a new biomaterial associated with a device- and/or implant-based treatment utilizing a biomaterial usually depends on the successful commercialization and implementation of a medical product (Chapter III.2.2). For any product, such as an implant or medical device, the needs of commercialization (involving development, design optimization, a viable fabrication process, financing, regulatory approval, reimbursement, manufacturing and scale-up, a suitable and profitable business model, marketing, etc.) are vital, and the scientific development, fabrication, clinical trials, and subsequent regulatory approval must occur in the context of, and concurrent with, business considerations (Figure III.2.1.1). Indeed, medical device innovation is complex; the generic process and the requisite skills in technological innovation in medicine, including identification, invention and implementation phases, have been recently described, both systematically and in detail (Zenios et al., 2010). Moreover, although demonstration of clinical effectiveness and safety are vital to clinical translation of any new medical product, today’s economic pressures demand serious consideration of cost-benefit and cost-effectiveness, i.e., the relative gain in health from a measure (years of life, pain-free gained) and the relative costs of different ways to achieve an equivalent gain in health, respectively (Sculco, 2010; Lammers et al., 2011; Moreno et al., 2012). Finally, as embodied by the total collection of chapters in this book, progress in biomaterials and their implementation in clinically-useful medical devices requires multidisciplinary collaboration, thinking, and communication, where engineers, physical scientists, biologists, and clinicians are on an equal footing, and share a common language and objectives – an approach generally termed “convergence” (Sharp and Langer, 2011).
FIGURE III.2.1.1 Key steps in technical development (flow chart on left) and non-technical considerations (box on right) must be integrated to achieve successful innovation in biomaterials and medical devices.
The chapters that comprise this section summarize the key principles enumerated above and provide a “toolkit” for medical device innovation. Specifically, the chapter by Lemons (Chapter III.2.3) describes consensus standards for biomaterials and devices. Consensus standards in general can be separated into categories of specifications, test methods, terminology (nomenclature and definitions), provisional, and guidances (Chapter III.2.3). Related to biomaterials, standards have been developed and repetitively tested for metallics, ceramics, polymerics, and combinations of these classifications. In broad terms for biomaterials of synthetic origin, biomaterials may also be classified in terms of biological responses such as bio-tolerant, -active, and -degradable. Also, since regulatory processes consider devices (rather than biomaterials, per se, grouping can also be made in terms of the clinical application. Consensus standards have provided an opportunity to document biomaterial charateristics needed for biocompatibility, the methods for testing and presentation of results (precision and accuracy), terminology including basic definitions, and importantly, guidelines for evolving device systems and the properties of new or modified biomaterials. Over past decades, as the device disciplines have evolved from synthetic origin bio-tolerant biomaterials to surface bioactive biomaterials, naturally-derived biomaterials, and to biodegradable and biointeractive biomaterials, the focus has shifted to Tissue Engineered Medical Product Standards (TEMPS). This shift has resulted in reconsideration of standards needed for evaluations, including a move from in vitro to in vivo testing methods. Also, consensus standards have become more harmonized throughout developed countries, especially as device products have expanded throughout the world. Many consensus standards for medical devices have now been evaluated and accepted for regulatory processes and approvals. Thus, in many submissions device developers only need to list “meets standard x.” This process has enhanced considerably the value of standards, especially when harmonized internationally.
Anders and Tolkoff (Chapter III.2.2) provide aspiring entrepreneurs a basic introduction to the considerations they can use to size up an idea in the context of clinical utility and commercial potential. Most medical and dental device applications are regulated by government agencies charged to ensure patient health and welfare. Thus, agencies evaluate safety and efficiency of devices and related treatments. In the USA, most devices constituted to include biomaterials are regulated by the US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH). As biomaterials, devices and treatments have evolved to combination products (comprising mixtures of materials, drugs and cells (and their products) many must be considered by combining expertise from the FDA centers regulating biologicals (including cells) and drugs. Duncan (Chapter III.2.4) summarizes the key concepts that govern the regulation of medical devices by the Food and Drug Administration in the USA; regulation abroad follows generally similar principles although not exactly the same approaches. Cahn and Erickson (Chapter III.2.5) discusses reimbursement, the process by which medical devices and any other medical services are paid for; this chapter emphasizes that reimbursement is often critical to market success and that those inventing, developing or marketing new medical devices have an understanding of how their products will be reimbursed. The integration of regulatory and reimbursement considerations is emphasized by several case histories of actual products presented by Baura (Chapter III.2.6). This is followed by related discussions of pertinent ethical and legal issues by Bianco et al. (Chapter III.2.7) and Mayesh and Vicari (Chapter III.2.8), respectively. Grunkemeier et al., in the following chapter in this section, addresses the special challenges associated with clinical trials of biomaterials and medical devices (Chapter III.2.9) that necessitate very different approaches than those used in the development and implementation of drugs. Langer and colleagues (Chapter III.2.10) write with considerable experience about the approach to creating small start-up companies to develop medical devices born in the university setting. In the last chapter in this section, Feigal (Chapter III.2.11) addresses the special regulatory aspects of the post-market period, when a product is in the marketplace, is no longer investigational and is available for commercial use.
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1Professor of Pathology and Health Sciences and Technology (HST), Harvard Medical School, Executive Vice Chairman, Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
2University Professor, Schools of Dentistry, Medicine and Engineering, University of Alabama at Birmingham, Birmingham, AL, USA