Managing Medical Devices within a Regulatory Framework

Managing Medical Devices within a Regulatory Framework

Editor

Beth Ann Fiedler, PhD

Table of Contents

Cover image

Title page

Related titles

Copyright

Dedication

List of Contributors

Foreword

Preface

Section 1. Medical Device Development and Regulatory Overview

Chapter 1. Reframing Product Life Cycle for Medical Devices

1.1. Introduction

1.2. FDA Total Product Life Cycle

1.3. European Commission Product Life Cycle

1.4. Summary

Definitions

Chapter 2. Overview of Medical Device Clinical Trials

2.1. Introduction

2.2. Medical Device Submissions Overview

2.3. Medical Device Clinical Trials

2.4. Regulatory Profile of the US Medical Device by Classification Type

2.5. Regulatory Profile of the EU Medical Device by Classification Type

2.6. Summary

Definitions

Chapter 3. Review Regulatory Guidelines by Device Classification Type

3.1. Introduction

3.2. Basic Overview of the Premarket Notification 510(k)

3.3. Premarket Approval Application Regulatory Path

3.4. Medical Device Class I

3.5. Medical Device Class II

3.6. Medical Device Class III

3.7. Summary

Definitions

Chapter 4. Manufacturing/Distribution Considerations

4.1. Introduction

4.2. US Preclinical Stage

4.3. US Postmarket Stage

4.4. European Union CE Marking: Premarketing Stage

4.5. EU Postmarket Stage

4.6. Summary

Definitions

Section 2. Defining and Meeting Regulatory Challenges in Clinical Engineering

Chapter 5. Defining and Meeting Regulatory Challenges in Clinical Engineering

5.1. Introduction

5.2. Biocompatibility

5.3. Risk Management

5.4. Sterility and Reusability

5.5. Summary

Definitions

Chapter 6. Role of Biocompatibility

6.1. Introduction

6.2. Biocompatibility

6.3. US Major Biocompatibility Guidance

6.4. Discussion and Recommendations

6.5. Summary

Definitions

Chapter 7. Risk Management

7.1. Introduction

7.2. The Upside of Interdisciplinary Collaborative Partnerships

7.3. Managing Risk in Healthcare Technology

7.4. Health Information Technology Management in Action

7.5. Summary

Definitions

Chapter 8. Sterility and Reusability

8.1. Introduction

8.2. Sterilization Guidance and Legislation for Medical Device Developers

8.3. Sterilization Guidance and Legislation for Manufacturing

8.4. Sterilization Guidance and Legislation for Hospitals

8.5. Discussion and Summary

Definitions

Section 3. European Markets

Chapter 9. European Union National Differences and Potential Impact on CE Marking

9.1. Introduction

9.2. Germany

9.3. United Kingdom

9.4. France

9.5. Italy

9.6. Discussion and Conclusions

Definitions

Chapter 10. Understanding the Transitioning Regulatory EU Market

10.1. Introduction

10.2. Clinical Trial Regulation

10.3. Summary

Section 4. Equipment Acquisition, Integration and Maintenance

Chapter 11. Evaluating New Medical Devices Purchases

11.1. Introduction

11.2. Medical Device Regulation General Overview

11.3. Evidence-Based Medicine

11.4. End User Purchasing Stakeholders

11.5. Clinical Evidence Strategies

11.6. Comparative Technologies

11.7. Medical Device Integration into Existing Workflows

11.8. Summary

Definitions

Chapter 12. Evaluating Reimbursement Strategies in the US

12.1. Introduction

12.2. Business of Medical Technology

12.3. Medical Device Identification and Regulatory Overview

12.4. Three Types of User Payment Methods

12.5. Discussion

12.6. Summary

Definitions

Chapter 13. Healthcare Facility Users’ Legal Responsibilities and Risks

13.1. Introduction

13.2. Premarket Approval in the US

13.3. Postmarket Surveillance: Good Manufacturing Practices

13.4. Device User Facilities: Postmarketing Regulatory Obligations

13.5. Special Regulatory Application for Device User Facilities

13.6. Comparison and Discussion of Obligatory Regulation in the US and EU

13.7. Summary

Definitions

Section 5. Data Management, Patient Safety, and Efficacy

Chapter 14. Clinical and Biomedical Engineering Evidence Strategy

14.1. Introduction

14.2. Important Overview for Medical Device Manufacturers: Complaints and Risk

14.3. Health Technology Basics

14.4. Clinical Development of Medical Devices

14.5. Discussion

14.6. Summary

Definitions

Chapter 15. Device Failure Tracking and Response to Manufacturing Recalls

15.1. Introduction

15.2. Regulation Definitions and Overview

15.3. Summary

Definitions

Chapter 16. Health Economics Outcomes Research and Evidence Strategies

16.1. Introduction

16.2. Health Economics for Medical Devices

16.3. Value Assessment Process

16.4. Clinical and Outcomes Data

16.5. Types of Economic Evaluation

16.6. Other Health Economics Proxy Measures

16.7. Dissemination Strategies and Tools for Health Economic Evidence

16.8. Conclusion

Definitions

Section 6. Future of Healthcare

Chapter 17. The Future of Health Technology Management

17.1. Introduction

17.2. Emerging Technologies: Seeing the Future Now

17.3. Planning Medical Device Development

17.4. Summary

Definitions

Chapter 18. Challenges of New Technology: Securing Medical Devices and Their Software for HIPPA Compliance

18.1. Introduction

18.2. Regulation

18.3. Challenges of Securing New Technology

18.4. Alert Mechanisms and Agency Resources

18.5. Compliance Solutions

18.6. Summary

Definitions

Acronyms

Chapter 19. Managing Smartphone and Tablet Applications

19.1. Introduction

19.2. Regulations

19.3. Managing Digital Technology: The Device is Right

19.4. Summary

Definitions

Index

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Copyright

Elsevier

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This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

Library of Congress Cataloging-in-Publication Data

A catalog record for this book is available from the Library of Congress

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library

ISBN: 978-0-12-804179-6 (print)

ISBN: 978-0-12-804192-5 (online)

For information on all Elsevier publications visit our website at https://www.elsevier.com/

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Dedication

I would like to dedicate this book to friends whose presence at timely points in my life, whether far or near, have made it better: Alice DiCroce, Brian Gerrits, and Cynthia Sweet.

List of Contributors

Y. David,     Principal, Biomedical Engineering Consultants, LLC Houston, TX, USA

A. Farid,     PE, MS, ITIL, CPAS Rawalpindi Institute of Cardiology (RIC) Rawalpindi, Punjab Pakistan

M. Ferguson,     Senior Director, Global Health Economics and Outcomes Research, AtriCure Minnetonka, MN, USA

B.A. Fiedler,     Independent Researcher, Jacksonville, FL, USA

L.J. Greathouse,     MPA Volusia County Fire Services, St. Augustine, FL, USA

M. Sanchez, Esq.,     Managing Partner FDA Atty, Washington, DC, USA

Foreword

In her latest book, Managing Medical Devices Within a Regulatory Framework, Dr. Beth Ann Fiedler offers a unique, focused, and extremely well-referenced overview of medical device acquisition, use, and management, not within the context of healthcare, but rather at its beginnings in the milieu of device regulation, clinical trials, and the often arduous path to eventual marketing that is applicable to the clinical environment. While readers may initially assume that this book deals only with medical device regulation in the US, ie, through and via its, federal Food and Drug Administration (FDA), they will be introduced early on and throughout to those requirements within the EU as well. In contrasting the similarities and differences between these two regulatory bodies, Dr. Fiedler and her impressive and seasoned list of contributing authors bring a larger and essential global perspective to this entire topic of medical device regulation. For medical device designers and those involved in the regulatory and marketing process, such awareness and perspective is simply crucial if their products are ever to find their way into use at the patient bedside.

As a review of Dr. Fiedler’s other books and publications would also reveal, she brings a distinctive mix of policy analysis and regulatory insight, not only from the US medical device industry, but from an international perspective as well, the latter being particularly essential given the ever-expanding global nature of the medical device marketplace. Having also worked within hospital-based biomedical engineering environments, Dr. Fiedler also brings a unique level of application and reality to this work as well.

In addition to the copious and detailed references, readers should also welcome both the end of chapter summaries contained within each of the book’s six major sections, as well as glossaries of key definitions and recommendations for additional reading. These sections include:

1. medical device development and regulatory overview

2. defining and meeting regulatory challenges in clinical engineering

3. European markets

4. equipment acquisition, integration, and maintenance

5. data management, patient safety, and efficacy

6. future of healthcare

It is in and throughout these section topics that Dr. Fiedler and her contributing authors construct the regulatory framework that surrounds and directly impacts the manner in which medical devices are used and managed within the healthcare environment. Most of the book’s 19 chapters (within these six sections) also contain helpful case studies that further reinforce key chapter concepts.

Even though this book is not directly targeted toward clinicians or other end users of medical devices, this audience would likely be amazed and perhaps comforted by the rigor and requirements promulgated by both the FDA and EU, all to insure the highest level of device efficacy and safety. Additionally, given the dependency device manufacturers and the regulatory process have on a continual need for timely medical input and review, clinicians may also find opportunities within this process where they could contribute as well.

Historically, the clinical engineering and medical device management literature has contained somewhat of a void when it comes to addressing the regulatory factors affecting its work and processes. Dr. Fiedler’s new book makes a sizable contribution toward filling this gap.

Larry Fennigkoh, Ph.D.

March 2016

Preface

Managing Medical Devices Within a Regulatory Framework came about when I found that there was a gap in material that did not address the various variables and stakeholders in the medical device total product life cycle: development, manufacturing, clinical review, and application to the patient in a healthcare environment. Existing resources aptly provide a study of one topic of interest from subject matter experts (SMEs) with in-depth knowledge, which I have relied upon in many aspects of this book. What seemed to be missing was the foundational information that outsiders did not have, which meant that some of the insightful material was lost to the novice and to some extent, even researchers with a doctorate like myself. However, the absence of a comprehensive understanding that linked all of the pieces of the puzzle together was evident, and I believe that this problem prohibited many from entering the realm of medical device development. You cannot participate in what you don’t understand. Thus, I began to gather information from credible biomedical organizations, webinars, industry leaders, medical device groups on social media, and literature to form the notion that this information was becoming increasingly important in the face of changing regulatory requirements.

However, an appropriate venue for such a book was lacking, despite the intent to systematically relay the complex nature of medical device development to help eliminate the frustration of innovators, quality personnel, risk managers, health administrators, health technology managers, biomedical and clinical engineers, and clinicians. Then I opened up my LinkedIn account to find an invitation to submit proposals from Fiona Geraghty, Acquisitions Editor, for Elsevier Publishing in the United Kingdom. Through the course of this year-long journey after contracting with Elsevier, I have appreciated Fiona and Alex White, Editor, for their feedback and availability. I am also grateful to a dear friend, Brian Gerrits, who provided a space for me to write, and to Larry Fennigkoh for his kind words and encouragement.

Of course, the proposal and contract was just the beginning of the process. I conducted several systematic literature searches (eg, EBSCO host, Proquest ABI, PubMed, and the United States National Library of Medicine at the National Institutes of Health) spanning the major sections of the book that formed the current sections. The databases represent input from business leaders, SMEs in clinical engineering and information systems, regulators, health administrators, and academic and clinical researchers. My focus was to see how people fit into the new regulatory framework equation to help bring forth solutions to unmet medical needs using knowledge of regulation and personal experience with medical devices as a biomedical engineering technician and occasional patient. These sections include (1) Medical Device Development and Regulatory Overview; (2) Defining and Meeting Regulatory Challenges in Clinical Engineering; (3) European Markets; (4) Equipment Acquisition, Integration, and Maintenance; (5) Data Management, Patient Safety, and Efficacy; and (6) the Future of Healthcare. Topical information was also researched through supplemental searches to fill in gaps in important information as these chapters developed. Contributing authors also conducted their own literature searches. I am thankful for the insightful information that the contributing authors provided to inform and add to the overall depth of the book.

Several items emerged true to my initial intuition: the misunderstood relevance of the medical device total product life cycle; the need to produce evidence supporting medical device decisions based on the increase in value-based purchasing that drives development, regulatory approval, and reimbursement; and the not-so-simple device classification process. That, my friends, is just some of what the first section has to offer.

The second section provides a specific regulatory overview of the current challenges in clinical engineering: biocompatibility, risk management, and sterility, while the third section focuses on regulation specific to the European Union. In Section 4, the topics revolve around methods to evaluate new equipment purchases and reimbursement strategies with a focus on legal responsibilities that will serve to reinforce earlier concepts in the book.

Section 5 takes the readers into a new way to look at evidence strategies, access to portals to obtain information on manufacturing recalls, and how health economics research is invading medical device development. Finally, Section 6 looks at the future of health technology management, challenges of securing patient confidentiality and interoperability of medical devices, and how to better manage applications for digital technology. Also in this section, my Goddaughter Olivia Grace Adams debuts her first graphic publication by honoring my request for a unique interpretation of the developments in technology with homage to Leonardo Da Vinci’s Vitruvian Man in Chapter 17. I am so excited to include this talented young artist in my book.

Finally, no book is without limitations. The more I delved into the details of such topics as reimbursement or biocompatibility, the more I realized how much more I could write. But, there are space limitations in every book. Nevertheless, I feel that this book has met the objective to inform the multiple stakeholder medical device environment of care with operational and clinical practice recommendations to regulatory changes for risk management, continuing education units to maintain credentials, and medical equipment practices that contribute to organizational quality. I hope that you and your patients benefit tremendously from this information.

Section 1

Medical Device Development and Regulatory Overview

Outline

Chapter 1. Reframing Product Life Cycle for Medical Devices

Chapter 2. Overview of Medical Device Clinical Trials

Chapter 3. Review Regulatory Guidelines by Device Classification Type

Chapter 4. Manufacturing/Distribution Considerations

Chapter 1

Reframing Product Life Cycle for Medical Devices

B.A. Fiedler¹,  and Y. David²     ¹Independent Researcher, Jacksonville, FL, USA     ²Principal, Biomedical Engineering Consultants, LLC Houston, TX, USA

Abstract

The medical device product life cycle (PLC) is linked to the regulatory processes in industry leaders in the United States, European Union and other countries who emulate their policies. Still, the link between PLC and regulation is not always clear to many. Product management through its life cycle is critical to end users and the companies that produce and market them. Understanding the inseparable link between regulation, markets, and the medical device industry is critical to the production of safe and effective devices, industry sustainable, clinical improvements, and the long-standing medical ethical position of ‘do no harm’.

Keywords

Conception phase; End of product life; European Union; Food and Drug Administration (FDA); Medical device; Product management; Prototype phase; Product life cycle; Regulatory requirements; Regulation; Total product life cycle; United States

1.1. Introduction

Product management through its life cycle is critical to end users and the companies that produce and market them. Major considerations include (1) production of operationally safe and effective devices; (2) financially positive return on investment made throughout the product development and manufacturing; (3) clinical improvement in care; and (4) the overarching element of do no harm. The regulation of medical devices is as much about risks as it is about markets and companies (Altenstetter, 2012, p. 364). While medical product legislation in the US had its beginning in 1938 under the Federal Food, Drug, and Cosmetic Act (FDA, 2012, 2014a), the significant impact on the design and manufacturing of medical products was the result of the Medical Device Amendment of 1976 (FDA, 2014a) that introduced the risk classification scheme giving the US Food and Drug Administration (FDA) the authority to require a premarket review process.

These legislative developments and others that followed both in the US and the world aimed at the establishment of a regulatory environment where processes and methods have been evolved to ensure the safety and effectiveness of medical products while promoting innovation. Therefore, understanding the FDA total product life cycle (TPLC) (FDA, 2015a) and the EU Medical Device Certification (MDD) (2009) processes for medical device development that leads to commercial distribution is important to achieving both consumer safety and product innovation. The global relevance is demonstrated by examining the US and the US medical device markets that, when combined, represent more than three-fourths share in a $300+ billion dollar industry (Kalorama Market Report, 2014; Eucomed, n.d.; Fierce Medical Devices Newsletter, 2012) that is growing at a rate of 4.4% a year (Eucomed, n.d.).

The introduction of the regulatory process distinguishes the medical device PLC from other industry concepts, such as the well-known product life cycle: introduction, growth, maturity, and decline. For example, the human factors element has gained a strong presence in medical device development as well as in the hospital environment of care (Duffy, 2011; Fennigkoh, 2005). Consequently, human factors engineering has driven changes in regulation guiding the medical PLC. The Agency for Healthcare Research and Quality recognizes the patient safety value of human factors engineering and the inherent risks, as interactions between and among healthcare workers, equipment, and environmental conditions depend on the application of various technologies to patients in order to save lives (Agency for Healthcare Research and Quality, 2015).

Human factors engineering is the discipline that attempts to identify and address these issues… by taking into account human strengths and limitations in the design of interactive systems that involve people, tools, technology, and work environments to ensure safety, effectiveness, and ease of use (Agency for Healthcare Research and Quality, 2015).

Two overarching directives in the FDA PLC process provide the foundation for the agency mandate to consistently determine that medical devices marketed in the US meet applicable safety and effectiveness requirements. They are found in 21 CFR 860.7(d)(1) and 21 CFR 860.7(e)(1). The clauses are noteworthy because every subsequent requirement in the Quality System Regulation, Current Good Manufacturing Practices (cGMP), and Recognized Standards stem from these points.

There is reasonable assurance that a device is safe when it can be determined, based upon valid scientific evidence, that the probable benefits to health from use of the device for its intended uses and conditions of use, when accompanied by adequate directions and warnings against unsafe use, outweigh any probable risks. The valid scientific evidence used to determine the safety of a device shall adequately demonstrate the absence of unreasonable risk of illness or injury associated with the use of the device for its intended uses and conditions of use.

21 CFR 860.7(d)(1), Reasonable assurance of safety

There is reasonable assurance that a device is effective when it can be determined, based upon valid scientific evidence, that in a significant portion of the target population, the use of the device for its intended uses and conditions of use, when accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.

21 CFR 860.7(e)(1), Reasonable assurance of effectiveness

Utilization of the product life cycle approach is one method to ensure product integrity. For manufacturing processes to be fully validated…there must be an integration of development work, process conformance, and continuing verification at each stage that provides assurance that the product or process will consistently remain in control throughout the entire product lifecycle (Pluta, 2011).

In this chapter, we provide an overview of the FDA TPLC, the EU PLC, and introduce important stages of the product life cycle for medical devices.

1.2. FDA Total Product Life Cycle

The FDA TPLC consists of several important characteristics including conception, prototype development, industry/regulatory collaboration, preclinical investigation, advanced clinical, marketing, and postmarketing activities that help to determine continuation of product compliance throughout its marketable life. These elements are discussed below to introduce the general overview of the process.

The FDA TPLC provides quality system guidance to a wide variety of companies that is independent of the manufacturing companies’ characteristics (eg, size, structure). In the highly competitive medical device industry, timing is critical to quality system life cycle elements such as design control, manufacturing, marketing, and postmarket management of medical products (Fig. 1.1). Fig. 1.1 highlights the complete life cycle stages initiated by conceptual design continuing through the preservation of intellectual property or licensure stage towards commercial use, potential modifications, and eventual end-of-life obsolesce.

The FDA TPLC is based on an industry acceptable model for quality systems established by the International Organization for Standardization (ISO) under two main directives. First, ISO 9001:2008 (International Organization for Standardization, n.d.a) is a quality management system that provides guidance and tools for corporations and organizations on how to consistently deliver good quality product and service (ISO 9001:2015 is undergoing review during the research/editing phase of this publication). Second, ISO 13485:2003 (International Organization for Standardization, n.d.b) specifies the requirements for a quality management system for medical devices. As part of a comprehensive quality system that covers the TPLC, the assurance process described in the Code of Federal Regulations Title 21, Chapter I, Subchapter H, Part 820 (FDA, 2014b) is systematically applied throughout the entire lifespan of the product. It is important to note that the design control does not end with the transfer of the design to manufacturing, but rather applies to all changes and modifications to the device or to the manufacturing processes, including modification that may occur after the device has been introduced to the market.

Figure 1.1  Representation of the Major Stages and Necessary Interaction Among Elements in the Total Product Lifecycle for Medical Devices. (From CDRH Vision - Total Product Life Cycle.http://www.fda.gov/ohrms/dockets/ac/01/slides/3799s1_11_Feigal/sld002.htm)

Design controls are components of the comprehensive quality system that covers the entire device life. Design control begins with development and approval of design inputs, including device design and testing associated manufacturing, verification, and validation testing processes (Fig. 1.2). Fig. 1.2 demonstrates the logical sequence of the requirements for compliance along the TPLC stages. An iterative review process is incorporated into a series of design and process changes that evolve the medical device into a product that more closely matches user needs until the product is ready for production (Kinsel, 2012). The waterfall design emphasizes that the device has undergone design input/output verification that tested features meets end user needs. The validation and verification review answer the questions, Was the device manufactured right? and Was the right device manufactured?

Products can also be identified by the duration of the product life cycle: short or long. Short deployment products are identified as single-use, disposable, or as a single patient device. Alternatively, products can have longer deployment duration and be identified as a durable device. The durable devices can also be classified as capital assets, depending on their value, that are designed to be used on multiple patients and endure repeated cleaning and sterilization processes applied between patient uses. Regardless of the duration of the deployment stage, all medical devices must be designed, manufactured, and marketed with compliance with patient safety and quality system controls. This indicates that each of the life cycle stages is important and impacts the other stages. In turn, the life cycle determines product deployment and ultimately, influences patient outcomes.

Figure 1.2  Design control documentation, evidence, and results are a minimum requirement in the total process life cycle for medical devices. Used by permission of the Medical Devices Bureau, Health Canada.

1.2.1. Conception

The first rule of medical device conceptual design is to make certain that the design fits into the accepted definition of a medical device. The FDA (2014c) clearly distinguishes products classified as a medical device from other items under their purview according to the following criteria:

an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: 1) recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, 2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or 3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.

Conception occurs in the early part of the early TPLC stage and is the formation of innovation for the purpose of advancing the technology toward commercialization (Schoonmaker et al., 2013; Markham et al., 2010). The innovation becomes product if the marketable use has been clearly identified (Nerker and Roberts, 2004). This stage usually depends on the availability of research and development resources and scientific leadership. The product progression rate through this phase can be limited when the preceding factors are absent or in short supply. The inception stage is usually an exciting stage where innovators begin to transform their idea from theoretical concept into a prototype product. The goal is to match research and development team efforts to market needs that form a concept that is technologically and financially feasible.

1.2.2. Prototype

In this stage, the team tests the design specifications and the ability to economically produce. Further, the team validates that the product meets its objectives and conducts tests and product audit trails as needed to demonstrate that the product is in compliance with applicable standards and regulations. Preparation for and introduction into the stream of commerce will follow, focusing on capturing the early adopters and to gain market share. At this junction, the patent process and securing of the intellectual property should be obtained, and the team of engineers who conceived the solution work closely with clinicians advising them on how to transition into the preclinical phase (Kaplan et al., 2004). Identification of regulatory compliance strategy now is essential for bringing the product into commercialization in a timely fashion.

1.2.3. Preclinical Investigation

Preclinical investigation is the stage in the product life cycle that incorporates and resolves conflicts between requirements and manufacturing capabilities. While in this stage, the product is subjected to verification and validation (V&V) processes. The output of the introduction stage has progressed now to the deployment of tools for verification of the relationship between design inputs and outputs and for validation that the product intended use has been met.

The manufacturer can now demonstrate that the product addresses the specific issue for which it was developed. The end of the stage delivers a compliant and market ready product where early adaptors will help launch and grow the investment needed to continue the product development in preparation for full market deployment.

Product development from the earliest phases requires active involvement of practicing clinicians. Clinicians and inventors are frequently involved in the creation of the product concept and are often an integral part of the design team. The clinicians will be essential in the conduct of animal testing (or clinical studies, as needed), while engineers will focus on bench testing (Kaplan et al., 2004). These activities permit the clinician and/or the engineer to obtain the required knowledge about product performance, failure modes, and risk mitigation strategies. Safety concerns during first clinical use and pilot phase mandate collaboration between engineers, inventors, and clinicians. At this phase, the clinician frequently takes on the leadership role and will need support of regulatory expert. Familiarity with the Institutional Review Board process and compliance to regulations guiding clinical study are essential (FDA, 2014d).

The classification of the product into Class I, II, or III is important to the product manufacturer because it identifies the amount of registration a product will encounter in particular at the premarket phase. The classification determines the extent of risk control that the product must exhibit in evaluating its safety and efficacy levels (FDA, 2014e). The minimum regulatory level necessary to assure the product safety and effectiveness is at the level identified as Class I. The US Congress originally designed the device classification process to assure the safety and efficacy of medical products without subjecting the product manufacturers to overregulation that might inhibit product innovation (FDA, 2014f).

In general, some Class II and most of the Class III products will be subject to the most comprehensive regulatory requirement, the Premarket Approval (PMA). A PMA submission may be necessary for a device manufacturer under several conditions including 1) the FDA determines that a Class I or II classification does not possess sufficient information using general controls, or 2) the product presents a potential unreasonable risk of injury. Successful medical device performance during premarket studies is an integral part of device approval leading to market.

1.2.4. Advanced Clinical/Postmarketing Studies

Clinical investigation of medical devices is the means of obtaining evidence for the evaluation of data about the safety and performance of medical product in its intended use (Higson, 2001). This includes any risks or side effects presented by the product during use. The FDA (1997) has set forth the following design control guidance. In this stage, the manufacturer must establish a field support program comprised of competent clinical and technical personnel, such as clinical engineers and biomedical equipment technicians, for technical support at the point of deployment. While there are several options to accomplish this product support program, they all aim at reducing deployment-related risk, improve uptime, and reduce cost of ownership over the life cycle of the product. This stage is also used for ongoing product features’ enhancement based on market feedback from users and the support teams.

As more medical products base their functionality on embedded intelligence during this phase of the TPLC, manufacturing interventions can be expected to increase in order to address software-related features and improve security patches and network interoperability. Managing safety problems that were identified through data received from the postmarket surveillance requirement is also addressed during this stage (FDA, 2014g).

Postmarket regulatory requirements essentially suggest that the PMA process has limitations and cannot mitigate all of the safety issues. Therefore, regulatory agencies adopted three distinct features into their postmarket requirements: adverse event reporting, surveillance, and focused patients registry (FDA, 2014h).

1.2.5. End of Life

The end of the technology life cycle (EOL) is a defined phase where manufacturers have communicated to users their intent to discontinue production (FDA, 2014i). This is normally followed by communication indicating that the product will no longer receive manufacturing support. The EOL determination is based on the duration of time that a product can remain safe and effective in clinical use (FDA, 2015b,c). Class III products, such as implantable devices and life support devices, have a limited life cycle span, and these EOL products require a planned period of time to allow users to make decision about deployment alternatives (Medtronic, 2013). An active market withdrawal is the final segment of the stage. While this is a customary part of the overall product life cycle, manufacturers of medical product must recognize that end-of-life milestones must be managed and clearly communicated to users.

The wide scope of medical technology types further removes clarity from the recognition of specific locations for transition points. At the end of the maturity stage, through which the product is generally available, the vendor may issue communication about his plan to stop the product marketing. This communication usually includes such items as the description of the product, last day for new orders, last day of manufacturing, and at times, also anticipated exhaustion time of spare parts availability and of technical support. From the manufacturer’s point of view, the end of product life (EOL) consists of combination of points of (1) the end of manufacturing; (2) end of support; and (3) the end of availability (Batterbee, 2012). This is the end of the withdrawal stage and the final point of the product life cycle. However, for users, transition from one product to another is different. Users may not be aware of planned end of life due to lack of communications or ignorance. Users may also find other alternatives, third party parts, and support that will continue to allow for sustaining of risk control level and of operation efficiency. In addition, users may be faced with no alternative, such as the case maybe in resource poor countries where aging equipment has been donated (WHO, 2000).

This stage may occur as a consequence of market demand, compliance challenges, effect of technological and manufacturing progression, as well as the introduction of competitive products making a product less competitive on the market. Lager adapters may be the only market share captured by this product.

Additionally, new markets for obsolete items in one nation may open up in other areas. This is most evident in resource-poor nations who may value the obsolete products of western counterparts (WHO, 2000). In this way, third-world nations can benefit from discontinued products from industrialized nations and thereby extend the product life for lack of better alternatives. Donations and local ingenuity often serve to keep the equipment functioning when spare parts are no longer available. However, it is difficult to manage life cycle in these environments as in other locations, and attention is needed to properly manage risks to patient and to staff (WHO, 2000). Therefore, it is important to understand that planned obsolesce in one regulatory system does not mean that the same criterion will be used in another part of the world, especially if the regulatory requirement are different.

As discussed earlier in this chapter, products transitioning through their life cycle from the early design stage to the planned obsolescence stage do not have precise or clearly defined transition points between the life cycle stages. This is especially true as the product undergoes engineering processes and improvements and at the last transition point of the planned obsolescence stage, the end of life. This last transition point of product life cycle must be managed so that manufacturers are communicating the intention to withdraw the product from the market, to cease support and availability of service team, replacement parts, sales, and manuals. In the EOL, a product is no longer available and has reached the end of vendor support life, including an end to technical guidance.

1.3. European Commission Product Life Cycle

Similar to the US, the EU must follow regulations given by the European Commission (EC) that include quality system requirements (Higson, 2001). Medical Device Directives explain the process of obtaining Conformité Européenne (French) in Europe and it is comparable to the cGMP section of the FDA design control in the US. The process is referred to as European Conformity or more commonly, CE Marking. The focus is on definition of intended use, development of requirements, development of V&V, and safe deployment (eg, risk mitigation, communication, and control).

General harmonization of medical products regulation across the EU market was achieved through the adoption of MDD issued by the EC. The MDD details the essential requirements that manufacturers and importers must meet to legally market and sell their products in the EU. The validation of conformity to the Directives is done through Notified Bodies (NBs) organizations that have been accredited by EU Member States. The NBs validate the compliance of medical product with the MDD and can then be documented with CE Marking (TUV SUD, n.d.). The European MDDs describe the responsibility of the product manufacturer who must submit conformity data to the Notified Bodies and answer all their inquiries before the CE mark can be attached to the product (Medical Device Certification, 2009).

Healthcare is primarily a domestic issue representing solutions that are influenced by political forces, population or disease characteristics of the local society, and reimbursement schema (Altenstetter, 2012). As such, the EC PLC consists of some similar phases as those in the US, but at the same time have several important different characteristics. Differences include that (1) there are no limits to a manufacturer’s responsibility; (2) manufacturers are responsible for both upstream suppliers and downstream users; (3) there is a different classification system; and (4) manufacturers must minimize environmental burden throughout the design and production phases to demonstrate reduced impact on resource consumption (Higson, 2001).

Another primary characteristic of the EU process is the reliance on a review process that is not centralized. Instead, they utilize harmonized directives and Notified Body to verify that the design of the product and its manufacturing conditions are in conformity as far as the design is in question. Additionally, the manufacturer is responsible for clinical evaluation and vigilance program after commercialization of the product (Higson, 2001).

1.4. Summary

This chapter has introduced the important elements of the product life cycle with an emphasis on the US and the EU. They include the (1) conception phase compromising the role of intellectual property in the framing of the future of the product life; (2) prototyping phase where the concept transitions from theory into a real product after discussion regarding budget, engineering design, and materials have been identified and addressed; (3) preclinical investigation; (4) advanced clinical and postmarket experiences; (5) market adoption and deployment; and finally, (6) product end of life. Items 3–4 are two major forces that shape product commercialization while the entire process meets continuous compliance with regulatory and technical standards and addresses clinical needs that promote patient safety.

Though the US and EU dominate global markets, other nations, such as Japan and China, should also be examined. However, one of the clear differences in the product life cycle phases exists at the end of product life cycle between resource-poor countries and others. Obsolescence of relatively costly technology without alternatives prevents the withdrawal of medical product from use even past its end-of-life phase.

Ultimately, the ability to predict how these influences in various combinations will reveal within the global TPLC process is left for time to unfold. However, we can predict with relative certainty that the impact of the dynamic changes can be reduced by increasing understanding of the underlying regulatory processes associated with the medical device product life cycle that monitors product development destined for the patient end user.

Case Study: Teaching Men to Fish in Rwanda

Is there life after medical device obsolescence? Yes! The World Health Organization (WHO) provides guidance and training to industrial nations that would like to donate used/refurbished equipment that meet specific, validated requests from developing nations (WHO, 2014). But the guidelines are rigid, as both donors and recipients must meet a series of checklists to determine if the donation plan will proceed (WHO, 2000).

For donors, part of the predonation plan consists of verification that equipment meets safety and other standards, and management participation in site preparation, training, equipment transfer, and installation (WHO, 2000, pp. 3–6). For recipients, responsibilities include identification of clinical need, feasibility studies, cost analysis, knowledge of equipment specifications, location selection, additional maintenance personnel, and access to spare parts and/or supplies associated with equipment