Biomedical Devices E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 357

Veröffentlichungsjahr: 2016

Beschreibung

Biomedical Devices: Design, Prototyping, and Manufacturing features fundamental discussions of all facets of materials processing and manufacturing processes across a wide range of medical devices and artificial tissues. * Represents the first compilation of information on the design, prototyping, and manufacture of medical devices into one volume * Offers in-depth coverage of medical devices, beginning with an introductory overview through to the design, manufacture, and applications * Features examples of a variety of medical applications of devices, including biopsy micro forceps, micro-needle arrays, wrist implants, spinal spacers, and fixtures * Provides students, doctors, scientists, and technicians interested in the development and applications of medical devices the ideal reference source

Leseprobe

Table of Contents

COVER

TITLE PAGE

COPYRIGHT

CONTRIBUTORS

FOREWORD

CHAPTER 1: OVERVIEW

1.1 INTRODUCTION

1.2 NEED FOR MEDICAL DEVICES

1.3 TECHNOLOGY CONTRIBUTION TO MEDICAL DEVICES

1.4 CHALLENGES IN THE MEDICAL DEVICE INDUSTRY

REFERENCES

CHAPTER 2: DESIGN ISSUES IN MEDICAL DEVICES

2.1 MEDICAL DEVICE DEVELOPMENT (MDD)

2.2 CASE STUDY

2.3 CONCLUSIONS

REFERENCES

CHAPTER 3: FORMING APPLICATIONS

3.1 FORMING

3.2 TYPICAL PROCESS PARAMETERS

3.3 MANUFACTURING PROCESS CHAIN

3.4 IMPLANTABLE DEVICES

3.5 BONE IMPLANTS

3.6 OTHER BIOMEDICAL APPLICATIONS

REFERENCES

CHAPTER 4: LASER PROCESSING APPLICATIONS

4.1 INTRODUCTION

4.2 MICROSCALE MEDICAL DEVICE APPLICATIONS

4.3 PROCESSING METHODS FOR MEDICAL DEVICE FABRICATION

4.4 BIOMATERIALS USED IN MEDICAL DEVICES

4.5 MICROJOINING OF SIMILAR AND DISSIMILAR MATERIALS

4.6 LASER MICROMACHINING FOR MICROFLUIDICS

4.7 LASER MICROMACHINING FOR METALLIC CORONARY STENTS

REFERENCES

CHAPTER 5: MACHINING APPLICATIONS

5.1 INTRODUCTION

5.2 MACHINABILITY OF BIOCOMPATIBLE METAL ALLOYS

5.3 SURFACES ENGINEERING OF METAL IMPLANTS

5.4 WEAR AND FAILURE OF METAL IMPLANTS

5.5 MICROMILLING-BASED FABRICATION OF METALLIC MICROCHANNELS FOR MEDICAL DEVICES

5.6 MACHINING-BASED FABRICATION OF POLYMERIC MICRONEEDLE DEVICES

5.7 A CASE STUDY: MILLING-BASED FABRICATION OF SPINAL SPACER CAGE

REFERENCES

CHAPTER 6: INKJET- AND EXTRUSION-BASED TECHNOLOGIES

6.1 INTRODUCTION

6.2 INKJET TECHNOLOGY

6.3 MATERIAL EXTRUSION TECHNOLOGY

REFERENCES

CHAPTER 7: CERTIFICATION FOR MEDICAL DEVICES

7.1 INTRODUCTION

7.2 THE MEDICAL DEVICES APPROVAL, REGISTRATION, OR CERTIFICATION

7.3 THE PREMARKET KEY ACTIVITY: THE DEMONSTRATION OF THE CONFORMITY TO THE SAFETY AND PERFORMANCE REQUIREMENTS

7.4 THE POSTMARKET KEY ACTIVITY: THE SURVEILLANCE

7.5 THE ROLE OF THE QUALITY MANAGEMENT SYSTEMS

7.6 THE VERIFICATION AND THE AUDITING

7.7 THE ROLE OF THE STANDARDS

7.8 EXAMPLES OF APPROBATION/CERTIFICATION ROADS IN SOME WORLD AREAS

7.9 IN-DEPTH STUDIES

REFERENCES

INDEX

END USER LICENSE AGREEMENT

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Guide

Cover

Table of Contents

FOREWORD

Begin Reading

List of Illustrations

Chapter 2: DESIGN ISSUES IN MEDICAL DEVICES

Figure 2.1 Total medical device life cycle (according to Center for Devices and Radiological Health (CDRH), US FDA).

Figure 2.2 Linear life cycle model of medical device according to El-Haik and Mekki [7].

Figure 2.3 Simplified schema of the linear medical device development model according to Pietzsch et al. [9].

Figure 2.4 Schema of waterfall model [16].

Figure 2.5 Schema of design for validation model (DFV-V model) according to Alexander and Bishop [15].

Figure 2.6 Design and manufacturing activities for developing a medical device.

Figure 2.7 Functional analysis of the prosthesis to replace the scapholunate interosseous ligament (SLIL).

Figure 2.8 Synthesis of the morphological matrix.

Figure 2.9 Conceptual design: compact system (concept 1) and ball-and socket-ball system (concept 2) and wired system (concept 3).

Figure 2.10 Evolution of the compact system.

Figure 2.11 Final scapholunate prosthesis (a) and its insertion in the bones (b).

Figure 2.12 Manufacturing steps.

Figure 2.13 (a) Display of WHATs and HOWs in QFD and (b) QFD competitive analysis.

Figure 2.14 (a) QFD physical contradictions and (b) TRIZ contradiction matrix.

Figure 2.15 Geometry solutions using TRIZ principles.

Figure 2.16 Customization parameters of final stent design.

Figure 2.17 Stent (a) directly manufactured using fab@home (b), a fused deposition modeling machine.

Chapter 3: FORMING APPLICATIONS

Figure 3.1 (a) Open-die forging; (b) closed-die forming; and (c) sheet stamping.

Source

: Schuler 1998 [2]. Reproduced with permission of Springer Berlin Heidelberg.

Figure 3.2 Typical sequence for T-shaped tube hydroforming process: (a) the tube in the hydroforming dies; (b) the produced part after hydroforming. Reproduced with permissions of Antonio Fiorentino.

Figure 3.3 Examples of biomedical devices used in orthopedics.

Source

: Figure courtesy of Chris Martin.

Figure 3.4 Examples of types of joints present in the human body.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons.

Figure 3.5 (a) Elbow joint scheme.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) Elbow prosthesis.

Source

: Sanchez-Sotelo, 2011 [13]. Reproduced with permission of The Open Orthopaedics Journal.

Figure 3.6 (a) Human knee joint scheme.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) Knee prosthesis.

Source

: Culjat et al., 2012 [16]. Reproduced with permission of John Wiley & Sons.

Figure 3.7 (a) Lateral view of human ankle.

Source

: Figure courtesy of Philip Chalmers. (b) Example of X-ray images of artificial joint inserted on ankle.

Source

: Barg et al., 2010 [19]. Reproduced with permission of Springer International Publishing.

Figure 3.8 Scheme of human hand bones.

Source

: Figure courtesy of Mariana Ruiz Villarreal.

Figure 3.9 (a) Examples of finger joints; (b) example of X-ray images of artificial joint inserted on shoulder.

Source

: Gibson 2005 [21]. Reproduced with permission of John Wiley & Sons.

Figure 3.10 (a) Shoulder scheme.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) Shoulder prosthesis.

Source

: Ekelund 2009 [22]. Reproduced with permission of Journal of Orthopaedic & Sports Physical Therapy. (c) Example of X-ray images of artificial joint inserted on shoulder.

Source

: Ekelund 2009 [22]. Reproduced with permission of Journal of Orthopaedic & Sports Physical Therapy.

Figure 3.11 (a) Human hip scheme.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) From left to right: Frontal plane cross-section of a femur; press fit implant; the original Chamley femoral stem and polyethylene cup; noncemented stem with a porous ingrowth surface.

Source

: Culjat et al., 2012 [16]. Reproduced with permission of John Wiley & Sons.

Figure 3.12 (a) Human wrist scheme.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons. (b) X-ray images of wrist prosthesis positioning.

Source

: Facca et al., 2010 [24]. Reproduced with permission of John Wiley and Sons.

Figure 3.13 Vertebral column scheme.

Source

: Tortora and Derrickson 2009 [12]. Reproduced with permission of John Wiley & Sons.

Figure 3.14 (a) Spine anatomy.

Source

: Kojić et al., 2008 [25]. Reproduced with permission of John Wiley & Sons. (b) Spinal vertebrae without spinal device and with spinal device.

Source

: Culjat et al., 2012 [16]. Reproduced with permission of John Wiley & Sons.

Figure 3.15 Skull and cranial bones.

Source

: Hollins 2012 [27]. Reproduced with permission of John Wiley & Sons.

Figure 3.16 Manufacturing process of cranial prosthesis.

Source

: Fiorentino et al., 2012 [34]. Reproduced with permission of John Wiley & Sons.

Figure 3.17 Pre-bent of a plate over AMT model.

Source

: Wilde et al., 2012 [38]. Reproduced with permission of Springer-Verlag.

Figure 3.18 From left to right: dentition scheme; titanium screw dental implant (resembling a tooth root).

Source

: Wingrove 2013 [44]. Reproduced with permission of John Wiley & Sons.

Chapter 4: LASER PROCESSING APPLICATIONS

Figure 4.1 Microscale medical device applications.

Figure 4.2 Various microchannel geometries fabricated with laser micromachining.

Figure 4.3 PDMS microchannel schematic.

Figure 4.4 Silicon-to-glass bonding with Nd:YAG laser.

Figure 4.5 Microchannels fabricated on PMMA and PDMS with laser micromachining in NIR and UV wavelengths.

Figure 4.6 Laser micromachining based PMMA and PDMS microchannel profiles.

Chapter 5: MACHINING APPLICATIONS

Figure 5.1 (a) Titanium alloy Ti-6Al-4V spinal fixation plate and (b) SS316L stainless steel bone crusher as produced with micromilling.

Figure 5.2 Burr formation in micromilling of channels in Ti-6Al-4V titanium alloy.

Figure 5.3 Micromilling of PMMA polymer to produce microneedle arrays.

Figure 5.4 Microneedle array-based patch prototypes produced with micromilling.

Figure 5.5 Examples of common disc problems.

Figure 5.6 Spinal spacer cage designs (Rutgers Manufacturing Automation Laboratory).

Figure 5.7 Two design models used in finite element analysis.

Figure 5.8 Boundary conditions and loads for the two designs.

Figure 5.9 Finite element mesh for the two designs (Rutgers Manufacturing Automation Laboratory).

Figure 5.10 (a) Design A with 160 N load on 59 teeth cage and (b) Design B with 100 N load on 59 teeth cage (Rutgers Manufacturing Automation Laboratory).

Figure 5.11 Surface obtained from the tool path strategy (Rutgers Manufacturing Automation Laboratory).

Figure 5.12 Steps in automated milling process (Rutgers Manufacturing Automation Laboratory).

Figure 5.13 (a) Designed and (b) prototype spinal spacer cage fabricated with milling process (Rutgers Manufacturing Automation Laboratory).

Chapter 6: INKJET- AND EXTRUSION-BASED TECHNOLOGIES

Figure 6.1 Binder jetting process overview.

Figure 6.2 Material jetting working principle.

Figure 6.3 Overview based material extrusion principles (a) filament-based extrusion, (b) syringe-based extrusion, (c) screw based.

Figure 6.4 Filament extrusion: problems caused by the (a) filament, (b) improper diameter filament, and (c) buckling.

Figure 6.5 Schematic of extrusion-based systems.

Figure 6.6 Fused deposition modeling process.

Figure 6.7 Working principle of multiphase jet solidification (MJS).

List of Tables

Chapter 2: DESIGN ISSUES IN MEDICAL DEVICES

Table 2.1 Identification of Functional Requirements (FRs) and Design Constraints (Cs) for New Prosthesis

Table 2.2 Attribute List of Stent

Chapter 4: LASER PROCESSING APPLICATIONS

Table 4.1 Comparison between Continuous Wave and Pulsed Lasers

Table 4.2 Manufacturing Process Comparison for Key Characteristics

Table 4.3 Process Parameters for Laser Processing of Polymers

Chapter 5: MACHINING APPLICATIONS

Table 5.1 Medical Implants and Alloy Materials Used

Table 5.2 Mechanical Properties of Alloys Used in Joint Replacements

Table 5.3 Biocompatibility of Biomaterials Including Metal Alloys

Table 5.4 Spinal Spacer Cage Design Methods

Table 5.5 Tools Utilized in Milling Process

Chapter 6: INKJET- AND EXTRUSION-BASED TECHNOLOGIES

Table 6.1 Additive Manufacturing Categories as Classifies by ASTM

Table 6.2 FDM Modeling Materials

Chapter 7: CERTIFICATION FOR MEDICAL DEVICES

Table 7.1 Checklist for Documenting the Premarket Conformity to the Safety and Performance Principles

Biomedical Devices

Design, Prototyping, and Manufacturing

Edited by

Tuğrul Özel

Paolo Jorge Bártolo

Elisabetta Ceretti

Joaquim De Ciurana Gay

Ciro Angel Rodriguez

Jorge Vicente Lopes Da Silva

Copyright © 2017 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Names: Özel, Tuğrul, 1967- editor. | Bártolo, Paulo, editor. | Ceretti, Elisabetta, 1966- editor. | Ciurana Gay, Joaquim De, editor. | Rodriguez, Ciro Angel, 1967- editor. | Silva, Jorge Vicente Lopes da, 1963- editor.

Title: Biomedical devices : design, prototyping, and manufacturing / edited by Tuğrul Özel, Paolo Jorge Bártolo, Elisabetta Ceretti, Joaquim De Ciurana Gay,

Ciro Angel Rodriguez, and Jorge Vicente Lopes Da Silva.

Description: Hoboken, New Jersey : John Wiley & Sons, 2016. | Includes bibliographical references and index.

Identifiers: LCCN 2016018375| ISBN 9781118478929 (cloth) | ISBN 9781119267041 (epub)

Subjects: LCSH: Medical electronics--Design and construction.

Classification: LCC R856 .B487 2016 | DDC 610.28/4--dc23 LC record available at https://lccn.loc.gov/2016018375

Cover image courtesy of the Editors.

CONTRIBUTORS

Aldo Attanasio

, Department of Mechanical Engineering and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy

Paulo Jorge Bártolo

, School of Mechanical, Aerospace and Civil Engineering, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK

Karen Baylón

, Department of Mechanical Engineering, Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico

Marino Bindi

, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy

Elisabetta Ceretti

, Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy

Luis Criales

, Department of Industrial and Systems Engineering, School of Engineering, Rutgers University, Piscataway, NJ, USA

Jorge Vicente Lopes Da Silva

, Technological Center Renato Archer, Centro de Tecnologia da Informação Renato Archer, Brazilian Ministry of Science and Technology, Campinas, São Paulo, Brazil

Domenico Dalessandri

, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy

Joaquim De Ciurana Gay

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Marco Domingos

, School of Mechanical, Aerospace and Civil Engineering, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK

Alex Elias-Zuñiga

, Department of Mechanical Engineering, Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico

Inés Ferrer

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Antonio Fiorentino

, Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy

Maria Luisa Garcia-Romeu

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Claudio Giardini

, Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Lombardy, Italy

Jordi Grabalosa

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Arne Hensten

, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway

Laura Laffranchi

, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy

Karla Monroy

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Tuğrul Özel

, Department of Industrial and Systems Engineering, School of Engineering, Rutgers University, Piscataway, NJ, USA

Corrado Paganelli

, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy

Ciro Angel Rodriguez

, Department of Mechanical Engineering, Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico

Stefano Salgarello

, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Lombardy, Italy

Lidia Serenó

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Daniel Teixidor Ezpeleta

, Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Thanongsak Thepsonthi

, Department of Industrial Engineering, Burapha University, Chon Buri, Thailand

Giuseppe Vatri

, Major Prodotti Dentari Spa, Moncalieri, TO, Italy

FOREWORD

There has been an increasing demand for biomedical devices including various instruments, apparatuses, implants, in vitro reagents, and similar articles to diagnose, prevent, or treat diseases, improve human health, prolong human life, and recover from serious injuries. Biomedical devices that we utilize are not only continuously getting smaller and more effective but are also designed with more customized functionalities. In response to that demand, new design innovations, new materials, and prototypes of novel medical devices have been introduced on a regular basis. Design, prototyping, and manufacturing techniques for these materials and designs have also been continuously developing in parallel to the needs in biomedical device demands. There have been a large number of books written about design and manufacturing of various products but biomedical device manufacturing remains less covered than other well-known microelectronics and consumer products.

This book brings authors from institutions around the world, perhaps one of the few wide-ranging books on manufacturing processes for medical devices with coverage of various materials including metals and polymers. The book aims to reach audiences such as practicing engineers who are working in medical device industry, students in the biomedical device manufacturing courses, and faculty/researchers who are conducting research in medical device design, prototyping, and manufacturing.

Chapter 1, written by Joaquim De Ciurana, Tuğrul Özel, and Lidia Serenó, provides an introduction with classification and regulation specification about medical devices with sample manufacturing processes and applications. Chapter 2, prepared by Inés Ferrer Real, Jordi Grabalosa, Alex Elias-Zuniga, and Ciro Rodriguez, summarizes design issues and methodologies applicable to well-known medical device prototypes. Chapter 3, prepared by Karen Baylón, Elisabetta Ceretti, Claudio Giardini, and M. Luisa Garcia-Romeu, describes the issues in modeling and analysis for forming processes along with the comparison of different modeling approaches. Chapter 4, prepared by Tuğrul Özel, Joaquim De Ciurana, Daniel Teixidor, and Luis Criales, describes some of the manufacturing processes based on laser processing with several examples for medical devices. Chapter 5, prepared by Tuğrul Özel, Elisabetta Ceretti, Thanongsak Thepsonthi, and Aldo Attanasio, discusses machining applications and manufacturing processes to be used for medical devices made out of metals and plastics. Extrusion- and inkjet-based processes and applications are presented in Chapter 6, which was prepared by Karla Monroy, Lidia Serenó, Joaquim De Ciurana, Paulo Jorge Bártolo, Jorge Da Silva, Marco Domingos, Corrado Paganelli, Marino Bindi, Laura Laffranchi, Domenico Dalessandri, Stefano Salgarello, Antonio Fiorentino, Giuseppe Vatri, and Arne Hensten prepared the Chapter 7 on certification of medical devices.

We thank all the authors who contributed to this book. We also extend our thanks to Ms Anita Lekhwani and Ms Sumathi Elangovan of John Wiley who assisted us in all stages of preparing this book for the publication.

T. Özel, P. Bártolo, E. Ceretti, J. Ciurana Gay, C. A. Rodríguez, J. V. Lopes Da SilvaJune 2016

Chapter 1OVERVIEW

Joaquim De Ciurana Gay, Tuğrul Özel and Lidia Serenó

Department of Mechanical Engineering and Industrial Construction, University of Girona, Girona, Catalonia, Spain

Department of Industrial and Systems Engineering, School of Engineering, Rutgers University, Piscataway, NJ, USA

1.1 INTRODUCTION

Medical devices are defined as articles that are intended to be used for medical purposes. Several official definitions exist for the term “medical device” depending on the geographic market. Therefore, *medical device definition, classification, and regulation follow market location and governmental regulations according to the required level of control considering invasiveness, contact to the patient, and potential risk in case of misuse or failure. This situation concerning the differences in classification strategies has blocked the spread of innovative medical devices across countries. Nevertheless, in 2011, the International Medical Device Regulators Forum (IMDRF) was conceived to discuss future directions to harmonize the medical device regulatory field and accelerate international convergence.

Two of the most important medical device markets worldwide are the European and the North American. Therefore, the official definitions and classifications of both regions are detailed in this chapter.

For the European market, medical devices are governed by a regulatory framework of three directives:

93/42/EEC: Medical Devices Directive (MDD)

90/385/EEC: Active Implantable Medical Device Directive (AIMDD)

98/79/EC:

In vitro

diagnostic medical devices (IVDMD)

According to them, a medical device is defined as “any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of:

diagnosis, prevention, monitoring, treatment or alleviation of disease,

diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,

investigation, replacement or modification of the anatomy or of a physiological process,

control of conception,

and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.”

Similarly, for the North American market and as a part of the Federal Food Drug and Cosmetic Act (FDC Act), a medical device is defined as “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,

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

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 on being metabolized for the achievement of any of its primary intended purposes.”

Therefore, any product labeled, promoted, or used in a manner that meets the above-mentioned definition will be regulated by the US Food and Drug Administration (US FDA) as a medical device and will be subjected to pre- and postmarketing regulatory controls.

Both definitions of medical devices exclude other regulated products such as drugs, the primary intended use of which is achieved through chemical action or by being metabolized by the body, biological products including blood and blood products, or products used with animals.

In order to classify a medical device, the manufacturer should, first of all, decide whether the product concerned is considered a medical device as defined in the previous section. Then, depending on the situation, medical devices can be classified following national or governmental rules. In this chapter, the classification given is based on the European Union (EU) and the US FDA regulations.

According to the EU, the classification of medical devices is based on the potential risks associated with the devices. This approach allows the use of a set of criteria that can be combined in various ways and be applied to a vast range of different medical devices and technologies. These criteria are referred to as the “classification rules” and are described in Annex IX of Directive 93/42/EEC. Therefore, the medical device manufacturer must determine the type of device following the rules listed in Annex IX. The rules depend on a series of factors including

duration:

how long the device is intended to be in continuous use,

invasiveness:

whether or not the device is invasive or surgically invasive,

type:

whether the device is implantable or active,

function:

whether or not the device contains a substance, which in its own right is considered to be a medicinal substance and has action ancillary to that of the device,

and are divided as follows:

Rules 1–4:

for noninvasive devices,

Rules 5–8:

for invasive devices,

Rules 9–12:

for active devices,

Rules 13–18:

special rules for products that merit a higher classification than they might otherwise be assigned.

When multiple rules apply, the manufacturer must use the highest risk class. Nevertheless, a small number of products may be more difficult to classify due to their unusual nature or situations where the classification would result in the wrong level of conformity assessment in light of the hazard represented by the devices.

Furthermore, based on these rules described in Directive 93/42/EEC, the devices are divided into four classes, ranging from low risk to high risk:

Class I:

low-risk medical devices,

Class IIa:

medium-risk medical devices,

Class IIb:

medium-risk medical devices,

Class III:

high-risk medical devices.

Thus, in order to classify a medical device, the manufacturer must determine the classification of the medical device (class I, class IIa, class IIb, or class III) considering the Annex IX rules described later. Then, a notified body has to carry out the appropriate conformity assessment procedure to validate and confirm the classification.

As an example, a manufacturer willing to classify a silicone tracheal stent must consider the rules associated with an invasive medical device (Rules 5–8):

Rule 5

(invasive in body orifice or stoma—not surgically)

If it is for transient use

Class I

If it is for short-term use

Class IIa

However

, if it is for oral cavity, ear canal, or nasal cavity

Class I

If it is for long-term use

Class IIb

However

, if it is for oral cavity, ear canal, or nasal cavity and it will not be absorbed by the mucous membrane

Class IIa

If it is connected to an active medical device in class IIa or higher

Class IIa

Rule 6

(surgically invasive—transient use)

If it is surgically invasive for transient use

Class IIa

If it is used to control/diagnose/monitor/correct a defect of the heart or the central circulatory system through direct contact

Class III

If it is used for the central nervous system (direct contact)

Class III

If it is a reusable surgical instrument

Class I

If it is used to supply energy or ionizing radiation

Class IIb

If it has a biological effect (mainly or wholly absorbed)

Class IIb

If it is intended to administer medicines in a potentially hazardous manner

Class IIb

Rule 7

(surgically invasive—short-term use)

If it is surgically invasive for short-term use

Class IIa

If it is used to control/diagnose/monitor/correct a defect of the heart or the central circulatory system through direct contact

Class III

If it is used for the central nervous system (direct contact)

Class III

If it is used to supply energy or ionizing radiation

Class IIb

If it has a biological effect (mainly absorbed)

Class III

If it undergoes chemical changes in the body, or if it administers medicines (not in teeth)

Class IIb

Rule 8

(surgically invasive—long-term use or implantable devices)

If it is surgically invasive for long-term use or if it is an implantable device

Class IIb

If it has to be placed in teeth

Class IIa

If it has to be in contact with the heart or central circulatory/nervous system

Class III

If it has a biological effect (or mainly absorbed)

Class III

If it undergoes chemical changes in the body, or if it administers medicines (not in teeth)

Class III

For specific derogation: breast implants, hip, knee, and shoulder joint replacements

Class III

Specifically for the example, the manufacturer must consider the following:

Duration:

the silicone stent will be placed inside the trachea for more than 30 day; therefore, the device is for long-term use (

Rule 8

).

Invasiveness:

the stent will be totally introduced inside the orifice of the trachea using a bronchoscope and anesthesia (surgical operation); therefore, the device is considered an implantable device (

Rule 8

).

Taking these considerations into account, a simple silicone tracheal stent must be considered a class IIb medical device, because it is a long-term implantable device not placed in teeth, without contact with the circulatory or nervous system, without a biological effect, which does not undergo chemical changes or administers medicine, and it is not a breast implant or a hip, knee, or shoulder joint replacement.

US Medical device classification, as in Europe, depends on the intended use of the device and also on indications for use. Moreover, classification is based on the risk the device poses to the patient and/or the user. There are several factors that may affect the risk including

the design of the medical device, which should include principles of inherent safety,

the manufacturing process, which must be well planned, under control, and validated,

the intended use, which will define the adequate scope of use excluding other places where the medical device is not intended for use,

the identification of the user, defining its expected experience, education, and training,

the safety or health of users, implying that the medical device should not compromise the safety of patients.

Most medical devices can be classified by finding the matching description of the device in Title 21 of the Code of Federal Regulations (CFR), Parts 862–892. The US FDA has established a classification of approximately 1700 generic types of medical devices grouping them in the CFR into several medical specialties referred to as panels:

Medical Specialty

Regulation Citation (21 CFR)

73

Anesthesiology

Part 868

74

Cardiovascular

Part 870

75

Chemistry

Part 862

76

Dental

Part 872

77

Ear, nose, and throat

Part 874

78

Gastroenterology and urology

Part 876

79

General and plastic surgery

Part 878

80

General hospital

Part 880

81

Hematology

Part 864

82

Immunology

Part 866

83

Microbiology

Part 882

84

Neurology

Part 884

85

Obstetrical and gynecological

Part 886

86

Ophthalmic

Part 888

87

Orthopedic

Part 864

88

Pathology

Part 890

89

Physical medicine

Part 892

90

Radiology

Part 862

91

Toxicology

Part 868

For each of the devices classified by the US FDA, the CFR gives a general description including the intended use, the class to which the device belongs, and information about marketing requirements. Therefore, the panel examines and classifies the device in three different classes of medical devices based on the level of control necessary to assure the safety and effectiveness of the device:

1. Class I

(Low Risk)—General Controls:

FDC Act lists general references to control the medical devices.

Some general controls include the following: the device cannot be adulterated or misbranded; the firm must be registered with the US FDA, must maintain records and reports, and must apply good manufacturing practices, etc.

2. Class II

(Medium Risk)—Special Controls:

For those devices, general controls are not sufficient; therefore, special controls are set.

Special controls include performance standards; postmarket surveillance; patient registries; guidelines; etc.

3. Class III

(High Risk)—Premarket Approval:

For those devices, general and special controls are not sufficient; therefore, premarket approval is needed.

Applications for premarket approval include reports about the safety and effectiveness of the device; a statement of components, properties, and elements of the device; description of the methods, manufacturing controls, packing; references to any relevant standard; sample of the device and components; proposed labeling; certification related to clinical trials; etc.

Thus, the class to which the medical device is assigned determines, among other things, the type of premarketing submission/application required for US FDA clearance to market. However, there are exceptions and exemptions for certain devices.

1.2 NEED FOR MEDICAL DEVICES

Medical devices are indispensable for effective prevention, diagnosis, treatment, and rehabilitation of illness and disease. They help to not only save and prolong life but also improve the quality of life. Therefore, identifying diseases, disabilities, and risk factors is a decisive step to develop new and efficient medical devices. However, besides medical and technological attributes, the development of medical devices is often influenced by other considerations such as markets, costs, and physician preferences.

Nowadays, there are more than 1.5 million different medical devices, including thermometers, surgical drapes, pacemakers, infusion pumps, heart-lung machines, dialysis machines, artificial organs, implants, prostheses, corrective lenses, etc. Currently, orthopedic implants make up the bulk of all devices implanted (∼1.5 million per annum worldwide) at a cost of around $10 billion. However, innovation will continuously serve as the fuel for market growth, bringing disruptive products and technologies to market.

New discoveries in biomaterials, technologies, computing, and biology will generate knowledge and growth of new treatments and cures, driving the medical device market to more cost-effective and patient-centered solutions.

Biomaterials are extremely linked to the performance of medical devices, and therefore, to the quality of life of patients. The definition of biomaterials has changed over time [1, 2] while several generations have been developed. However, these generations should be interpreted as the evolution of the requirements and properties of the medical devices. We can group them as follows:

Inert Biomaterials:

During the 1960s and 1970s, a first generation of biomaterials was developed for implantation and generation of medical devices. The goal of these inert biomaterials was to replace damaged tissue and provide structural support with a minimal tissue response in the host [3].

Bioactive Biomaterials:

In the 1980s and 1990s, a second generation of biomaterials, which was able to elicit a specific biological response at the interface of the material, began to develop. The bioactivity was accomplished by using coatings or similar strategies in order to increase and improve implant lifetime by optimizing the interface with the host tissue. These bioactive materials allowed the creation of more effective and less invasive medical devices [4–6]. Nowadays, this type of biomaterials is still used in many commercial products, for example, in dentistry and orthopedics [7].

Biodegradable Biomaterials:

Besides the advantages of bioactive materials, long-term implants were generally associated with infections, reactions due to toxicity or immunological processes, mechanical implant failure due to fatigue, etc. As a consequence, a third generation of biomaterials was developed. These biomaterials have the capability to degrade and be absorbed offering the possibility to overcome the drawbacks of permanent implants [3].

Smart Biomaterials:

Progress in biology, proteomics, and bioengineering during the last decade has led to the development of a fourth generation of biomaterials [8–12]. Smart biomaterials are willing to mimic nature's hierarchical structures and mechanisms to actively repair and regenerate damaged tissue by stimulating specific cellular responses. However, the re-creation of the tissue extracellular matrix is complicated and represents one of the challenges of the biomaterials field. However, important progress has been made in the design and manufacturing of scaffolds for tissue engineering and regenerative medicine. Nevertheless, despite their considerable advantages, only few smart biomaterials are being used for clinical applications so far.

While the first generation of biomaterials is still used in a wide range of applications, smart biomaterials will open innovative and new possibilities of treatments and applications.

Concerning the type of material, the vast majority of medical devices (stents, orthopedic implants, bone fixators, artificial joints, etc.) are made of metallic materials due to their strength, toughness, and durability. An extensive review on this topic has been done by Hanawa [13]. Specifically, metals have high strength, high elasticity, high fracture toughness, and high electrical conductivity when compared with ceramics and polymers. However, improvements of corrosion resistance and mechanical durability are needed in order to avoid environmental and health concerns over heavy metals used for medical purposes. In this context, there is a need to research and improve mechanical and surface properties of metals, because these features are key to tissue compatibility. Therefore, their physical properties (mechanical, biodegradable, magnetic, etc.) must be improved by redesigning metallic alloys and biofunctionalizing their surface.

Titanium alloys, such as Ti-6Al-7V, Ti-6Al-7Nb, Ti-6Al-2.5Fe, Ti-13Zr-13Ta, Ti-6Al-2Nb-1Ta, and Ti-15Zr-4Nb-4Ta, have been widely used for medical and dental applications. This type of α + β titanium alloy shows high corrosion resistance, specific strength, and good tissue compatibility. Because of their Young's modulus and corrosion resistance, titanium alloys are preferred over stainless steel and cobalt-chromium alloys for orthopedic and dental applications. However, their low elongation is often associated with fractures. Thus, the development of α + β titanium alloys with high elongation and sufficient strength is needed because no optimal titanium alloy is available so far. In addition, Young's modulus of metallic materials is still higher than cortical bone, inducing stress shielding and fracture. To solve these problems, metals with lower Young's modulus are needed. Several β-type titanium alloys with a low Young's modulus, including Ti-12Mo-6Zr-2Fe, T-15Mo, and Ti-15Mo-5Zr-2Al, have been developed for this purpose [14, 15]. On the other hand, ultrahigh-molecular-weight polyethylene and poly(methyl methacrylate) are being used to fill porous titanium alloys in order to obtain materials with reduced Young's modulus [16, 17].

Titanium-nickel alloys have been used to manufacture various medical devices, such as stents, guide wires, and endodontic reamers, due to their specific mechanical properties (shape memory, superelasticity, and damping). Nevertheless, material fractures, pitting, and crevice corrosion have been recently reported [18–21]. In fact, there is a significant problem of toxicity and allergy due to the release of nickel ions. Thus, alloys with better corrosion and fatigue properties must be developed. In fact, there is a huge demand for developing superelastic and shape-memory alloys without using nickel. Some alloys, such as Ti-Sn-Nb, Ti-Mo-Sn, Ti-Nb-O, and Ti-Nb-Al, have been produced with good shape-memory but not enough recovery strain and superelastic deformation stress. On the other hand, nickel-free austenitic stainless steel materials are being developed to obtain materials with better corrosion resistance and strength for medical purposes. Some examples are Fe-(19-23)Cr-(21-24)Mn-(0.5-1.5)Mo-(0.85-1.1)N alloy (BioDur®108), Fe-18Cr-18Mn-2Mo-0.9N alloy, and the Fe-(15-18)Cr-(10-12)Mn-(3-6)Mo-0.9N alloy. Co-Cr alloys exhibit excellent corrosion resistance and good wear resistance. However, when using these alloys as orthopedic prosthesis, they produce stress shielding in the adjacent bone. The lack of mechanical stimuli on the bone may lead to the failure and loosening of the implant due to bone resorption. Therefore, osseointegration is another relevant requirement for metallic implantable devices. To solve this problem, there is a need to develop techniques and methodologies to modify their surface in order to give them biofunctionality and improve tissue compatibility. This requirement is currently being fulfilled by using dry and wet processes, which are the most conventional and predominant surface modification techniques [22, 23]. Research in this field is ongoing for techniques that involve the immobilization of biofunctional molecules. However, due to difficulties in ensuring appropriate safety, quality, and durability of those treatments, these are still not used commercially. Further research is needed in order to study the biofunctionalization of metallic materials to use them in innovative technologies such as tissue engineering.

Another important requirement for some medical devices is the ability to be absorbed by the body. This feature is typical of some polymeric materials, but not metallic ones. In fact, there are two metallic materials that should be considered bioabsorbable: iron and magnesium. However, strict control of corrosion rates must be achieved for biodegradable magnesium alloys due to a certain degree of late recoil and neointima formation.

Metallic materials, such as stainless steels, Co-Cr alloys, and titanium alloys, become magnetized when a magnetic field is applied inducing the appearance of artifacts and the disablement of the magnetic resonance imaging (MRI) diagnostic tool. Since this is an important and widely used diagnostic tool, there is a need to develop medical devices made of materials with low magnetic susceptibility. In this sense, materials such as Au-Pt-Nb, Ti-Zr, Zr-Nb, and Zr-Mo alloys are being proposed due to their reduced magnetic susceptibility compared with other material such as Co-Cr-Mo and Ti alloys [24, 25]. However, some of them are difficult to process because of their tensile strength and elongation rates.

Alumina, zirconia, and porous ceramics are commonly employed to develop implantable medical devices such as femoral heads and hip prostheses. Their microstructure depends on the manufacturing system employed and is proportional to the mechanical and biological properties. Ceramic biomaterials show good wear rates, corrosion resistance, biocompatibility, and high strength [7]. Nevertheless, there is a need to increase the quality of ceramic materials to improve their low fracture toughness. On the other hand, porous ceramics (e.g., hydroxyapatite) used to mimic trabecular bone are exposed to mechanical collapse risk, and also their compression strength can be affected by aging. Bioactive ceramics, such as bioactive glasses (BGs), glass-ceramics, and calcium phosphates (CaPs), have been used as bone substitutes for decades due to their similitude with bone mineral structure. However, owing to their low tensile strength, poor mechanical properties, and low fracture toughness, they cannot be used for load-bearing applications. Further studies are needed to improve the mechanical features of these kinds of ceramic materials.

On the other hand, the use of polymers in surgery, prosthetics, pharmacology, and drug delivery is essential. Many polymeric compounds are considered biomaterials and used in many applications: silicones (tubes, plastic surgery), polyurethanes (catheters, cardiac pumps), polytetrafluoroethylene (orthopedics), nylon-type polyamides (sutures), polymeric compounds based on methyl methacrylate (cements, odontology, prostheses), etc. However, there is a need to improve their biostability and performance in terms of clinical applications because the release of wear debris is often present in those materials leading to undesirable effects.