A Primer on Engineering Design of Biomedical Devices

95 Pages·2013·4.206 MB·English

by  Carl A. Nelson

A Primer on Engineering Design of
Biomedical Devices
Carl A. Nelson, PhD
University of Nebraska
A Primer on Engineering Design of Biomedical Devices
Second e-book edition © 2013 by Carl A. Nelson
All rights reserved
No part of this book may be copied or distributed without written permission of the
author.
Table of Contents

Unit 1: Understanding Biomedical Systems and Devices
Chapter 1: Introduction to Biomedical Device Design ........................................................1
1.1 – The FDA and Device Design .................................................................................1
1.2 – Topics for Thought and Discussion ......................................................................4
1.3 – Problems ................................................................................................................5
1.4 – References for Further Study ................................................................................5
Chapter 2: Defining the Intended Function of a Device ......................................................6
2.1 – Viscoelastic Tissues: Their Properties and Behaviors ...........................................6
2.2 – The Body’s Fluid Systems ...................................................................................17
2.3 – Summary and Relation to Device Design ............................................................23
2.3 – Topics for Thought and Discussion .....................................................................24
2.4 – Problems ..............................................................................................................24
2.5 – References for Further Study ...............................................................................26
Chapter 3: Introduction to Biocompatibility ......................................................................28
3.1 – The Bio-Environment ..........................................................................................28
3.2 – Stability and Degradation ....................................................................................29
3.3 – Surfaces and Biocompatibility.............................................................................29
3.4 – Topics for Thought and Discussion .....................................................................31
3.5 – Problems ..............................................................................................................31
3.6 – References for Further Study ...............................................................................32
Chapter 4: Introduction to Metals as Biomaterials ............................................................33
4.1 – Corrosion .............................................................................................................33
4.2 – Stainless Steels ....................................................................................................34
4.3 – Cobalt-Chromium Alloys ....................................................................................35
4.4 – Titanium...............................................................................................................35
4.5 – Other Alloys ........................................................................................................36
4.6 – Topics for Thought and Discussion .....................................................................37
4.7 – Problems ..............................................................................................................37
4.8 – References for Further Study ...............................................................................38
Chapter 5: Introduction to Ceramics and Composites as Biomaterials .............................39
5.1 – Alumina ...............................................................................................................40
5.2 – Zirconia ................................................................................................................40
5.3 – Calcium Phosphates .............................................................................................40
5.4 – Glass ....................................................................................................................40
5.5 – Carbon .................................................................................................................41
5.6 – Ceramics Overview .............................................................................................41
5.7 – Composites ..........................................................................................................41
5.8 – Topics for Thought and Discussion .....................................................................43
5.9 – Problems ..............................................................................................................44
5.10 – References for Further Study .............................................................................44
Chapter 6: Introduction to Polymers as Biomaterials ........................................................45
6.1 – Types of Polymers and Their Properties .............................................................45
6.2 – Elastomers ...........................................................................................................47
6.3 – Hydrogels.............................................................................................................48
6.4 – Molecular Weight Distributions ..........................................................................48
6.5 – Biodegradation and Hydrolysis ...........................................................................49
6.6 – Topics for Thought and Discussion .....................................................................50
6.7 – Problems ..............................................................................................................51
6.8 – References for Further Study ...............................................................................51

Unit 2: Designing Biomedical Devices
Chapter 7: Choosing Biomaterials using Performance Indices .........................................52
7.1 – General Guidelines for Choice of Biomaterials ..................................................52
7.2 – Performance Indices for Material Selection ........................................................53
7.3 – Topics for Thought and Discussion .....................................................................55
7.4 – Problems ..............................................................................................................55
7.5 – References for Further Study ...............................................................................56
Chapter 8: Defining and Meeting Product Requirements ..................................................57
8.1 – Screening Matrix .................................................................................................57
8.2 – Functional Decomposition ...................................................................................58
8.3 – Concept Generation: Morphological Chart .........................................................60
8.4 – Concept Evaluation: Pugh Decision Matrix ........................................................60
8.5 – Axiomatic Design ................................................................................................62
8.6 – Quality .................................................................................................................63
8.7 – Topics for Thought and Discussion .....................................................................66
8.8 – Problems ..............................................................................................................67
8.9 – References for Further Study ...............................................................................67
Chapter 9: Techniques for Detailed Design of Devices .....................................................69
9.1 – Design for Manufacture .......................................................................................69
9.2 – Design for Assembly ...........................................................................................71
9.3 – Practical Considerations Relevant to Medical Devices .......................................73
9.3 – Topics for Thought and Discussion .....................................................................74
9.4 – Problems ..............................................................................................................74
9.5 – References for Further Study ...............................................................................75
Chapter 10: Failure Analysis and Prevention ....................................................................76
10.1 – Failure and Reliability .......................................................................................76
10.2 – Failure Modes and Effects Analysis (FMEA) ...................................................77
10.3 – Sensitivity Analysis ...........................................................................................79
10.4 – Robust Design....................................................................................................80
10.5 – Topics for Thought and Discussion ...................................................................82
10.6 – Problems ............................................................................................................83
10.7 – References for Further Study .............................................................................83

Appendix A: Table of some polymer properties and typical uses
Appendix B: Sample QFD chart for a surgical tool design problem
Appendix C: Sample DFA evaluation table
Appendix D: Sample FMEA template
Chapter 1: Introduction to Biomedical Device Design

The purpose of this text is to introduce concepts of design methodology in the context of
biomedical engineering and medical devices in particular. The desired result is that the
reader will develop an understanding of the entire process of medical device
development, from problem definition through concept generation and refinement to the
final product. To some extent, this requires one to become familiar with some aspects of
various engineering and science disciplines, including biology, mechanics, kinematics,
chemistry, etc.

To gain the correct perspective for this study, it is necessary to understand the importance
of the various steps that are involved in the design of medical devices and related
technologies. Therefore, we will begin by describing the motivation for following a
rigorous procedure in design. This will be followed by an introduction to select modeling
techniques and other basic information related to the human body, or the environment in
which biomedical devices are designed to operate. Material selection, an important step
in the design process, will then be discussed. Finally, a variety of techniques and
methodologies for design will be presented.

1.1 The FDA and Device Design

The US Food and Drug Administration (FDA) was created in 1906 with the mission of
ensuring that products are both effective and safe for consumers. In 1938, the FDA was
granted power to enforce its mission. As its name implies, the FDA has jurisdiction over
the safety and effectiveness of food products, drugs, and medical devices. We will
concern ourselves here only with medical devices.

A key to understanding the FDA is to know that it does not regulate the practice of
medicine. Rather, it regulates commerce and marketing of products within its
jurisdiction. For instance, if a surgeon decides to design a new tool, build a prototype in
his garage, and use it on a patient, the FDA has no authority to prohibit this. If he then
decides to produce and sell this new tool, he must then abide by the FDA’s regulations.

The FDA defines a medical device as a non-drug material intended for use in diagnosis,
cure, prevention, or treatment of disease, or one created with the intent to affect the
structure or function of the body. An important aspect of any medical device is which
structure or function of the body it is intended to affect. Therefore, no device is approved
for general use; devices are only approved for specific uses.

The process of gaining approval for a medical device from the FDA can involve several
steps depending on the type of device. These can include a Pre-Market Notification
application, a Pre-Market Approval application, and an Investigational Device Exemption
application. For many devices, the minimum basic requirements are to file a Pre-Market
Notification, register any business involved in production, marketing, or sale, list the
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device officially with the FDA, follow so-called good manufacturing practices, and
maintain detailed records.

1.1.1 Registration and Listing

The FDA requires that any company involved in the manufacture, labeling, packaging, or
distribution of medical devices register their business with the FDA. These companies
must also provide to the FDA a list of all medical devices that they have a part in
marketing or producing.

1.1.2 Pre-Market Notification

The Pre-Market Notification application is commonly referred to as the 510(k). The goal
of this application is to establish that the device in question is “substantially equivalent”
to an existing approved device. Substantial equivalence means that the device has the
same or similar technological characteristics and is intended for the same use. Existing
approved devices are called predicate devices, and a 510(k) application may refer to
many predicate devices. Equivalence is claimed by comparing and contrasting features
of the new device and the predicates. If the characteristics or functions are different, one
must indicate why this does not affect the safety or efficacy of the device. Generally, the
510(k) application also includes samples of labeling, indicating the intended use and
function of the device. Data from laboratory evaluations are usually included, but
clinical tests are not required.

1.1.3 Clinical Research and Institutional Review Boards

Any entity performing clinical research (on human subjects) must have an Institutional
Review Board (IRB). This group of individuals is charged with determining whether the
risk to the subjects is equitable, the selection of subjects is equitable, their informed
consent is sought and documented, and that their privacy and confidentiality are
maintained. The IRB also ensures that test data are monitored to ensure the safety of the
subjects.

1.1.4 Investigational Device Exemption

Investigational Device Exemption (IDE) applications enable medical devices to be
shipped or transported for purposes of clinical trials prior to the device receiving
clearance to be sold on the open market. These applications include reports of prior
investigations, descriptions of methods, facilities, and controls used, and so forth. They
also include samples of agreements between the researchers or investigators, lists of
involved IRBs, copies of informed consent forms, samples of labeling, etc.

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1.1.5 Pre-Market Approval

The Pre-Market Approval application (PMMA) is a lot like the 510(k) application but is
more involved. Generally, clinical research is involved in this step, so an IDE has
already been filed. The PMMA includes a detailed description of the device,
performance standards used in its evaluation, results of clinical and laboratory testing,
and an assessment of the device’s environmental impact. Samples of proposed labeling
are also included, as well as samples of the device itself.

1.1.6 Device Classification

The FDA classifies devices based on their intended function and the level of risk which
may be associated with their use. Class I devices are not life-sustaining, and their failure
poses no risk to a person’s life. Therefore, there is no need for performance standards for
such devices. In fact, simpler Class I devices can even be exempt from the basic
requirements of a 510(k) application. Class II devices are not life-sustaining, but their
failure can post some risk of harm. Therefore, these devices must meet specific controls
or performance standards. Class III devices are life-sustaining, and/or their failure could
pose a serious risk to life or health. Generally, Class III devices require a full PMMA
process, which can take years in the current system. In short, the determining factor
which decides the device classification is the potential for risk to life and health. Risk
can depend on direct effects of device failure, systemic or secondary effects, duration of
device contact with the human body, and even the degree of difficulty of failure
detection. For devices intended to help restore proper functionalities in the body, one
must consider the change in a person’s health relative to the “diseased” state, not
necessarily from the fully healthy state, when considering the effects of device failure.

Many examples of medical devices and their FDA classification can be found at:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm

1.1.7 Good Lab and Manufacturing Practices

During the device development and testing phase, the FDA requires that so-called Good
Lab Practices (GLP) be followed. These include internal audits and inspections,
mechanisms for approval of study protocols, and detailed reports of data to support any
information provided to the FDA.

During the manufacturing phase, Good Manufacturing Practices (GMP) must be
followed. The GMP are a list of rules providing a minimum standard of safety
throughout the manufacturing process. In short, the GMP stipulate that the design
process and manufacturing controls must be documented in detail. Also included in the
GMP is compliance with the ISO 9001 industry standard related to quality management.

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1.1.8 Industry Standards

Standards are guidelines representing the common viewpoint of manufacturers, users,
consumers, and regulators. Compliance with standards is generally voluntary, and in the
case of medical devices compliance is not enforceable unless specifically stipulated by
the FDA. There are many bodies which publish standards related to medical devices,
including AAMI, ASTM, ANSI, and ISO. Most of these standards are published with
annual revisions.

There are two standards with the highest relevance to biomedical devices. The first of
these is ASTM volume 13.01 – Medical Devices. This standard primarily addresses the
use of biomaterials in device design. It covers manufacture, chemical requirements,
mechanical requirements, test methods and best practices, special tests, and certification.

The other important standard related to medical devices is ISO 10993. This is a standard
for evaluation of medical devices. Part 1 of the standard helps to decide which types of
tests are necessary, and the rest of the standard describes how to perform these tests.
Much of Part 1 is summarized in a table at:
http://www.ethoxint.com/laboratory/tox-table.htm

As in FDA device classification, factors influencing the tests and other recommendations
contained in these standards include duration of tissue-device contact and type of contact
(e.g., skin-contact devices vs. implanted devices).

1.1.9 Summary

As has become evident, the process of bringing a biomedical device to market can be
long and involved. Rather than focus on the details of the approval process, let us simply
summarize by saying that detailed documentation is the key to FDA compliance.
Furthermore, detailed documentation of the steps in the design process can also be used
as a tool for achieving effective and high-quality designs. This premise is a primary
motivation for the remainder of this text.

1.2 Topics for Thought and Discussion

1) Why is it important to understand the regulations that govern medical devices before
starting the design process?
2) Can you summarize the pathways to FDA approval for different classes of medical
devices?
3) What is the importance of predicate devices in the FDA classification process?
4) How would you succinctly state the FDA’s mission? What is the most important
implication of this for product engineers?

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1.3 Problems

1) Without looking at the FDA database, classify the following devices (I, II, or III).
Give an explanation (a few words) of your reasoning for each. Then verify your
answers by checking the database. If your assessment is different from what you find
in the database, state what assumptions you may have made that caused the
difference. Based on information in the database, list the 7-digit regulation numbers,
submission type (describing the device approval pathway), and any recognized
consensus standard.
a) Umbilical clamp/cutter for newborn babies
b) Operating room shoe cover
c) Surgical knife/scalpel
d) Silicone breast implant
e) Laser for use in dental soft tissue ablation
f) Infusion pump
g) Metal orthodontic bracket
h) Prosthetic mechanical “hook” limb component
i) External cardiac compressor
2) Research and provide a more detailed description of GLP and GMP.
3) Research any specific relevant standard contained in ISO 10993 or ASTM 13.01, and
give a detailed description of what it outlines.
4) Visit your IRB’s website, and summarize its particular mission and any interesting
information you found there.

1.4 References for Further Study

1) Ethox Intl. Inc., 2013. Toxicology Table, online at
http://www.ethoxint.com/laboratory/tox-table.htm.
2) King, P. H. and Fries, R. C. (eds.), 2003. Design of Biomedical Devices and Systems,
Dekker.
3) Fries, R. C., 2013. Reliable Design of Medical Devices, 3rd ed., CRC Press.
4) US Food and Drug Administration, 2013. Device Classification Database, online at
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm.

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Chapter 2: Defining the Intended Function of a Device

Successfully bringing a medical product to market hinges on FDA approval (or other
regulatory bodies, outside the United States). As pointed out in the previous chapter, the
approval process is first concerned with identification of the intended function of the
device and comparison with devices having similar function.

Not coincidentally, analysis of the function of a device is an important part of the design
process as well. Systematically identifying the intended device function(s) can
sometimes lead to an improved understanding of how those functions might be
accomplished. It is important, especially early in the design process, that one distinguish
between function (what the device should do) and form (how the function is
accomplished).

The process of rigorously identifying the functions of a product is called functional
decomposition. Typically, one begins by stating the overall function, and then creating
descriptions of subfunctions. With the subfunctions arranged logically, the process is
repeated (subfunctions are refined) until single actions are obtained. Each low-level
subfunction should be stated as a verb, with a possible object (e.g., circulate blood). We
will return to the topic of functional decomposition in greater detail in a later chapter.

Because medical devices include those which attempt to affect the function of the body, it
is important to start with an understanding of how the body works. This knowledge
provides a basis from which to design medical devices starting with the definition of
intended function. Therefore, the remainder of this chapter is devoted to providing an
overview of some characteristics of tissues, organs, and systems in the body, with an
emphasis on the engineering perspective, including mathematical modeling. This will aid
in determining device function and identifying engineering specifications for devices.

2.1 Viscoelastic Tissues: Their Properties and Behavior

On a very basic level, human tissue is a composite material. The soft tissues of the body
are largely made up of two components called elastin and collagen. Simply summarized,
elastin gives tissues their compliance, and collagen gives them strength and toughness.

2.1.1 Elastin

A long, cross-linked molecule called elastin is the most linearly elastic biosolid known.
In terms of mechanical properties (Young’s modulus in particular), elastin (E = 0.6 MPa)
can be compared to lightly vulcanized rubber (E = 1.4 MPa).

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