Documente Academic
Documente Profesional
Documente Cultură
BIOM 9410
Module 3
LEARNING OUTCOMES
At the end of this module, you should be able to
MODULE_15_3 1
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
INTRODUCTION
Refer back to the Medical Device Product Development and Marketing Map
presented in Module 1 and the description of GLP in Module 2. The information in
this module relates to one of the wide range of tests that are carried out according to
GLP at an early stage of the development of a medical device.
Imagine that basic research at the university or research institution has resulted in a
product concept. In the product development and nonclinical testing stage, these
ideas and concepts are turning into design specifications, prototype devices and a
set of preferred materials for manufacture. In order to determine the safety and
efficacy of these devices, a wide variety of tests are performed on the prototypes and
the materials that have been selected for use in manufacture and one range of tests
performed relates to the “biocompatibility” of the device.
For those of you who haven’t done the Biocompatibility course, let’s discuss what
biocompatibility is first. Unfortunately, there is no single, all-encompassing
description of biocompatibility. In the book, Biological performance of materials:
fundamentals of biocompatibility (1992), Jonathan Black describes biocompatibility
as “biological performance in a specific application that is judged suitable to that
situation”. David Williams in his book, The Williams Dictionary of Biomaterials
(1999), says it is “the ability of a material to perform with an appropriate host
response in a specific application”.
1. Material responses or how the biomaterial responds to the living system and
2. Host or living system responses or how the living system responds to the
material (other than the intended therapeutic response)
MODULE_15_3 2
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
When a biomaterial is exposed to a living system, a number of events that alter that
material occur immediately. Other factors can cause more gradual changes in the
material over time.
On initial contact with living systems, all materials adsorb proteins and other
molecules. This alters the surface characteristics of the material or what the living
system “sees” when it looks at the material. Some other material alterations that can
occur on contact with living systems include:
• Corrosion and/or
• Wear
These material alterations can lead to altered physical properties, altered chemistry
and/or the release of leachables and/or degradation products. All of these effects
can affect the “biocompatibility” of the material.
2. Host Responses
Biomaterials that come into contact with living systems usually cause some form of
trauma to the tissue, ranging from minor disruption of the skin to major surgical
trauma. Even non-invasive diagnostic devices such as transcutaneous ultrasound
can cause elevation of temperature in tissues that can damage cells. Host
responses are responses seen in “living systems”. Living systems can be humans,
sheep dogs or any other living system. Host responses can be categorised into two
main types based on location of the response:
MODULE_15_3 3
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
• inflammation
• tissue remodelling
• hypersensitivity and
• rejection
• carcinogenesis and
• genotoxicity
MODULE_15_3 4
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
Initial material selection usually begins with a set of mechanical and physical
specifications defined by the physical requirements of the device. For example, the
physical requirements of a subclavian catheter relate to the required size and
flexibility of the device.
For regulatory reasons, it is usually more expedient to use and gain regulatory
approval for a material already used in similar medical applications to the device
being developed. This means the approach to materials selection is usually
conservative and the tendency is almost always to use an existing medical material
with known responses and physical/chemical characteristics rather than attempting
to use a new material with unknown responses.
MODULE_15_3 5
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
MODULE_15_3 6
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
ISO 10993 is implemented in various ways around the world. The general concepts
embodied in the standard are described on the website
http://www.mddionline.com/article/considerations-biocompatibility-evaluation-
medical-devices.
The FDA’s description of the implementation of ISO 10993 in the USA can be found
at
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocum
ents/ucm080735.htm.
http://www.mhra.gov.uk/home/groups/es-era/documents/publication/con007509.pdf
In summary, the ISO 10993 suite of standards is based on the following principles:
MODULE_15_3 7
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
MODULE_15_3 8
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
http://www.mddionline.com/article/practical-guide-iso-10993-5-
cytotoxicity
MODULE_15_3 9
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
MODULE_15_3 10
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
determine the tests required. The flowcharts and tables used for this categorisation
can be found in ISO 10993 - 1 (available at the Australian Standards website through
the UNSW electronic library – Sirius). The FDA has used a slightly modified version
of these tables in the past but we will use the ISO version in this course.
• Surface-contacting devices
• Implant devices
MODULE_15_3 11
GRADUATE SCHOOL OF BIOMEDICAL ENGINEERING
BIOM 9410 REGULATORY REQUIREMENTS OF MEDICAL TECHNOLOGY
Once the nature and duration of contact have been determined, the tables in ISO
10993-1, then define the set of tests to be carried out for that particular material and
application.
SUMMARY
4. Biocompatibility testing can include in vitro and in vivo laboratory studies and
nonclinical trials.
MODULE_15_3 12