Biomedical Engineering Reference
In-Depth Information
Both ISO 1135-3 and ISO 3826-4 list requirements for cell culture cytotoxicity,
short-term intramuscular implantation, hemolysis in vitro, delayed contact sensiti-
zation, intracutaneous irritation, pyrogenicity, and sterility.
In the case of innovative devices, the frequent absence of a specific standard
creates the risk of an incomplete evaluation and the unsuitable use of a medical
device, and therefore the risk of serious or repetitive incidents that will hinder the
development of a valuable technique. Standardization also means selection of tests
and adoption of the formal, sometimes rather time consuming, procedure of set-
ting up a standard. The consequences are that methods for very specific scientific
problems are not included in a standard and that the most recent developments in
testing methods may not be reflected in such a standard. Standards for complex or
invasive devices are particularly in need of development. For some of these devices,
there is no consensus among existing standards on what are appropriate tests. For
example, there is disagreement on the testing of hemodialyzers. The French and
German standards require hemolysis testing on an eluate from the hemodialyzer,
whereas FDA guidelines require the following tests: cytotoxicity in vitro, hemoly-
sis, complement activation, cell adhesion, protein adsorption, whole-blood clotting
time for thrombogenicity, pyrogenicity, genotoxicity, acute systemic toxicity, intra-
cutaneous injection, implantation, guinea pig maximization for delayed sensitiza-
tion, subchronic toxicity, thrombogenicity by examining platelet and fibrinogen
turnover, thrombus formation, and the resulting emboli. The FDA requirements
do not delineate the biological system and exposure protocol that are necessary
for interpretation of the measurements. For example, a whole-blood clotting time
assay may not be meaningful because heparin anticoagulants are used during he-
modialysis procedures.
11.5 Regulatory Agencies
11.5.1 The Food and Drug Administration
Standards establish basic requirements for safe development and implementation of
medical devices, minimizing the risk caused to the patients when used. The new de-
vice must be proven not only safe but also effective in curing or ameliorating a spe-
cific disease. Standardized tests should be used while developing medical devices.
The advantages of standards are mainly enhanced reproducibility, resulting in a
comparison of the data obtained from different laboratories. Standards are used in
some countries as regulatory requirements rather than being voluntary guidelines.
Regulators play an important role in ensuring safety by specifying standard require-
ments that medical devices and therapeutics must meet before they can be placed
on the market. In the United States, the FDA (www.fda.gov) is responsible for the
regulation of drugs and medical devices. In the United Kingdom, the Medicines and
Healthcare Products Regulatory Agency (www.mhra.gov.uk/) is involved in ensur-
ing the acceptable safety of medicines and medical devices. The Therapeutic Goods
Administration (www.tga.gov.au/) is essentially Australia's counterpart to FDA.
The FDA is responsible for ensuring that human and veterinary drugs, bio-
logical products, medical devices, and electronic products that emit radiation are
