 |
|
|
Using Risk
Assessment in the Biological Evaluation of Medical Devices
An evaluation of biocompatibility is an important part of the overall safety
assessment of any medical device. This evaluation may be conducted using various test methods, including analytical chemistry,
in vitro tests, and in vivo animal studies. The basic requirements for biocompatibility testing have been harmonized internationally under the International Organization for Standardization (ISO). The master list of
recommendations for medical devices is listed in ISO 10993-1 Biological evaluation of medical devices - Evaluation and Testing.
The biocompatibility test matrix listed in this standard categorizes devices based on the type and duration of patient contact.
Generally, the more invasive the route of exposure or more extensive the duration of use with a device, the greater and more complex the
number of tests to demonstrate biological safety. ISO 10993-1 does not prescribe a specific list of tests for any particular
medical device. Instead it provides a framework that can be used to design a customized biocompatibility testing program, often
incorporating chemical characterization of device materials as well as standardized animal toxicity studies.
Device design engineers should generally consult with an experienced device
toxicologist and their clinical investigators to determine how best to address the biocompatibility test matrix. The rationale for
the testing strategy should be properly documented and include an evaluation of each biological effect category. In some
situations, not all the tests suggested in the matrix of ISO 10993-1 are essential or relevant for a particular device. While in
other cases, the suggested tests may not be sufficient to completely evaluate a medical device for a specific application. Both
situations call for a biological risk assessment to be performed by a qualified individual to thoroughly evaluate the overall biocompatibility of a
medical device and its component materials.
A biological risk assessment can often evaluate the compatibility between the device materials and
biological tissues or fluids without the need for extensive testing by using data that is readily available. This data may be
derived from previous device submissions, from suppliers of materials or components, or from clinical experience with predicate devices containing
similar materials. Expertise from qualified personnel can help determine if the available historical data reduces the
toxicological risks associated with a device to an acceptable level. This becomes especially relevant when a manufacturer decides
not to perform tests for a biological effect specified by the biocompatibility matrix for their particular category of devices.
Manufacturers may also use analytical characterization of device
materials to demonstrate that a device has a low risk of producing a particular biological effect, possibly eliminating the need for
extensive biocompatibility testing. Analytical testing is also useful for comparison of biomaterials from two different suppliers
or to examine the influence of sterilization, surface modification, or aging on a material’s chemical composition. The
information can then be used as a reference for continued monitoring of device materials to ensure consistency with future production
lots. To evaluate devices for potentially toxic leachable substances and their bioavailability, materials are typically extracted
under exaggerated conditions of time and temperature. By linking the subsequent analysis of extracted compounds with a
toxicological risk assessment, pertinent information can be gathered regarding the device materials and their propensity to elicit an adverse
biological response.
Based on the guidelines of ISO 10993-17: Biological evaluation of
medical devices - Methods for the establishment of allowable limits for leachable substances, this type of assessment determines how an
individual might likely come into contact with a leachable chemical agent, the amount of exposure to the chemical, and the probable toxic effects of
the substance. According to part 17, the estimated dose of each device substance potentially exposed to the patient is compared to
health-based exposure levels derived from information available in toxicological databases. If the dose of the leachable substance
exposed to the patient is less than the dose of the chemical compound(s) shown to produce adverse effects in similar situations, then it can be
predicted that adverse biological effects are unlikely to occur in patients using the medical device. The majority of
materials and finished devices produce no observable adverse effect when tested at the physiological or anatomical limits of the in vitro and animal
models commonly used in non-clinical evaluations, resulting in a qualitative assessment of device materials. However, depending on
the range of the input data, a comprehensive risk assessment can result in quantitative outcomes to better define the compatibility between the
materials used and biological tissues, cells, and body fluids.
To summarize, risk assessment of a medical device involves a systematic
approach to categorizing and analyzing scientific information on the hazardous properties of materials and inherent leachable substances and the
extent of potential human exposure to them. The assessment considers the chemical nature of the materials, prior use of the
materials in predicate devices, and biological test data to augment the overall biocompatibility evaluation of a medical device in support of a
regulatory submission.
Having a well-defined program before deciding on the testing regimen may
save a manufacturer time and money and possibly accelerate time to market.
Back to
Top
|
Metallic Medical Components: Quantifying Residues
According to 21 CFR 820.70, “Each
manufacturer shall establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably be expected
to have an adverse effect on product quality.” While there are several methods by which to monitor the cleanliness of
materials, ASTM 2459-05 offers a method for qualitative assessment of the amount of residue from metallic medical components for single use
devices. This method does not advocate a level of cleanliness, but offers techniques to quantify residue when extracted with
aqueous and non-aqueous solvents. The method will not capture all types of residue, but rather provides an indication of relative
cleanliness. Materials that should be considered when developing a program should include adhesives, solvents, cleaning agents
(detergents), processing aids, as well as insoluble particulates.
Before beginning a cleaning study, it is important to
consider a plan for validation, so that a documented procedure for obtaining, recording and interpreting results is in place. It
is necessary to ensure that the test method is repeatable and reliable.
The first step is identifying the potential residues or
contaminants by considering each step of the manufacturing process and gathering information from Material Safety Data Sheets (MSDS), certificate of
analysis (C of A), as well as package inserts from vendors. By evaluating the information appropriately, the proper solvents can
be chosen to most effectively remove potential residues from the surface of the device.
The next step is to determine an effective extraction
technique. One option for this is a sonication extraction, which is performed below the boiling point of the chosen solvent.
Alternatively, the device can be extracted using a soxhlet extraction, in which the solvent is boiled and any vaporized solvent is returned to the
extraction flask. Both are effective techniques, however as part of the validation it is essential to determine the time and
temperature based on the extraction efficiency of the target residues.
To verify that the methods chosen are effective, the
components of interest should be spiked with the known possible contaminants and the extractions carried out. In order to be
considered effective the extraction efficiency should be greater the 75% of the target residues.
Once a valid method has been investigated and is in
place, random samples should be taken form a variety of lots. There should be an adequate number of replicates used to establish
reproducibility with sample sizes large enough to gain adequate detection limits of any trace residues. During the extraction
process it is necessary to consider both the soluble and insoluble residues collected. This total value is what is used to determine the residue on
the device. This information, combined with a toxicological assessment of the known contaminants of the device, can be used to establish baseline
information and limits for cleanliness of the device. Materials should be monitored on a routine basis to ensure nothing is
changing in the process and show that the same high quality cleaning process is maintained overtime.
Back to Top
|
NAMSA and MedicSense Partner to Keep Pace With Rapid Growth in
Israel
In March
2008, NAMSA announced a new partnership with MedicSense in Petah Tikva, Israel. Because of the formation of the partnership,
MedicSense is now the official sales representative of NAMSA and Biomatech
for NAMSA's clients in Israel.
Adi Ickowicz, MedicSense’s co-CEO and NAMSA’s new National Account Manager for Israel, says “We are proud to
represent NAMSA the leading company in the world in the field of device evaluation and biocompatibility and functional testing. The
new partnership between MedicSense and NAMSA will be a meaningful opportunity for both companies to extend their presence and influence in the rapidly
increasing and dynamic Biomedical industry in Israel.”
MedicSense
has over 15 years experience in the Bio-Med industry providing regulatory, CRO and QA services. They have expertise in guiding
clients through the entire development process from initial concept to regulatory plan, verification and validation, clinical studies, pre-marketing
clearance and post-marketing compliance. Their vast experience will assist NAMSA’s clients in Israel in complying with
international standards as well as worldwide regulatory organizations.
MedicSense Ltd.
14 Imber Street,
Kiryat Arie,
Petach Tikva
Israel 49511
Phone : +972-3-9233666
Fax: +972-3-9231274
Primary Contact: Mr. Adi Ickowicz
|
NAMSA Welcomes New Pathologists: Dr. Alan Metz and Dr. Robert
Parker
In June of 2007, NAMSA welcomed Dr.
Alan Metz as a Board Certified Veterinary Pathologist in the Toxicology Department of the Ohio laboratory.
Dr. Metz holds a Doctorate in
Veterinary Medicine from Michigan State University and is a Diplomate of the American College of Veterinary Pathologists. His primary expertise over
the last 21 years is in the areas of toxicologic pathology and cardiovascular pathology.
Prior to joining NAMSA, Dr. Metz was
a Senior Scientific Advisor and former Director of Toxicologic Pathology at Pfizer, Ann Arbor. He is a member of the American College of Veterinary
Pathologists, the American Veterinary Medical Association and the Society of Toxicologic Pathologists. Dr. Metz has also coauthored over 40 abstracts
and manuscripts as well as a book chapter.
He is currently a reviewer for the
Journal of Ophthalmic Pharmacology and Therapeutics and has previously served in this capacity for the American Journal of Veterinary Research. Dr.
Metz is also a former member of an FDA Expert Working Group on Biomarkers of Cardiac Injury.
Dr.
Robert Parker joined NAMSA in December 2007 as a Board Certified Veterinary Pathologist in the Toxicology Department of the Ohio laboratory.
Dr. Parker holds Doctorates in
Veterinary Medicine from Auburn University and Experimental Pathology from the University of Alabama at Birmingham. He is a
Diplomate of the American College of Veterinary Pathologists. His primary expertise is in the areas of experimental pathology, laboratory animal
pathology and toxicologic pathology where he brings over 25 years of experience.
Dr. Parker joined NAMSA after working
for Pfizer and Warner–Lambert/Parke–Davis as a Pathologist and Senior Research Associate. With over 10 years experience as a faculty
member at the University of Alabama at Birmingham, the Pennsylvania State University and the University of Tennessee, he has presented and published
numerous papers.
He is a currently a reviewer for
Veterinary Pathology and has served in this capacity for the Journal of the American Veterinary Medical Association, the American Journal of
Veterinary Research and Laboratory Animal Science.
Industry
Events:
June 3 - 5, 2008, New York, NY - Jacob K. Javits Convention
Center
Booth # 1237
|
|
|
|
|
