The document provides an overview of biocompatibility testing for polymers used in medical devices, defining biocompatibility as the ability of a material to elicit a suitable biological response without toxicity. It outlines the necessity of structured assessments mandated by regulatory bodies like the FDA and ISO to ensure safety, along with the three testing levels: preclinical, in vivo, and clinical trials. Additionally, it details various biological tests for assessing material safety, including cytotoxicity, sensitization, irritation, and other toxicity tests.

1. BIOCOMPATIBILITY
TESTING OF POLYMERS
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2. What is biocompatibility?
 Biocompatibility - ability of material to elicit an
appropriate biological response on a given
application in the body.
 The ability of a material to perform with an
appropriate host response in a specific
application", Williams' definition.
 "The quality of not having toxic or injurious
effects on biological systems".
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3. Medical devices and their component materials may leach
compounds or have surface characteristics that may produce
undesirable effects when used clinically. The selection and
evaluation of materials and devices intended for use in
humans requires a structured program of assessment to
establish biocompatibility and safety.
Current regulations, whether in accordance with the U.S.
Food and Drug Administration (FDA), the International
Organization for Standardization (ISO), or the Japanese
Ministry of Health, Labor and Welfare (JMHLW), require that
manufacturers conduct adequate safety testing of their
finished devices through pre-clinical and clinical phases as
part of the regulatory clearance process.
NEED
BIOCOMPATIBILITY TESTING
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4. ISO 10993-1 and FDA G95-1 Guidelines
Guidelines
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5. Three levels for biocompatibility testing
 Level 1 Series of preclinical test in animals and
in vitro studies. These studies can be used as a
screening phase but should be followed with
more detailed investigation
 Level 2 In usage test in animals at the sites
where the materials have to be used.
 Level 3 Clinical trial in humans, after the data
have been sufficiently screened in the first two
levels
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6. Classification of biological test
1. Cytotoxicity test
2. Sensitization
3. Intracutaneous Reactivity
4. Irritation
5. Systemic Toxicity (Acute Toxicity)
6. Sub chronic Toxicity (Sub acute Toxicity)
7. Chronic Toxicity.
8. Implantation
9. Haemocompatibility
10. Genotoxicity
11. Carcinogenicity
12. Reproductive & Developmental Toxicity
13. Biodegradation
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7. Cytotoxicity
 Cytotoxicity test asses cell death caused by
a material measuring cell number or growth
before and after exposure to that material .
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8. Sensitization
 These tests estimate the potential for contact
sensitization of medical devices, materials
and / or their extracts using suitable animal
models. These tests are appropriate because
exposure or contact to even minute quantities
of potential leachables can result in allergic
or sensitization reactions Mandatory for all
biomaterials
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9. Irritation Test
 These tests estimate the irritation potential of
medical devices, materials or their extracts,
using appropriate sites for implant tissue such
as Skin Eye Mucous membrane in a suitable
animal model. These tests are performed
using appropriate route (skin, eye or mucosa)
and duration of exposure or contact to
determine irritant effects of materials or
potential leachables.
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10. Intracutaneous Reactivity
 Intracutaneous Reactivity Assesses the
localized reaction of tissue to medical device /
material extracts. These tests are carried out
in such devices, where determination of
irritation by dermal or mucosal tests are not
appropriate
 Eg : Devices having access to the blood path
OR where material extractables are
hydrophobic
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11. Systemic Toxicity (Acute Toxicity)
 Systemic Toxicity (Acute Toxicity) Estimates
the potential harmful effects of either single or
multiple exposures, during the period of less
than 24 hours, to medical devices, materials
or their extracts in suitable animal model
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12. Sub chronic Toxicity
(Sub acute Toxicity)
 Sub chronic Toxicity (Sub acute Toxicity)
Estimates the potential harmful effects of
either single or multiple exposures, during the
period of NOT less than 24 hours to a period
not greater than 10% of the life span of the
animal model, to medical devices, materials
or their extracts in suitable animal model
 Note: These tests may be waived for
materials which has chronic toxicity data
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13. Pyrogenicity tests carried out to detect
material mediated pyrogenic reactions of
extracts of medical devices or materials
Note :Pyrogenicity tests are also conducted
to ensure the safe level of endotoxins in the
finished / sterlized product
Pyrogenicity tests
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14. Genotoxicity
 Genotoxicity These tests apply mammalian or
non-mammalian cell culture techniques to
determine gene mutations changes in
chromosomal structure and number other
 DNA or gene toxicities caused by the device,
material or their extracts.
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15. Implantation
 Implantation Assesses the local pathological
effects on the living tissue, at both the gross
level and microscopic levels Sample of the
material or the device is surgically implanted
in an appropriate site (muscle, dentin or
bone) based on the intended application
 Note: For a material, these tests are
equivalent to sub chronic toxicity tests, if
systemic effects are also investigated.
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16. Haemocompatibility
 Haemocompatibility Evaluates the effects
on blood or blood components by blood
contacting devices or materials. Haemolysis
tests determine the degree of blood cell
lysis and release of haemoglobin caused by
device / material samples.
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17. Chronic Toxicity
 Chronic Toxicity Estimates the effects of
either single or multiple exposures, during
the period of at least 10% of the life span of
the animal model, to medical devices,
materials or their extracts in suitable animal
model.
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18. Carcinogenicity
 These tests determine the tumorigenic
potential of medical devices, materials or their
extracts. The test duration shall cover a period
over the major portion of the life span of the
animal model Can be carried out along with
chronic toxicity studies
 Note: Required to be conducted only if there
are suggestive data from other sources
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19. Reproductive & Developmental
Toxicity
 It studies the potential effects on reproductive
function embryonic development (teratogenicity)
prenatal and early post natal development
 Note : Need to be conducted only if the device
has potential impact on the reproductive
potential of the subject
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20. Biodegradation
 Where the potential for resorption /
degradation exists, these tests determine the
process of degradation biotransformation
elimination of degradation products
 Note : ISO 10993 is not very specific on the
norms for selection of biodegradation studies;
only the method is described.
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