Gap assessment for
Biocompatibility testing of Medical device as per ISO 10993-1:2009 Vs ISO 10993-1:2018
Sr.
ISO 10993- 1:2009
No.
1 NA
2 NA
3 NA
4 Section 4.3, a) the material(s)
of manufacture
5 NA
6 Section 4.3, leachable
substances (see ISO 10993-
17)
7 NA
8 NA
9 Section 4.6 All tests shall be
conducted according to
recognized current/valid best
laboratory /quality practices,
for example GLP or ISO /IEC
17025, where applicable, and
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ISO 10993-1:2018
Section 1. Scope is modified to include the devices or
materials which have direct or indirect contact with
patients. The scope was also modified to include all
types of medical devices including active, non-active,
implantable and non-implantable medical devices.
Section 4.1. Inclusion of risk management process,
which involves identification of biological hazards,
estimation of the associated biological risks and
determination of their acceptability.
Section 4.1. Inclusion of following criteria for the
evaluation.
Medical device configuration (e.g. Size, geometry,
surface properties) and a listing of a medical device’s
materials of construction (qualitative) and where
necessary, the proportion and amount (mass) of each
material in the medical device (quantitative).
Section 4.3, a)the material(s) of construction (i.e. all
direct and indirect tissue contacting materials)
Section 4.3. inclusion of new criteria i.e.
c) packaging materials that directly or indirectly
contact the medical device can transfer chemicals to
the medical device and then indirectly to the patient or
clinian.
Section 4.3 leachable substances (see ISO 10993-17
and ISO 10993-18)
Section 4.3 is modified for the inclusion of description
of device constituents and chemical characterization
material before biological testing.
Section 4.4 is modified to include the new criteria for
biological testing.
Biological testing is usually not necessary, if material
characterization (e.g. physical and chemical)
demonstrates equivalence to a previously assessed
medical device or material with established safety (see
ISO 10993-18 and ISO/TR 10993-19).
This point has been removed from the current version.
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ISO 10993- 1:2009 ISO 10993-1:2018
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the data shall be evaluated by
competent,
informed professionals
10 NA Section 4.6 new inclusion criteria was added i.e.
In certain circumstances, such as for specific medical
devices, or biological endpoint assessments, if a non-
standardized, non-validated test is necessary,
additional information regarding the rationale for the
study design and data interpretation should be
provided
11 Section 4.7 Section 4 is modified to include evaluation of
biological safety of medical device by the
manufacturer over the whole life-cycle of a medical
device
12 Section 4.8 Section 4 is modified to include re-usable medical
devices.
Biological safety shall be evaluated for the maximum
number of validated processing cycles by the
manufacturer.
13 NA Section 5.2.1 Inclusion of non-contacting medical
devices.
14 NA Section 5.2.3 New medical devices were added under
Tissue/bone/dentin
Medical devices or components that do not necessarily
directly contact tissue or bone but serve as conduits to
delivery fluids to the tissue or bone
15 Section 5.3 Permanent contact Section 5.3.1. modified to Long-term exposure (C)
(C)
16 NA Under Section 5.3. new medical devices were added
like Transitory-contacting medical devices and
Medical devices with multiple contact duration
categories
17 NA Under section 6.1, Physical and chemical information
for biological risk analysis a new criteria was added
for implant medical device in contact with blood.
18 Under section 6.1 following NA
criteria was made obsolete.
The results of the risk
assessment can lead to the
conclusion that additional
material characterization is
necessary, for example, where
the margin of safety is not
considered adequate if the
entire amount of a
particular chemical were to
leach out. In such cases,
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ISO 10993- 1:2009
No.
appropriate extraction testing,
simulating clinical
exposure, can be used to
estimate the degree of clinical
exposure to the chemical
constituent. The
acceptability of the level of
leachables shall be established
in accordance with ISO
10993-17.
19 NA
20 Section 6.2.2.3 Delayed-type Section 6.3.2.2 Sensitization
hypersensitivity
21 Section 6.2.2.5 systemic
toxicity (Acute)
22 Section 6.2.2.11
carcinogenicity
23 6.2.2.7 Genotoxicity
24 6.2.2.8 Implantation
Accuprec Research Labs Pvt. Ltd., Ahmedabad
ISO 10993-1:2018
New Section 6.2 was added to include Gap Analysis
and selection of biological endpoints of assessment.
For example, pharmacopeial plastics’ testing is
typically conducted on raw materials, whereas ISO
10993 evaluates the medical device in its final stage.
Therefore, data from such pharmacopeial testing is not
sufficient for the final medical device without
appropriate justification.
section was split into two different sections as section
6.3.2.5 Material-mediated pyrogenicity and 6.3.2.6
Acute systemic toxicity
6.3.2.11 Carcinogenicity.
Carcinogenicity may be addressed with a risk
assessment including chemical identification of
impurities, extractable or leachable chemicals, patient
exposure to these chemicals, weight of evidence
(WOE) and mode of action (MOA) information, if
available.
In the absence of any significant cancer risk, it is rare
for carcinogenicity tests to be considered appropriate
for medical devices. However, if it is determined that
carcinogenicity testing of the final medical device is
needed, it is possible that lifetime studies or transgenic
models will be appropriate.
Section 6.3.2.10, Genotoxicity, is modified to include
chemical identification of impurities / leachables if the
in vitro test is positive.
Section 6.3.2.9 Implantation effects is modified to
include hemocompatibility if applicable and conduct
one single implantation study instead of
chronic/subchronic study.
For instance, chronic/subchronic/subacute and acute
systemic toxicity endpoints can be built into a single
study. One can consider an experimental design where
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ISO 10993- 1:2009 ISO 10993-1:2018
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a clinically relevant quantity of material is implanted
in the relevant organ or tissue to assess local effects,
and an exaggeration of the anticipated clinical
exposure/dose is implanted possibly at a remote
location so the systemic exposure provides a suitable
measure of exaggeration.
25 6.2.2.12 Reproductive and 6.3.2.12 Reproductive and developmental toxicity
developmental toxicity Reproductive and developmental toxicity should be
addressed for novel materials, materials with a known
reproductive or developmental toxicity, medical
devices with relevant target populations (e.g. pregnant
women), and/or medical devices where there is the
potential for local presence of medical device
materials in the reproductive organs
26 6.2.2.13 Biodegradation 6.3.2.13 Degradation
In vivo degradation tests might not be necessary if an
in vitro/in vivo comparison for the absorbable medical
device has been previously demonstrated and in vitro
degradation studies show that only the probable
products of degradation are present in the predicted
quantities, and produced at a rate similar to those that
have a history of safe clinical use.
27 6.2.2.14 Toxicokinetic studies 6.3.2.14 Toxicokinetic studies
Addition of following criteria.
Toxicokinetic studies shall be considered if
a) substantial quantities of nano-objects are likely
or known to be released from a medical device
into the body during clinical use, or
b) drug and device combination products.
Specific considerations for toxicokinetics studies with
nanomaterials are given in ISO/TR 10993-22
28 Annex B Annex B (informative)
(informative) Guidance on the conduct of biological evaluation
Guidance on the risk within a risk management process
management process B.3.1.2 Risk analysis
B.2.2 Risk analysis Physical and chemical material properties are relevant
to biological safety and will need to be identified.

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 Annex A (informative) Biological evaluation tests – ISO 10993-Part1, 2009

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 Table A.1 — Endpoints to be addressed in a biological risk assessment, ISO 10993-Part 1, 2018

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