SIST EN 30993-4:2000

Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood (ISO 10993-4:1992)

This part of ISO 10993 provides a guide for agencies, manufacturers, research laboratories and others for evaluating the interactions of medical and dental materials and devices with blood.   It describes:  a)  a classification of medical and dental devices that are intended for use in contact with blood, based on the intended use and duration of contact as defined in ISO 10993-1;   b)  the fundamental principles governing the evaluation of the interaction of devices with blood;  c) the rationale for structured selection of tests, together with the principles and scientific basis of these tests.  Detailed requirements for testing cannot be specified because of the limitations in knowledge and precision of tests for interactions of devices with blood.

Biologische Beurteilung von Medizinprodukten - Teil 4: Auswahl von Prüfungen zur Wechselwirkung von Blut mit Fremdoberflächen (ISO 10993-4:1992)

Dieser Teil von EN 30993 präsentiert eine Richtlinie für Zulassungsbehörden , Hersteller, Forschungslaboratorien und andere, die sich mit der Bewertung von Wechselwirkungen von medizinischen und zahnmedizinischen Werkstoffen und Produkten mit Blut befassen. Er legt fest: a) eine Klassifizierung medizinischer und zahnmedizinischer Produkte, die für den Kontakt mit Blut vorgesehen sind, auf der Basis der vorgesehenen Anwendung und der Dauer der Exposition wie in EN 30993-1 festgelegt.

Evaluation biologique des dispositifs médicaux - Partie 4: Choix des essais concernant les actions avec le sang (ISO 10993-4:1992)

Cette partie de la norme ISO 10993 fournit aux agences, aux fabricants, aux laboratoires de recherche, etc, un guide pour évaluer les interactions des matériaux et dispositifs médicaux et dentaires avec le sang. Elle comporte: a) une classification des dispositifs médicaux et dentaires destinés à être en contact avec le sang lors de leur utilisation; cette classification est fondée sur l'utilisation prévue et sur la durée du contact telle qu'elle est définie dans la norme ISO 10993-4.

Biološko ovrednotenje medicinskih pripomočkov - 4. del: Izbira preskusov za ugotavljanje interakcij s krvjo (ISO 10993-4:1992)

General Information

• Status: Withdrawn
• Publication Date: 31-Dec-1999
• Withdrawal Date: 28-Feb-2003
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: VAZ - Healthcare
• Current Stage: 9900 - Withdrawal (Adopted Project)
• Start Date: 01-Mar-2003
• Due Date: 01-Mar-2003
• Completion Date: 01-Mar-2003
• Directive: 90/385/EEC - Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Mandate: M/BC/CEN/89/9 - Joint Standardization request to CEN/CENELEC concerning harmonized standards relating to horizontal aspects in the field of medical devices
• Ref Project: EN 30993-4:1993 - Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood (ISO 10993-4:1992)

Relations

• Replaced By: SIST EN ISO 10993-4:2003 - Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood (ISO 10993-4:2002)
• Effective Date: 01-Mar-2003

Standards Content (Sample)

SLOVENSKI STANDARD
01-januar-2000
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO,]ELUDSUHVNXVRY]D
XJRWDYOMDQMHLQWHUDNFLMVNUYMR,62
Biological evaluation of medical devices - Part 4: Selection of tests for interactions with
blood (ISO 10993-4:1992)
Biologische Beurteilung von Medizinprodukten - Teil 4: Auswahl von Prüfungen zur
Wechselwirkung von Blut mit Fremdoberflächen (ISO 10993-4:1992)
Evaluation biologique des dispositifs médicaux - Partie 4: Choix des essais concernant
les actions avec le sang (ISO 10993-4:1992)
Ta slovenski standard je istoveten z: EN 30993-4:1993
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

INTERNATIONAL IS0
STANDARD 10993-4
First edition
1992-l 2-15
Biological evaluation of medical devices -
Part 4:
Selection of tests for interactions with blood
gvalua tion biologique des dispositifs mgdicaux -
Par-tie 4: Choix des essais concernant /es interactions avec le sang
Reference number
IS0 10993-4:1992(E)
IS0 10993=4:1992(E)
Contents
Page
. . . . . . . . . . . . . . . . . . . . . . .~.~.
1 Scope
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 Normative reference
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
3 Definitions
.,,,.~.,.,,,.,,. 1
4 Abbreviations
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5 Devices contacting blood
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
5.1 Non-contact devices
............................................ 2
5.2 External communicating devices
5.3 Implant devices .
..........................................................................................
6 Tests
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1 General recommendations
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2 Test methods
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3 Types of tests
Annexes
A Evaluation of cardiovascular devices and prostheses during in vivo
function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.................... 13
B Laboratory tests: principles and scientific basis
............................................................................
C Bibliography
63 IS0 1992
All rights reserved. No part of this publication may be reproduced or utilized in any form or
by any means, electronic or mechanical, including photocopying and microfilm, without per-
mission in writing from the publisher.
International Organization for Standardization
Case Postale 56 l CH-1211 Geneve 20 l Switzerland
Printed in Switzerland
ii
IS0 10993=4:1992(E)
Foreword
IS0 (the International Organization for Standardization) is a worldwide
federation of national standards bodies (IS0 member bodies). The work
of preparing International Standards is normally carried out through IS0
technical committees. Each member body interested in a subject for
which a technical committee has been established has the right to be
represented on that committee. International organizations, governmental
and non-governmental, in liaison with ISO, also take part in the work. IS0
collaborates closely with the International Electrotechnical Commission
(I EC) on all matters of electrotechnical standardization.
Draft International Standards adopted by the technical committees are
circulated to the member bodies for voting. Publication as an International
Standard requires approval by at least 75 % of the member bodies casting
a vote.
International Standard IS0 10993-4 was prepared by Technical Committee
lSO/TC 194, Biological evaluation of medical devices.
IS0 10993 consists of the following parts, under the general title Biological
evaluation of medical devices:
- Part 1: Guidance on selection of tests
- Part 2: Animal welfare requirements
- Part 3: Tests for genotoxicity, carcinogenicity and reproductive
toxicity
- Part 4: Selection of tests for interactions with blood
- Part 5: Tests for cytotoxicity: in vitro methods
- Part 6: Tests for local effects after implantation
- Part 7: Ethylene oxide sterilization residuals
- Part 8: Clinical investigation
- Part 9: Degradation of materials related to biological testing
- Part 10: Tests for irritation and sensitization
- Part 11: Tests for systemic toxicity
- Part 12: Sample preparation and reference materials
Future parts will deal with other relevant aspects of biological testing.
Annexes A, B and C of this part of IS0 10993 are for information only.
. . .
III
IS0 10993=4:1992(E)
Introduction
The initial source for developing this part of IS0 10993 was the publi-
cation, Guidelines for blood/material interactions: Report of the National
Heart, Lung, and Blood Institute working group [26]; chapters 9 and 10.
This publication is being revised [29].

INTERNATIONAL STANDARD IS0 10993=4:1992(E)
Biological evaluation of medical devices -
Part 4:
Selection of tests for interactions with blood
the standard indicated below. Members of IEC and
1 Scope
IS0 maintain registers of currently valid International
Standards.
This part of IS0 10993 gives guidance to agencies,
manufacturers, research laboratories and others for
IS0 10993-I : 1992, Biological evaluation of medical
evaluating the interactions of medical devices with
devices - Part 1: Guidance on selection of tests.
blood.
It describes:
a) a classification of medical and dental devices that
3 Definitions
are intended for use in contact with blood, based
on the intended use and duration of contact as
For the purposes of this part of IS0 10993, the defi-
defined in IS0 10993-l;
nitions given in IS0 10993-l and the following defi-
nitions apply.
b) the fundamental principles governing the evalu-
ation of the interaction of devices with blood;
3.1 blood/device interaction: Any interaction be-
tween blood or any component of blood and a device
c) the rationale for structured selection of tests, to-
resulting in effects on the blood, or on any organ or
gether with the principles and scientific basis of
tissue or on the device. Such effects may or may not
these tests.
have clinically significant or undesirable conse-
quences.
Detailed requirements for testing cannot be specified
because of the limitations in knowledge and precision
3.2 ex vivo: Term applied to test systems that shunt
of tests for interactions of devices with blood.
blood directly from a human subject or test animal
into a test chamber. If using an animal model, the
blood may be shunted directly back into the animal
(recirculating) or collected into test tubes for evalu-
ation (single pass). In either case, the test chamber is
2 Normative reference
located outside the body.
The following standard contains provisions which,
through reference in this text, constitute provisions
of this part of IS0 10993. At the time of publication,
4 Abbreviations
the edition indicated was valid. All standards are sub-
ject to revision, and parties to agreements based on
this part of IS0 10993 are encouraged to investigate Table 1 provides a list of abbreviations used in the
the possibility of applying the most recent edition of context of this part of IS0 10993.

IS0 10993=4:1992(E)
Table 1 - Abbreviations
Meaning
Abbreviation
Bb Product of alternate pathway complement activation
Beta-thromboglobulin
B TG
&d Product of classical pathway complement activation
C3a, C5a (active) complement split products from C3 and C5
D-Dimer Specific fibrin degradation products (F XIII cross-linked fibrin)
ECMO Extracorporeal membrane oxygenator
E.M. Electron microscopy
FDP Fibrin/fibrinogen degradation products
FPA Fibrinopeptide A
Prothrombin activation fragment 1 + 2
h+2
Product of central C complement activation
iC3b
Interleukin-1
IL-l
Inferior vena cava
IVC
Magnetic resonance imaging
MRI
PAC-1 Monoclonal antibody which recognizes the activated form of platelet surface glycoprotein llb/llla
PET Positron emission tomography
PF-4 Platelet factor 4
PT Prothrombin time
PTT Partial thromboplastin time
RIA Radioimmunoassay
Monoclonal antibody which recognizes the alpha granule membrane component GMP140 exposed
S-l 2
during the platelet release reaction
Product of terminal pathway complement activation
SC5b-9
Thrombin-antithrombin complex
TAT
Terminal complement complex
TCC
TT Thrombin time
von Willebrand factor
VWF
devices for the collection of blood,
5 Devices contacting blood
devices for the storage and administration of blood
Devices contacting blood are categorized in
and blood products (e.g. tubing, needles and
IS0 10993-l :1992, clause 5.
bags).
5.1 Non-contact devices
(See subclause 5.1.1 of IS0 10993-1:1992.)
5.2.2 External communicating devices in contact
An example is in vitro diagnostic devices.
with circulating blood [see 5.1.3c) of
IS0 10993-I :I9921 include but are not limited to
5.2 External communicating devices
cardiopulmonary bypass,
(See subclause 5.1.3 of IS0 10993-l :1992.)
extracorporeal membrane oxygenators,
These are devices that contact the circulating blood
haemodialysis equipment,
and serve as a conduit into the vascular system. Ex-
amples include but are not limited to those in 5.2.1
donor and therapeutic apheresis equipment,
and 5.2.2.
devices for absorption of specific substances from
5.2.1 External communicating devices that serve as
blood,
an indirect blood path [see subclause 5.1.3 a) of
IS0 10993-I :I 9921 include but are not limited to interventional cardiology and vascular devices,
cannulae,
percutaneous circulatory support systems,
extension sets, temporary pacemaker electrodes.

IS0 10993=4:1992(E)
6.1.3 Testing of materials which are candidates to
5.3 Implant devices
be components of a device should be conducted for
screening purposes. However, such tests do not
These are devices (see 5.1.4 of IS0 10993-I :I 992)
serve as a substitute for the requirement that the
that are placed largely or entirely within the vascular
complete device be tested under conditions which
system. Examples include but are not limited to
simulate clinical application.
mechanical or tissue heart valves,
6.1.4 Tests which do not simulate the conditions of
a device during use may not predict accurately the
prosthetic or tissue vascular grafts,
nature of the blood/device interactions which may
occur during clinical applications. For example, some
circulatory support devices (ventricular-assist de-
short-term in vitro or ex viva tests are poor predictors
vices, artificial hearts, intra-aortic balloon pumps),
of long-term in vivo blood/device interactions [22],
inferior vena cava filters, .
cm
stents,
6.1.5 It follows from the above that devices whose
intended use is ex v;vo (external communicating)
arteriovenous shunts,
should be tested ex viva and devices whose intended
use is in viva (implants) should be tested in vivo in an
blood monitors, animal model under conditions simulating where
possible clinical use.
internal drug delivery catheters,
6.1.6 In vitro tests are regarded as useful in screen-
pacemaker electrodes,
ing external communicating devices or implants but
may not be accurate predictors of blood/device inter-
intravascular membrane oxygenators (artificial
actions occurring upon prolonged or repeated ex-
lungs).
posure or permanent contact (see 6.3.2). Devices
intended for non-contact use only do not require
evaluation of blood/device interactions. Devices which
come into very brief contact with circulating blood
6 Tests
(e.g. lancets, hypodermic needles, capillary tubes)
generally do not require blood/device interaction test-
ing.
6.1 General recommendations
6.1.7 The two recommendations in 6.1.5 and 6.1.6,
together with clause 5, serve as a guide for the
6.1.1 Where possible, tests should use an appropri-
selection of tests listed in 6.2.1.
ate model or system which simulates the geometry
and conditions of contact of the device with blood
6.1.8 Disposable laboratory equipment used for the
during clinical applications, including duration of con-
collection of blood and performance of in vitro tests
tact, temperature, sterile condition and flow con-
on blood should be validated to ascertain that there is
ditions. For devices of defined geometry such as
no significant interference with the test being per-
vascular grafts of varying lengths, the relation of sur-
formed. This can be conducted by performing tests
face area (length) to test results should be evaluated.
on reference standards and comparing results with
those obtained by a clinically approved technique.
paramete rs should be in
The selected methods and
state of t he art.
acco rdance with the current
6.1.9 If tests are selected in the manner described
and testing is conducted under conditions which
NOTE 1 Only blood-contacting parts should be tested.
simulate clinical applications, the results of such test-
ing have the greatest probability of predicting clinical
performance of devices. However, species differ-
6.1.2 Controls shall be used u
...