Biological evaluation of medical devices —Part 4: Selection of tests for interactions with blood
1 Scope
This document specifies general requirements for evaluating the interactions of medical devices with blood.
It describes
a) a classification of medical 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 according to specific categories, together with the principles and scientific basis of these tests.
Detailed requirements for testing cannot be specified because of limitations in the knowledge and precision of tests for evaluating interactions of devices with blood. This document describes biological evaluation in general terms and may not necessarily provide sufficient guidance for test methods for a specific device.
The changes in this document do not indicate that testing conducted according to prior versions of this document is invalid. For marketed devices with a history of safe clinical use, additional testing according to this revision is not recommended.
2 Normative references
The following documents contain provisions which, through reference in this text, constitute indispensable provisions of this document. For dated references, only the edition cited applies. For undated references, the latest edition (including any amendments) applies.
ISO 10993-1 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process
Note: GB/T 16886.1-2022 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process (ISO 10993-1: 2018, IDT)
ISO 10993-12 Biological evaluation of medical devices — Part 12: Sample preparation and reference materials
Note: GB/T 16886.12-2017 Biological evaluation of medical devices — Part 12: Sample preparation and reference materials (ISO 10993-12: 2012, IDT)
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1, ISO 10993-12 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
——IEC Electropedia: available at http://www.electropedia.org/
——ISO Online browsing platform: available at http://www.iso.org/obp
3.1
anticoagulant
agent which prevents or delays blood coagulation
Examples: Heparin, ethylenediaminetetraacetic acid (EDTA), sodium citrate.
3.2
blood/device interaction
interaction between blood or a blood component and a device
3.3
coagulation
phenomenon that results from activation of the clotting (coagulation) factor cascade
Note to entry: Factors of the coagulation cascade and fibrinolytic systems can be measured following exposure to devices either in vitro or in vivo.
3.4
complement system
part of the innate immune system consisting of over 30 distinct plasma proteins, including enzymes, cofactors, and cellular receptors which may be involved in the promotion of thrombosis
Note 1 to entry: Effector molecules produced from complement components are possible components in the phenomena of inflammation, phagocytosis and cell lysis. Complement activation related to immunotoxicity, hypersensitivity and generation of anaphylatoxins is not covered in this document. (See ISO/TS 10993-20.)
Note 2 to entry: The focus in this document is complement activation as it can promote and accelerate haemolysis, platelet and leukocyte activation and thrombosis on device material surfaces. (See also Annex E on complement activation.)
3.5
direct blood contact
term used when the device or device material comes into physical contact with blood or blood constituents
3.6
embolization
process whereby a blood thrombus, or foreign object, is carried in the bloodstream and which may become lodged and cause obstructed blood flow downstream
3.7
ex vivo test system
term applied to a test system that shunts blood directly from a human subject or test animal into a test chamber located outside the body
Note to entry: If using an animal model, the blood may be shunted directly back into the animal (recirculating) or collected in test tubes for evaluation (single pass). In either case, the test chamber is located outside the body.
3.8
haematology
study of blood that includes quantification of cellular and plasma components of the blood
3.9
haematocrit
ratio of the volume of erythrocytes to that of whole blood in a given sample
Foreword i
Introduction iv
1 Scope
2 Normative references
3 Terms and definitions
4 Abbreviated terms
5 Types of devices in contact with blood (as categorized in ISO 10993-1)
5.1 Non-blood-contact devices
5.2 External communicating devices
5.2.1 General
5.2.2 External communicating devices that serve as an indirect blood path
5.2.3 External communicating devices directly contacting circulating blood
5.3 Implant devices
6 Characterization of blood interactions
6.1 General requirements
6.2 Categories of tests and blood interactions
6.2.1 Recommended tests for interactions of devices with blood
6.2.2 Non-contact devices
6.2.3 External communicating devices and implant devices
6.2.4 Limitations
6.3 Types of tests
6.3.1 In vitro tests
6.3.2 Ex vivo tests
6.3.3 In vivo tests
Annex A (Informative) Preclinical evaluation of cardiovascular devices and prostheses
Annex B (Informative) Recommended laboratory tests — Principles, scientific basis and interpretation
Annex C (informative) Thrombosis — Methods for in vivo testing
Annex D (Informative) Haematology/haemolysis — Methods for testing — Evaluation of haemolytic properties of medical devices and medical device materials
Annex E (Informative) Complement — Methods for testing
Annex F (Informative) Less common laboratory tests
Annex G (Informative) Tests which are not recommended
Bibliography
Biological evaluation of medical devices —Part 4: Selection of tests for interactions with blood
1 Scope
This document specifies general requirements for evaluating the interactions of medical devices with blood.
It describes
a) a classification of medical 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 according to specific categories, together with the principles and scientific basis of these tests.
Detailed requirements for testing cannot be specified because of limitations in the knowledge and precision of tests for evaluating interactions of devices with blood. This document describes biological evaluation in general terms and may not necessarily provide sufficient guidance for test methods for a specific device.
The changes in this document do not indicate that testing conducted according to prior versions of this document is invalid. For marketed devices with a history of safe clinical use, additional testing according to this revision is not recommended.
2 Normative references
The following documents contain provisions which, through reference in this text, constitute indispensable provisions of this document. For dated references, only the edition cited applies. For undated references, the latest edition (including any amendments) applies.
ISO 10993-1 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process
Note: GB/T 16886.1-2022 Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process (ISO 10993-1: 2018, IDT)
ISO 10993-12 Biological evaluation of medical devices — Part 12: Sample preparation and reference materials
Note: GB/T 16886.12-2017 Biological evaluation of medical devices — Part 12: Sample preparation and reference materials (ISO 10993-12: 2012, IDT)
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1, ISO 10993-12 and the following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
——IEC Electropedia: available at http://www.electropedia.org/
——ISO Online browsing platform: available at http://www.iso.org/obp
3.1
anticoagulant
agent which prevents or delays blood coagulation
Examples: Heparin, ethylenediaminetetraacetic acid (EDTA), sodium citrate.
3.2
blood/device interaction
interaction between blood or a blood component and a device
3.3
coagulation
phenomenon that results from activation of the clotting (coagulation) factor cascade
Note to entry: Factors of the coagulation cascade and fibrinolytic systems can be measured following exposure to devices either in vitro or in vivo.
3.4
complement system
part of the innate immune system consisting of over 30 distinct plasma proteins, including enzymes, cofactors, and cellular receptors which may be involved in the promotion of thrombosis
Note 1 to entry: Effector molecules produced from complement components are possible components in the phenomena of inflammation, phagocytosis and cell lysis. Complement activation related to immunotoxicity, hypersensitivity and generation of anaphylatoxins is not covered in this document. (See ISO/TS 10993-20.)
Note 2 to entry: The focus in this document is complement activation as it can promote and accelerate haemolysis, platelet and leukocyte activation and thrombosis on device material surfaces. (See also Annex E on complement activation.)
3.5
direct blood contact
term used when the device or device material comes into physical contact with blood or blood constituents
3.6
embolization
process whereby a blood thrombus, or foreign object, is carried in the bloodstream and which may become lodged and cause obstructed blood flow downstream
3.7
ex vivo test system
term applied to a test system that shunts blood directly from a human subject or test animal into a test chamber located outside the body
Note to entry: If using an animal model, the blood may be shunted directly back into the animal (recirculating) or collected in test tubes for evaluation (single pass). In either case, the test chamber is located outside the body.
3.8
haematology
study of blood that includes quantification of cellular and plasma components of the blood
3.9
haematocrit
ratio of the volume of erythrocytes to that of whole blood in a given sample
Contents of GB/T 16886.4-2022
Foreword i
Introduction iv
1 Scope
2 Normative references
3 Terms and definitions
4 Abbreviated terms
5 Types of devices in contact with blood (as categorized in ISO 10993-1)
5.1 Non-blood-contact devices
5.2 External communicating devices
5.2.1 General
5.2.2 External communicating devices that serve as an indirect blood path
5.2.3 External communicating devices directly contacting circulating blood
5.3 Implant devices
6 Characterization of blood interactions
6.1 General requirements
6.2 Categories of tests and blood interactions
6.2.1 Recommended tests for interactions of devices with blood
6.2.2 Non-contact devices
6.2.3 External communicating devices and implant devices
6.2.4 Limitations
6.3 Types of tests
6.3.1 In vitro tests
6.3.2 Ex vivo tests
6.3.3 In vivo tests
Annex A (Informative) Preclinical evaluation of cardiovascular devices and prostheses
Annex B (Informative) Recommended laboratory tests — Principles, scientific basis and interpretation
Annex C (informative) Thrombosis — Methods for in vivo testing
Annex D (Informative) Haematology/haemolysis — Methods for testing — Evaluation of haemolytic properties of medical devices and medical device materials
Annex E (Informative) Complement — Methods for testing
Annex F (Informative) Less common laboratory tests
Annex G (Informative) Tests which are not recommended
Bibliography
