Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
1 Scope
This document specifies:
——the general principles governing the biological evaluation of medical devices within a risk management process;
——the general categorization of medical devices based on the nature and duration of their contact with the body;
——the evaluation of existing relevant data from all sources;
——the identification of gaps in the available data set on the basis of a risk analysis;
——the identification of additional data sets necessary to analyse the biological safety of the medical device;
——the assessment of the biological safety of the medical device.
This document applies to evaluation of materials and medical devices that are expected to have direct or indirect contact with:
——the patient's body during intended use;
——the user’s body, if the medical device is intended for protection (e.g., surgical gloves, masks and others).
This document is applicable to biological evaluation of all types of medical devices including active, non-active, implantable and non-implantable medical devices.
This document also gives guidelines for the assessment of biological hazards arising from:
——risks, such as changes to the medical device over time, as a part of the overall biological safety assessment;
——breakage of a medical device or medical device component which exposes body tissue to new or novel materials.
Other parts of GB/T 16886 cover specific aspects of biological assessments and related tests. Device-specific or product standards address mechanical testing.
This document excludes hazards related to bacteria, moulds, yeasts, viruses, transmissible spongiform encephalopathy (TSE) agents and other pathogens.
2 Normative references
The following referenced documents are indispensable for the application of this standard. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.
GB/T 16886.2-2011 Biological evaluation of medical devices - Part 2: Animal welfare requirements (ISO 10993-2: 2006, IDT)
GB/T 16886.11-2021 Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-11: 2017, IDT)
YY/T 0316-2016 Medical devices - Application of risk management to medical devices (ISO 14971: 2007, IDT)
ISO 10993-2 Biological evaluation of medical devices - Part 2: Animal welfare requirements
ISO 10993-3 Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
Note: GB/T 16886.3-2019 Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity (ISO 10993-3: 2014, IDT)
ISO 10993-4 Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood
Note: GB/T 16886.4-2022 Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood (ISO 10993-4: 2017, IDT)
ISO 10993-5 Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity
Note: GB/T 16886.5-2017 Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity (ISO 10993-5: 2009, IDT)
ISO 10993-6 Biological evaluation of medical devices - Part 6: Tests for local effects after implantation
Note: GB/T 16886.6-2022 Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO 10993-6: 2016, IDT)
ISO 10993-7 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals
Note: GB/T 16886.7-2015 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals (ISO 10993-7: 2008, IDT)
ISO 10993-9 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products
Note: GB/T 16886.9-2017 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9: 2009, IDT)
ISO 10993-10 Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization
Note: GB/T 16886.10-2017 Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization (ISO 10993-10: 2010, IDT)
ISO 10993-11 Biological evaluation of medical devices - Part 11: Tests for systemic toxicity
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)
ISO 10993-13 Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices
Note: GB/T 16886.13-2017 Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13: 2010, IDT)
ISO 10993-14 Biological evaluation of medical device - Part 14: Identification and quantification of degradation products from ceramics
Note: GB/T 16886.14-2003 Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14: 2001, IDT)
ISO 10993-15 Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys
Note: GB/T 16886.15-2003 Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys (ISO 10993-15: 2000, IDT)
ISO 10993-16 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables
Note: GB/T 16886.16-2021 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables (ISO 10993-16: 2017, IDT)
ISO 10993-17 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances
Note: GB/T 16886.17-2005 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances (ISO 10993-17: 2002, IDT)
ISO 10993-18 Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process
Note: GB/T 16886.18-2011 Biological evaluation of medical devices - Part 18: Chemical characterization of materials (ISO 10993-18: 2005, IDT)
ISO/TS 10993-20 Biological evaluation of medical devices - Part 20: Principles and methods for immunotoxicology testing of medical devices
Note: GB/T 16886.20-2015 Biological evaluation of medical devices - Part 20: Principles and methods for immunotoxicology testing of medical devices (ISO/TS 10993-20: 2006, IDT)
ISO 14971 Medical devices - Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions 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
biocompatibility
ability of a medical device (3.14) or material (3.12) to perform with an appropriate host response in a specific application
3.2
biological risk
combination of the probability of harm to health occurring as a result of adverse reactions associated with medical device (3.14) or material (3.12) interactions, and the severity of that harm
3.3
biological safety
freedom from unacceptable biological risk (3.2) in the context of the intended use
3.4
chemical constituent
any synthetic or natural substance that is used in a process for manufacturing materials (3.12) and/or medical devices (3.14), including the base material(s), additives (antioxidants, UV stabilizers, color additives, dyes, etc.), and processing aids (solvents, lubricants, antifoaming agents, etc.)
3.5
data set
information, such as physical and/or chemical characterization, toxicity data, etc. from a variety of sources necessary to characterize the biological response to a medical device
3.6
direct contact
medical device (3.14) or medical device component that comes into physical contact with body tissue
3.7
externally communicating medical device
medical device (3.14) or medical device component that is partially or wholly located outside the body but has either direct or indirect contact with the internal body fluids and/or tissues
3.8
final product
medical device (3.14) or medical device component that has been subjected to all manufacturing processes for the “to be marketed” medical device including packaging and if applicable, sterilization
3.9
geometry
device configuration
shape and relative arrangement of the parts of the medical device (3.14)
3.10
implant
medical device (3.14) which is intended to be totally introduced into the human body or to replace an epithelial surface or the surface of the eye by means of clinical intervention and which is intended to remain in place after the procedure
3.11
indirect contact
medical device (3.14) or medical device component through which a fluid or gas passes, prior to the fluid or gas coming into physical contact with body tissue (in this case the medical device or medical device component itself does not physically contact body tissue)
3.12
material
synthetic or natural polymer, metal or alloy, ceramic, or composite, including tissue rendered nonviable, used as a medical device (3.14) or any part thereof
3.13
material characterization
broad and general process of collecting existing information about a material’s chemistry, structure and other properties, and if appropriate, new data, to facilitate the evaluation of these properties
3.14
medical device
any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software, material (3.12) or other similar or related article, intended by the manufacturer to be used, alone or in combination, for human beings, for one or more of the specific purpose(s) of:
——diagnosis, prevention, monitoring, treatment or alleviation of disease;
——diagnosis, monitoring, treatment, alleviation of or compensation for an injury;
——investigation, replacement, modification, or support of the anatomy or of a physiological process;
——supporting or sustaining life;
——control of conception;
——disinfection of medical devices;
——providing information for medical purposes by means of in vitro examination of specimens derived from the human body;
and does not achieve its primary intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its intended function by such means. Medical devices include dental devices.
Note: Products which may be considered to be medical devices in some jurisdictions but not in others include:
——disinfection substances;
——aids for persons with disabilities;
——devices incorporating animal and/or human tissues;
——devices for in vitro fertilization or assisted reproduction technologies.
[Source: GHTF/SG1/N071: 2012, 5.1, modified]
3.15
nanomaterial
material (3.12) with any external dimension in the nanoscale or having internal structure or surface structure in the nanoscale
[Source: ISO/TR 10993-22: 2017, 3.7, modified]
3.16
non-contacting
indicates that the medical device (3.14) or medical device component has neither direct nor indirect contact with body tissues
3.17
physical and chemical information
knowledge regarding formulation, manufacturing processes, geometric and physical properties and type of body contact and clinical use that is used to determine whether any additional biological or material characterization testing is needed
3.18
risk analysis
systematic use of available information to identify hazards and to estimate the risk
[Source: YY/T 0316-2016, 2.17, modified]
3.19
risk assessment
overall process comprising a risk analysis (3.18) and a risk evaluation (3.20)
[Source: YY 0316-2016, 2.18]
3.20
risk evaluation
process of comparing the estimated risk against given risk criteria to determine the acceptability of the risk
[Source: YY 0316-2016, 2.21]
3.21
risk management
systematic application of management policies, procedures and practices to the tasks of analysing, evaluating, controlling and monitoring risk
[Source: YY 0316-2016, 2.22]
3.22
toxic
capable of causing an adverse biological response
3.23
toxicological hazard
potential for a chemical substance or material (3.12) to cause an adverse biological reaction, taking into account the nature of the reaction and the dose required to elicit it
3.24
toxicological risk
probability of a specified degree of an adverse reaction occurring in response to a specified level of exposure
3.25
toxicological threshold
limit, such as a tolerable intake (TI), tolerable exposure (TE), allowable limit (AL) value, or Threshold of Toxicological Concern (TTC) below which adverse effects are not expected for relevant biological endpoints
3.26
transitory contact
medical device (3.14) or medical device component that has a very brief duration of contact with body tissue
4 General principles applying to biological evaluation of medical devices
4.1 The biological evaluation of any material or medical device intended for use in humans shall form part of a structured biological evaluation plan within a risk management process in accordance with YY/T 0316-2016, Annex I, as given in Figure 1 of this document. This risk management process involves identification of biological hazards, estimation of the associated biological risks, and determination of their acceptability. Annex B provides guidance on this process. The biological evaluation shall be planned, carried out, and documented by knowledgeable and experienced professionals.
The risk management plan should identify aspects of the biological evaluation requiring specific technical competencies and shall identify the person(s) responsible for the biological evaluation.
The evaluation shall include documented, informed consideration of advantages/disadvantages and relevance of:
a) 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);
b) the physical and chemical characteristics of the various materials of construction and their composition;
Note 1: Where this information is already documented within the risk management for the medical device, it can be included by reference.
c) any history of clinical use or human exposure data;
Note 2: Previous regulatory approval history can be relevant.
d) any existing toxicology and other biological safety data on product and component materials, breakdown products and metabolites;
e) test procedures.
Evaluation can include both a review of relevant existing preclinical and clinical data and actual testing. Such an evaluation might result in the conclusion that no testing is needed if the material has a demonstrable safe history of use in a specified role and physical form that is equivalent to that of the medical device under design. The type of information that can be useful to demonstrate equivalence is included in Annex B. Testing is usually not necessary when sufficient information is already available to perform a risk assessment of the material and/or the medical device (see Annex C).
4.2 In the selection of materials to be used in the medical device manufacture, the first consideration shall be fitness for purpose with regard to characteristics and properties of the material, which include chemical, toxicological, physical, electrical, morphological and mechanical properties.
Foreword i
Introduction iv
1 Scope
2 Normative references
3 Terms and definitions
4 General principles applying to biological evaluation of medical devices
5 Categorization of medical devices
5.1 General requirements
5.2 Categorization by nature of body contact
5.2.1 Non-contacting medical devices
5.2.2 Surface-contacting medical devices
5.2.3 Externally communicating medical devices
5.2.4 Implant medical devices
5.3 Categorization by duration of contact
5.3.1 Contact duration categories
5.3.2 Transitory-contacting medical devices
5.3.3 Medical devices with multiple contact duration categories
6 Biological evaluation process
6.1 Physical and chemical information for biological risk analysis
6.2 Gap analysis and selection of biological endpoints for assessment
6.3 Biological testing
6.3.1 General requirements
6.3.2 Testing for evaluation
7 Interpretation of biological evaluation data and overall biological risk assessment
Annex A (Informative) Endpoints to be addressed in a biological risk assessment
Annex B (Informative) Guidance on the conduct of biological evaluation within a risk management process
Annex C (Informative) Suggested procedure for literature review
Bibliography
Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
1 Scope
This document specifies:
——the general principles governing the biological evaluation of medical devices within a risk management process;
——the general categorization of medical devices based on the nature and duration of their contact with the body;
——the evaluation of existing relevant data from all sources;
——the identification of gaps in the available data set on the basis of a risk analysis;
——the identification of additional data sets necessary to analyse the biological safety of the medical device;
——the assessment of the biological safety of the medical device.
This document applies to evaluation of materials and medical devices that are expected to have direct or indirect contact with:
——the patient's body during intended use;
——the user’s body, if the medical device is intended for protection (e.g., surgical gloves, masks and others).
This document is applicable to biological evaluation of all types of medical devices including active, non-active, implantable and non-implantable medical devices.
This document also gives guidelines for the assessment of biological hazards arising from:
——risks, such as changes to the medical device over time, as a part of the overall biological safety assessment;
——breakage of a medical device or medical device component which exposes body tissue to new or novel materials.
Other parts of GB/T 16886 cover specific aspects of biological assessments and related tests. Device-specific or product standards address mechanical testing.
This document excludes hazards related to bacteria, moulds, yeasts, viruses, transmissible spongiform encephalopathy (TSE) agents and other pathogens.
2 Normative references
The following referenced documents are indispensable for the application of this standard. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.
GB/T 16886.2-2011 Biological evaluation of medical devices - Part 2: Animal welfare requirements (ISO 10993-2: 2006, IDT)
GB/T 16886.11-2021 Biological evaluation of medical devices - Part 11: Tests for systemic toxicity (ISO 10993-11: 2017, IDT)
YY/T 0316-2016 Medical devices - Application of risk management to medical devices (ISO 14971: 2007, IDT)
ISO 10993-2 Biological evaluation of medical devices - Part 2: Animal welfare requirements
ISO 10993-3 Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
Note: GB/T 16886.3-2019 Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity (ISO 10993-3: 2014, IDT)
ISO 10993-4 Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood
Note: GB/T 16886.4-2022 Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood (ISO 10993-4: 2017, IDT)
ISO 10993-5 Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity
Note: GB/T 16886.5-2017 Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity (ISO 10993-5: 2009, IDT)
ISO 10993-6 Biological evaluation of medical devices - Part 6: Tests for local effects after implantation
Note: GB/T 16886.6-2022 Biological evaluation of medical devices - Part 6: Tests for local effects after implantation (ISO 10993-6: 2016, IDT)
ISO 10993-7 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals
Note: GB/T 16886.7-2015 Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals (ISO 10993-7: 2008, IDT)
ISO 10993-9 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products
Note: GB/T 16886.9-2017 Biological evaluation of medical devices - Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9: 2009, IDT)
ISO 10993-10 Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization
Note: GB/T 16886.10-2017 Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization (ISO 10993-10: 2010, IDT)
ISO 10993-11 Biological evaluation of medical devices - Part 11: Tests for systemic toxicity
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)
ISO 10993-13 Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices
Note: GB/T 16886.13-2017 Biological evaluation of medical devices - Part 13: Identification and quantification of degradation products from polymeric medical devices (ISO 10993-13: 2010, IDT)
ISO 10993-14 Biological evaluation of medical device - Part 14: Identification and quantification of degradation products from ceramics
Note: GB/T 16886.14-2003 Biological evaluation of medical devices - Part 14: Identification and quantification of degradation products from ceramics (ISO 10993-14: 2001, IDT)
ISO 10993-15 Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys
Note: GB/T 16886.15-2003 Biological evaluation of medical devices - Part 15: Identification and quantification of degradation products from metals and alloys (ISO 10993-15: 2000, IDT)
ISO 10993-16 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables
Note: GB/T 16886.16-2021 Biological evaluation of medical devices - Part 16: Toxicokinetic study design for degradation products and leachables (ISO 10993-16: 2017, IDT)
ISO 10993-17 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances
Note: GB/T 16886.17-2005 Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances (ISO 10993-17: 2002, IDT)
ISO 10993-18 Biological evaluation of medical devices - Part 18: Chemical characterization of medical device materials within a risk management process
Note: GB/T 16886.18-2011 Biological evaluation of medical devices - Part 18: Chemical characterization of materials (ISO 10993-18: 2005, IDT)
ISO/TS 10993-20 Biological evaluation of medical devices - Part 20: Principles and methods for immunotoxicology testing of medical devices
Note: GB/T 16886.20-2015 Biological evaluation of medical devices - Part 20: Principles and methods for immunotoxicology testing of medical devices (ISO/TS 10993-20: 2006, IDT)
ISO 14971 Medical devices - Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions 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
biocompatibility
ability of a medical device (3.14) or material (3.12) to perform with an appropriate host response in a specific application
3.2
biological risk
combination of the probability of harm to health occurring as a result of adverse reactions associated with medical device (3.14) or material (3.12) interactions, and the severity of that harm
3.3
biological safety
freedom from unacceptable biological risk (3.2) in the context of the intended use
3.4
chemical constituent
any synthetic or natural substance that is used in a process for manufacturing materials (3.12) and/or medical devices (3.14), including the base material(s), additives (antioxidants, UV stabilizers, color additives, dyes, etc.), and processing aids (solvents, lubricants, antifoaming agents, etc.)
3.5
data set
information, such as physical and/or chemical characterization, toxicity data, etc. from a variety of sources necessary to characterize the biological response to a medical device
3.6
direct contact
medical device (3.14) or medical device component that comes into physical contact with body tissue
3.7
externally communicating medical device
medical device (3.14) or medical device component that is partially or wholly located outside the body but has either direct or indirect contact with the internal body fluids and/or tissues
3.8
final product
medical device (3.14) or medical device component that has been subjected to all manufacturing processes for the “to be marketed” medical device including packaging and if applicable, sterilization
3.9
geometry
device configuration
shape and relative arrangement of the parts of the medical device (3.14)
3.10
implant
medical device (3.14) which is intended to be totally introduced into the human body or to replace an epithelial surface or the surface of the eye by means of clinical intervention and which is intended to remain in place after the procedure
3.11
indirect contact
medical device (3.14) or medical device component through which a fluid or gas passes, prior to the fluid or gas coming into physical contact with body tissue (in this case the medical device or medical device component itself does not physically contact body tissue)
3.12
material
synthetic or natural polymer, metal or alloy, ceramic, or composite, including tissue rendered nonviable, used as a medical device (3.14) or any part thereof
3.13
material characterization
broad and general process of collecting existing information about a material’s chemistry, structure and other properties, and if appropriate, new data, to facilitate the evaluation of these properties
3.14
medical device
any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software, material (3.12) or other similar or related article, intended by the manufacturer to be used, alone or in combination, for human beings, for one or more of the specific purpose(s) of:
——diagnosis, prevention, monitoring, treatment or alleviation of disease;
——diagnosis, monitoring, treatment, alleviation of or compensation for an injury;
——investigation, replacement, modification, or support of the anatomy or of a physiological process;
——supporting or sustaining life;
——control of conception;
——disinfection of medical devices;
——providing information for medical purposes by means of in vitro examination of specimens derived from the human body;
and does not achieve its primary intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its intended function by such means. Medical devices include dental devices.
Note: Products which may be considered to be medical devices in some jurisdictions but not in others include:
——disinfection substances;
——aids for persons with disabilities;
——devices incorporating animal and/or human tissues;
——devices for in vitro fertilization or assisted reproduction technologies.
[Source: GHTF/SG1/N071: 2012, 5.1, modified]
3.15
nanomaterial
material (3.12) with any external dimension in the nanoscale or having internal structure or surface structure in the nanoscale
[Source: ISO/TR 10993-22: 2017, 3.7, modified]
3.16
non-contacting
indicates that the medical device (3.14) or medical device component has neither direct nor indirect contact with body tissues
3.17
physical and chemical information
knowledge regarding formulation, manufacturing processes, geometric and physical properties and type of body contact and clinical use that is used to determine whether any additional biological or material characterization testing is needed
3.18
risk analysis
systematic use of available information to identify hazards and to estimate the risk
[Source: YY/T 0316-2016, 2.17, modified]
3.19
risk assessment
overall process comprising a risk analysis (3.18) and a risk evaluation (3.20)
[Source: YY 0316-2016, 2.18]
3.20
risk evaluation
process of comparing the estimated risk against given risk criteria to determine the acceptability of the risk
[Source: YY 0316-2016, 2.21]
3.21
risk management
systematic application of management policies, procedures and practices to the tasks of analysing, evaluating, controlling and monitoring risk
[Source: YY 0316-2016, 2.22]
3.22
toxic
capable of causing an adverse biological response
3.23
toxicological hazard
potential for a chemical substance or material (3.12) to cause an adverse biological reaction, taking into account the nature of the reaction and the dose required to elicit it
3.24
toxicological risk
probability of a specified degree of an adverse reaction occurring in response to a specified level of exposure
3.25
toxicological threshold
limit, such as a tolerable intake (TI), tolerable exposure (TE), allowable limit (AL) value, or Threshold of Toxicological Concern (TTC) below which adverse effects are not expected for relevant biological endpoints
3.26
transitory contact
medical device (3.14) or medical device component that has a very brief duration of contact with body tissue
4 General principles applying to biological evaluation of medical devices
4.1 The biological evaluation of any material or medical device intended for use in humans shall form part of a structured biological evaluation plan within a risk management process in accordance with YY/T 0316-2016, Annex I, as given in Figure 1 of this document. This risk management process involves identification of biological hazards, estimation of the associated biological risks, and determination of their acceptability. Annex B provides guidance on this process. The biological evaluation shall be planned, carried out, and documented by knowledgeable and experienced professionals.
The risk management plan should identify aspects of the biological evaluation requiring specific technical competencies and shall identify the person(s) responsible for the biological evaluation.
The evaluation shall include documented, informed consideration of advantages/disadvantages and relevance of:
a) 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);
b) the physical and chemical characteristics of the various materials of construction and their composition;
Note 1: Where this information is already documented within the risk management for the medical device, it can be included by reference.
c) any history of clinical use or human exposure data;
Note 2: Previous regulatory approval history can be relevant.
d) any existing toxicology and other biological safety data on product and component materials, breakdown products and metabolites;
e) test procedures.
Evaluation can include both a review of relevant existing preclinical and clinical data and actual testing. Such an evaluation might result in the conclusion that no testing is needed if the material has a demonstrable safe history of use in a specified role and physical form that is equivalent to that of the medical device under design. The type of information that can be useful to demonstrate equivalence is included in Annex B. Testing is usually not necessary when sufficient information is already available to perform a risk assessment of the material and/or the medical device (see Annex C).
4.2 In the selection of materials to be used in the medical device manufacture, the first consideration shall be fitness for purpose with regard to characteristics and properties of the material, which include chemical, toxicological, physical, electrical, morphological and mechanical properties.
Contents of GB/T 16886.1-2022
Foreword i
Introduction iv
1 Scope
2 Normative references
3 Terms and definitions
4 General principles applying to biological evaluation of medical devices
5 Categorization of medical devices
5.1 General requirements
5.2 Categorization by nature of body contact
5.2.1 Non-contacting medical devices
5.2.2 Surface-contacting medical devices
5.2.3 Externally communicating medical devices
5.2.4 Implant medical devices
5.3 Categorization by duration of contact
5.3.1 Contact duration categories
5.3.2 Transitory-contacting medical devices
5.3.3 Medical devices with multiple contact duration categories
6 Biological evaluation process
6.1 Physical and chemical information for biological risk analysis
6.2 Gap analysis and selection of biological endpoints for assessment
6.3 Biological testing
6.3.1 General requirements
6.3.2 Testing for evaluation
7 Interpretation of biological evaluation data and overall biological risk assessment
Annex A (Informative) Endpoints to be addressed in a biological risk assessment
Annex B (Informative) Guidance on the conduct of biological evaluation within a risk management process
Annex C (Informative) Suggested procedure for literature review
Bibliography
