GB/T 16886.3-2019Biological evaluation of medical devices -- Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity (English PDF)

Foreword

GB/T 16886 "Biological evaluation of medical devices" consists of the following

parts.

- Part 1.Evaluation and testing within a risk management process;

- 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 in vitro cytotoxicity;

- Part 6.Tests for local effects after implantation;

- Part 7.Ethylene oxide sterilization residuals;

- Part 9.Framework for identification and quantification of potential

degradation products;

- Part 10.Tests for irritation and skin sensitization;

- Part 11.Tests for systemic toxicity;

- Part 12.Sample preparation and reference materials;

- Part 13.Identification and quantification of degradation products from

polymeric medical devices;

- Part 14.Identification and quantification of degradation products from

ceramics;

- Part 15.Identification and quantification of degradation products from

metals and alloys;

- Part 16.Toxicokinetic study design for degradation products and leachables;

- Part 17.Establishment of allowable limits for leachable substances;

- Part 18.Chemical characterization of materials;

- Part 19.Physico-chemical, morphological and topographical

characterization of materials;

- Part 20.Principles and methods for immunotoxicology testing of medical

devices.

This Part is Part 3 of GB/T 16886.

This Part is drafted in accordance with the rules given in GB/T 1.1-2009.

This Part replaces GB/T 16886.3-2008 "Biological evaluation of medical

devices - Part 3.Tests for genotoxicity carcinogenicity and reproductive toxicity".

Compared with GB/T 16886.3-2008, in addition to editorial changes, the main

technical changes are as follows.

- CHANGE the test strategy by adding in vivo test and follow-up evaluation;

- ADD Annex A "Guidance on selecting an appropriate sample preparation

procedure in genotoxicity testing";

- ADD further in vitro and in vivo tests, to assess the genotoxic potential of

medical devices;

- ADD Annex B "Flowchart for follow-up evaluation";

- CHANGE the former Annex C to Annex E "Considerations for

carcinogenicity studies performed as implantation studies" and develop

specifications;

- ADD Annex F "In vitro tests for embryo toxicity".

This Part, using translation method, is identical to ISO 10993-3.2014 "Biological

evaluation of medical devices - Part 3.Tests for genotoxicity, carcinogenicity

and reproductive toxicity".

China's documents which have a consistent correspondence with the

international documents normatively referenced in this Part are as follows.

- GB/T 16886.1-2011 Biological evaluation of medical devices - Part 1.

Evaluation and testing within a risk management process (ISO 10993-

1.2009, IDT)

- GB/T 16886.2-2011 Biological evaluation of medical devices - Part 2.

Animal welfare requirements (ISO 10993-2.2006, IDT)

- GB/T 16886.6-2015 Biological evaluation of medical devices - Part 6.Tests

for local effects after implantation (ISO 10993-6.2007, IDT)

- GB/T 16886.12-2017 Biological evaluation of medical devices - Part 12.

Sample preparation and reference materials (ISO 10993-12.2012, IDT)

- GB/T 16886.18-2011 Biological evaluation of medical devices - Part 18.

Chemical characterization of materials (ISO 10993-18.2005)

Attention is drawn to the possibility that some of the elements of this document

may be the subject of patent rights. The issuing authority of this document shall

not be held responsible for identifying any or all such patent rights.

This Part was proposed by National Medical Products Administration.

This Part shall be under the jurisdiction of National Technical Committee 248

on Biological Evaluation of Medical Devices of Standardization Administration

of China (SAC/TC 248).

Drafting organizations of this Part. Shandong Quality Inspection Center for

Medical Devices, Sichuan University.

Main drafters of Part. Hou Li, Sun Xiaoxia, Liang Jie, Yuan Tun, Li Qiu.

The previous editions of the standard replaced by this Part were released as

follows.

- GB/T 16886.3-1997, GB/T 16886.3-2008.

1 Scope

This Part of GB/T 16886 specifies strategies for risk estimation, selection of

hazard (source) identification tests and risk management, with respect to the

possibility of the following potentially irreversible biological effects arising as a

result of exposure to medical devices.

2 Normative references

The following documents are indispensable for the application of this document.

For the dated references, only the editions with the dates indicated are

applicable to this document. For the undated references, the latest edition

(including all the amendments) are applicable to this document.

ISO 10993-1 Biological evaluation of medical devices - Part 1.Evaluation

and testing within a risk management process

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.

4 Requirements for test strategies

Testing may be warranted for additional states of the device such as, wear

debris generated from the device or materials that cure in situ (e.g. cements,

adhesives and pre-polymer mixtures) unless toxicological risk assessment

determines no cause for concern from additional device/material states. For

guidance on in situ curing devices see ISO 10993-12.

5 Genotoxicity tests

Unless the sample can be dissolved in a solvent compatible with the test system,

appropriate extraction solvents shall be chosen on the basis of its ability to

maximize extraction of the material or medical device to a level at which the

concentration of genotoxic residues would be sufficient to produce a positive

response in the test system, but without degradation of the device or the test

sample.

6 Carcinogenicity tests

Carcinogenicity testing of genotoxic materials shall be scientifically justified. In

most instances for genotoxic materials, a carcinogenic hazard can be

presumed and the risk managed accordingly.

7 Reproductive and developmental toxicity tests

Sample preparation shall be in accordance with ISO 10993-12.Whenever

possible the medical device shall be tested in a form representative of its final

state. Additional testing may be warranted for additional states of the device

such as, device or materials that cure in situ (e.g. bone cements, adhesives

and pre-polymer mixtures).

8 Test report

If relevant, the test report shall include at least the following details.

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