GB/T 16886.12-2023Biological evaluation of medical devices - Part 12: Sample preparation and reference materials (English PDF)

Foreword

This Document was drafted as per the rules specified in GB/T 1.1-2020 Directives for

Standardization – Part 1.Rules for the Structure and Drafting of Standardizing Documents.

This Document is Part 12 of GB/T (Z) 16886 Biological Evaluation of Medical Devices. GB/T

(Z) 16886 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 leachable;

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

--- Part 18.Chemical characterization of medical device materials within a risk management

process;

--- Part 19.Physio-chemical, morphological and topographical characterization of materials;

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

--- Part 22.Nanomaterials guide;

--- Part 23.Tests for irritation.

This Document replaced GB/T 16886.12-2017 Biological Evaluation of Medical Devices - Part

12 Sample Preparation and Reference Materials. Compared with GB/T 16886.12-2017, the

major technical changes of this Documents are as follows besides the structural adjustments

and editorial modifications.

a) Change the "Scope" to cover only the extraction of biological evaluation tests (see Clause

1 of this Edition; Clause 1 of the 2017 Edition);

b) Delete the terms and definitions of "accelerated extraction" and "simulated use

extraction" (see 3.1 and 3.14 of the 2017 Edition); and change the definitions of "strict

extraction", "extreme extraction", "extractables" and "leachable" (see 3.3, 3.4, 3.7 and

2017 Edition).

This Document equivalently adopts ISO 10993-12.2021 Biological Evaluation of Medical

Devices – Part 12.Sample Preparation and Reference Materials.

Please note some contents of this Document may involve patents. The issuing agency of this

Document shall not assume the responsibility to identify these patents.

This Document was proposed by National Medical Products Administration.

This Document shall be under the jurisdiction of National Technical Committee on Biological

Evaluation on Medical Device of Standardization Administration of China (SAC/TC 248).

Drafting organizations of this Document. Shandong Medical Device and Drug Packaging

Inspection Institute; and Sichuan University.

Chief drafting staffs of this Document. Liang Jie, Sun Xiaoxia, Sun Lingxiao, Yuan Tun, and

Qu Qiujin.

The historical editions replaced by this Standard are as follows.

--- GB/T 16886.12-2000 was first-time published in 2000; first-time revised in 2005; and

second-time revised in 2017.

--- It is third-time revised hereby.

1 Scope

This Document specifies requirements and gives guidance on the procedures in the preparation

of samples and the selection of reference materials for medical device testing primarily in

biological test systems primarily in accordance with one or more parts of the ISO 10993 series.

Specifically, this document addresses the following.

2 Normative References

There are no normative references in this Document.

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.

Substance that can be released from a medical device or material using either extraction

solvents or extraction conditions, or both, that are expected to be at least as aggressive as the

conditions of clinical use.

4 General Requirements

When identifying hazards and estimating risk in relation to medical devices, hazards that arise

from changes in the manufacturing process, or insufficient control of the manufacturing process,

shall be considered in the design and preparation of test samples, as described in ISO 14971.

5 Reference Materials (RMs)

Certification of a RM is a procedure that establishes the numerical or qualitative value of the

biological response of the material under the specified test conditions. This process serves to

validate the testing of the material for that particular response and results in the issuance of a

certificate.

6 Use of RMs as Experimental Controls

RMs or CRMs shall be used in biological tests as control materials to demonstrate the suitability

of a procedure to yield a reproducible response, i.e., positive or negative, or both. Any material

used in this way shall be characterized with each biological test procedure for which the use of

the material is desired.

7 Test Sample Selection

Testing shall be performed on the final product, representative samples from the final product,

materials processed in the same manner as the final product (see ISO 10993-1), or on

appropriate extracts of any of these. The choice of test sample shall be justified.

8 Test Sample and RM Preparation

Test samples and RMs shall be handled with care to prevent contamination. Any residue from

the manufacturing processes, intentional or unintentional additives or contaminants, shall be

considered integral to the medical device, medical device portion or component, or

representative sample.

9 Selection of Representative Portions from a Medical Device

When different materials are present in a single medical device, the potential for synergies

and interactions shall be considered in the choice of test sample.

10 Preparation of Extracts of Samples

The extraction shall be performed in clean, chemically inert, closed containers with minimum

dead space.

In the case of products that polymerize in situ, the samples to be tested shall represent the

intended clinical conditions of use in order to provide information on the potential toxicity of

the reacting components in the polymer during the curing process.

11 Records

Records of the sample and its preparation shall include, but not be limited to.

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