Foreword

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This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of medical devices, in collaboration with the European Committee for Standardization (CEN) Technical Committee CEN/TC 206, Biological and clinical evaluation of medical devices, in accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).

This sixth edition cancels and replaces the fifth edition (ISO 10993‑1:2018), which has been technically revised.

The main changes are as follows:

this document has been completely reorganised and the title has been aligned with the risk management framework described in ISO 14971;
content has been added to provide guidance and clarification of calculation of exposure duration;
content has been added to provide guidance on characterization of the device and identification of biological hazards;
the identification of biological effects (previously referred to as biological end points) has been modified;
the term “externally communicating” has been replaced by language which reflects the specific tissue contact of device components;
the term “effects after implantation” has been changed to “local effects after tissue contact” as some non-implanted devices also will need this type of assessment;
Annex A has been revised to move most of the content to the main text and the remaining text in Annex A is now confined to the provision of guidance on materials characterization;
Annex B has been added to explain the rationale for the changes to biological effects listed in Table 1 to Table 4.

A list of all parts in the ISO 10993 series can be found on the ISO website.

Any feedback or questions on this document should be directed to the user’s national standards body. A complete listing of these bodies can be found at www.iso.org/members.html.

Introduction

The aim of this document is to provide guidance and requirements for the biological evaluation of a medical device within a risk management process to protect humans from biological risks arising from the use of medical devices and the materials from which they are made. Biological risk evaluation compares the estimated biological risk against given risk criteria to determine the acceptability of the biological risk as part of the overall risk management.

Biological evaluation is primarily concerned with medical device biological safety, through consideration of risks associated with biological hazards. Nonetheless, some activities undertaken in the course of biological evaluation in addition to assessments of long-term safety can also generate information on device performance. For example, functional implant models can be used to assess long-term responses such as tissue ingrowth. Biological evaluation, as described in this document, is synonymous with biocompatibility evaluation.

Biological evaluation is conducted on the finished medical device. The principles and methods described can also be useful in the evaluation of candidate materials or prototype devices during a medical device development process, and data obtained from such evaluations can be of value in the assessment of the finished medical device.

Medical device design is wide-ranging, and, at one extreme, a medical device consists only of a single material, which can exist in more than one physical form, while at the other extreme, is a complex article consisting of numerous components made from multiple materials. Biological safety cannot be considered in isolation from the overall medical device design and can require the balancing of conflicting requirements. For example, the choice of the best material with respect to its biological safety can result in a less functional medical device.

The evaluation of biological safety is conducted in the context of the intended use of a particular medical device. Materials can be safe in one medical device and not in another. It is impossible to make generalized conclusions about the safety of a particular material for all medical applications. Biological responses that are regarded as adverse, caused by a material in one application, are not necessarily regarded as adverse in a different situation.

Physical and chemical information supports the overall biological evaluation and can be used to inform testing needs, if any. When biological testing is required, such testing is based upon in vitro, ex vivo or in vivo models. The interpretation of the results of biological tests requires caution because the inherent variability in biological responses between species and individuals means that the biological response observed in animal or cell culture models can differ from those observed in clinical use. Differences in response to the same material among individuals means that some individuals can have adverse reactions, even to well-established materials. Thus, biological evaluation is an exercise in risk management. When applied to the evaluation of candidate materials or prototype devices during a medical device development process, biological evaluation allows the informed and timely consideration of risk control measures such as use of alternative materials, manufacturing processes or designs.

The biological evaluation process described in this document draw on all available sources of information relevant to biological safety of the medical device, including post-market information. This approach allows a comprehensive review of the medical device, the identification of biological hazards and the biological harms which can arise and estimation of the associated risks. This comprehensive approach allows for the identification of any gaps in the existing data set and the consequent need for supplementary assessments (e.g. chemical analysis and hazard identification, biological testing to refine a biological risk estimate) to be conducted.

This document is supported by a wide range of test methods and guidance published in other documents in the ISO 10993 series, as well as other standards. Those who use this document can also consider more specific guidance contained in device-specific standards, where available. For some complex or novel materials or technologies, it can be difficult to use the established methods described in the ISO 10993 series. This document allows for the use of alternative procedures where scientifically justified.

The welfare of animals is very important and the selection of test methods and evolution of testing within the ISO 10993 framework is directed to continue to reduce, refine and, where possible, replace the use of animals for biological testing.

1 Scope

This document specifies the requirements and general principles governing the biological evaluation of medical devices within a risk management process according to ISO 14971.

This document applies to the biological evaluation of medical devices that have direct contact or indirect contact with either:

a patient's body during intended use or reasonably foreseeable misuse; or
the body of other users who are not patients, if the medical device is intended for personal protection (e.g. medical gloves, surgical masks).

Biological evaluation assesses the biological safety of the medical device by considering the biological risks associated with:

constituents of a medical device; and
tissue-device interactions (including physical effects).

The biological evaluation specified in this document can address the biological safety of the medical device, considering the life cycle from design and development through initial use of the finished medical device to final decommissioning or withdrawal from use. The biological evaluation considers both the biological safety of the finished device in first use, and the significance of any changes to the medical device which can occur throughout the life cycle. However, the evaluation of risks related to environmental impacts of decommissioning of medical devices are not within the scope of this document. This document does not mandate re-testing of medical devices that are already on the market and have established and acceptable safety profiles (see 6.6.2).

This document can be useful to support clinical or usability evaluations of medical devices. For example, a biological evaluation is a pre-requisite for conducting a clinical trial. This means that principles outlined in this document can be applied to the evaluation of prototype or development stage devices, as well as to finished medical devices.

Other parts of the ISO 10993 series cover specific aspects of biological evaluation, such as chemical characterization, biological testing, sample preparation, animal welfare and toxicological risk assessment.

For some types of medical devices, specific requirements from other standards (outside the ISO 10993 series) can be considered with a justification for the approach taken if there are differences between the requirements of the ISO 10993 series and those provided in other standards. For example, the ISO 18562 series provides specific requirements for biological evaluation of breathing gas pathway medical devices and ISO 7405 provides specific requirements for biological evaluation of dental devices.

The evaluation of risks related to infectious agents [e.g. bacteria, moulds, yeasts, viruses, transmissible spongiform encephalopathy (TSE) agents] is not within the scope of this document.

NOTE 1 The evaluation of bacterial endotoxins is addressed by ISO 11737‑3.

NOTE 2 The evaluation of risks related to viruses, TSE agents and other pathogens originating from materials of animal origin is addressed by the ISO 22442 series.

2 Normative references

3 Terms and definitions

4 General principles

4.1 Biological evaluation within the ISO 14971 risk management framework

4.2 Biological evaluation process

4.3 Medical device life cycle

4.4 Animal welfare

5 Biological evaluation plan

6 Biological risk analysis

6.1 General approach

6.2 Identification of characteristics related to biological safety

6.3 Identification of biological hazards, biologically hazardous situations and potential biological harms

6.4 Categorization of medical device and determination of scope of evaluation

6.5 Biological effects for evaluation

6.6 Gap analysis

6.7 Biological equivalence

6.8 Testing

6.9 Biological risk estimation

7 Biological risk evaluation

8 Biological risk control

9 Biological evaluation report

10 Production and post-production activities

Bibliography

ISO 10993-1:2025

Biological evaluation of medical devices — - Part 1: Requirements and general principles for the evaluation of biological safety within a risk management process

Current

Published:

18 Nov 2025