The determination of the biocompatibility of medical devices and their component materials and the evaluation are of great importance for ensuring product safety. Any negative influence on patients in their environment should be avoided. The biocompatibility of implants is particularly relevant in this context.

The biological evaluation of medical devices is regulated by the international series of standards ISO 10993 – Biological evaluation of medical devices. It currently consists of 18 individual standards as well as specific technical reports and additional guidelines. In October 2018, a new edition of ISO 10993-1 -Evaluation and testing as part of a risk management process – was published.

The following is a summary of the main changes and additions to the new ISO 10993-1 compared to the 2009 edition:

1. importance of physical properties.

In the flowchart outlining the systematic approach to a biological evaluation of medical devices, the physical properties of the evaluated device play an important role in deciding which procedures to follow when completing the biological evaluation.

2 Amended and new definitions

The definitions chapter has been significantly changed to include more than 15 new terms. Most of these are from other standards in the 10993 series and ISO 14971 – Medical devices – Application of risk management to medical devices.

3. new aspects in biological evaluation

More aspects need to be considered in biological evaluation. Chapter 4 provides a detailed description of all aspects to be considered. In addition, an evaluation of the advantages and disadvantages for the design of the device being evaluated must be performed (i.e., configuration, quantitative and qualitative evaluation of component materials).

New aspects relevant to the overall biological evaluation of medical devices have been added, namely all direct and indirect tissue-contacting materials (e.g., packaging).

4. further reduction of animal testing

As seen in other revisions to the ISO 10993 series, the reduction of animal testing is of great importance. For many endpoints in vitro, alternative methods are recommended as “first choice” methods. Additional endpoints requiring specific assessment tests have been included in Table A1 in Annex I.

The responsible expert should rationalize the selection of appropriate tests, the interpretation of data generated by the tests, and the need for additional data to complete the biological evaluation. The standard also provides guidance and direction on which tests are appropriate for specific medical device categories.

A gap analysis and selection of biological endpoints for evaluation is suggested in Chapter 6.2.

Several techniques are available to perform chemical and material characterizations. Either directly on material samples or on prepared material extracts. These tests, developed over many years, are relevant, sensitive, rapid, and inexpensive, and provide extremely valuable information for determining material safety and biocompatibility. The detailing of the characterization and the appropriate evaluation should be done with consideration of the device and material properties that are relevant to the safety and performance of the product.

5. involvement of the risk management process.

Annex B “Guidance on the risk management process” has been renamed “Guidance on the conduct of biological evaluation within a risk management process” and includes the presentation of the risk management process according to ISO 14971.

Due to this involvement, the respective chapter is more comprehensive and covers the consideration of biological risks within the biological evaluation of the medical device, starting with the development phase. New concepts for risk assessment are described and implemented, starting with the application of the new ISO 10993-1 standard.

The assessment and corresponding tests within the risk management process according to the 2018 edition of ISO 10993-1 can be summarized as follows:

Biohazard risk assessment

Identification of the relevant toxicological endpoints

Risk assessment of the identified biological hazards

Strategic planning to identify hazards and assess the risks of known hazards

Testing strategy with a rationale for the tests selected or waived.

Biological safety plan is required.

Other standards in the ISO 10993 series are recommended with respect to the extent to which they should be considered in the biological evaluation of the medical device being evaluated, e.g., ISO 10993-17: Establishment of allowable limits for leachable substances and ISO 10993-18: Chemical characterization of materials.

6. in the case of no or temporary physical contact.

For more information on the evaluation of different medical device categories with no or only temporary body contact, see Chapter 5 Nanomaterials; absorbable materials are discussed in Chapter 4.3.

7 Evaluate the entire life cycle or processing cycle.

An important aspect of the new ISO 10993-1 edition: the biological safety of a medical device must be evaluated by the manufacturer throughout the life cycle of a medical device. Reusable devices are to be evaluated by the manufacturer considering the maximum number of validated processing cycles.

What is the overall impression of this new ISO 10993-1 edition?

More comprehensive chemical characterization of all components with direct or indirect tissue contact, consideration of equivalent products or materials, and regularly updated risk assessment are the pillars of this new edition.

Currently, EN ISO 10993-1:2009 and AC2010 are still harmonized under the MDD. However, manufacturers should be prepared for the new ISO version to eventually be adopted under either the MDD or MDR. And you can never be too prepared too early.

Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.