Let’s Get It Clear: Is it safe to touch?
An MDR checklist will include the biocompatibility properties of any materials which might come into contact with the skin or other parts of the body. Things are about to get easier…
This month’s article covers a rather dry subject, but, for users of equipment it is important for their safety considerations, and for manufacturers there are important cost implications relating to whether they end up having to incur added costs and delays.
What we will be looking at is the need for testing for biocompatibility of the materials used in the manufacture of a product where the product may come into contact with the user’s skin (or internal organs). The key ISO set of standards is the ISO 10993 series: the starting point of these is Part 1, for which a revision is about to be published, and the good news is that the new edition takes a more pragmatic (and therefore less expensive) approach to managing the risks.
ISO 10993 is a series of international standards for the biological evaluation of medical devices to ensure they are safe for patient contact. It uses a risk-based approach to assess biocompatibility, which is the “ability of a medical device or material to perform with an appropriate host response in a specific application”. This involves creating a Biological Evaluation Plan (BEP) to identify potential risks and determine necessary testing for endpoints like cytotoxicity, sensitization, and irritation.
Evaluation of safety
The international working group responsible for the ISO 10993 standards, ISO TC194 WG1, has taken the pragmatic approach in revising ISO 10993-1 to align the biological evaluation of medical devices with the structured risk management principles of ISO 149717. The update reflects evolving regulatory expectations and promotes scientifically justified, ethically responsible evaluations. The new edition de-emphasizes the use of in vitro or in vivo testing, while presenting a broader perspective of consideration of all evidence of biological safety.
Before this revision, manufacturers were repeatedly having to go down the same path, where there was considered to be any risk from the materials used in their products, of having to go through a series of laboratory tests as prescribed in Part 5 of the series, and then the possibility of having to go onto in vivo (i.e. animal testing) as described for example in Part 10. Further, a recent report has indicated that data from Part 5 tests has been determined to be unreliable2.
Key aspects of the new edition of ISO 10993
Risk-based approach: The standard has shifted to a risk-based strategy, where manufacturers first perform a risk assessment to understand the materials and processes involved before determining which tests are necessary.
Biological evaluation plan (BEP): Manufacturers must develop a BEP, which involves reviewing all available data and identifying any gaps that require further investigation or testing.
Contact duration: Devices are categorized by how long they will be in contact with the patient (limited, prolonged, or long-term exposure), which helps determine the extent of the required evaluation.
Endpoints for evaluation: The standards guide testing for various biological endpoints, including most importantly: Cytotoxicity,Sensitization and Irritation, and also systemic toxicity, genotoxicity and pyrogenicity.
What’s new?
What’s new?The main changes compared to the previous edition are as follows:
- the document has been completely reorganised and the title has been aligned with the risk management framework described in ISO 14971
- additional content has been added to provide more guidance and clarification of calculation of exposure duration
- additional content has been added to provide more 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 nonimplanted devices also will need this type of assessment
- Annex A has been revised to provide only guidance on materials characterization, the rest of its former content has been incorporated into the main text
- Annex B has been added to explain the rationale for the changes to biological effects listed in Table 1 to Table 4.
Table 1 covers biological effects for medical devices in contact with intact skin (Figure 1), Table 2 to 4 each add further boxes to be considered for devices respectively in contact with: intact mucosal membranes, either breached or compromised surfaces (skin or mucosal membranes) or internal tissues other than circulating blood, and circulating blood.
Types of acceptable evidence beyond testing
What are the alternatives that are now acceptable? ISO 10993-1:2025 encourages the use of diverse, scientifically valid evidence to support biological safety, including:
- Chemical characterization and toxicological risk assessments
- Material and process knowledge, including historical biocompatibility data.
- Clinical experience and post-market surveillance.
- Published literature and peer-reviewed studies.
- Biological equivalence to predicate devices.
- Structured gap analysis to identify cost-effective data needs.
These sources should be evaluated for evidential value, and testing should only be performed if the risk management process identifies a biological hazard that cannot be addressed through existing data.
Structured risk management integration
Biological evaluation is now explicitly embedded within the ISO 14971 process:
- Risk estimation guides the need for testing.
- Evaluation must be planned, justified, and documented by qualified professionals.
- The goal is to demonstrate that residual biological risk is acceptable, and that no hazardous situation remains requiring further control.
Sources of acceptable evidence
There are listings in different parts of the world of chemicals that experience and existing testing have been shown to be biologically safe. This includes, for example, Annex A from the FDA GSA guidance3 (see Figure 2 for listed safe materials); EMEA REACH compliance, indicating absence of Substances of Very High Concern (SVHC)4,5; or Oeko-Tex compliance of textiles6, indicating over 1000 harmful substance have been tested and the textiles are certified as harmless to human health.
Beyond this, the manufacturer can use: a history of safe use from the supplier; published literature; industry reportable events; EU MDR clinical evaluation reports; and/or other registration or post-market surveillance evidence.
I would like to acknowledge the information in this article supplied by Kara Kopplin, the ISO TC173 Assistive Products liaison expert on ISO TC174 WG1.
References
- 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.
- Gruber, Sarah, and Angela Nickel. Toxic or not toxic? The specifications of the standard ISO 10993-5 are not explicit enough to yield comparable results in the cytotoxicity assessment of an identical medical device. Frontiers in medical technology5 (2023)
- https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and
- https://echa.europa.eu/candidate-list-table
- https://echa.europa.eu/substances-restricted-under-reach
- http://www.oeko-tex.com
- ISO 14971:2019, Medical devices — Application of risk management to medical devices
Further items can be found at www.beshealthcare.net. If you are interested in receiving further information on the topic, please contact barend@beshealthcare.net
.
Dr Barend ter Haar has been involved in seating and mobility for over 30 years, including lecturing internationally and developing international seating standards.
