Biological safety of medical devices: Biocompatibility, cleanliness, and sterility

The biological safety of medical devices encompasses two key aspects: the biocompatibility of the materials, including the identification of potential hazards due to contaminants or material-related changes caused by manufacturing processes; and the identification of potential risks from infectious microorganisms.

Insufficient biocompatibility can lead to adverse reactions, primarily in the patient, but also potentially in users and third parties. To avoid such reactions, a toxicological risk assessment is often necessary.

Inadequate cleanliness, such as residual microorganisms, and insufficient sterility can increase the risk of infection for both patients and users.

As a medical device manufacturer, you are required under your risk management system to ensure biocompatibility in accordance with ISO 10993-1 and other applicable standards. For reusable and/or sterile products, additional requirements apply depending on the reprocessing and sterilization methods used, to ensure product cleanliness and sterility.

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Our services in the field of biological safety

Biocompatibility

GAP analyses of your existing documentation, tailored to your target countries and the applicable regulatory requirements
Consulting on required testing and development of customized test strategies in accordance with ISO 10993-1
Identification of “worst-case products”
Liaison with the testing laboratory for your studies, including request for quotations and acting as study monitor
Preparation of Biological Evaluation Plans and Biological Evaluation Reports
If needed: toxicological risk assessment in accordance with ISO 10993-17, also available as a standalone service
Audit preparation for clients in the field of biological safety
Support during supplier audits, e.g., at the testing laboratory

Sterilization/reprocessing

Development of cleaning, disinfection, and sterilization concepts, including consideration of all relevant interfaces
Preparation of validation plans and validation reports for cleaning, disinfection, and/or sterilization, in accordance with the requirements of the respective target countries
Identification of "worst-case products"
Liaison with the testing laboratory for your studies, including request for quotations and acting as study monitor
Evaluation of the impact of reprocessing on the biocompatibility of medical devices
Audit preparation for clients in the field of biological safety
Support during supplier audits, e.g., for sterilization service providers

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Infographic: Biological Safty - Metecon GmbH

Biocompatibility of medical devices: Evaluation, requirements, and implementation

Biocompatibility is a central element of biological safety assessment. The goal is to avoid unwanted biological reactions resulting from the product's contact with the human body. A well-founded biocompatibility assessment starts as early as the development phase – and continues throughout the entire product lifecycle.

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Biological evaluation according to ISO 10993-1: Getting started the right way

Biological evaluation begins with material selection. The chosen materials must meet not only technical specifications but also biocompatibility requirements. Manufacturing, cleaning, and sterilization processes must not compromise biocompatibility – or only to a justifiable degree. Even early-stage material characterization can significantly contribute to successful market approval, particularly when conducted with expert guidance.

Identified risks are incorporated into the Biological Evaluation Plan (BEP) and categorized and assessed according to ISO 10993-1. Data gaps are closed through a targeted testing strategy.

Think internationally and product-specifically in biological evaluations

Take country-specific guidance documents into account when planning to enter additional markets – and adapt the test strategy in the Biological Evaluation Plan (BEP) accordingly.
Review applicable product-specific standards. For example, dental devices, gas-conducting medical devices, and intraocular lenses are subject to their own requirements.

Need clarity on standards and requirements?
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Biocompatibility in the context of other regulatory requirements

ISO 10993-1 clearly states that biological evaluation is closely interlinked with other regulatory disciplines, including:

risk management,
verification and validation (e.g., testing, cleaning, or sterilization concepts),
clinical evaluation, and
post-market surveillance (PMS).

Findings from these areas influence the biological evaluation—and vice versa.

Our team of experts will help you leverage these intersections effectively and document everything in a regulatory-compliant manner.

Choosing test laboratories: Managing chemical and biological testing effectively

A robust test strategy is crucial – as is selecting the right testing laboratories. We recommend laboratories accredited to ISO 17025 and, if applicable, certified under Good Laboratory Practice (GLP), depending on the target market (e.g., the U.S.). ISO 17025 ensures technical precision, while GLP is key to regulatory acceptance of the results.

Recommended test laboratories:

CleanControlling Medical GmbH & Co. KG
Eurofins Medical Device Testing
NAMSA
Hohenstein Laboratories GmbH & Co. KG (for gas-conducting devices)
UL Solutions (for intraocular lenses)

TIP: Always check the current validity of any accreditations and certifications.

Interpreting test reports: When is a toxicological risk assessment necessary?

Results from biological testing feed directly into the Biological Evaluation Report (BER). If chemical testing was conducted, such as chemical characterization or target analysis, a toxicological risk assessment may be required, in accordance with ISO 10993-17. This should be carried out by experienced toxicologists.

New risks identified during testing may require further studies or a risk–benefit assessment. The Biological Evaluation Report (BER) can only be finalized once all data gaps are closed.

Biological evaluation post market launch: When is an update needed?

Biological safety evaluation doesn’t end with market approval - it continues throughout the product’s lifecycle. New insights, product modifications, or PMS results may necessitate a partial or complete re-evaluation.

We support you in the ongoing biological evaluation – even after your product has been successfully launched.
Feel free to contact us.

Toxicological risk assessment according to ISO 10993-17: Proper evaluation of substances

In general, a distinction is made between a toxicological assessment of chemical substances and a toxicological risk assessment specifically for medical devices. The ISO 10993-17 standard is designed to identify and evaluate potential adverse effects and associated health risks.

This process starts within the broader biological safety assessment framework as defined by ISO 10993-1. Chemical characterization of the device components, as specified in ISO 10993-18, is an essential step. During screening procedures, various analytical methods are used to identify and quantify so-called leachables (substances that may leach from the device) and extractables (substances that can be extracted under lab conditions).

The results are then assessed through exposure estimation and the determination of product-specific limits. Finally, the toxicological relevance is interpreted in the context of biocompatibility. If all potential hazards are ruled out, the product may be deemed safe – possibly with further biological testing.

If data is insufficient, additional studies or a risk–benefit analysis may be necessary.

Need support in evaluating your toxicological data?
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Who is qualified to conduct a toxicological risk assessment?

Regulations offer only vague guidance on who is authorized to conduct toxicological risk assessments. Naturally, such assessments should be carried out by qualified toxicologists. However, most companies don’t have in-house experts with this specialization.

If you have highly experienced personnel who thoroughly understand the data and can interpret it responsibly, internal evaluation may be feasible in some cases.
Still, we recommend that toxicological risk assessments be performed by trained toxicologists – especially when dealing with complex analyses or international submissions.

If you’ve already completed chemical characterization and now require toxicological expertise:
Have questions? Reach out to our team.

Cleaning, disinfection, and sterilization of medical devices: What is required and when?

This depends on your specific medical device and how you plan to bring it to market.

If you intend to market your devices as sterile, your sterilization method – as well as your production environment, processes, and packaging concepts – must be appropriately designed and implemented. At this stage, a robust hygiene management system or even cleanroom manufacturing may already be required.

If your medical devices are designed for repeated reprocessing, you’ll need to make key decisions early on – for example, on the reprocessing method (automated or manual). This has downstream implications, such as determining parameters for cleaning and, where applicable, disinfection, as well as selecting a suitable sterilization method.
The sequence described here provides only an overview. In practice, preparatory measures for cleaning and/or sterilization are often needed as part of manufacturing, such as in-process controls.

Want to set up or optimize your cleaning and sterilization concepts?
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Verification and validation: What is required and when?

In addition to verifying that your medical device is suitable for the intended processes, you, as the manufacturer, are required to validate critical processes.

Depending on the type of process (e.g., automated versus manual cleaning), different requirements apply. Things get more complex when:

equipment validations (e.g., cleanroom validation),
post-sterilization performance testing, or
lifecycle analyses must be included.

Here, too, requirements vary based on product type, user group, and market access strategy.

Interfaces with biological safety: Everything is connected

All processes related to cleaning and sterilization are closely linked to other regulatory areas—especially:

biocompatibility,
risk management,
clinical evaluation, and
verification and validation.

These interfaces should be considered and documented from the outset to ensure your biological safety strategy is coherent and regulatory-compliant.

Our Metecon experts are well-versed in all relevant areas.
We’ll help you make your processes safe and efficient.

Our team of experts is here for you – experienced, reliable, and by your side.

Whether it's biocompatibility, toxicological risk assessment, or sterilization strategies: We support you with expertise, foresight, and a clear focus on regulatory compliance.

Let’s talk – we look forward to hearing from you.