When biological safety comes up in a medical device project, the first question is often:
Which biocompatibility tests do we need?
That is understandable, but it is usually not the best place to start.
Biological evaluation is not simply a list of laboratory tests. It is a risk-based process for understanding what a patient or user may be exposed to through the device, what biological hazards may result from that exposure, what information already exists, and what additional evidence is needed to demonstrate safety.
That is the role of the Biological Evaluation Plan (BEP) and, ultimately, the Biological Evaluation Report (BER).
The BEP defines the strategy. The supporting evidence may include material information, chemical characterization, existing data, scientific literature, toxicological assessment and biological testing where necessary. The BER then brings that evidence together and documents the overall biological safety conclusion.
The important point is that the process should begin with understanding the device, not with ordering tests.
Start with the Biological Evaluation Plan
A good BEP establishes how biological safety will be assessed before significant testing work begins.
The plan considers the device’s intended use, nature and duration of body contact, materials, manufacturing processes, available evidence and relevant biological hazards. Based on this information, it identifies which endpoints need to be addressed and how they can be supported.
This risk-based approach is central to the ISO 10993 series. The current ISO 10993-1:2025 further aligns biological evaluation with the ISO 14971 risk-management process and places additional emphasis on areas such as materials characterization, exposure and identification of biological hazards.
The BEP should therefore guide the evidence and testing strategy, rather than being written afterwards to justify tests that have already been selected.
At MDS, our existing biological evaluation approach follows the same principle: the BEP first defines the biological risks and appropriate evaluation strategy, after which testing and other supporting work can be planned proportionately.
The main material is rarely the whole story
One of the most important parts of biological evaluation is understanding what the device is actually made of.
Manufacturers may naturally focus on the primary material. A device may, for example, be described as a silicone device, a stainless-steel instrument or a polyurethane catheter.
For biological evaluation, that description is often not detailed enough.
Relevant direct and indirect body-contacting materials need to be understood, including the actual material grade and composition where possible. Depending on the device, this may also include adhesives, coatings, colorants, additives, lubricants and other substances that can contribute to the patient’s exposure.
The same principle applies to constituents introduced through manufacturing or processing.
This is why biological evaluation can quickly become a detailed information-gathering exercise. It is not enough to know that a component is “plastic” or “medical grade.” The evaluator needs to understand what that material actually is and whether there are substances or processes that could introduce biological risk.
European guidance similarly emphasises detailed information on body-contacting materials, including information such as generic and brand names, grades, specifications, additives and colorants where applicable.
What information should manufacturers collect?
The quality of the biological evaluation depends heavily on the quality of the information available.
For relevant materials and components, useful documentation commonly includes the material trade name and grade, supplier and manufacturer information, manufacturing site, Technical Data Sheet (TDS), Safety Data Sheet or Material Safety Data Sheet (SDS/MSDS), and available certificates or declarations concerning biocompatibility, REACH/SVHC, RoHS or other relevant requirements.
Existing biological or chemical test reports can also be valuable.
These documents do not automatically demonstrate biological safety, but they provide important inputs into the assessment.
An SDS may identify hazardous constituents requiring closer toxicological evaluation. A supplier declaration may provide useful information about material composition or previous biological testing. A certificate may help establish the history and specification of a particular material.
The key is to understand what each document actually demonstrates.
A supplier statement saying that a material is “biocompatible”, for example, does not automatically establish that the finished device is biologically safe in its particular intended use.
The finished device still needs to be assessed in the context of how it is manufactured, processed and used.
Manufacturing can change the biological safety picture
Understanding the starting materials is important, but biological evaluation cannot stop there.
The finished medical device may have gone through several manufacturing and processing steps before it reaches the patient. Components may be bonded, coated, cleaned, sterilized, packaged or otherwise processed, and each of these steps can potentially introduce new substances or alter the characteristics of the materials already present.
This is why the evaluator also needs a sufficient understanding of how the device is manufactured and which substances are used during production.
Relevant information may include adhesives, processing aids, lubricants, cleaning agents, mould-release agents, sterilization residues and other substances that could remain on or migrate from the finished device.
In practice, the biological evaluation should therefore consider not only what materials were originally purchased, but also what happens to those materials during manufacturing and what ultimately reaches the finished device.
This becomes especially important when several suppliers or contract manufacturers are involved. Material specifications and processing information need to remain traceable across the manufacturing chain so that the biological evaluation reflects the device that is actually placed on the market.
The focus should ultimately remain on the finished device and the actual patient exposure. Even well-characterized starting materials do not automatically demonstrate the biological safety of the final product if manufacturing, cleaning, sterilization or other processing steps may have changed the exposure profile.
Chemical characterization can become an important part of the picture
For some devices, material documentation and existing evidence are not sufficient on their own.
Chemical characterization may be needed to identify substances that could be released from the device under its conditions of use.
This can include consideration of extractables and leachables, degradation products, manufacturing residuals and other chemical constituents.
ISO 10993-18 provides the framework for chemical characterization, while subsequent toxicological evaluation can be used to assess whether identified substances create an unacceptable biological risk.
However, the appropriate strategy depends strongly on the device.
Chemical characterization is not simply a standard test package that can be applied in the same way to every product. Complex devices, electronics, sensors or large assemblies may present practical questions about representative extraction and exposure conditions.
These issues are another reason why the biological evaluation strategy should be established before testing is commissioned.
A testing-free strategy is not an evidence-free strategy
One particularly important misconception is that biological evaluation always requires a complete set of new biological tests.
It does not.
Existing material information, previous testing, scientific literature, chemical characterization, clinical experience and other evidence may sometimes be sufficient to address particular biological risks.
The ISO 10993 approach is deliberately risk-based and supports avoiding unnecessary testing where adequate evidence already exists. The current ISO 10993-1 also explicitly promotes efficient testing strategies and reduction of unnecessary animal use.
But avoiding new testing places greater importance on the quality of the underlying justification.
If the strategy relies heavily on existing evidence, materials need to be identified carefully. Their composition, grade, supplier, manufacturing history and available supporting certificates become particularly important.
In other words:
A testing-free strategy is not a documentation-free strategy.
It can require substantial work to demonstrate why the available information adequately addresses the relevant biological risks.
When testing is required, test the right thing
Another common issue is deciding what should actually be tested.
If information about a raw material is incomplete, the solution is not necessarily for the device manufacturer to arrange biological testing of that individual raw material.
Material suppliers are generally the primary source for material composition and specification information.
The medical device manufacturer’s responsibility is to demonstrate the biological safety of the finished device in its intended configuration and use.
Depending on the identified risks, this may require biological testing, chemical characterization, toxicological evaluation or a combination of approaches.
MDS’s existing ISO 10993 services include biological testing, chemical characterization, toxicological evaluation and literature-based assessment where appropriate.
The important part is selecting the work based on the biological evaluation rather than applying the same test battery to every device.
Biological endpoints depend on the device
Cytotoxicity, sensitization and irritation are among the biological endpoints frequently considered in medical device evaluations, but biological evaluation should not be reduced to those three tests.
The relevant endpoints depend on factors such as the type of body contact, duration of exposure, materials, device design and identified biological hazards.
Depending on the device, the evaluation may need to consider additional areas such as systemic toxicity, genotoxicity, implantation effects, hemocompatibility or other device-specific risks.
The BEP is where this reasoning should be documented.
Each relevant endpoint should be addressed through appropriate existing evidence, testing or a scientifically justified rationale.
This is one of the key differences between a risk-based biological evaluation and simply ordering a standard biocompatibility test package.
The BER should tell the complete biological safety story
The Biological Evaluation Report brings the evaluation together.
It should not simply be a collection of laboratory reports.
The BER should explain what the device is, how it contacts the body, what materials and relevant substances are present, how manufacturing may affect those materials, what evidence is available, what additional testing or characterization has been performed, and what biological risks remain.
Where chemical substances or degradation products are identified, toxicological assessment may also be required.
The report then provides the overall biological safety conclusion and becomes part of the technical documentation supporting regulatory assessment.
This is consistent with MDS’s existing approach to BER preparation, which combines material review, chemical characterization, biocompatibility testing where required, toxicological evaluation and the final documented safety justification.
Better biological evaluation starts with better information
The most efficient biological evaluation projects are often the ones where biological safety is considered early.
Material trade names and grades are documented. Suppliers and manufacturing sites are known. TDS and SDS documentation is collected. Manufacturing substances and processes are understood. Existing certificates and biological evidence can be located.
When this information is available, the toxicologist can make better decisions about what is already known and what still needs to be demonstrated.
When it is missing, the evaluation may require considerably more investigation before an appropriate testing strategy can even be defined.
For manufacturers, the practical lesson is simple:
Do not begin biological evaluation by asking which tests to order. Begin by understanding the device, its materials, its manufacturing process and the evidence you already have.
From there, the BEP can establish a proportionate strategy, any necessary testing or characterization can be performed, and the BER can bring the evidence together into a clear biological safety justification.
MDS supports manufacturers throughout this process, from BEP preparation and material review to ISO 10993 testing coordination, chemical characterization, toxicological assessment and final BER preparation.
If you are preparing or updating the biological evaluation of a medical device, we can help identify what information is needed, what existing evidence can be used and where additional evaluation or testing may be appropriate.
You can contact us at sales@mdsfinland.com or via Book a Meeting.
