The most common mistake in biocompatibility work is to take ISO 10993 for a list of tests to be carried out in sequence. Part 1 of the standard explicitly rejects this: biological evaluation is an ASSESSMENT carried out within a risk management process. Testing is done only for an endpoint that cannot be closed with existing data.
Classification comes first
The evaluation starts from how the device contacts the body. The type of contact falls into three main groups: surface contacting devices, externally communicating devices and implanted devices. The duration of contact is divided into limited, prolonged and permanent. The intersection of these two axes determines which biological endpoints must be assessed.
Endpoints and their parts
| Biological endpoint | The relevant part |
|---|---|
| Cytotoxicity | ISO 10993-5 |
| Sensitisation | ISO 10993-10 |
| Irritation / intracutaneous reactivity | ISO 10993-23 |
| Acute and repeated dose systemic toxicity | ISO 10993-11 |
| Genotoxicity | ISO 10993-3 |
| Implantation — local tissue effects | ISO 10993-6 |
| Haemocompatibility | ISO 10993-4 |
| Chemical characterisation | ISO 10993-18 |
| Toxicological risk assessment | ISO 10993-17 |
Not every cell in the matrix says "carry out a test". The standard requires the endpoint to be ASSESSED; that assessment can also be closed with existing literature, material history or chemical characterisation. The MDR and ISO 10993-1 position animal testing as a last resort.
The rising role of chemical characterisation
In recent years chemical characterisation under ISO 10993-18 has moved to the centre of biological evaluation. The approach is this: the substances that could come out of the material are determined analytically, a toxicological threshold is assessed for each substance and compared against the amount to which the patient will be exposed. Where the margin is sufficient, some endpoints can be closed without testing.
The sample must be in its final form
The evaluation is made on the final form of the device that will contact the patient. Sterilisation, cleaning residues and manufacturing aids directly affect the result. A result obtained with an unsterilised sample does not represent the series production product.
A suggested order
- Define the device's type and duration of contact.
- List the endpoints to be assessed according to ISO 10993-1.
- Collect the material history and existing data.
- Carry out chemical characterisation under ISO 10993-18.
- Separate out the endpoints that can be closed with toxicological risk assessment.
- Plan testing for the remaining endpoints.
- Bring the findings together in the biological evaluation report.
Why an evaluation process rather than a list of tests?
For years, biological evaluation was read as a table of the form "these tests are done for this device". Today's approach in the standard series is different, and grasping this shapes the whole file: the task is not to tick off a list of tests, but to identify the RISKS relating to the device's biological safety and decide, for each one, what sufficient evidence looks like.
The concrete consequence of this approach is: where existing data is sufficient, no test is carried out. If the composition of the material is known, the same material has long been used under the same contact conditions and literature data exists, that data can be submitted as evidence. Testing is carried out to close a data gap; it is not an end in itself.
The two axes that determine the evaluation
| Axis | What it determines |
|---|---|
| The nature of the contact | Does the device contact the surface, the bloodstream, or is it placed within tissue or bone? The further inward the contact goes, the greater the burden of evidence. |
| Contact time | The evidence expected differs for limited, prolonged and permanent contact; when the duration category changes, the file is reassessed. |
These two axes together determine which biological endpoints must be addressed: cytotoxicity, sensitisation, irritation, acute and chronic systemic effects, genotoxicity, effects at the implantation site, haemocompatibility and so on. For each endpoint the file contains either test data or a justified exemption.
The role of chemical characterisation
The most marked shift of weight in the series in recent years has been towards chemical characterisation. The logic is this: if we know the substances that could pass from the device into the body and their quantities, we can assess the risk using the known toxicological data for those substances. This route reduces animal testing and gives a more specific answer. In practice, extraction studies and analytical screening identify the substances that could transfer, and a toxicological risk assessment follows.
Items that determine the defensibility of the file
- That the evaluation was made on the FINAL PRODUCT: the same raw material can behave differently after different processing and sterilisation.
- That the sterilisation method and its residues are included in the evaluation; sterilisation residue is a source of biological risk in its own right.
- That manufacturing aids (mould release agents, cutting fluids, adhesives) are taken into account; these do not appear in the material recipe but remain on the surface.
- That the evaluation is renewed on a change of material or supplier; the phrase "the same class of polymer" is not evidence of equivalence.
- That exemption justifications are written and supported; where an endpoint is skipped without justification, the file is considered incomplete.
A biological evaluation report is not a test report but an ASSESSMENT document interpreting test and literature data together; it is signed by a qualified assessor and linked to the device's risk management file.