Biocompatibility testing used to mean running a fixed list of biological tests. Today ISO 10993-1 asks for a risk-based evaluation instead, and that opens the door to answering some biological questions with chemistry and toxicology rather than animal studies.

Start with what is already known

Before planning any test, gather the existing evidence: the materials and their history of safe use, prior test data, published literature, and similarity to devices already on the market. Where this evidence is strong and relevant, some endpoints may need little or no new data.

Chemical characterisation (ISO 10993-18)

Chemical characterisation identifies what could come out of a device during use. Extractables studies use exaggerated conditions to find what could be released; leachables studies look at what actually is released under conditions closer to clinical use. The result is a list of compounds and the amounts a patient could be exposed to.

Toxicological risk assessment (ISO 10993-17)

Each identified compound is then assessed by a toxicologist. Its estimated exposure is compared with a tolerable level derived from toxicological data, giving a margin of safety. Where data are limited, recognised approaches such as the threshold of toxicological concern can be applied.

  • If every compound has an acceptable margin of safety, that evidence can support the safety case for systemic toxicity endpoints.
  • If a compound raises concern, the assessment shows exactly which risk needs further work, so any testing is targeted.

Where this approach helps most

  • Material, supplier or process changes to a device that is already on the market
  • Long-term implants, where systemic and chronic endpoints would otherwise need lengthy studies
  • Programmes aiming to reduce animal testing in line with the 3Rs principle

Some endpoints, such as cytotoxicity, sensitisation and irritation, are still commonly addressed by testing, and the right mix always depends on the device. The value of a well-reasoned evaluation is that every test you do run has a clear purpose.

What reviewers look for

A testing reduction is only accepted when the justification is clear: the chemistry must be adequate for the device, the exposure estimates must be conservative, and the toxicological conclusions must be traceable. That reasoning belongs in the Biological Evaluation Plan and is concluded in the Biological Evaluation Report.