Biological evaluation, toxicological risk assessment and E&L

The situation

You are here for one of a small number of reasons. A laboratory has quoted a battery of tests and you suspect you do not need all of it. A notified-body or FDA reviewer has asked for a toxicological risk assessment, or has rejected the one you have. A supplier has changed a material, a colourant or a sterilisation process, and nobody can say which parts of the biological evaluation that invalidates. Or you are building the file for the first time and want it done once.

In each case the work starts in the same place: the device's nature and duration of contact under ISO 10993-1:2025, the materials and processes that make it, and the question of which biological endpoints that combination requires you to address. Only after that question is answered does anyone talk about testing.

What goes wrong when this is handled late

Testing bought before the evaluation is planned is the most common and most expensive error. A battery run on a device that was never categorised correctly produces reports that answer the wrong questions, and a reviewer notices. Tests run without chemical characterisation leave the toxicological endpoints unaddressed no matter how many biological assays were passed. Evaluations written as a list of passed tests, without the risk-management reasoning the 2025 edition now requires explicitly, come back with deficiency letters that take longer to answer than the original work would have taken to do properly.

The second error is treating the biological evaluation as a one-time document. Every material change, every new supplier declaration and every process change is a question for the evaluation, and a file that cannot show the question was asked is a file with a gap.

What Authentcare does

Assess. Categorise the device under ISO 10993-1:2025 by nature and cumulative duration of contact, including reasonably foreseeable misuse. Review the materials, formulation, processing aids, sterilisation and packaging for what they contribute. Review the chemical characterisation and test data you already hold. Identify, endpoint by endpoint, what is addressed and what is not.

Develop. Write the biological evaluation plan with the rationale for every endpoint decision. Design the extractables and leachables study where one is needed: extraction conditions that reflect clinical use, the analytical evaluation threshold derived and justified, and a brief the laboratory can quote against without guessing. Write the toxicological risk assessment when the characterisation data arrives. Consolidate everything into the biological evaluation report, and write the change assessment when something changes later.

Coordinate. Brief the laboratory, answer its questions, review the report on return against the brief and against the standard, and raise and close the gaps. Explain the evaluation to a reviewer in a structured dialogue or a deficiency response.

The illustration below is the endpoint logic abstracted from Authentcare's own plan structure. Most endpoints end in the upper box; the lower box is short, and every entry in it has a written reason.

The toxicological risk assessment

The TRA is where this practice is deepest, and it is where files most often fail. A good TRA under ISO 10993-17:2023 takes each compound the chemical characterisation identified, finds or derives a tolerable intake from the toxicological literature with the uncertainty factors stated, estimates the patient's exposure from the extraction data and the clinical use, and compares the two as a margin of safety, with the conclusion and its confidence written plainly. Where the literature is thin, the assessment says so and says what was done about it, rather than borrowing a value from an unrelated context and hoping no one checks.

The TRA is offered as a fixed-scope deliverable in two tiers by compound count, with larger lists quoted as a project. The assessment is issued under document control with its sources listed, so that when a tolerable intake is revised in the literature the compounds it affects can be found in minutes.

What you receive

• Biological evaluation plan (BEP) to ISO 10993-1:2025, with device categorisation, exposure reasoning, endpoint-by-endpoint rationale and a justified test list
• Toxicological risk assessment (TRA) to ISO 10993-17:2023, compound by compound, with tolerable-intake derivation, exposure estimation and margin-of-safety conclusions
• Extractables and leachables study design to ISO 10993-18:2020+A1:2022, including analytical evaluation threshold derivation and the laboratory brief
• Breathing-gas-pathway evaluation plan and assessment to ISO 18562-1 to -4:2024
• Biological evaluation report (BER) consolidating the evidence and the conclusion
• Laboratory briefs, report reviews and gap closure notes for each test commissioned
• Change assessments for material, supplier or process changes, stating which endpoints are affected

Frameworks and editions

Applicability is device-specific. Which of these apply, and in what combination, depends on device type, intended purpose, classification and target market; the applicability assessment at the start of every engagement settles it in writing.

What this engagement excludes

• Laboratory testing of any kind; analytical, in-vitro or in-vivo work is performed by accredited laboratories and invoiced by them
• Formulation or material selection advice beyond the regulatory consequences of a choice
• Clinical evaluation; where clinical data is needed to close a biological endpoint, that is scoped separately
• Notified-body or FDA fees