Toxicological Risk Assessment of Medical Device in Accordance with  ISO 10993

Written By Vivek Dadhania

Medical devices may come into direct or indirect contact with the human body, sometimes for minutes, sometimes for years. Any exposure to chemical substances from device materials must be quantitatively evaluated to ensure it does not pose unacceptable health risks. This requirement is addressed through the ISO 10993 series, which provides the international framework for the biological evaluation of medical devices.

Within the broader scope of biological evaluation, Toxicological Risk Assessment (TRA) is a central component. It evaluates chemical safety, supports risk-based decisions on biological testing, and provides a scientifically justified rationale for the safety of device materials. It has become a cornerstone of ISO 10993 compliance, enabling manufacturers to demonstrate material safety in alignment with FDA and EU MDR expectations.

Overview of ISO 10993 Standards

ISO 10993 is a multi-part international standard series that provides a structured framework for evaluating the biological safety of medical devices. ISO 10993-1 defines the principles of biological evaluation and encourages a structured biological evaluation plan (BEP) and Toxicological Risk Assessment guided by science-driven rationale.

Key principles include:

  • Assessment based on nature and duration of body contact

  • Risk-based evaluation approach

  • Provide scientific justification for waived endpoints

  • Consideration of physical and chemical characteristics

  • Use of existing data wherever scientifically justified

  • Support replacement of animal testing with alternative in vitro or in silico methods

What Is Toxicological Risk Assessment?

Toxicological Risk Assessment is the systematic evaluation of potential health risks from chemical substances in medical devices, in accordance with ISO 10993-17.

Toxicological risk assessment process typically includes:

  • Chemical Characterization (ISO 10993-18)

Identify materials, extractables, and leachables and define the chemical profile for exposure assessment

  •  Exposure Estimation

Calculate patient exposure based on device type, frequency, duration, and contact route

  • Comparison to Toxicological Threshold

Reference established toxicological limits, tolerable intake, or NOAELs and derive margins of safety

  •  Weight-of-Evidence Assessment

Integrate in vitro, in silico, clinical, and literature data and consider uncertainties and conservative assumptions

  • Risk Conclusion and Documentation

Determine acceptability of identified risks and document justification 

Extractables and Leachables: TRA in Practice

Medical devices may release chemical substances during use, particularly those made from polymers, coatings, inks, or adhesives. The toxicological assessment is applied to evaluate these substances by:

  • Identifying potential chemical constituents through chemical analysis

  • Estimating patient exposure using worst-case scenarios

  • Comparing exposure levels to toxicological thresholds

  • Assessing cumulative and long-term risks

This process is generally performed in accordance with ISO 10993-18 (chemical characterization) and ISO 10993-17 (toxicological risk assessment) and is especially important for implantable and long-term contact devices.

FDA and EU MDR Expectations 

Both US and EU regulators expect biocompatibility to be addressed through a risk-based biological evaluation in accordance with the ISO 10993 framework, supporting the overall biocompatibility strategy.

In regulatory submissions, reviewers typically expect:

  • A documented biological evaluation aligned with ISO 10993-1, clearly describing the device’s intended use, contact type, and duration

  • Toxicological risk assessment reports, where chemical exposure is relevant, demonstrating comparison of patient exposure to substance-specific toxicological limits

  • A clear justification for biological test selection, omission, or waivers, supported by existing data and risk assessment

  • Alignment with current ISO 10993 revisions and applicable regulatory guidance

  • Transparent documentation of assumptions, uncertainties, and conservative decision-making

Incomplete or poorly justified biocompatibility assessments are a common source of requests for clarification, additional testing, or regulatory delays.

Common Challenges in Toxicological Risk Assessment

Medical device manufacturers may face challenges such as:

  • Complex or multi-component material compositions

  • Limited toxicological data for novel substances

  • Interpreting ISO 10993 requirements correctly

  • Balancing biological testing with risk-based justification

  • Addressing evolving regulatory expectations and feedback efficiently

These challenges highlight the importance of a structured, expert-led approach to biocompatibility and toxicological risk assessment.

How SciQra Supports Toxicological Risk Assessment and ISO 10993 Compliance

SciQra provides expert support for ISO 10993 aligned Biological Evaluation and Toxicological Risk Assessment, including:

  • Biological evaluation strategy and gap assessment

  • Preparation of Biological Evaluation Plan (BEP) and Biological Evaluation Report (BER)

  • Toxicological risk assessment of materials and constituents

  • Extractables and leachables safety evaluation

  • Scientific justification for waived tests

  • Regulatory-ready documentation for FDA and EU MDR submissions

With a science-driven, regulator-aligned approach, SciQra helps manufacturers meet regulatory expectations, reduce unnecessary testing, and accelerate market access.

Frequently Asked Questions

Is ISO 10993 biocompatibility assessment mandatory?

Yes, any device that comes into contact with the human body requires evaluation. The depth and type of assessment depend on the nature and duration of contact, making risk-based decisions essential in accordance with the USFDA and EU MDR requirements. 

Can toxicological risk assessment replace all biological tests?

Not entirely. TRA cannot replace all testing, but when supported by robust chemical characterization, exposure estimates, and scientific rationale, it can significantly reduce or waive certain biological tests, minimizing unnecessary animal use and development costs. The key is a weight-of-evidence approach aligned with ISO 10993 principles.

Does ISO 10993 apply to all medical devices?

The application of ISO 10993 is device-specific. A short-term external device will have different endpoints than a long-term implantable device. TRA ensures that chemical safety is evaluated in context, tailoring testing to real patient exposure and clinical relevance.



Vivek Dadhania https://sciqra.com/
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