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.