Toxicological Risk Assessment (TRA) for Medical Devices

Toxicological Risk Assessment

At TECOLAB, toxicological risk assessments are conducted in line with ISO 10993 standards to support medical device safety and compliance.

ISO 10993-1

Framework for biological evaluation and risk management of medical device

ISO 10993-17

Toxicological risk assessment of chemical constituents from medical device.

ISO 10993-18

Chemical characterization of medical devices (Extractables & leachables)

Medical devices are designed to improve and save lives, but they must also be proven safe for human use. A key part of this evaluation is determining whether chemicals released from a device could pose a risk to patients. This is where Toxicological Risk Assessment (TRA) plays a critical role. Guided by internationally recognized standards such as ISO 10993-1 and ISO 10993-17, TRA provides a structured, science-based approach to assess chemical exposure and ensure it remains within levels that are safe for patients.

The following sections provide an overview of ISO 10993-1, ISO 10993-17, and ISO 10993-18 and their roles in toxicological risk assessment.

ISO 10993-1 : Biological evaluation framework

ISO 10993-1 establishes the overall framework for biological evaluation within a risk management process. It requires manufacturers to adopt a risk-based approach, considering factors such as the nature, duration, and frequency of patient contact.

A key component of this framework is the development of a Biological Evaluation Plan (BEP), which defines the overall evaluation strategy. The BEP outlines how biological safety will be assessed, including:

Identification of relevant biological endpoints
Identification of potential biological hazards
Justification for the use of testing, literature data, chemical characterization, or TRA

The BEP is typically developed during the early stages of device development and updated when significant changes occur.

These evaluations are documented in a Biological Evaluation Report (BER), which presents the overall safety assessment.

ISO 10993-18 : Chemical characterization

ISO 10993-18 focuses on the chemical characterization of medical devices by identifying and quantifying substances that may be present in or released from the device. It supports biological evaluation by providing data needed to assess toxicological risks.

It is typically applied when extractables and leachables (E&L) are required, new materials are introduced, there is prolonged patient contact, or available data is limited. The extent of characterization depends on the device, its use, and existing information. In some cases, such as disinfectants, its application may depend on scientific justification and regulatory expectations, and additional evaluation may still be required.

ISO 10993-17 : Toxicological risk assessment

ISO 10993-17 specifies the methodology for assessing whether exposure to chemical substances from a medical device is without appreciable harm to health. This involves identifying relevant chemical constituents, deriving tolerable intake (TI) or tolerable contact levels (TCL) based on toxicological data, applying appropriate uncertainty factors, and comparing estimated exposure with these limits to evaluate risk. A step-by-step overview of how TRA is conducted is presented in the following section.

The evaluation typically begins with ISO 10993-1, where a BEP is developed to define the overall strategy. This is followed by ISO 10993-18, which focuses on identifying and characterizing chemical substances that may be present or released from the device. Based on this information, ISO 10993-17 is then applied to assess whether exposure to these substances is safe. In certain cases, ISO 10993-18 may be omitted if sufficient data and scientific justification are available. Finally, the outcomes are reviewed within the framework of ISO 10993-1 to ensure a complete and consistent biological evaluation.

Now that we’ve explored the ISO standards, you may be wondering—what is TRA, and why is it so often required?

TRA is a key component of medical device safety evaluation, used to determine whether chemicals released from a device—such as extractables and leachables—could pose a health risk to patients. It answers a critical question:

Are the substances released from this device safe at the levels patients are exposed to?

TRA integrates chemistry, exposure assessment, and toxicology to identify substances present, determine patient exposure, and evaluate potential health effects.

Rather than relying solely on biological testing, modern approaches emphasize chemical characterization and risk-based evaluation, enabling more targeted and efficient assessments while maintaining a high level of patient safety.

Now that we understand what TRA is, let’s explore how it is performed in practice. The process can be broken down into four key steps:

Step 1: Compound selection

The TRA process begins by identifying potential chemical substances associated with a medical device. These may be identified through extractables and leachables (E&L) studies in accordance with ISO 10993-18, or through a worst-case assessment based on the device’s materials and intended use. However, not every detected compound requires detailed evaluation.

Step 2: Hazard assessment

Once relevant compounds are identified, toxicological data is collected from scientific literature and regulatory databases to understand potential health effects.

Where sufficient data is available, safety limits are established by:

Determining the Point of Departure (PoD) such as NIL, MIL, LOAEL, NOAEL
Calculating the Tolerable Intake (TI), Cancer Risk Specific Dose (CRSD), Tolerable Contact Level (TCL)
Applying appropriate uncertainty factors

These calculations depend on the type of toxicological effect, such as non-genotoxic, genotoxic, or irritating effects.

Where compound-specific data is unavailable or limited, a conservative approach may be applied using the Threshold of Toxicological Concern (TTC), or by leveraging data from structurally or toxicologically similar compounds using established toxicological models or read-across approaches.

Step 3: Exposure assessment

Once the hazard is understood, the next step is to estimate how much of each substance a patient could be exposed to under worst-case conditions. This is expressed as the Estimated Exposure Dose (EEDmax).

Step 4: Risk characterization

Finally, risk characterization is performed by comparing the estimated exposure with the derived safe limits, typically expressed as the Margin of Safety (MoS). This determines whether the identified risks are acceptable for the intended use of the device.

The MoS can be interpreted as follows:

MoS > 1 → Risk is typically considered acceptable
MoS < 1 → Further evaluation may be required

Do terms like 👉 TSL, AET, TQmax, TTC, TCL, TI, NOAEL, LOAEL, CRSD… and the overall process feel overwhelming?

Don’t worry ! We simplify the process and provide clear support at every step.

Here’s what we do, in simple terms:

Step 1 : Identify harmful chemicals

We check what substances are present in or released from the device

Step 2 : Estimate exposure

We calculate the highest possible amount a patient could be exposed to

Step 3 : Define safe limits

We use scientific data to define how much is considered safe for humans

Step 4 : Compare exposure to limits

We check if the amount from the device stays within safe levels

Step 5 : Assess device safety

If everything is within safe limits, it’s acceptable — otherwise, we take further action

Why choose TECOLAB

Cost-effective solutions tailored to your needs
End-to-end support throughout the entire process, at no additional cost

We’re happy to support you. Contact us today to get started.

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