Medical Device Systemic Toxicity Testing Services Following ISO 10993-11

Why Companies Trust NAMSA

118K+

Medical Device Tests Conducted Last Year

Board-Certified DaBT Toxicologists on Staff

800

Biological Evaluation Plans and Reports Prepared Last Year

Major US and EU Labs Performing ISO 10993 Testing

Systemic toxicity testing evaluates the potential for substances released from a medical device to cause adverse effects in organs or systems distant from the point of contact. This is a crucial, high-stakes regulatory requirement, especially for devices with prolonged or permanent patient contact.

The ISO 10993-11 standard, entitled “Biological evaluation of medical devices – Part 11: Tests for systemic toxicity” defines the rigorous in vivo and non-animal methods used to assess acute, subacute, subchronic, and chronic exposure risks.

NAMSA has more than five decades of biological safety expertise, providing GLP-compliant systemic toxicity testing and strategic toxicological risk assessments to secure your global regulatory approvals.

Let NAMSA Help Refine Your Systemic Toxicity Testing Strategy

In modern biocompatibility, the systemic toxicity evaluation follows a tiered, risk-based approach, prioritizing non-animal methods where scientifically justifiable. Our Toxicologists design a strategy focused on minimizing in vivo studies while maximizing data acceptance by regulatory bodies. NAMSA follows a tiered approach to systemic toxicity testing.

Step	Focus	NAMSA Services	Regulatory Rationale
Tier 1: Chemical Characterization	Identify the Hazard (ISO 10993-18)	Extractables & Leachables (E&L) Testing: Comprehensive chemical analysis to identify and quantify all substances that may leach from the device.	Data is used to establish chemical exposure levels, which is the foundation for all subsequent risk assessments.
Tier 2: Toxicological Risk Assessment (TRA)	Quantify the Risk (ISO 10993-17)	Board-Certified TRA: Our toxicologists use E&L data to compare patient exposure levels to established safety limits (TTC, MoS) for each chemical.	If exposure is proven safe based on known chemical toxicity, further in vivo testing is often waived, saving substantial time and cost.
Tier 3: *In Vivo* Testing	Confirm Safety (ISO 10993-11)	GLP-Compliant Animal Studies: Only necessary if chemical data is insufficient, complex leachables are found, or TRAs do not confirm safety.	Provides definitive proof of safety to regulators when chemical data alone is not adequate.

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Don’t risk delays due to incomplete or poorly justified toxicity data. Leverage NAMSA’s integrated approach to move confidently toward market clearance.

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NAMSA Performs Acute, Subacute and Chronic Toxicity Testing

Systemic toxicity is typically evaluated in studies of acute, sub-acute, sub-chronic, and chronic duration based on the device’s intended exposure.

Study Type	Patient Contact Duration	Primary Endpoint
Acute Systemic Toxicity Essential for all new materials and components lacking previous data.	Single, short exposure (e.g., <24 hours).	Adverse effects within 72 hours of exposure.
Subacute/Systemic Toxicity Required for medium-term contacting devices (e.g., temporary catheters).	Short-Medium-term exposure (24 hours to 30 days).	Toxicological effects across multiple organ systems.
Subchronic Systemic Toxicity Required for medium-term contacting devices (e.g., temporary catheters).	Medium-term exposure (30 to 90 days).	Toxicological effects across multiple organ systems.
Chronic Systemic Toxicity Integrates with long-term implantation studies (ISO 10993-6) for permanent implants.	Long-term exposure (greater than 90+ days).	Long-term cumulative toxicity

Why NAMSA is the Premier Choice for Acute, Subacute/Subchronic, and Chronic Toxicity Testing of Medical Devices

Systemic toxicity evaluation demands the highest level of scientific rigor, regulatory strategy, and in vivo expertise. As the company that pioneered the medical device safety industry, NAMSA offers a strategic advantage that minimizes risk and accelerates your timeline.

Toxicological Risk Assessment (TRA) Leadership: Our team of Board-Certified Toxicologists is unparalleled in the industry, specializing in using ISO 10993-17 to justify in vivo test waivers based on chemical data, potentially saving months of development time and money.
Integrated Testing & Preclinical Expertise: We seamlessly combine ISO 10993-18 E&L data with your systemic toxicity study design. When in vivo testing is required, it is performed in our GLP-compliant and AAALAC-accredited facilities, ensuring the integrity and global acceptance of your data by regulatory authorities such as the FDA, EMA, and PMDA.
Proven Regulatory Acceptance: Having prepared hundreds of Biological Evaluation Reports (BERs) that successfully incorporate systemic toxicity strategies, we know precisely what evidence regulators require for high-risk, long-term devices.

Frequently Asked Questions (FAQs)

Systemic toxicity studies are classified based on the intended duration of patient contact with the device:

Acute: Tests for adverse effects resulting from a single, short-term exposure (typically observed over 24 hours).
Subacute/Subchronic: Tests for effects from repeated or continuous exposure over an extended period (usually 14 to 90 days), required for medium-term contacting devices.
Chronic: Tests for cumulative effects from long-term or permanent exposure (typically >90 days), often integrated with chronic implantation studies.

Historically, yes. However, modern regulatory guidance emphasizes a tiered, risk-based approach. If the device is complex or long-term, systemic toxicity must be evaluated, but the testing can often be waived if:

Chemical Characterization (ISO 10993-18) is performed to identify all leachable substances.
A Toxicological Risk Assessment (TRA) (ISO 10993-17) is conducted by a qualified toxicologist to prove that patient exposure to every leachable substance is below a safe threshold (e.g., Tolerable Intake or Safety Margin).

The TRA is the most critical element of modern systemic toxicity compliance. It uses the chemical data from the device to compare the estimated patient exposure to recognized, safe toxicological limits for each leachable compound. If a TRA concludes that no leachable is present at a concentration high enough to cause systemic toxicity, it provides a strong, scientifically defensible justification to waive in vivo systemic toxicity testing altogether, greatly accelerating time to market.

An Acute Systemic Toxicity study (if required) involves exposing a test animal to extracts from the medical device via an appropriate route (e.g., injection) and observing them for signs of toxicity for up to 72 hours. Endpoints typically include:

Gross observations (behavior, body weight)
Clinical pathology and hematology (blood tests), as appropriate
Macroscopic and microscopic analysis of major organs (necropsy and histopathology) to look for signs of tissue damage or inflammation, as appropriate

Absolutely. Systemic toxicity is highly susceptible to residual chemicals from the manufacturing and sterilization processes (such as ethylene oxide, cleaning agents, or uncured monomers). The device submitted for systemic toxicity evaluation (whether for E&L testing or an in vivo study) must be the final, finished product in its final, clinical-use sterilized state to ensure the entire patient exposure risk is accurately assessed.