What Is Acute Systemic Toxicity Testing?
Acute Systemic Toxicity Testing, as defined by ISO 10993-11, is a standardized in vivo procedure designed to evaluate the potential of medical devices or their extracts to induce systemic toxic effects following a single exposure. This assessment is performed using laboratory animals, typically rodents, and focuses on identifying harmful biological responses—such as organ damage or physiological dysfunction—that occur within 24 to 72 hours after administration via clinically relevant routes, such as intravenous, intraperitoneal, or oral pathways.
The test aims to simulate realistic clinical conditions in order to detect toxic reactions that may result from the migration of chemicals from the device into the systemic circulation. By adhering to rigorous methodological criteria established by international regulatory frameworks, this testing serves as a fundamental component in the biological evaluation of medical devices, ensuring they meet safety standards prior to clinical use.
Acute Systemic Toxicity Testing Procedure (ISO 10993-11)
The acute systemic toxicity testing procedure, guided by ISO 10993-11, is a detailed in vivo protocol used to evaluate the potential of a medical device or its extracts to produce systemic toxic effects following a single exposure. The process is conducted under controlled laboratory conditions and consists of the following steps:
Preparation of Test Item
Extracts of medical devices are tested. Extraction is performed using both polar and non-polar solvents under specified conditions (e.g., 37°C for 24–72 hours), mimicking clinical use scenarios. The extract must be filtered and tested for sterility before administration.
Animal Selection
Healthy adult rodents (usually mice or rats) are selected, considering species-specific responses and ethical standards. The animals should be acclimatized before testing to reduce variability.
Dosing Procedure
A single, clinically relevant dose of the extract is administered through a suitable route (intravenous, intraperitoneal, or oral). The volume and concentration are carefully calculated based on the animal’s body weight, ensuring comparability across subjects.
Observation Period
Animals are observed continuously for the first few hours post-dosing and periodically for up to 72 hours. Clinical signs (e.g., changes in respiration, locomotion, posture, or behavior), body weight, and mortality are documented meticulously to detect any systemic effects.
Post-Mortem Examination
Animals are euthanized humanely at the end of the study or earlier if moribund. A gross necropsy is performed, and key organs (e.g., liver, kidneys, heart) are examined for pathological changes to identify the target organ of toxicity.
Data Interpretation and Reporting
Data are evaluated statistically and toxicologically to determine the test article’s potential for systemic toxicity. If adverse effects are observed, further classification (e.g., LD₅₀ estimation) may be required.
This methodical approach ensures robust scientific assessment and regulatory confidence in the safety of medical devices.
Acute Systemic Toxicity Testing Administration Routes
Below is a detailed explanation of the various administration routes used in Acute Systemic Toxicity Testing as specified in ISO 10993-11. Each method is selected based on the intended clinical exposure route of the medical device or its extract:
Intraperitoneal
The test substance is injected directly into the peritoneal cavity of the animal. This method allows for rapid absorption and is commonly used for systemic exposure assessment. It is particularly effective in detecting generalized toxicity across multiple organ systems.
Intramuscular
This involves delivering the substance into a muscle, typically the thigh or gluteal muscle. It models systemic exposure from devices like injectable drug-delivery systems or implantables and is slower in absorption compared to intravenous administration.
Subcutaneous
The material is administered under the skin, allowing gradual absorption. This route is useful for testing transdermal devices, drug patches, or materials designed for subdermal implantation.
Oral Gavage
In this method, the substance is delivered directly to the stomach via a feeding tube. It simulates ingestion and is ideal for evaluating toxicity of materials intended for oral exposure (e.g., coatings on ingestible capsules).
Intravenous
This method involves injecting the substance into the bloodstream, offering immediate systemic distribution. It is the most direct and controlled route, appropriate for evaluating intravenous catheters, blood-contacting devices, or injectable drugs.
Each route plays a specific role in modeling how patients might realistically be exposed to materials in clinical use, thereby supporting accurate safety evaluations.
Acute Systemic Toxicity Testing Lab
At International & Accredited Lab Nikopharmad Laboratory Network, we are committed to providing accurate, reliable, and high-quality Systemic toxicity testing services for medical devices and pharmaceutical products. Holding the esteemed ISO 17025 certification and ILAC accreditation, we adhere to internationally recognized standards, ensuring that our testing processes meet the highest quality and regulatory requirements.
Why Choose Nikopharmad Laboratory?
ILAC accreditation
Nikopharmad Laboratory is proudly certified with ISO 17025 and holds ILAC accreditation. These prestigious certifications ensure that our laboratory operates with the highest standards of quality and competence, providing reliable and internationally recognized testing services for medical devices and pharmaceutical products. Our commitment to maintaining these certifications demonstrates our dedication to excellence and compliance with global regulatory requirements.
Comprehensive Testing Capabilities
We offer a broad range of biocompatibility tests, each designed to assess the safety and performance of your products in compliance with international regulatory frameworks.
Expertise and Experience
With extensive experience in the medical and pharmaceutical sectors, our laboratory is equipped with cutting-edge technology and a team of highly trained professionals who ensure accurate, timely, and thorough testing results.
Efficient and Timely Results
We understand the importance of time in product development. Our laboratory strives to deliver fast and reliable results, ensuring your products are tested and ready for market entry as efficiently as possible.
Confidentiality and Integrity
At Nikopharmad, we prioritize the confidentiality of your sensitive data and intellectual property. Our strict adherence to confidentiality agreements guarantees that your information remains protected throughout the testing process.
Global Compliance and Support
Whether you are preparing to enter the FDA, or other global markets, our laboratory ensures that your products comply with all necessary regulatory standards, facilitating a smooth path to market approval.
Choose Nikopharmad for Your Acute Systemic Toxicity Testing Needs
By choosing Nikopharmad International Laboratory, you are selecting a trusted partner that not only meets but exceeds international testing standards. Our ISO 17025 certification, expert team, and commitment to excellence make us the ideal choice for ensuring the safety, compliance, and success of your medical devices and pharmaceutical products.
conclusion
Acute Systemic Toxicity Testing is a vital component of the biocompatibility assessment framework outlined in ISO 10993-11, ensuring that medical devices and their components do not elicit harmful systemic effects when introduced into the body. By simulating realistic exposure scenarios through validated routes of administration such as intravenous, intraperitoneal, and oral gavage, this test provides critical data on the short-term safety profile of materials used in medical technologies. Its primary objective is to detect toxicological responses that could impact vital organs or physiological systems within 72 hours of a single dose exposure. As emphasized by experts and regulatory bodies, ASTT plays a pivotal role in upholding patient safety and supporting the regulatory approval of medical devices.
Reference:iso.org