The Role of Acute Systemic Toxicity Testing in Biocompatibility: Expert Advice from Notified Bodies

Biocompatibility testing serves as a cornerstone in ensuring the safety and efficacy of medical devices. Among the array of tests employed, the Acute Systemic Toxicity Test (ASTT) holds significant importance in evaluating the potential adverse effects of materials or substances on systemic health. This article delves into the significance of ASTT in biocompatibility testing, elucidates its key components, and incorporates insights and recommendations from notified bodies, and the regulatory entities responsible for assessing conformity to regulatory requirements.

 

Significance of ASTT in Biocompatibility Testing:

 

  1. Early Hazard Identification:

ASTT facilitates the early detection of potential hazards linked to medical device materials or components. Through acute systemic toxicity testing, manufacturers can promptly identify substances that may pose systemic health risks, enabling informed decision-making during product development.

 

  1. Regulatory Compliance:

In the European Union, the Medical Device Regulation (EU MDR 2017/745) mandate biocompatibility evaluations in accordance with harmonized standards. The ISO 10993-1 standard provides a framework for the biological evaluation of medical devices, including acute systemic toxicity testing. Compliance with these regulations is critical for obtaining CE marking and ensuring market access in the EU.

 

  1. Safety Assurance:

ASTT delivers essential data on the acute effects of materials or substances on systemic health, thereby safeguarding patients and healthcare professionals. By identifying and mitigating potential risks, manufacturers can enhance the safety profile of their devices and maintain public trust.

 

Components of ASTT:

 

  1. Test Design and Protocol:

ASTT requires a meticulously designed protocol to ensure compliance with ISO 10993-11 and OECD guidelines. This includes selecting appropriate animal models, defining dose levels, and establishing observation periods that reflect relevant clinical exposure scenarios.

 

  1. Dose-Response Assessment:

During testing, varying doses of the test substance are administered to experimental animals to observe signs of toxicity, such as clinical symptoms, body weight changes, and mortality. The dose-response relationship provides critical insights into the potential toxicological impact.

 

  1. Data Analysis and Interpretation:

Data from ASTT is analyzed to assess the severity of toxic effects and their implications for human health. Risk assessments are conducted in alignment with ISO 10993-17 to determine acceptable exposure levels.

 

  1. Reporting and Documentation:

Comprehensive documentation is essential for regulatory submissions. Test reports must include detailed descriptions of the experimental procedures, results, and conclusions and must comply with the EU MDR and ISO 10993-11 requirements for chemical characterization and risk assessment.

 

Recommendations from Notified Bodies:

 

  1. Emphasis on Data Quality:

Notified Bodies emphasize the importance of generating high-quality, reproducible data in ASTT. Adhering to Good Laboratory Practices (GLP) and obtaining ISO 17025 accreditation ensures that test results are reliable and accepted by EU regulators.

 

  1. Consideration of Alternative Methods:

The EU strongly supports the reduction, refinement, and replacement (3Rs) of animal testing. Notified Bodies encourage the use of alternative methods, including validated in vitro models and computational approaches, where possible. These alternatives can supplement or replace traditional animal studies and align with the principles outlined in Directive 2010/63/EU on the protection of animals used for scientific purposes.

 

  1. Robust Risk Assessment:

Notified Bodies stress the necessity of integrating ASTT results into a comprehensive biological evaluation and risk assessment process. This involves leveraging all available data, including results from chemical characterization and toxicological assessments, to ensure the safety of medical devices.

 

Conclusion

 

Acute Systemic Toxicity Testing (ASTT) is a critical component of biocompatibility evaluations for medical devices in the EU. By adhering to harmonized standards such as ISO 10993-1 and incorporating insights from Notified Bodies, manufacturers can ensure compliance with EU MDR requirements, improve data quality, and explore alternative methods to reduce reliance on animal testing.

 

Although the process of ASTT and biocompatibility testing can be complex, there is no need for concern when partnering with experienced and reliable laboratories. Choosing a trusted laboratory like EBI – European Biomedical Institute – ensures that every step of the testing process is conducted with the highest level of expertise, adherence to regulatory standards, and a focus on patient safety. With EBI’s extensive experience and commitment to quality, manufacturers can navigate the complexities of biocompatibility testing with confidence, knowing that they are in capable hands. This partnership enables smooth regulatory approvals and market access while ensuring compliance with the rigorous demands of the European medical device sector.

 

About the Author: Prof. Łukasz Szymański

 

Prof. Łukasz Szymański is an expert in medical device biocompatibility testing, serving as the Chief Scientific Officer (CSO) of the ISO 17025-accredited and GLP-certified European Biomedical Institute (EBI) and North American Biomedical Institute (NABI). As a dedicated researcher and a key contributor to advancing safety standards in the biomedical field, Prof. Szymański plays an integral role in shaping scientific innovations and regulatory compliance within the industry.