Adapting to Change: Genotoxicity Testing Under the Proposed Revision of ISO 10993-1

Why is Genotoxicity Evaluation Important?

Genotoxicity testing is a critical component of the biological evaluation of medical devices, ensuring that these devices do not pose genetic risks to patients. Genotoxicity tests are designed to assess the potential for gene mutations, changes in chromosome structure and number, and other DNA or gene toxicities caused by medical devices, materials, and/or their extracts. This comprehensive evaluation is essential for identifying any genetic damage that could result from the use of medical devices, thereby safeguarding patient health.

What’s New? Key Changes in the Upcoming Revision

Exposure to genotoxic agents plays a crucial role in carcinogenesis, a multistage process where each successive exposure to genotoxic agents increases the risk of cancer development. Systemic exposure allows these genotoxic agents to distribute across various tissues, thereby exacerbating the overall risk. The ISO 10993-1:2018 edition does not provide consistent recommendations for genotoxicity and carcinogenicity evaluations across medical device categories with the same durations of contact. The proposed revision introduces changes to address these inconsistencies. Additionally, Annex B of the proposed revision elaborates on the necessity of these updates and emphasizes the importance of assessing genotoxicity for a wider array of devices.

According to ISO 10993-1:2018, genotoxicity assessment is primarily required for medical devices that have prolonged (more than 1 day to 30 days) or long-term (more than 30 days) contact with the body, including those that come into contact with blood, bone, mucosa, or other tissues. While limited contact devices usually do not need extensive testing unless they pose specific risks, such as being made from novel materials or intended for sensitive populations like neonates.

However, the proposed revision of ISO 10993-1 significantly broadens the scope of genotoxicity assessments, introducing several key changes outlined below.

• A genotoxicity evaluation has been added for medical devices that prolonged contact with mucosal, breached or compromised surfaces and indirect contact with blood, with the exception of those that only contact intact skin.
• For all other medical devices with prolonged contact categories, that require systemic toxicity evaluation, a genotoxicity assessment is required.
• All medical devices that come into contact with circulating blood need genotoxicity evaluation. This also includes devices with limited contact with circulating blood, specifically to implantable devices, devices made with novel materials, and devices used in extracorporeal circuits. 

Understanding the Impact- What Manufacturers Need to Know!

The expanded genotoxicity requirements in the proposed revision of ISO 10993-1 will have several impacts on manufacturers:

1. Increased Testing and Validation Costs: Manufacturers will need to conduct genotoxicity assessments for a wider range of devices, including those with limited duration blood contact. This will likely increase the costs associated with testing and validation, as more devices will require comprehensive evaluations.
2. Extended Development Timelines: The additional testing requirements may extend the development timelines for new devices. Manufacturers will need to allocate more time for genotoxicity assessments, potentially delaying product launches.
3. Enhanced Safety and Compliance: While the increased genotoxicity testing requirements may pose challenges, they also enhance the safety and compliance of medical devices. By ensuring that all devices with prolonged contact are thoroughly evaluated for genotoxic risks, manufacturers can better protect patient safety and meet compliance.
4. Risk Management Integration: The integration of genotoxicity evaluation into a risk management process will ensure that potential risks are identified and mitigated early in the device development lifecycle. This holistic approach should consider both normal use and reasonably foreseeable misuse, providing a robust safety assessment. 

In summary, the proposed revision of ISO 10993-1 represents a significant shift towards a more comprehensive and systematic approach to genotoxicity evaluation. This evolution in standards underscores the commitment to patient safety and the continuous improvement of medical device regulations.