+1 (888) 794-0077
Safe & Compliant: Mitigating Risks After Device Modifications

Safe & Compliant: Mitigating Risks After Device Modifications

The medical device regulatory environment is continuously evolving. As regulatory body expectations become more demanding, manufacturers need to evaluate the safety implications of changes to their devices and processes.

Manufacturing modifications are one example that can affect a medical device’s compliance and possibly end-user safety. Changes to supply chains and manufacturing processes may pose more than just logistical challenges—they can potentially alter a product’s chemical makeup, impact toxicological risk assessments (TRAs) and even put a device’s regulatory approval at risk.

Whether changes to a manufacturing process are planned or reactive, it is critical to understand the implications they may have on a medical device’s material composition and what that means for evaluating biological safety concerns. When modifications to the device or the process occur, ensure your team takes the right steps to protect the end-user and meet or maintain regulatory approval.

Keeping an Eye on Potential Pitfalls

The manufacturer is responsible for identifying, addressing and eliminating potential risks before implementing modifications to the device design or a manufacturing process. There is always the possibility that adjustments may go wrong and cause obstacles or delays. Companies must be intentional in identifying challenges that can affect a device’s chemical makeup at all stages of the product lifecycle.

When design changes occur, there may also be new materials or processes at play. These changes can affect the outcome of chemical characterization and toxicological risk assessments – and could potentially lead to retesting a device altogether. Evaluating device toxicity is critical to gauging potential patient safety risks and assists in gaining regulatory approval. 

It is essential to consider the various regulations that device or material modifications could fail to satisfy – as well as new standard updates that may soon come into effect. For example, the updates to ISO 10993  should always be considered when making changes to a device or process.

Even when no red flags from the manufacturing process arise, a modified device may contain new unknown risks. Ensure your team assesses new device risks that could be associated with the changes and undergo further testing when necessary to protect end-user safety. Your testing partner can help you determine when additional testing is needed.

Recognizing the Common Link

For many established products, one variable that sticks out as the most volatile to change is material choice. When an element in your device makeup changes, differences in raw material composition and quality can falter when it’s time to evaluate toxicity.

When proven safe through testing and risk assessment, a device’s material and chemical composition allow it to function accurately and consistently. But, even altering just one component can put the compatibility of these selections in flux, and the impact on your end-user may be unclear. Laboratory testing partners are more than willing to provide their perspective in determining the necessary next steps when there are material changes in a device. They may suggest additional testing such as material characterization, validation testing, biocompatibility and risk assessments to prove the device is still safe and meets regulatory standards.

Innovate While Playing It Safe

Protecting patient safety and maintaining regulatory compliance is the top priority, so it is essential to consider the risks associated with manufacturing and chemical changes and take the necessary precautions to minimize potential hurdles. Addressing obstacles before they arise can support safer products and successful regulatory submission. Modifications aren’t just manageable—they’re an opportunity to strengthen your understanding of a medical device’s chemical composition through purposeful planning and connection with the right partners.

To stay up to date on the latest industry news and regulatory changes, follow us on LinkedIn.

For early access and exclusive content sent straight to your inbox, subscribe today to our premium content.

WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. As an innovation-driven and customer-focused company, WuXi AppTec helps our partners improve the productivity of advancing healthcare products through cost-effective and efficient, socially responsible and sustainable solutions. With industry-leading capabilities such as R&D and manufacturing for small molecule drugs, cell and gene therapies, and testing for medical devices, WuXi AppTec’s open-access platform is enabling more than 4,200 collaborators from over 30 countries to improve the health of those in need – and to realize our vision that “every drug can be made and every disease can be treated.”

The Evolving Outlook on Toxicological Risk Assessments

The Evolving Outlook on Toxicological Risk Assessments

Around the world, various regulatory factors are driving the evolution of medical device risk evaluation. The industry is beginning to recognize the limitations of biocompatibility testing. While the data it can provide still have a pivotal role in the assessment process, it may not be able to measure other factors that are becoming increasingly important to consider, such as carcinogenicity or reproductive and developmental toxicological concerns. When it comes to patient and practitioner safety, you must address these risks.

Chemistry, toxicological risk assessment (TRA) and biocompatibility are necessary components of a biological evaluation. A biological evaluation provides evidence-based data focused on device nature and duration of patient contact which ultimately supports the safety of a device. With the additional expectations regarding chemistry were provided in 10993-18:2020, it is natural that the expectations of toxicological risk assessments also need to be further harmonized. ISO 10993-17 is under revision to provide guidance on toxicological risk assessments. 

Driving Forces

The toxicological risk assessment and biological testing are conducted to address the biological endpoints appropriate for the device duration and nature of body contact, to support the biological safety of the device. Regulations are the main driver behind the growing role of TRAs, including the EU Medical Device Regulation (MDR) and 2020 guidance from the U.S. FDA. These documents not only help to set expectations, such as the analytical evaluation threshold (AET) but also support the methodologies and approaches to performing this analysis.

ISO 10993 Biological Evaluation of Medical Devices

The ISO 10993 series of standards highlight the importance of biological evaluations as a part of the overall medical device risk management program. Part 1 demonstrates a need for detailed physical and chemical information, and if manufacturers do not provide sufficient data, additional testing, such as E/L studies, will be necessary before designing a biocompatibility testing plan.

In addition, Part 18, updated in 2020, faced an overhaul in its latest revision. This update increased the requirements for characterization of medical device chemical constituents in a final finished form of a medical device. This section has made it challenging for some to achieve characterization to the levels required by regulators. However, as the industry adjusts, the role of this data will become more evident as appropriate TRAs will rely on this information.

FDA Guidance on use of ISO 10993-1

For manufacturers seeking approval in the United States, it is important to consider that the U.S. FDA does not recognize all clauses of all parts of ISO 10993. The FDA Guidance on the Use of ISO 10993-1 most recently published in 2020, which is almost identical to the 2016 version, provides FDA recommendations that may differ from the ISO 10993 requirements.

ISO 14971 Application of Risk Management to Medical Devices

This document requires risk management, including biological evaluation, to continue throughout a product’s lifecycle.

ISO/TS 21726 Biological Evaluation of Medical Devices

When conducting chemical characterization and TRAs, applying the threshold of toxicological concern (TTC) will often reference this technical specification.

Medical Device Regulation

The EU MDR currently recognizes the most current versions of ISO 10993 standards as “state of the art,” meaning notified bodies expect applications to meet current ISO 10993 requirements.  

Collating this information and staying updated is a complicated task. Fortunately, lab testing partners not only have an extensive background on regulatory standards but often play a part in shaping what the future of these standards will be.

Upcoming: ISO 10993-17

While not expected to publish until at least 2021, ISO 10993-17 is currently in the revision process and will provide additional guidance on conducting a TRA. The majority of the standard is expected to change, from defining terminology to summarizing recommended steps in the process. Performing these assessments will likely become more standardized, but this does not indicate process simplicity.

Because TRAs consider device risk as a combination of hazard and the level of exposure, detailed background on the device and its use are critical. Manufacturers need to provide as much contextual understanding of a device’s materials, production process and potential exposure parameters (e.g. maximum clinical use, and patient populations). These considerations are important in the design of chemical characterization and the conduct of a valid toxicological risk assessment. Without this information, the result may be under or over-predicting patient risk; both may lead to undesirable outcomes for different reasons.

Partnering with an informed, reliable testing partner can help prevent potential issues with changing guidance. Qualified, expert judgment will be necessary for many parts of this process, such as when scientists evaluate the results for the margin of safety for medical device chemical constituents. It can be an added benefit if the lab performing your device’s TRA has an inside look at what standards are coming.

An Evolving Outlook

As medical devices continue to evolve, so will the standards. Our industry continues to drive innovation, which is something to celebrate. While there are still opportunities for improvement, chemical characterization plays a critical role in modernizing the biological evaluation of medical devices.

For a more in-depth review of the TRA process, watch our webinar “Toxicological risk assessment of medical devices and proposed updates to 10993-17, including the application of TTC values.”

To stay up to date on the latest industry news and regulatory changes, follow us on LinkedIn.

For early access and exclusive content sent straight to your inbox, subscribe today to our premium content.

Established in December 2000, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. With industry-leading capabilities such as R&D and manufacturing for small molecule drugs, cell and gene therapies, and testing for medical devices, WuXi AppTec’s open-access platform is enabling more than 4,100 collaborators from over 30 countries to improve the health of those in need – and to realize our vision that “every drug can be made and every disease can be treated”.