According to ISO 10993-1:2018, “the biological evaluation of any material or medical device intended for use in humans shall form part of a structured biological evaluation plan within a risk management process in accordance with ISO 14971.” Based on the nature of contact and available information, these evaluations incorporate the “risk-based approaches to determine if biocompatibility testing is needed,” as stated in the FDA Guidance document, Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process.” Since biocompatibility and the regulations in ISO 10993 and ISO 14971 are so complicated and continually in flux, many sponsors struggle to know how to categorize their device and/or which tests should be performed.
When a checklist approach is used to address all endpoints for a device, it sometimes becomes a burdensome task, requiring unnecessary testing that could be difficult to interpret from a patient-safety perspective. ISO 10993 clearly states that there are some cases wherein the risk can be mitigated by means other than testing. Furthermore, the unnecessary testing of all endpoints can significantly impact the testing costs and timeline for a project. A risk-based evaluation requires a testing plan—specifically tailored to the device—that reviews the available information and risks posed to the patient during use and defines the most appropriate pathway for testing through the selection of relevant tests and/or the description of the representative test article to be used for testing, while explaining the reasons behind the choice.
While working with sponsors, we have encountered a few common issues that result from this checklist approach:
- Chemistry testing for extractables and leachables (E&L) is performed for devices, such as limited contacting medical devices where biologically relevant endpoints of concern cannot be effectively mitigated by this extensive testing strategy.
- Some animal testing is performed when it will not generate useful data. Testing for material-mediated pyrogenicity is a good example of this, as the testing does not adequately mimic the use of many devices, such as topically applied creams and gels.
- Cytotoxicity testing is performed without ensuring proper testing conditions. This occurs frequently when a device contains materials known to be cytotoxic.
The first two issues contribute to unnecessary testing costs and delays, while the second issue also increases the animal burden used for testing. The third issue increases costs and delays when failing results accrue and must be evaluated.
At Nelson Labs we help with these issues by using the risk-based approach stated above, which may involve a thorough evaluation of the device, including a review of the materials, written justification, and clinical history, to write the biological evaluation plan (BEP), which is specifically catered to each device, to assist with the submission process. The BEP is written by a group of our experts to ensure the optimal testing plan for your device, in accordance with the framework provided in standard and guidance documents, such as ISO 10993-1:2018, and FDA guidance on the use of ISO 10993-1 (2020). Clause 4.5 states that, “All known possible biological hazards shall be taken into account for every material and final product but this does not imply that testing for all possible hazards will be necessary or practical.” Our team relies on a scientific approach to determine the most appropriate testing methods for each device, which is in accordance with clause 7 of ISO 10993-1:2018, which states that, “Expert assessors who have the necessary knowledge and experience shall determine and document
- the strategy and planned content for the biological evaluation of the medical device;
- the criteria for determining the acceptability of the material for the intended purpose, in line with the risk management plan;
- the adequacy of the material characterization; [and]
- the rationale for selection and/or waiving of tests.”
At Nelson Labs, we remain committed to our mission, Safeguarding Global Health® and to ensuring the safety of the medical devices that are either submitted for regulatory clearance or currently in use throughout the world. Patient safety is our utmost priority, and our goal is to assist as much as needed, whether it’s designing the optimal testing plan, materials analysis/review, addressing negative test results, responding to feedback from the regulatory agencies, or directly assisting with the regulatory bodies. We take pride in helping our sponsors resolve or prepare for audits and to make the submission process as smooth as possible.