• by Amanda Huynh (Mittal Consulting)

Quite often, medical device executives are apathetic towards biocompatibility testing, rightfully questioning, “So what?” and trying to delay it as much as possible. However, postponing biocompatibility testing too long may lead to financial loss and even further delays in the commercialization of the medical device. Therefore, it is most advantageous for medical device companies to consider putting together a biocompatibility plan tailored to their needs early on in the product lifecycle.

In a recent case, Philips faced a biocompatibility lawsuit for their CPAP sleep apnea machine which was recalled in 2021. The Philips CPAP device was recalled for injury caused by the degradation of the foam (comprised of polyester-based polyurethane (PE-PUR)) inside the device and releasing chemical particles that inhaled or swallowed by users leads to asthma, cancer, inflammation, or other adverse effects. The delay in communicating with the FDA regarding biocompatibility testing led to a consumer lawsuit and was settled for $1.1 billion and of that $25 million is for medical monitoring in April 2024. It is noted that in a public statement, “Philips and Philips Respironics do not admit any fault or liability, or that any injuries were caused by Respironics’ devices.”

Due to failure to meet biocompatibility requirements, Philips faced device recalls, FDA mediation, and litigation which overall had effect on the company monetarily and through bad publicity.¹

Biocompatibility

The FDA requires a Biocompatibility Assessment to be conducted for all classes of medical devices (I, II and III), regardless of whether they need pre-review by the FDA before commercialization. Biocompatibility is a strategic road map that demonstrates to the FDA the potential risks arising from the use of the medical device in the patient’s body, along with a mitigation plan. This plan shows that, despite any minor adverse events, the medical device is safe and effective (e.g., through literature review, animal study testing and/or a suite of biocompatibility testing).

Chemical Characterization vs. Chemical Analysis

Two biocompatibility terms that are often erroneously interchanged are Chemical Characterization and Chemical Analysis. Chemical Analysis provides specific quantitative and qualitative reports on the material’s chemical composition. It is a subcomponent of Chemical Characterization, using testing data to support the claims made during the characterization process.

Chemical Characterization , on the other hand, is the process of understanding the specific chemical composition from the chemical analysis, including chemical structure and interactions (e.g., sensitization—how the material interacts with the patient’s body—and degradation over time). Chemical Characterization is a comprehensive assessment to ensure the safety and effectiveness of the medical device over time.

Choosing the Best Fit

Selecting standards should be based on the medical device, the components required for testing the device, the company’s time commitment, and budget considerations. General standards are guidelines the FDA outlines exact testing or key requirements for medical device companies to follow.

It is important to note that in ISO 10993-17: Biological Evaluation of Medical Devices – Part 17: Toxicological Risk Assessment of Medical Device Constituents, chemical characterization can be used alongside toxicological risk assessment (TRA) as a substitute for biological testing.² This approach assesses multiple biocompatibility points together, reducing time and minimizing the need for animal testing.

Mittal Consulting’s Remarks

It is beneficial for medical device companies at all stages (e.g., start-ups, accelerators, mid-size) to put together a biocompatibility plan before any testing or studies are started to reduce the need for re-testing, which can be financially taxing for manufacturers. If there is uncertainty, a Q-submission is recommended for medical device companies to discuss specific study designs with the FDA before conducting certain studies. Contact Mittal Consulting to discuss your medical device’s biocompatibility plan.

References

[1]  Chappell, B. (2024, April 29). What consumers should know as philips agrees to $1.1 billion CPAP settlement. NPR. https://www.npr.org/2024/04/29/1247774390/cpap-philips-sleep-apnea-injury-lawsuit, accessed Sept 27, 2024

[2] Center for Devices and Radiological Health.  (Sept 20, 2024). Chemical analysis for biocompatibility assessment of Medical Devices. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemical-analysis-biocompatibility-assessment-medical-devices?utm_medium=email&utm_source=govdelivery, accessed Sept 26, 2024

[2] Center for Devices and Radiological Health. (Sept 8, 2023). FDA’s biocompatibility guidance on use of ISO 10993-1. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and, accessed Sept 26, 2024

[3] Maude adverse event report: RESPIRONICS, Inc.. philips CPAP device; ventilator, non-continuous (respirator). accessdata.fda.gov. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/detail.cfm?mdrfoi__id=20113769&pc=BZD&device_sequence_no=1, accessed Sept 27, 2024