Toxicological risk assessment for extractables & leachables from medical devices is routinely conducted to support biocompatibility and establish device safety. Gradient’s expertise in chemistry and toxicology is suited to assessing large, complex extractable datasets that account for clinical condition, treatment frequency/duration, and the expected patient population for the device. Read-across and chemical grouping approaches help streamline review of large datasets and aid in evaluation of chemicals with limited toxicity data. With a team of board certified toxicologists (DABTs) and chemists working together, chemical category and surrogate choices are justified based on chemical and physical characteristics, as well as toxicity and toxicokinetic data points. Gradient’s team of scientists have decades of in-house experience at medical device companies and a strong track record in helping clients achieve regulatory approval and address inquiries from US FDA and European Union (EU) notified bodies (e.g., ISO 10993 series, ISO 14971, ISO 18562 series, ICH M7, EU MDR).
Gradient Expertise:
Publications:
Alverson, AK; Cohen, JM. 2022. “Read-Across Assessments for Data-Poor Medical Device Extractables: Best Practices and Potential Pitfalls.” Poster #3478/P856. Presented at the Society of Toxicology (SOT) 61st Annual Meeting and ToxExpo, March 27-31.
Chang, R; Alverson, AK; Cohen, JM. 2022. “A Rubric for Identifying Potentially Genotoxic Polycyclic Amines and Derivation of a Chemical Class-Specific TTC.” Poster #3474/P852. Presented at the Society of Toxicology (SOT) 61st Annual Meeting and ToxExpo, March 27-31.
Hadley, IG; Chang, R; Cohen, JM. 2022. “Review of Chemical Category Assessment Strategies for Medical Device Extractables.” Poster #3475/P853. Presented at the Society of Toxicology (SOT) 61st Annual Meeting and ToxExpo, March 27-31.
Mashankar, PA; Hadley, IG; Chang, R; Cohen, JM. 2022. “Expert Review of Cramer Classification Predictions for Medical Device Extractables.” Poster #3477/P855. Presented at the Society of Toxicology (SOT) 61st Annual Meeting and ToxExpo, March 27-31.
Cohen, J; Chang, RY. Fall 2020. “US FDA partial recognition of ISO 10993-18:2020 – Implications for toxicological risk assessment.” MDCPSS Newsl. 11(1):12-14.
Cohen, JM. 2020. “Predictive Toxicology Approaches for Medical Device Biocompatibility Assessment.” Abstract #1044. Presented at the Society of Toxicology (SOT) 59th Annual Meeting and ToxExpo, Anaheim, CA, April 16.
European Union Medical Device Regulation Biocompatibility and CE Marking Support
Gradient addressed regulatory deficiencies relating to biocompatibility and clinical safety for the purpose of CE marking in the European Union (EU). Gradient reviewed documentation for four medical device orthopedic implant systems, including prior regulatory submissions, compositional profiling, material specifications, biocompatibility data, and clinical history. Our reports document the safety of each device and their respective components and materials of construction. These reports will be used for submission for EU Medical Device Regulation (MDR) approval.
Biocompatibility Assessment of a Neurovascular Medical Device
Gradient provided a comprehensive biocompatibility summary report to support a previously rejected 510(K) submission to the US FDA. The updated US FDA report included a comprehensive review of biocompatibility and toxicology test reports, a critical review and risk assessment of tantalum nanoparticle toxicity, and ISO 10993-compliant toxicological risk assessments of extractable and leachable compounds.
Toxicological Risk Assessment and Equivalency Evaluation of Extractables of a Dialyzer
Gradient provided fit-for-purpose toxicological risk assessments and toxicological equivalency evaluations for chemicals identified in extracts of a dialyzer. In accordance with ISO 10993-17 and US FDA guidance, Gradient identified toxicological data for relevant endpoints and used these data to derive chemical- and device-specific safety margins. Our reports assisted in the US FDA product approval.
Toxicological Risk Assessment of Extractables & Leachables for Humidifier Drug Delivery Device
Gradient provided toxicological risk assessments associated with inhalation exposure to extractable compounds detected in components of a respiratory device. In accordance with ISO 10993-17 and the ISO 18562 series guidance, Gradient identified toxicological data for relevant endpoints and used these data to derive chemical- and device-specific allowable limits and calculate safety margins for patients. Our report was submitted to the US FDA and resulted in device approval for the US marketplace.
Patent Litigation Case for a Medical Device
For a patent litigation case, Gradient evaluated the safety profile of a polymeric coating for application in a syringe pre-filled with a biological drug product. We reviewed toxicity data and protein adsorption properties of the polymeric coating, adhering to the biological safety assessment framework detailed in the ISO 10993 series of standards. Our findings were prepared in a written declaration and presented in an oral deposition.
