Select Projects

Toxicological Risk Assessment (TRA) of Extractables and Leachables from Dialysis Equipment:  Conducted toxicological risk assessments for compounds identified in extracts from dialysis equipment.  In accordance with ISO 10993-17, ICH M7, and US Food and Drug Administration (US FDA) guidance, Gradient identified toxicological data for relevant endpoints and used these data to derive chemical- and device-specific safety margins.  For this work, Gradient partnered with an analytical testing laboratory.  The client used our TRAs to support a safety evaluation of the medical device.

Nonclinical Safety Assessment of Biopharmaceutical Impurities:  Conducted human health hazard and risk assessments for potential impurities in a cell-based cancer treatment.  Some of the evaluated impurities included chemical process impurities, residual viral vector, plasmid DNA, and continuous cell line residuals.  We provided the client with detailed monographs on each impurity, and, when possible, a permissible exposure limit for the impurity.  These monographs were used by the client as manufacturing guidance and as supporting documents for regulatory applications and meetings.

Patent Litigation Regarding Syringes Pre-filled with a Biological Drug Product:  For a patent litigation case, Dr. Cohen evaluated the safety profile of a polymeric coating for application in a syringe pre-filled with a biological drug product.  To this end, Dr. Cohen 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.  Dr. Cohen’s opinions addressed whether a toxicologist, as a member of a biomedical product development team, would have considered the polymeric coating to be safe for use in the pre-filled syringe.  Dr. Cohen’s findings were prepared in a written declaration and also presented in an oral deposition.

Carcinogenicity Assessment of California’s Proposition 65-Listed Chemical:  Evaluated the carcinogenicity potential of the Proposition 65-listed fragrance chemical beta-myrcene.  We reviewed animal toxicity data, including carcinogenicity studies in rodents conducted by the National Toxicology Program (NTP), and applied a linear no-threshold response extrapolation to derive a no significant risk level (NSRL).  Our method was based on the anticipated approach that could be taken by the California Office of Environmental Health Hazard Assessment (CalOEHHA) and current best practices for carcinogenicity risk assessment.  We also considered uncertainties in the animal carcinogenicity data and the relevance of findings to the potential for carcinogenicity in humans.

PBPK Exposure Assessment:  Evaluated the significance of lead present in a variety of consumer products for comparison with Proposition 65-proposed lead limits.  Performed lead modeling using the Leggett plus model to quantify the overall impact on blood lead and bone lead concentrations of intermittent intake of lead from the product as compared to the impact of a daily intake of lead at the proposed Proposition 65 limits.