At Chemva, we provide a scientifically robust TRA of potential health risks, supporting regulatory submissions and determining the safety of your products.

Our TRA Approach, briefly:

• Hazard Identification: We begin by identifying chemical constituents detected during E/L studies. Each substance is evaluated for potential toxicological hazards, such as carcinogenicity, genotoxicity, reproductive toxicity, and systemic toxicity. This step involves reviewing scientific literature, toxicological databases, and regulatory classifications to determine the inherent hazards of each compound.​
• Exposure Assessment: Next, we estimate the potential exposure levels of identified substances to patients. This involves calculating the amount of each chemical that could be released from the product during its intended use, considering factors like duration of contact, frequency of use, and the amount of substance that may migrate into the body. We use conservative assumptions to ensure patient safety.​
• Dose-Response Assessment: In this phase, we assess the relationship between the exposure level of each substance and the likelihood of adverse health effects. We determine the Tolerable Intake (TI) for each compound, which is the maximum amount considered safe for human exposure. This involves applying uncertainty factors to account for variations in human sensitivity and data limitations.
• Risk Characterization: Finally, we compare the estimated exposure levels to the TI values to calculate the MoS (margin of safety) for each substance. An MoS greater than 1 indicates that the exposure is within acceptable safety limits. If the MoS is less than 1, we assess the need for risk mitigation strategies, such as reformulating the product or implementing additional controls.
• Additional Resources: Depending on the product, additional tools and techniques will be applied to establish the safety of chemical constituent such as toxicological screening limit (TSL), threshold of toxicological concern (TTC), and read-across or analogue data utilization.

Our Approach

• Grouping Strategy Development: For a TRA, we group reported E/L constituents based on structural similarities, physical and chemical properties, toxicological properties, and toxicokinetic, ensuring a comprehensive approach in justifying our analogues and grouping practices.

Read-Across Justification:
When available tools like TSL and TTC cannot assess the safety of an E/L compound, we rely  on our materials science, chemistry, and toxicology expertise to locate and utilize data of suitable analogue(s). Our read-across practices are based on globally recognized practices per ISO 10993-17 and OECD guidelines by considering  structural similarities, physical and chemical properties, toxicological properties, and toxicokinetic, ensuring a comprehensive approach in justifying our analogues and grouping practices.

Our Approach

• Map Equivalency to Regulatory Expectations: Using frameworks like the ISO 10993-18 biological equivalence model, we guide you in determining whether material changes require new testing or can be justified via literature and analytical comparison.
• Outside of the Box Thinking: We develop strategies to establish biological and materials equivalency using supplier information as well as materials science characterization tools (i.e., DSC, tensile testing, GPC) without relying on complex extractable/leachable studies.
• Design Test Plans: We collaborate with your internal teams or external laboratories to select tests and associated parameters. For example, for extractable/leachable studies, we recommend extraction conditions and appropriate analytical techniques to align testing with ISO 10993-18 and USP <1663>/<1664>.
• Interpret Data and Draft Technical Justifications: We review and interpret third-party lab data to assess chemical, physical, and material equivalence. We also support toxicological risk assessment efforts in line with ISO 10993-17 and ICH Guidelines.

Anchored in International Standards

Our consulting is based on the principles in ISO 10993 and/or USP, which define biological equivalence overall through a tiered framework:

• Chemical Equivalence: Similar chemical constituents with no added toxicological risk
• Physical Equivalence: Comparable physical properties (e.g., morphology, surface finish)
• Material Equivalence: A combination of chemical and physical sameness
• Contact Equivalence: Same clinical use and contact scenarios
• Biological Equivalence: Achieved when material and contact equivalence are established

Common Use Cases

• Substitution of polymers or additives in medical devices
• Packaging material changes in pharmaceuticals
• Manufacturing process alterations impacting material profiles
• Regulatory support for 510(k), PMA, DMF, and EU MDR submissions

Our Approach

• Regulatory Strategy Development: Crafting tailored approaches to genotoxic impurity assessment, considering the specific requirements of ICH M7 (R2) for pharmaceuticals and relevant guidelines for medical devices and packaging systems.
• In Silico (Q)SAR Analysis Coordination: Utilizing complementary (Q)SAR methodologies such as expert rule-based and statistical-based models to predict bacterial mutagenicity, as recommended by ICH M7 guidelines.
• Risk Classification and Control Strategy: Assisting in classifying impurities based on their mutagenic potential and recommending appropriate control strategies.

Our Approach

Regulatory Strategy Development: Crafting tailored approaches to carcinogenicity assessment, considering the specific requirements of ICH M7 (R2) for pharmaceuticals and ISO 10993-17 for medical devices and packaging systems.

In Silico (Q)SAR Analysis Coordination: Utilizing complementary (Q)SAR methodologies such as expert rule-based and statistical-based models to predict mutagenicity and carcinogenicity potential of a reported E&L compound.