Our Regulatory Consulting services focuses on the areas of biocompatibility, chemical characterization, and materials science.

We understand that each market presents unique challenges and opportunities. Our approach involves a thorough analysis of your product's specific attributes, intended use, and target markets to develop a tailored biocompatibility strategy that aligns with your overall regulatory approach.

Our collaboration encompasses the entire product lifecycle, from initial concept through to post-market surveillance, ensuring compliance at every stage.​

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Our Approach

• Regional Planning: Our recommendations for biocompatibility and chemical characterization consider global requirements. Depending on the market of interest, we provide guidance that enables efficient use of time and resources. We have experience supporting our clients for submission in USA, EU, UK, and Canada.

Our consulting services are designed to help you create scientifically sound and regulator-ready strategies for BEP development, ensuring product safety and compliance.

Our Consulting Approach Includes:

• Regulatory Strategy Development: Crafting tailored approaches to BEP development, considering the specific requirements of ISO 10993-1 for medical devices and relevant USP guidelines for pharmaceutical packaging systems.
• Risk Assessment Planning: Identifying potential biological risks associated with device materials and advising on mitigation strategies to ensure continued compliance and product safety.
• Test Plan Design: Collaborating with clients to design appropriate testing protocols, including selection of relevant biological endpoints and analytical techniques, that align with regulatory standards and product-specific considerations.
• Data Interpretation and Reporting: Assisting in the interpretation of analytical data obtained from third-party laboratories, providing insights into potential biocompatibility issues and their implications.

At Chemva, we provide scientifically rigorous MRAs that combine chemical characterization, toxicological profiling, and risk-based decision-making to support regulatory submissions and minimize unnecessary testing.

An MRA evaluates whether a material or device component, when used in its intended clinical context, presents an unacceptable biological risk due to its composition, impurities, processing residues, or degradation potential.

What We Can Assess in an MRA

Our toxicologists and material scientists collaborate to assess:

• The physical and chemical information of each material in contact with the body, including base materials, additives, and process-related substances.
• Nature and extent of exposure, based on the material’s contact type, duration, and anatomical interaction with the body.
• Potential for degradation or leachable, considering how processing, sterilization, and clinical use may affect material composition or stability.
• Toxicological risk of impurities, residuals, and degradation products, relying on a combination of supplier data, literature review, and regulatory toxicology databases.
• Historical and clinical use of the material, when applicable, to support safety claims through precedent.

Our MRA supports strategic waiver or deferral of testing under the following ISO 10993 standards when justified

• ISO 10993-9: Framework for degradation product assessment
• ISO 10993-13 / -14 / -15: Degradation products from polymers, ceramics, and metals
• ISO 10993-16: Toxicokinetic of degradation products (partially addressed in conjunction with TRA and E&L data)
• ISO 10993-19: Physicochemical characterization
• ISO 10993-20: Immunotoxicology evaluation

Why an MRA Matters

• An MRA informs key parts of the BEP and is often used to support test deferrals or waivers, minimizing unnecessary in vivo testing.
• It also helps define whether additional chemical characterization or toxicological analysis is required that ultimately streamlining your regulatory submission pathway and reinforcing confidence in your product's safety profile.
• MRA also establishes if cohorts of concerns (CoC) chemicals per ISO/TS 21726 are present in a device or drug packaging, which may require targeted chemical screening and assessment.
• By applying expert toxicological judgment alongside recognized regulatory expectations, Chemva ensures your MRA is not only defensible, but strategically aligned with FDA, EU MDR, and international expectations.

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.

Developed in accordance with ISO 10993-1:2018 and integrated into the risk management framework outlined in ISO 14971:2019, the BER provides a comprehensive analysis of the device's potential biological risks, and the strategies employed to mitigate them.​

Our BER Approach

The BER's primary objective is to demonstrate that a medical device is biologically safe for its intended use. By compiling the following information, the BER facilitates regulatory submissions and supports the device's market approval process.:

• Summarizing all relevant biological data, including material characterizations, chemical analyses, and toxicological assessments.
• Evaluating the device's interaction with biological systems based on its nature and duration of contact.
• Identifying any potential biological hazards and outlining the rationale for the selected testing strategy or justification for test waivers.
• Providing a clear conclusion on the device's biocompatibility, supported by scientific evidence and expert judgment.​
• Addressing any testing deviations
• Addressing observed adverse effects and considering the results of other endpoints to draw a comprehensive conclusion

Our Approach

• Regulatory Strategy Development: Crafting tailored approaches to implantation study design, considering the specific requirements of ISO 10993-6:2016 for medical devices and relevant USP guidelines for pharmaceutical packaging systems.
• Study Design Planning: Advising on the selection of appropriate study parameters such as implantation sites, animal models, and observation periods based on the device's intended use, duration of contact, and material composition.
• Analytical Methodology Guidance: Collaborating with clients to design appropriate testing protocols, including histopathological evaluation and scoring systems, that align with regulatory standards and product-specific considerations.
• Data Interpretation and Reporting: Assisting in the interpretation of analytical data obtained from third-party laboratories, providing insights into potential local tissue reactions and their implications.

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

• We provide theoretical degradation assessment and designing bench-top experiments to evaluate potential degradations. A Degradation assessment is a pivotal component in evaluating the biocompatibility of medical devices, especially those intended for long-term implantation. This process systematically identifies and quantifies degradation products that may form over time, ensuring they do not pose unacceptable biological risks to patients.​
• Regulatory Strategy Development: Crafting tailored approaches to degradation studies, considering the specific requirements of ISO 10993-9, ISO 10993-13, ISO 10993-14, and ISO 10993-15 for medical devices and relevant USP guidelines for pharmaceutical packaging systems.
• Study Design Planning: Advising on the selection of appropriate study parameters such as degradation conditions, analytical methods, and observation periods based on the device's intended use, duration of contact, and material composition.
• Analytical Methodology Guidance: Collaborating with clients to design appropriate testing protocols, including identification and quantification of degradation products, that align with regulatory standards and product-specific considerations.
• Data Interpretation and Reporting: Assisting in the interpretation of analytical data obtained from third-party laboratories, providing insights into potential degradation products and their implications.