Our MRAs follow principles outlined in ISO 10993-1 and ISO 10993-18, incorporating device-specific factors like duration and type of contact, surface area, and patient population.
We integrate analytical data, manufacturing process knowledge including packaging and sterilization steps, literature findings, and our expert knowledge to provide a complete picture of material safety, without relying on unnecessary testing.

Our MRA evaluates

• Whether Cohorts of Concern (CoC) per ISO/TS 21726 are present
• Note:  Establishing the absence of CoC chemicals is critical to justify the use of an AET (Analytical Evaluation Threshold) in accordance with ISO 10993-18.
• Whether materials or impurities may exhibit carcinogenic, genotoxic, or endocrine-disrupting properties
• Whether any additional toxicological evaluation or analytical testing is warranted

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

Study Design

We design chemical characterization studies (i.e., extractables and leachable (E&L)).

We develop tailored experiments that encompass both targeted and non-targeted analyses for medical device extracts, ensuring the identification and quantification of known and unknown chemical constituents when needed.

Our experimental design outlines:

• Solvent selection considering the device materials
• Temperature and time
• Extraction condition such as exhaustive, exaggerated, or simulated
• Collected extracts handling
• Appropriate analytical techniques fitting the study objectives. Examples of tool include GC-MS, LC-MS, and ICP-MS, to detect a wide range of organic and inorganic compounds as well as FTIR, NMR, and GPC.
• Regulatory standards and guidance like ISO 10993-18 and FDA Draft Guidance on Chemical Characterization

Protocol Review

An extractable or leachable study is an expensive and requires significant time commitment. Hence, it is crucial to ensure the contract laboratories can provide a seamless service.

Our partners trust us to review their chemical characterization study protocols to ensure ISO 10993-18 and regional expectations (i.e., FDA, EU MDR) are met.

In addition to the details outlined under Study Design, we evaluate:

• Analytical evaluation threshold (AET) calculation
• Surrogates’ selection per device’s materials and Materials Risk Assessment report
• Detection methods for chemical analysis
• Uncertainty factor database and reliability
• Effect of processing steps on extracts
• Review of spike and recovery data

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 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

• Project Scoping and Objective Definition: Collaborating with your team to understand the specific goals of the reverse engineering project, whether it's to replicate a material, improve performance, or analyze a competitor's product
• Analytical Strategy Development: Advising on the selection of appropriate analytical techniques (e.g., FTIR, GC-MS, SEM) and outlining a step-by-step plan for material characterization.
• Data Interpretation and Reporting: Assisting in the interpretation of analytical data obtained from third-party laboratories, providing insights into material composition, structure, and potential performance implications.
• Regulatory and Compliance Guidance: Offering expertise on relevant industry standards and regulations to ensure that reverse-engineered materials meet necessary compliance requirements.

Applications of Our Services

• Polymer and Composite Materials: Deconstructing plastic components to identify base resins, fillers, and additives.
• Adhesive Systems: Understanding the formulation of adhesives for applications in medical devices depending on exposure environment and design challenges.
• Coating Technologies: Analyzing surface coatings to determine composition, thickness, and application methods.