Our Consulting Approach Includes:

• Regulatory Strategy Development: Crafting tailored approaches to non-targeted screening and targeted screening (when a chemical of concern needs investigation) considering the specific requirements of ISO 10993 and USP guidelines for medical devices and USP guidelines for pharmaceutical packaging systems.
• Analytical Methodology Guidance: Advising on the selection of appropriate analytical techniques (e.g., LC-HRMS, GC-MS, ICP-MS) and outlining a step-by-step plan for comprehensive chemical analysis.
• Data Interpretation and Reporting: Assisting in the interpretation of analytical data obtained from third-party laboratories, providing insights into potential unknown compounds and their implications and preparing toxicological risk assessments (TRA).
• Risk Assessment Planning: Identifying potential risks associated with unidentified extractables and leachables and advising on mitigation strategies to ensure continued compliance and product safety.

Applications of Our Services:

• Medical Device Components: Evaluating materials for potential extractables that could affect biocompatibility and performance.
• Pharmaceutical Packaging: Analyzing packaging materials to detect and assess how leachables may impact drug product quality and patient safety.
• Regulatory Submissions: Supporting the preparation of documentation and justification for non-targeted screening results in regulatory filings, including 510(k) submissions.

Study Design

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

We design experiments depending on the product. For medical devices, we help develop protocols for exhaustive, exaggerated, and stimulated extractions based on contact duration and device materials. For drug products, we help design leachable studies and stimulated extractable studies depending on the regulatory needs and drug formulation.

Furthermore, 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 

At Chemva, we offer comprehensive E/L protocol review services, aligning with international standards such as ISO 10993-18, USP guidelines, and other regional regulatory documents. Our objective is to optimize study designs, mitigate potential pitfalls, and facilitate successful regulatory submissions.​

Key Components of E/L Protocol Review‍

• Study Objectives and Scope Definition
• Extraction Generation Conditions
• Extraction Modification Steps
• Analytical Methodology Assessment
• Analytical Evaluation Threshold (AET) Justification
• Quality Control Measures
• Reporting
• Regulatory Compliance Verification
  

Benefits of  E/L Protocol Review

• Risk Mitigation: Identifying and addressing potential issues early in the study design phase reduces the likelihood of costly delays or study repetitions.​
• Resource Optimization: By ensuring the study is appropriately scoped and designed, we help optimize resource utilization, avoiding potential unnecessary testing or overextending study parameters.

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.