Products, packaging, equipment components, and medical devices are made from diverse materials formulated to meet their intended performance requirements. These materials must meet applicable safety standards, including assessment of potential interactions with contained or delivered liquids. Under certain conditions, formulation chemicals may unintentionally migrate into products, such as water, food, and drugs, when they come into contact with these items. ToxStrategies’ experts have extensive experience in evaluating the hazards, including toxicity, from extractable and leachable (E/L) constituents that may be found in the materials, and in assessing the potential risks that these incidental chemical exposures pose to patients, consumers, and the environment.
Material extraction studies use aggressive solvents and conditions to characterize the chemical composition of the consumer product or medical device. Leachable chemical constituents are identified under conditions that more closely reflect real-world use. Leachable constituents are generally considered a subset of the extractable chemicals and are more relevant for evaluating potential exposures or risks.
Our experts also estimate potential exposures using measured E/L concentrations and the best available science for exposure models. By integrating hazard and exposure data, we conduct robust risk evaluations for product use, including risks to consumers or patients. Our transparent, defensible approaches help minimize delays and support informed decision-making.
Our Capabilities
E/L Studies for Pharmaceuticals
- Support for drug regulatory approval
- Study design to evaluate potential for patient exposure and risk to E/L constituents from components used in pharmaceutical manufacturing and processing
- Derivation of substance-specific toxicity thresholds
- Interpretation of data using frameworks from relevant pharmaceutical guidance and regulations:
- USP <665>: Plastic Components and Systems Used in Pharmaceutical Manufacturing
- USP <1661>: Evaluation of Plastic Packaging Systems and Their Materials of Construction with Respect to Their User Safety Impact
- USP <1663>: Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems
- USP <1664>: Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems
- ICH Q3D(R2): Elemental Impurities
- ICH Q3E: Guideline for Extractables and Leachables
- ICH M7(R2): Guideline on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk
E/L Studies for Medical Devices
- Evaluation of medical device safety
- Study design for E/L testing
- Preparation of toxicological risk assessment to evaluate tolerable intake of E/L constituents
- Interpretation of data using frameworks from relevant medical device guidance and regulations:
- ISO 10993-1: Biological Evaluation of Medical Devices (2025)
- ISO 10993-17: Toxicological Risk Assessment of Medical Device Constituents (2023)
- ISO 10993-18: Chemical Characterization of Medical Device Materials Within a Risk Management Process (2020)
E/L Studies for Consumer Products and Environmental Impacts
- Study design to evaluate exposures of E/L constituents from consumer and industrial products
- Interpretation of data using US EPA Leaching Environmental Assessment Framework (LEAF) Methods and Guidance (Methods 1313, 1314, 1315, and 1316)
- Compilation and analysis of occupational, environmental, and consumer exposure measurements including California Proposition 65 compliance
- Conceptual exposure model development
- Predictive exposure modeling for conditions of use
- Environmental fate predictions
- Quantitative human and ecological risk assessment
- Uncertainty analyses
Example Project #1: Risk Assessment for Drug Manufacturing Single Use Components
ToxStrategies used E/L data and an evaluation of the manufacturing process to estimate potential organic and elemental compound exposures from plastic and glass processing components to potential patients receiving a new pharmaceutical. Potential exposures were conservatively estimated based on the amount of drug product that may come into contact with the components and the amounts of E/L compounds that could be extracted or leached. These exposures were then compared to International Council for Harmonisation (ICH) permissible daily exposure values to determine margins of safety. Where patient exposures had the potential to exceed these default thresholds, we derived chemical-specific toxicity values using scientific literature and read-across modeling. This analysis demonstrated that conservatively estimated risk was far below any level of concern.
Example Project #2: Risk Assessment for Chemicals in Plastic Containers
Upon discovering chemicals in a plastic container may have been able to migrate to liquid contents sold to consumers, ToxStrategies advised on E/L experimental studies. These data were used in robust models to determine the likelihood and magnitude of potential chemical exposures to consumers, workers, and the environment across the entire product life cycle. Toxicity values were also derived for the chemicals of concern using the best available science. This work confirmed that even under highly conservative scenarios, there would be a low risk of adverse health or environmental effects from exposure to the chemicals from the product.
Example Project #3: Metals Leaching from Steel Slag
ToxStrategies evaluated the environmental relevance of concentrations of several metals leached from steel slag using the full suite of US Environmental Protection Agency Leaching Environmental Assessment Framework (LEAF) methods. Our experts considered the potential for metals to leach into groundwater and surface water if the slag were to be used for landscaping or paving purposes. This screening-level analysis concluded that a detailed risk assessment would be unlikely to find adverse human or environmental health risks from the metals that could potentially leach from the slag under the proposed uses.
Example Project #4: Development of Pediatric-Specific Tolerable Intake (TI) Values for a Medical Device
ToxStrategies evaluated the pediatric safety of extractables identified from a medical device intended for pediatric patients. While TI values specific to adult patients were already available, TIs applicable to children and neonates had not been developed. In order to support marketing of the device in these new patient populations, ToxStrategies conducted robust targeted literature assessments to identify the presence (or absence) of pediatric-specific safety data in the public domain. Where applicable, these data were used to support derivation of patient population-specific TIs, especially in instances where the extractables exhibited pediatric-specific toxicities warranting use of an alternative point of departure to best support patient safety.