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The demonstration of medical device ISO 10993 biocompatibility is an essential requirement for marketing authorization in all major markets. Gaining approval for a medical device requires the informed collection and evaluation of data by a qualified expert to ensure a successful device regulatory submission. Gradient has the technical expertise to develop a holistic biological safety evaluation tailored to your device, or will review your existing plans and reports for gaps and regulatory pitfalls.
Whether you choose to have Gradient provide a comprehensive Biological Safety Evaluation, or expert consulting for specific elements of the evaluation, Gradient's medical device team takes a practical approach biocompatibility evaluations. Gradient leverages existing data whenever possible but will provide expert guidance in the event testing is required. In addition to ISO 10993-1 Annex A biocompatibility testing guidance, Gradient specializes is ISO 10993-18 Material/ Chemical Characterizations and ISO 10993-17 Toxicological Risk Assessments. With numerous certified toxicologists and chemists working together, Gradient can guide device manufactures on the proper selection solvents and test conditions reduce uncertainty within chemical characterization. Gradient also provides tailored toxicological risk assessments to establish safe levels of exposure for assessing potential patient risks in a manner compliant with international guidances and regulatory requirements (e.g. ISO 10993 series, ISO 14971, ISO 18562 series, ICH M7, EU MDR). Gradient provides toxicological risk assessment support to evaluate product liability and personal injury claims related to various medical devices.
Gradient's expert toxicologists have years of experience supporting regulatory inquiries from FDA and EU notified bodies. Gradient understands the complexity of biological safety evaluations and can help troubleshoot test results or change control activities (e.g. new supplier or material).
- Strategic planning for biological safety analysis
- Authorship of Biological Safety Evaluation Plans/Report
- Review of existing biocompatibility data for gaps
- Leveraging of existing data and/or justifications for waiving of testing
- ISO 10993-1 endpoint justification and/or test selection
- ISO 10993-18 material characterization data collection and solvent selection/justificationExtractable & leachable toxicological risk assessments
- Toxicological equivalency evaluation
- EU Medical Device Regulation (MDR) gap assessment and compliance support including:
- Biocompatibility gap assessment
- Benefit-Risk assessments for the presence of CMR and/or endocrine-disrupting substances
- FDA and Notified body question and deficiency resolution
- Cleaning validation plans
- Product liability support
Gradient is a member of Science Exchange.
EU MDR Biocompatibility and CE Marking SupportFull Description
Gradient addressed regulatory deficiencies relating to biocompatibility and clinical safety for the purpose of CE Marking in the European Union (EU). Additionally, for the purpose of establishing compliance under EU Medical Device Regulation (EU MDR, 2017/745), Gradient reviewed all relevant documentation for four medical device systems, including prior regulatory submissions, compositional profiling, material specifications, biocompatibility data, and clinical history. This information was collated, organized and documented to establish the safety of each device and their respective components and materials of construction. Our reports will aid in the approval of said medical devices under the EU MDR.
Establish Biological Evaluation Plan for a Family of Implant Devices and Surgical InstrumentsFull Description
Gradient drafted a comprehensive Biological Evaluation Plan (BEP) for a family of permanent implant devices and limited contact surgical instruments constructed from the same stainless steel material. The scope of our BEP focused on establishing compliance to the ISO 10993 series guidances and the EU MDR 2017/745 regulation. Our BEP will aid in ensuring proper testing and documentation of each device (and the respective components and materials of construction) to support safety as well as regulatory compliance in both the US and the EU markets.
Toxicological Risk Assessment of Extractables of Permanent Implant DevicesFull Description
Gradient provided fit-for-purpose toxicological risk assessments (TRAs) for chemicals identified in extracts of a permanent implant screw. In accordance with ISO10993-17 and US FDA guidance, Gradient identified toxicological data for relevant endpoints and used these data to derive chemical- and device-specific safety margins. For data-poor compounds, Gradient conducted weight-of-evidence analysis and applied read-across data where appropriate. For this work, Gradient partnered with an analytical testing laboratory for the device analyses. The client used our TRAs to support a safety evaluation of the medical device.
Toxicological Risk Assessment of Extractables and Leachables from Dialysis EquipmentFull Description
Gradient conducted toxicological risk assessments (TRAs) for compounds identified in extracts from dialysis equipment. In accordance with ISO 10993-1 and ISO10993-17, Gradient identified toxicological data for relevant endpoints and used these data to derive chemical- and device-specific safety margins. For data-poor compounds, Gradient conducted weight-of-evidence analyses that applied read-across data, or adopted thresholds of toxicological concern in accordance with ICH M7 and ISO 21726 guidance as appropriate. Our report was submitted to the FDA for regulatory review, and ultimately resulted in regulatory acceptance of the device to the US marketplace.
Toxicological Risk Assessment of E&L for Humidifier Drug Delivery DeviceFull Description
Gradient provided fit-for-purpose toxicological risk assessments (TRAs) associated with inhalation exposure to extractable compounds detected in components of a respiratory device. In accordance with ISO10993-17 and the ISO 18562 series guidances, Gradient identified toxicological data for relevant endpoints and used these data to derive chemical- and device-specific allowable limits and calculated safety margins for various intended patient populations (adults, children, infants, and neonates). For data-poor compounds, Gradient conducted weight-of-evidence analyses that applied read-across data where appropriate. Our report was submitted to the FDA for regulatory review, and ultimately resulted in regulatory acceptance of the device to the US marketplace.
Health Risk Evaluation for a Medical ProductFull Description
Gradient evaluated a medical diagnostic gel's ingredients to determine their potential to produce skin sensitization or dermal irritation. We evaluated the concentrations of ingredients in the product in comparison to effect levels noted in human and animal studies. Our evaluation helped the gel's manufacturer understand the likelihood of dermal sensitization or irritation possible with use of the product as directed.
Risk Assessment of Residues on Orthopedic DevicesFull Description
Gradient assessed the potential for adverse human health effects due to lubricating oil and fatty acid residues detected on several types of orthopedic implants. We reviewed literature regarding health effects of the base oil and other materials and established critical effect levels, which we compared to estimated exposure levels associated with the materials detected on the medical implants.
Evaluation of Sterilant Exposures for a Medical DeviceFull Description
Gradient conducted a California Proposition 65 exposure analysis of ethylene oxide residues (a byproduct of sterilization) on a medical device. We developed a model to track residue decay over time based on literature regarding desorption of ethylene oxide from polyethylene. The model results were combined with anticipated use patterns and indoor inhalation rates to assess risks for potential users.
Recommendation of Appropriate Toxicity Study Design for Medical DeviceFull Description
Gradient reviewed the literature for toxicity and metabolic information for both rats and humans for an organic chemical. The data were evaluated in order to determine the proper dose levels and regimen for a subchronic toxicity study that would inform a future risk assessment.
Evaluation of Medical Device CytotoxicityFull Description
Gradient evaluated the plausibility of claims regarding potential cytotoxicity of an implantable medical device. We critically reviewed the available in vitro and in vivo experimental data and human clinical studies of the device and its components, and we assessed the weight of the evidence for potential adverse effects.
Safety Evaluation of Breast ImplantsFull Description
Gradient assessed the plausibility of claims regarding potential health risks of saline-filled breast implants. We evaluated whether the peer-reviewed literature and pre- and post-market studies of breast implants indicate that they can cause a variety of health conditions. We assessed the state of the epidemiology evidence, considering how study quality affects the interpretation of results.
Medical Malpractice Case Regarding Dialysis EquipmentFull Description
Gradient evaluated the possible toxicology, pharmacokinetics, and timing of health effects associated with exposure to chemicals used to sterilize dialysis equipment. We reviewed the toxicology literature to identify potential cardiac effects associated with intravenous exposure to patients during dialysis. We also investigated biochemical reactions between dialysis sterilants and human blood to better understand their pharmacokinetics and residence time in the human body. Our results informed the client of potential risks posed by dialysis sterilants.