The Materials and Chemical Characterization Program at the FDA’s Center for Devices and Radiological Health (CDRH) conducts regulatory science research to ensure safe and effective development of medical devices. This is one of 20 research programs at the CDRH Office of Science and Engineering Laboratories (OSEL).
Materials and Chemical Characterization and Medical Devices:
Medical devices are manufactured using a variety of materials, including metals, ceramics, and polymers. However, the synthesis, processing, and fabrication of these materials may affect the biostability and biocompatibility of the devices across the entire range of medical specialties. Ultimately, these factors determine whether the material is suitable for a specific application. Establishing material suitability often requires rigorous chemical characterization of potential extractable and leachable compounds that can impact biocompatibility, as well as characterization of the propensity of the material to degrade over time, for example, due to corrosion, oxidation, and/or hydrolysis. Often these assessments are time-consuming and costly, and the implications for clinical performance can be ambiguous.
Regulatory Science Gaps and Challenges
The major regulatory science gaps and challenges that drive the Materials and Chemical Characterization Program are:
- Clinical relevance of the extractable and leachable results obtained with traditional methods for assessing patient exposure to leachable chemicals of medical devices is typically ambiguous.
- Lack of understanding in:
- using screening approaches to estimate quantities of different compounds,
- obtaining regulatory approvals for material/manufacturing changes, and
- developing chemical characterization methods to replace biocompatibility assays.
- The current approaches to estimating patient exposure have questionable clinical relevance, which often requires additional testing and/or justifications.
- Lack of accelerated test methods to support long-term stability of polymers in regulatory submissions that reduce the testing burden.
- Lack of understanding of immunological response to metals in medical devices.
- Lack of specific guidelines for establishing and applying in vitro to in vivo correlations for absorbable materials
The Materials and Chemical Characterization Program is intended to fill these knowledge gaps by developing regulatory science tools which will provide consistent, less burdensome, and more clinically relevant test methods and models for evaluating medical device material biostability and biocompatibility.
Material and Chemical Characterization Activities
The Materials and Chemical Characterization Program focuses on regulatory science research in these areas:
- Chemical characterization - Following the 2020 standard of ISO 10993-18, there have been major challenges in reviewing and accepting chemical analysis studies that are used to support chemical characterization (CC) for toxicological risk assessment (TRA) in regulatory submissions. The Chemical Characterization subprogram aims to increase the transparency and consistency of chemical analysis testing.
- CHemical RISk calculators (CHRIS) - One of the major challenges in evaluating the potential risk of leachable compounds in medical device materials is that there is no accepted method to establish patient exposure to these compounds, which may include leachables, such as color additives. The CHRIS subprogram focuses on developing physics-based exposure models to predict patient exposure and developing easy-to-use web applications that enable rapid screening-level risk assessments to be conducted based on the models.
- Polymer Biostability - Polymers stability testing in support of regulatory submissions is challenging due to (i) variability in material formulations and device applications, (ii) lack of fully characterized use conditions, and (iii) difficulty translating benchtop studies to clinical outcomes. This effort is focused on developing validated accelerated aging methodologies to reduce the testing burden and developing guidelines for establishing correlations between in vitro testing and in vivo performance.
- Metal implant toxicity - Based on the CDRH review of biological responses to metal implants and the public advisory committee meeting of the Immunology Devices Panel in November 2019, several gaps in understanding of immunological response to metals in medical devices were identified. The primary goal of this effort is to define patient populations that may be at an elevated risk of adverse response to implanted metals or metal alloys and to develop more clinically relevant screening tools for premarket device evaluation.
- Materials safety summaries - Medical device developers may not consider material biostability or biocompatibility at the design stage of device development. To promote designing for safety and effectiveness early in device development, the goal of this effort is to generate comprehensive safety profiles for commonly used device materials based on systemic literature reviews and real-world device performance data, and to develop user friendly tools for interrogation of the collated information. For more information, see Medical Device Material Safety Summaries.
For more information, email OSEL_materialandchemperformance@fda.hhs.gov.