Navigating the FDA's New Draft Guidance on Chemical Analysis for Medical Devices
24 Jan 2025
What You Need to Know
In September 2024, the FDA issued the Draft Guidance "Chemical Analysis for Biocompatibility Assessment of Medical Devices Draft Guidance for Industry". In this document, the FDA provides recommendations for analytical chemistry testing to evaluate the biocompatibility of medical devices or a device component as part of their overall biocompatibility assessment for a device during submission. This guidance covers analytical chemistry testing methods used for medical devices in general. However, it recognizes that specific methods may be required for individual medical devices, depending on the materials used for construction or if there are any established approaches from the past.
The document aims to promote consistency and quality of analytical studies and reports and facilitate the review of these studies during medical device submissions.
What is chemical characterization?
Chemical characterization of medical device materials is used to characterize the chemical substances that may be released from the medical device to the body and can help address certain risks during biocompatibility evaluation. Furthermore, chemical characterization can be considered supportive or an alternative to biological testing for evaluating some biocompatibility endpoints when followed by a toxicological risk assessment (TRA) described in the ISO 10993-17 standard. Indeed, chemical characterization studies may be used to support chemical equivalence after the change of materials or the manufacturing of a device or in comparison to a device of similar materials, where biocompatibility has already been demonstrated.
In a practical sense, chemical characterization involves a process of data gathering concerning the materials of construction, their chemical ingredients, and chemical residues originating from the manufacturing process or other treatments. In most cases, exposure of test articles to solvents is performed under controlled conditions, which are often setup up to exceed the worst case. Different extraction methods are applied followed by chemical analysis of the extractables and data reporting.
Recommended study approach
The guidance highlights the importance of gathering preliminary information on device materials and the manufacturing process covering the ingredients, such as base polymer, plasticizers, stabilizers, surfactants, and colour additives, all listed as information that should be provided. Additionally, the potential presence of "cohort of concern" compounds should be highlighted and investigated with dedicated methods if there is a risk of their presence. The device's intended use should be considered and used to determine the clinically relevant worst-case exposure. This insight supports an informed device-specific chemical characterization plan.
The documents indicate that non-targeted chemical analysis is suitable for the general screening of extractables. Still, following this, targeted analysis may be necessary to confirm the identity of certain analytes or accurately determine the quantity of specific substances exceeding analytical evaluation threshold values such as suspected genotoxic or mutagenic compounds.
The screening analysis and methods highlighted are aligned with general best practice for E&L studies, such as those from the Product Quality Research Institute (PQRI) or the United US Pharmacopeia and others, perhaps exceeding the requirements in some cases.
Extraction conditions and solvents
The draft guidance's recommendations for the extraction conditions and solvents are aligned with intended clinical use and aligned with ISO 10993-18. Any deviation from recommended solvents and conditions must be justified.
The new guidance also takes material variability into account. Three batches of materials need to be extracted and analyzed separately using all the analytical techniques. The highest concentrations of the detected compounds from all experiments should then be considered for the later toxicological risk evaluation to cover the worst case.
Key steps in sample preparation, analytical testing, and the evaluation of results
In general, the guidance recommends individual extraction for single materials of device construction to enable correlation to the origin of detected extractables. Special attention is required where particulates are observed during extraction. Techniques like HS-GC/MS, GC/MS, LC/MS are recommended to profile the organic component of the extractables. ICP/MS analysis for the determination of elemental extractables is also recommended.
Looking ahead
The draft guidance provides a detailed explanation of the FDA's interpretation of ISO 10993-18 concerning the design and justification of analytical studies for chemical characterization. As a result, the process for product registrations in the USA may become more complex in the future. This document was open for comment up until Dec 19th 2024. The FDA will now consider comments received on the draft guidance before it begins work on the final version of the guidance.
If you would like to find out more on this topic please download our complete Q&A with our expert.
You can also find out more online:
- ISO 10993-18 Medical Device Chemical Characterization and Extractables Leachables for Biocompatibility of Materials
- Biocompatibility Testing and Evaluation
- Medical Device Testing and Scientific Support Services
