FDA guideline | ISO 10993-18
Author: Clothilde Lechenault-Bergerot, Head of the Extractables & Releasables Division
Exporting medical devices (MDs) to the United States represents a major opportunity for European manufacturers.
However, navigating the US regulatory landscape and meeting the strict requirements of the Food and Drug Administration (FDA) can be complex, especially when it comes to compliance with specific standards such as ISO 10993* and in particular clause 18, dedicated to the evaluation of the biocompatibility of medical materials.
This standard, which is essential for ensuring the safety and efficacy of medical devices, plays an important role in the FDA approval process, a prerequisite for accessing the US market.
Understanding ISO 10993-18: Chemical Characterization of Materials
ISO 10993-18 is a crucial standard in the world of medical devices, as it defines guidelines for the chemical evaluation of medical materials intended to come into direct or indirect contact with the human body. Its main objective is to ensure that these materials are biocompatible, meaning that they do not pose any risk of toxic reaction, irritation, or sensitization to patients.
Compliance with ISO 10993-18 is therefore essential for medical device manufacturers who wish to market their products in Europe and the United States.
It involves conducting extensive analytical studies to identify and quantify the chemicals that may be released from the device into the patient’s body. This process assesses not only the risks associated with these substances but also the need for additional biological testing to ensure the safety of the device.
What are the requirements for exporting medical devices to the US market according to ISO 10993-18?
When submitting a biocompatibility dossier for medical devices to the notified body responsible for evaluating it, the requirements may be more stringent for submissions to the US market compared to the EU market.
The chemical characterization study can therefore be adapted to maximize the chances of successful approval.
The table highlights the key requirements to successfully export your medical device to the U.S. market in line with FDA standards.
US requirements | Level of importance | |
Number of extraction solvents | 3 solvents (polar, semi-polar, non-polar) | Depending on the medical device’s risk assessment |
| Number of reference standards for semi-quantification | 3 standards for GC-MS / 5 standards per mode for LC-MS | Increasingly required |
Identification of detected extractables | As many as possible must be identified; the precise composition of the MD must therefore be provided to the analytical laboratory | Mandatory |
Number of extraction replicates | Triplicates | Unless justification is provided (e.g., regarding the reproducibility of the MD manufacturing process) |
If concentration of extracts is required to reach the AET for analytical techniques | Ensure no loss of extractables; comparison of concentrated vs. non-concentrated extracts + spiking with reference standards | Increasingly required |
Ionization source chosen for LC-MS | ESI, and APCI in certain cases | Depending on the type of polymer the MD is composed of |
Therefore,
Entering the US market for a medical device is a journey fraught with regulatory and technical obstacles, yet it remains an unparalleled opportunity for growth and international recognition.
The ISO 10993-18 standard, which focuses on the chemical characterization of materials, establishes a solid foundation for biocompatibility assessment—a critical requirement for FDA approval.
FILAB laboratory works alongside partner toxicologists both in France and abroad to ensure independence and objectivity. This collaborative approach allows for the challenging of ideas and methodologies by integrating diverse perspectives, all while maintaining a singular focus : meeting technical and regulatory requirements that can often be imprecise.
In the face of the stringent requirements for entering the U.S. market, mastery of ISO 10993-18 proves essential. Medical device manufacturers must navigate a complex landscape of testing, analyses, and regulatory compliance, where every detail matters.
In this context, partnering with a chemical and materials laboratory specialized in chemical characterization—and backed by a network of toxicology partners—becomes a major strategic asset.
*What is the ISO 10993 series of standards ?
ISO 10993 is a series of international standards developed to evaluate the biocompatibility of medical devices that come into contact with the human body.
It covers the tests and criteria necessary to ensure that these devices do not cause toxic, irritating, or sensitizing reactions, or any other adverse biological effects.
The objective is to guarantee patient and user safety by assessing the interaction between the medical device and body tissues, cells, and fluids.
Within the ISO 10993 framework, Part 18 focuses specifically on the chemical characterization of medical device materials.