International Standard Iso 10993-1
Georgeanna Abson
The ISO 10993 set entails a series of standards for evaluating the biocompatibility of medical devices to manage biological risk. These documents were preceded by the Tripartite agreement and is a part of the international harmonisation of the safe use evaluation of medical devices.[1]For the purpose of the ISO 10993 family of standards, biocompatibility is defined as the "ability of a medical device or material to perform with an appropriate host response in a specific application".
The following table provides a framework for the development of a biocompatibility evaluation. Different biological endpoints may require evaluation for particular medical devices, including either additional or fewer endpoints than indicated. If it is unclear in which category a device falls, consulting device-specific guidances or contacting the appropriate US Food and Drug Administration (FDA) review division for more information is possible. The table "Endpoints to be addressed in a biological risk assessment" was revised by the 2018 edition of ISO 10993-1. The selection of endpoints for the biocompatibility evaluation is determined by the nature of body contact (e.g. implant device) and contact duration (e.g. long term contact of more than 30 days).
Specifically, FDA recognizes this standard and, in 2020, published a guidance document for recommended Use of International Standard ISO 10993-1 to help manufacturers understand biocompatibility testing considerations and apply risk-based biocompatibility evaluations, in accordance with the standard, in product submissions for entering the US market.
Conducting a biological risk assessment is an essential first step of demonstrating the biocompatibility of your medical device, in accordance with ISO 10993-1, and should be done within the framework of a risk management process.
Knowledge gaps and other significant findings discovered during the first phase of the biological evaluation process will then need to be compiled into a biological evaluation plan (BEP). Your BEP will serve as your initial risk assessment and guide you in addressing known risks, typically done by way of biocompatibility testing and/or further evaluation.
FDA provides a framework for the development of biocompatibility evaluation endpoints, including examples of some suggested endpoints. Some medical devices may require evaluation of different endpoints, or a combination.
FDA expects manufacturers to objectively explain why and how potential risks have been assessed. Include this information both within your BEP that you share with FDA as part of the pre-submission process, if possible. While a pre-submission is not required, it is strongly recommended as it offers many benefits to manufacturers.
Prior to the publication of ISO 10993-1, it was acceptable for manufacturers to run through a checklist of tests, but now, both ISO and the FDA expect clear justification that proves adequate biological testing has been done and all identified risks have been addressed. In order, biological testing must be conducted.
For example, if a component touches the skin of its user, does it have the potential to cause any reaction or harm? In other words, biocompatibility testing serves to control and limit the risk of medical devices and materials, or processes involved, when used on end users.
You also need to include a formal statement confirming the biological risk analysis and risk controls that have been completed. This report will be used to demonstrate that your medical device will not cause any undue risks to patients or any intended users during the course of its use.
An underlying theme of ISO 10993-1 and the related FDA guidance document is being able to demonstrate the safety of a medical device through objective evidence from risk-based biological testing and evaluation methods.
Greenlight Guru aligns with the latest ISO, FDA, and other regulations and standards, helping you conduct testing with ease and mitigate risk without the hassle. Get your free demo of Greenlight Guru today.
Looking for a design control solution to help you bring safer medical devices to market faster with less risk? Click here to take a quick tour of Greenlight Guru's Medical Device QMS software
Etienne Nichols is a Medical Device Guru and Mechanical Engineer who loves learning and teaching how systems work together. He has both manufacturing and product development experience, even aiding in the development of combination drug-delivery devices, from startup to Fortune 500 companies and holds a Project...
While not explicitly specified in ISO 10993-1:2018 and ISO 10993-11:2018, the FDA does not consider a 14-day subacute toxicity test sufficient for prolonged term devices with a contact duration of more than 14 and up to 30 days if the systemic toxicity needs to be conducted to evaluate these endpoints. Instead, the FDA recommends, that the choice of the test duration should be based on the duration of device use.
Based on our experience with the previous version of the FDA guidance document which contained several additional requirements and differences compared to the ISO 10993 standards, we recommend carefully reviewing FDA-specific requirements before planning laboratory tests to avoid deficiencies or unnecessary tests.
According to ISO 10993-1:2018, the current version of part 1 of the standard, biocompatibility is the ability of a medical device or material to perform with an appropriate host response in a specific application. Any device that comes into direct or indirect contact with the skin must be tested for biocompatibility. A medical device that makes indirect contact with the skin is one that encounters a liquid, gas, or another medium, that makes direct contact with the patient or user.
Medical devices are most commonly made of metals, plastics, and fabrics, which are composed of chemicals with varying properties. Manufacturers must gather physical and chemical information about the device, which is vital to its biological and material evaluation and characterization.
For devices with components that are made of or utilize novel chemicals or materials, or those known to cause adverse effects, ISO 10993 requires rigorous risk assessment and management according to the standards of ISO 14971. Furthermore, there are prescribed data endpoints that set the foundation for determining the biocompatibility of medical devices and their intended uses and components.
Biocompatibility assessment is a vital part of risk management according to ISO 14971. Ensuring compliance with risk management and biocompatibility assessment standards requires buy-in from all departments, from marketing and design to quality assurance and regulatory affairs.
It is vital that you begin considering ISO 10993-1:2018 in the early stages of product design. Part 1 of the standard will refer to additional parts, as listed in the following section. Completing your complete chemical characterization and toxicology assessment early in the process will help ensure the biocompatibility of your medical device during the design phase and expedite your device registration and time to market.
ISO 10993 is made up of 23 different sections or parts, each of which is maintained and updated separately. Previews of the standard can be viewed on the ISO website, but full versions of the standard need to be purchased.
The resulting inefficiencies lead to problems such as marketing products with expired certificates, missing certificates, inaccurate and/or incomplete submissions, and even non-compliance with current regulatory requirements. Having a holistic RIM system is central to staying in compliance with standards, regulations, and guidance in the many markets around the world. Rimsys is the only RIM system of its kind built specifically for the medtech industry.
Adapting the biological evaluation to the market you want to put your product in is sometimes called regulatory toxicology. While there are usually underlying reasons for the approval requirements, they are sometimes difficult to interpret. The ultimate goal is to have safe products while also gaining quick market access. This webinar offers perspectives from speakers based in Europe who have extensive experience in working with different Notified Bodies (NB) and products of different risk classes. They also plan to highlight how the requirements differ from the US FDA. They will share challenges and experiences gathered during their time as consultants in the field.
Chemical characterization of medical devices is conducted following the requirements and guidance in ISO 10993-18:2020. The purpose of generating an extractables profile of chemical constituents is to support a toxicological risk assessment that addresses systemic toxicity (acute, subacute, subchronic, and chronic), genotoxicity, carcinogenicity, and reproductive/developmental toxicity. Chemical characterization includes screening, through exaggerated or exhaustive extractions and non-targeted analytical methods, that often produces hundreds of extractables. ISO 10993-17:2023 provides new requirements and guidance for assessing toxicological risk of medical device extractables data that reduces the burden of conducting toxicological risk assessments. In this second part of a two-part webinar, the factors to consider and methods for calculating chemical specific worst-case estimated exposure doses (EEDmax) and margin of safety (MoS) values will be presented. The application of EEDmax and MoS in accordance with ISO 10993-17:2023, based on the relevancy of the generated extractables data to the medical device intended use, for time-period specific exposures and harms of chemical substances will also be presented. To facilitate understanding of ISO10993-17:2023, the webinar will conclude with examples in which ISO 10993-17:2023 approaches are demonstrated.
Chemical characterization of medical devices is conducted following the requirements and guidance in ISO 10993-18:2020. The purpose of generating an extractables profile of chemical constituents is to support a toxicological risk assessment that addresses systemic toxicity (acute, subacute, subchronic, and chronic), genotoxicity, carcinogenicity, and reproductive/developmental toxicity. Chemical characterization includes screening, through exaggerated or exhaustive extractions and non-targeted analytical methods, that often produces hundreds of extractables. ISO 10993-17:2023 provides new requirements and guidance for assessing toxicological risk of medical device extractables data that reduces the burden of conducting toxicological risk assessments. In this first part of a two-part webinar, the requirements and guidance related to hazard identification, including when and how to apply a toxicological screening limit (TSL) to prioritize chemicals for toxicological risk assessment, what factors to consider when deriving tolerable intake (TI) values, and when and how to apply the Threshold of Toxicological Concern (TTC) will be presented. The selection and documentation of the point of departure (PoD), the use of appropriate uncertainty factors, and special considerations for infants 6 months or younger in accordance with ISO 10993-17:2023 will also be presented. In the second part of this webinar, exposure dose estimation and margin of safety to support toxicological risk evaluation will be presented.
c80f0f1006