Genotoxicity, Carcinogenicity, and Reproductive Toxicity according to ISO 10993

The manufacturing of medical devices is subject to numerous global standards and legal regulations. As an industry concerned with human health, allowing no room for negligence, experience, professionalism, and expert support are essential at all stages, starting from research and development. Before a medical device can be introduced to the market, it must undergo a statutory process. In this context, various controls and laboratory analyses are paramount. Based on ISO 10993, a procedure compliant with FDA requirements must be implemented.

Before delving into the "Genotoxicity, Carcinogenicity, and Reproductive Toxicity" studies included in these analyses within our article, we will first clarify how medical devices are classified and which class is relevant for the aforementioned tests.

How are medical devices classified?

According to the classification system established by the FDA, 1700 types of medical devices are categorized into 16 medical specialties. Each of these products is assigned to one of three classes, depending on its potential risk to patients, product type, application area, and duration of use.

– Class 1 – Medical Devices: Stethoscopes, bandages, bed accessories, latex gloves, surgical masks

Medical devices in this class are considered to have the lowest risk. Consequently, they are subject to less stringent control procedures compared to the general process.

– Class 2 – Medical Devices: Blood pressure cuffs, pregnancy tests, syringes, blood transfusion devices, motorized wheelchairs, contact lenses, certain diagnostic software

This class comprises 43% of medical devices and includes products with moderate risk. In addition to general controls, they must undergo special controls regarding their performance, labeling, clinical test data, and conformity requirements.

– Class 3 – Pacemakers, defibrillators, implanted prostheses, cochlear implants, breast implants, intraocular lenses, renal stents

These products, belonging to the highest risk group, undergo more rigorous testing and analysis procedures and must fully complete all certification stages. They are subject to general controls and premarket approval.

Insights into Genotoxicity Studies

The CDRH (Center for Devices and Radiological Health) and CBER (Center for Biologics Evaluation and Research) require genotoxicity testing for medical devices that come into contact with bone, mucous membranes, or other tissues for more than 24 hours up to 30 days or longer. Furthermore, this may also be required for medical devices already legally marketed, regardless of their duration of use. For products with a large surface area, and thus an increased potential for chemical leaching, as well as for products that come into contact with blood outside the body, genotoxicity testing may be necessary if there is a possibility of substances entering the systemic circulation.

When an in vitro genotoxicity test on mammalian cells is required:

When an in vitro genotoxicity test is required:

These tests must be conducted with the support of authorized and accredited laboratories.

Carcinogenicity Testing for Medical Devices and Related Details

In addition to products used for wound healing (which come into contact with damaged or injured surfaces), products that come into contact with the external environment and are implanted must also be tested for carcinogenicity. The FDA recommends that medical devices in contact with the body for more than 30 days be evaluated for their carcinogenic potential. Even if a product passes the genotoxicity test, it should still be assessed for carcinogenicity. In such cases, it should be considered that non-genotoxic carcinogens may be present and that the carcinogenic effect depends on various factors.

Why is Reproductive Toxicity of Medical Devices Assessed?

The potential effects on reproductive function, embryonic development (teratogenicity), and prenatal and early postnatal development must be evaluated for medical devices and materials. This includes the following medical devices:

– Implant materials where chemical leachates may come into contact with reproductive organs. In such cases, the nature or duration of contact is irrelevant.

– Materials or components of products that come into contact with reproductive organs

For further information on the ISO 10993 standard and the work conducted under this standard, as well as for support with the certification, testing, and analysis of your products, please do not hesitate to contact us. Our team of experts is readily available to assist you with any inquiries on this subject.