The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of medical devices, has published a guidance document dedicated to brain-computer interface (BCI) devices. The present article describes specific aspects related to BCI devices allowed to be marketed and used in the US.
It is important to mention that FDA guidance documents are intended to provide additional clarifications on the applicable regulatory framework and recommendations to be considered by medical device manufacturers and other parties involved. Due to their legal nature, the provisos of guidance documents issued by the Agency are non-binding and describe a recommended approach. The authority explicitly states that an alternative approach could be applied, provided such an approach complies with current regulatory requirements and has been approved by the FDA in advance.
First, the Agency emphasizes the importance of biocompatibility matters associated with BCI devices as they contain patient-contacting materials. According to the document, medical device manufacturers shall duly access the biocompatibility of any and all materials used for device elements that are intended to be in direct contact with the patient’s tissue surface. If the components used for a device have been already used in similar devices for a certain period of time, and there is a history of such use, and data available, it would be sufficient to make reference to the appropriate FDA-recognized voluntary consensus standard the material in question complies with, or to a Letter of Authorization (LOA) for a device Master File (MAF).
If there is no similar medical device on the market, the manufacturer shall duly conduct a biocompatibility risk assessment and present its results. According to the guidance, the assessment should explain the relationship between the identified biocompatibility risks, the information available to mitigate the identified risks, and any knowledge gaps that remain. In this regard, the authority refers to the guidance dedicated biological evaluation of medical devices under the International Standard ISO-10993-1.
The particular scope of assessment and testing required depends on the design of the BCI device in question. As stated by the FDA, all BCI devices could be divided into the following categories:
- Category 1: Implant in permanent contact (>30 days) with neural tissue/bone, cerebrospinal fluid (CSF), and blood (indirect contact with blood through CSF as CSF is reabsorbed into the venous system). The aspects to be considered in such case include, inter alia, cytotoxicity, acute system toxicity, and neurotoxicity.
- Category 2: Implant in permanent contact (>30 days) with neural and non-neural tissue/bone (i.e., muscle, not intended directly or indirectly to contact CSF or blood).
- Category 3: External communicating device with limited (≤ 24 hours) tissue/bone contact.
- Category 4: Surface device with limited (≤ 24 hours) / prolonged (> 24 hours – 30 days) / permanent (> 30 days) contact with intact skin. In the case of such devices, the scope of assessment could be limited to cytotoxicity, sensitization, and irritation or intracutaneous reactivity.
Another important aspect to be considered with regard to BCI devices relates to sterility as such products could be supplied sterile. According to the guidance, in such cases, the medical device manufacturer shall provide a detailed description of the sterilization method employed, including the description of the process itself, as well as details about the sterilization chamber and site. The authority also states that for chemical sterilants (e.g., Ethylene Oxide (EO), H2O2), the maximum levels for sterilant residuals that remain on the device, and an explanation of why those levels are acceptable for the device type and the expected duration of patient contact. Additionally, the manufacturer shall describe in detail the particular sterilization method used to validate the sterilization cycle and also indicate the applicable sterility assurance level (SAL).
In order to ensure protection against the risks associated with febrile reaction, the scope of assessment should also cover aspects related to pyrogenicity. For this purpose, the medical device manufacturer shall assess whether the BCI device subject to review complies with the applicable pyrogen limit specifications. The authority also encourages manufacturers to provide the routine batch release Limulus Amebocyte Lysate (LAL) monitoring procedures. It is stated that for devices intended to be labeled as “non-pyrogenic,” it is recommended that both bacterial endotoxins and material-mediated pyrogens be addressed.
Shelf Life and Packaging
According to the applicable regulatory requirements, the packaging of medical devices shall ensure integrity in order to ensure the device remains sterile and fully functional within the whole period of its shelf life. In this regard, the medical device manufacturer shall provide a detailed description of the packaging itself, as well as the procedures of package integrity testing, together with the results of such testing and conclusions. The scope of evaluation shall include an assessment of the aging process together with strength testing. As it is stated by the FDA, with respect to evaluating the effects of aging on device performance or functionality, shelf-life studies should evaluate the critical device properties to ensure it will perform adequately and consistently during the entire proposed shelf life. For this purpose, the manufacturer shall also conduct bench testing. According to the guidance, the manufacturers are encouraged to submit the protocols of shelf-life testing. The Agency recommends conducting real-time aging in order to determine the effects of aging. Should the manufacturer decide to apply accelerated aging instead, a detailed description of the process should be provided to the authority in order to evaluate the accuracy and reliability of the testing results obtained.
Electrical Safety and Electromagnetic Compatibility (EMC)
Apart from the aspects described above, the FDA also pays attention to the assessment of risks associated with the use of electrical energy. According to the guidance, BCI devices should be tested to demonstrate that they perform as anticipated in their intended use environment, while the appropriate testing should be carried out in accordance with the applicable FDA-recognized voluntary consensus standards, including the following:
- ANSI/AAMI ES60601-1: Medical electrical equipment – Part 1: General requirements for basic safety and essential performance;
- ANSI/AAMI/IEC 60601-1-2: Medical electrical equipment – Part 1-2: General requirements for basic safety and essential performance – Collateral standard: Electromagnetic disturbances – Requirements and tests.
- ISO 14708-1: Implants for surgery – Active implantable medical devices – Part 1: General requirements for safety, marking and for information to be provided by the manufacturer.
In summary, the present FDA guidance highlights the most important aspects to be considered by medical device manufacturers with regard to BCI devices. The document outlines the scope of testing to be performed in order to evaluate the safety and performance of these products, as well as the scope of information to be submitted to the authority when applying for marketing approval.
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