On February 12, 2016, the U.S. Food and Drug Administration (FDA) held a webinar to clarify their current policy in relation to the use of color additives in medical devices. Under Chapter VII, section 721 of the Federal Food, Drug, and Cosmetic, color additives are subject to FDA approval before they may be used in medical devices that come in contact with the bodies of people for a “significant period of time”. Of particular importance, FDA clarified in the webinar the interpretation of “significant period of time” by the Office of Device Evaluation (ODE) within the Center of Devices and Radiological Health (CDRH). According to the webinar, “ODE does not consider use of a color additive in or on a device to be in contact with the body for a ‘significant period of time’ if the contact duration is 30 days or less”.
For new devices, FDA further clarified their expectations related to color additives in terms of contact duration as follows:
- For devices with no patient contact or in contact with intact skin for up to 30 days, no color additive information is needed for FDA review.
- For devices with other types of contact and a contact duration of less than 24 hours:
- For devices with less than 1-minute contact duration, no color additive information is needed for FDA review unless performance testing reveals evidence of release.
- For devices with greater than 1-minute contact duration, no color additive information is needed for FDA review if cytotoxicity, sensitization, and irritation (CSI) testing is performed with acceptable results and there is no change in the color/turbidity or presence of particulates observed in device extracts. If CSI testing is not performed with acceptable results or there is a change in the color/turbidity and/or presence of visible particulates in device extracts, then color additive information and risk assessment (as described below) will be needed for FDA review.
- For devices with other types of contact for 24 hours and up to 30 days:
- If CSI testing and other biocompatibility testing recommended in FDA’s G95-1 Blue Book Memorandum is performed with acceptable results and there is no change in the color/turbidity or presence of particulates observed in device extracts, then no color additive information is needed for FDA review. If any of the above are not true (e.g., irritation testing shows slight toxicity, no genotoxicity testing performed, presence of color or particulates is observed in the device extracts), then color additive information and risk assessment (as described below) will be needed for FDA review. FDA also clarified that if information is provided to demonstrate the particulates are not due to the leaching of color additives, then color additive information is not needed.
- For devices with tissue contact greater than 30 days, regardless of the type of contact, the following color additive information is needed for FDA review:
- Chemical name and Chemical Abstracts Service (CAS) Number.
- Purity information, such as CFR color listing (e.g., 21 CFR 73 and 21 CFR 74), raw material’s Certificate of Analysis (COA), or testing for impurities.
- Maximum amount of each color additive per device by weight.
- Alternative to supplying the above information, another device that is legally marketed in the U.S. and has the same color additive, matrix material, processing, and type and duration of tissue contact as well as similar intended use may be identified. If the color additive amount in your device is less than or equal to the comparator device, or the color additive and impurity amounts in your device are less than their tolerable intake (TI), then no additional information is needed for FDA review. However, additional risk assessment may be needed if the color additive amount in your device is higher than the comparator device or if the color additive amount is the same or less than the comparator, but the conditions of device use are not comparable (e.g., contact type or duration differ). Depending on the results of the risk assessment, it may be necessary to reduce the amount of color additive in the device or employ other risk mitigation options.
For changes to existing devices, the changes should be assessed for their ability to affect color additive release. If the change is not likely to affect the release of color additive based on available evidence, then no color additive information is needed for FDA review.
When interpreting FDA’s policy, it is important to note that patient contact means both direct and indirect patient contact and the categories of patient contact duration should include the potential for repeated use of the device. The above summarizes what information should be provided to FDA in terms of the color additive(s) only; however, it is recommended to refer to FDA’s G95-1 Blue Book Memorandum or any device-specific guidance or regulations for a summary of any additional information or biological testing that should be provided for your device type.
FDA’s color additive policy applies to 510(k), Premarket Approval (PMA), de novo, and Humanitarian Device Exemption (HDE) marketing applications, but not for Investigational Device Exemptions (IDEs), unless there is a toxicity risk identified for any of the color additives used to manufacture the device.
In the webinar, FDA stated that their policy related to color additives in medical devices is planned to be published in a draft Level 1 guidance document in the future, which means the draft guidance will be available for public comment prior to being finalized.