- FDA is soliciting feedback on a proposed framework to change medical device labeling to require long-term devices to identify all constituent materials that might come into contact with human tissue and to require patient labeling be added to a broader class of medical devices. Stakeholders are encouraged to submit comments before the August 18, 2021 deadline.
- The proposed framework does not adequately address important issues such as risk information, toxicological testing, raw materials, trade secret protection, and supply chain changes.
- Medical device materials continue to be an area of interest for FDA, and one where we are likely to see additional regulatory scrutiny moving forward.
On May 20, 2021, FDA’s Center for Devices and Radiological Health published a discussion paper entitled “Conveying Materials Information about Medical Devices to Patients and Healthcare Providers: Considerations for a Framework,” which contemplates requiring medical device labeling to disclose certain materials used in the device.1 Although not a draft guidance, the paper presents a framework for consideration and comment by stakeholders. Comments are due by August 18, 2021. This alert discusses FDA’s proposal, how the proposal would change medical device labeling, the origins of the proposed new framework, and key considerations and implications for industry.
The framework laid out by FDA would make significant changes to current medical device labeling requirements.
FDA regulations have historically required medical device labeling to include the manufacturer name and place of business, intended use of the device, and adequate directions for use of the device.2 FDA has long advised manufacturers that device labeling must include sections regarding the device’s indications for use, contraindications, warnings, precautions, special patient populations, and adverse reactions.3 While FDA has advised that the “contraindications” section of the labeling should note if there is a known hypersensitivity to a material in the device, FDA has generally left it up to manufacturers to decide whether to list materials in the device on the labeling.4
FDA’s proposed new framework contemplates requiring the labeling of long-term medical devices—those intended to be in contact with the patient for 30 days or more—to identify all constituent materials that might reasonably be expected to come into contact with human tissue. These materials include, for example: metals, polymers, ceramics, naturally derived animal products, naturally derived non-animal products, composites, and manufacturing residuals. FDA proposes naming conventions that would include elemental or chemical names (rather than abbreviations), trade names, animal species and tissue type, plant or bacterial source and material type, and color additives according to the naming conventions used in food and cosmetic labeling. These conventions are intended to “promote transparency and reader comprehension.”5
Additionally, FDA proposes adding specific information about toxicological risks of component materials to medical device labeling.6 FDA describes “toxicological risks” as impurities or residuals that are either known or identified during non-clinical evaluation. In this respect, the discussion paper contemplates that such labeling would not only be beneficial for long-term medical devices, but could also be helpful for labeling of over-the-counter products and short-term devices where small materials changes could significantly impact safety and effectiveness.
Finally, FDA is considering requiring manufacturers to include patient labeling (i.e., labeling targeted to the patient or lay caregiver such as patient brochures or implant cards), which is not currently required for all long-term medical devices. Patient labeling would include a basic description of the device and a listing of patient-contacting materials.
According to FDA, the primary purpose of identifying component materials in medical device labeling would be “to improve informed decision-making through transparency about materials in such devices to which an individual may have had or could develop an immunological response resulting in adverse health consequences.”7 At the same time, FDA is striving to “balance mitigation of risks with least burdensome principles.”8
Prior Attempts to Include Materials in Device Labeling
The broad framework FDA has laid out would bring a dramatic change to the case-by-case approach FDA has traditionally taken.
Distinct from the approach FDA is now considering, FDA has previously advised manufacturers to list certain materials in the device on the labeling based on case-by-case public health needs. For example, in 2003 FDA developed a labeling regulation that requires disclosure on medical device labeling if the product contains natural rubber latex.9 This labeling regulation was a public health measure prompted by FDA’s learning of increased deaths associated with sensitivity to natural latex contained in medical devices.
More recently, FDA recommended including an allergen warning on nitinol-containing device labeling.10 Nitinol is an alloy of nickel and titanium that is extensively used in cardiovascular devices. This labeling recommendation was prompted by the industry’s increased use of nitinol in devices and by nitinol’s complex and unique properties distinct from conventional metals such as stainless steel and titanium.
FDA has also recommended including material lists on labeling for breast implants, including “chemicals that might be released from breast implants, and heavy metals present in breast implants” along with “context to the levels of risk/exposure of the chemicals and heavy metals listed.”11 This labeling recommendation was prompted by FDA’s learning of new information regarding risks of breast implants and by concerns that some patients were not receiving and/or understanding information regarding the benefits and risks of breast implants.
Outside of these circumscribed materials and devices, FDA has recommended that labeling intended for patients should “list materials in the device so patients with hypersensitivities can easily identify their risks.”12 Patient labeling, however, is not currently required by FDA for all medical devices, but rather is recommended only for a subset of devices such as those operated by patients and their caregivers.
Origins of FDA’s Discussion Paper
FDA’s discussion paper traces its origins back to several medical device mass torts of recent years, where it has been alleged that the materials used in the devices were related to reported adverse events. In response to these highly publicized claims, FDA held a public meeting of the Immunology Devices Panel in 2019 to discuss immunologic responses to metal-containing devices.
The public submitted 463 electronic comments to the open meeting, including some from the medical device industry and physician and dentist associations, and most from patients and patient advocacy groups.13 The American Academy of Dermatology Association and the American Contact Dermatitis Association, a group representing 13,800 dermatologists, submitted a letter advocating for more transparent labeling of metal and non-metal components in medical devices in such a way as to protect trade secrets and encourage innovation. Patient advocate organizations requested a slew of changes including, among other things, labeling of materials, disclosure of material safety data sheets of component materials, no trade secret protection for implantable devices, extensive FDA-funded biocompatibility testing, and a new, more stringent regulatory pathway for approval of changes in material sourcing. The panel members also supported adding a “list of elemental composition” to device labeling.14
Although the Immunology Devices Panel was focused on metal-containing devices, FDA believes that a broader approach to material safety evaluation is warranted to promote greater clarity, predictability, and consistency across device labeling.15 According to FDA, the addition of materials to device labeling could facilitate better informed decision-making by patients and healthcare providers as well as facilitate identification of whether an adverse event is caused by a hypersensitivity or immunologic response to a device material.
Considerations for Industry
The FDA’s framework raises more questions than it answers. Below are a few of the considerations the discussion paper does not address but will be important for industry.
First, although the FDA says that it seeks to improve informed consent by adding information regarding the potential risk of hypersensitivity or immunologic responses, simply listing constituent materials may not achieve that purpose. Either manufacturers would be responsible for adding that risk information, which could impose an undue burden, or patients and doctors would be responsible for finding that information from other sources, which are not guaranteed to be reliable.
Second, the discussion paper suggests that “toxicological risks” for constituent materials may need to be added to device labeling. But it does not specify how manufacturers should obtain that information, e.g., through their own testing already required by FDA regulations, through additional unspecified testing, from the manufacturers of constituent materials, or otherwise. Nor does it specify whether FDA will weigh in on whether a constituent material poses a toxicological risk, or whether or how manufacturers should distinguish between toxicological risks that may pose clinical risks versus those that have no or minimal clinical risk.
Third, the proposed requirement to include trade names for constituent materials in device labeling may pose a unique burden on manufacturers. Setting aside the business issues and possible unintended consequences that this proposal may occasion, such as disruptions to the supply chain, FDA’s framework is far from clear. For example, if a raw material supplier changes due to supply chain or other issues, must the device labeling change each time the brand of constituent material changes? Must that labeling change be paired with additional information such as a Dear Customer letter to call attention to the change? Each additional obligation increases the burden on the manufacturer and, ultimately, may inhibit the manufacturer’s ability to deliver medical devices to doctors and patients in need.
Fourth, the discussion paper leaves unstated whether the constituent materials list should identify the raw materials used to manufacture the device or the materials in the finished device. Because materials may change during the manufacturing process and because risk information may be different for raw materials versus materials that have gone through the manufacturing process, additional clarity on this point will be needed.
Fifth, the discussion paper does not explain how device-related trade secrets and other proprietary information about device materials will remain protected. By comparison, in the cosmetics context FDA requires products to have a list of all ingredients and rarely grants trade secret exemptions, but “fragrance and flavor ingredients do not need to be listed individually on cosmetic labels, because they are the ingredients most likely to be ‘trade secrets.’”16 The discussion paper does not propose any trade secret exemption for medical devices or otherwise address this issue.
The discussion paper signals that medical device materials continues to be an area of interest for FDA, and one where we are likely to see additional regulatory scrutiny moving forward. Stakeholders should consider submitting feedback before the August 18, 2021 deadline, and continue to monitor whether this proposal develops into a draft guidance or otherwise requires changes to their device labeling.
1) Conveying Materials Information about Medical Devices to Patients and Healthcare Providers: Considerations for a Framework, FDA Center for Devices and Radiological Health (May 20, 2021), https://www.fda.gov/media/148860/download (“FDA Discussion Paper”).
2) 21 CFR 801; FDA website on Device Labeling, https://www.fda.gov/medical-devices/overview-device-regulation/device-labeling; Labeling – Regulatory Requirements for Medical Devices, FDA 89-4203 (August 1989), https://www.fda.gov/media/74034/download.
3) Guidance on Device Labeling #G91-1, FDA Final Blue Book Memo (March 1991), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/device-labeling-guidance-g91-1-blue-book-memo.
4) See id.
5) FDA Discussion Paper at 7.
7) FDA Discussion Paper at 2.
8) FDA Discussion Paper at 5.
9) User Labeling for Devices that Contain Natural Rubber 921 CFR 801.437), Guidance for Industry (April 2003).
10) Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol, Guidance for Industry and FDA Staff, pages 15-16 (Oct. 2020), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-clinical-assessment-medical-devices-containing-nitinol.
11) Breast Implants - Certain Labeling Recommendations to Improve Patient Communication, Guidance for Industry and FDA Staff, page 10 (Sept. 2020). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breast-implants-certain-labeling-recommendations-improve-patient-communication.
12) Guidance on Medical Device Patient Labeling, Final Guidance for Industry and FDA Staff, page 12 (Apr. 2001), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-medical-device-patient-labeling.
13) See comments to Immunology Devices Panel of the Medical Devices Advisory Committee available at https://www.regulations.gov/document/FDA-2019-N-3767-0001/comment.
14) FDA Discussion Paper at 2-3.
15) FDA Discussion Paper at 3.
16) FDA, “Trade Secret” Ingredients, available at https://www.fda.gov/cosmetics/cosmetics-labeling/trade-secret-ingredients.