November 3, 2020
U.S Federal Drug Administration (FDA) recently issued draft guidance for specific devices made from polymers and fabrics regarding the type of biocompatibility information provided in a premarket submission.
The agency indicated that polymers and fabrics pose a very low biocompatibility risk because they have a long history of safe use in medical devices that contact intact skin. For such devices, the agency suggests justifying the omission of biocompatibility testing for frequently used intact skin-contacting medical devices with enough rationale. This approach also supports the principles of the “3Rs” to reduce, refine and replace animal testing when feasible.
This approach relies on certain parts of the Quality System Regulation (QS Regulation, 21 CFR 820). The agency expects to maintain the Device Master Record by the manufacturer includes purchasing controls (21 CFR 820.50); production and process controls for manufacturing (21 CFR 820.70); receiving, in-process, and finished device acceptance (21 CFR 820.80); analysis of quality data (21 CFR 820.100(a)(1)) and complaints (21 CFR 820.198).
The agency recommends that manufacturers uniformly look for process complaints and timely issues related to cytotoxicity, irritation or sensitization. Those are indications of redness (erythema), swelling (edema), irritation, sensitization (delayed Type IV hypersensitivity),
allergy, and immune response or other reactions on the skin where the device has contact.
The draft guideline applicable to medical devices that contact intact skin surfaces only; have limited (≤24 hours), prolonged (>24 hours to 30 days) and long-term (>30 days) durations of contact, including repeat use devices.
The FDA has identified specific device materials mentioned below in this policy when they are in contact with only intact skin surfaces. The agency intends to periodically reassess the list of device materials and exclusion characteristics mentioned below.
|Acrylonitrile butadiene styrene (ABS)||
Polyethylenes, including low-density polyethylene (LDPE) and high-density polyethylene (HDPE)
|Fluoropolymers including polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), polyvinylidene fluoride (PVDF), and fluorinated ethylene propylene (FEP)||Polyethylene terephthalate (PET)|
|High impact polystyrene (HIPS)||Polymethylmethacrylate (PMMA)|
|Polyamides, including nylon;||
|Polybutylene terephthalate (PBT)||Polyphenolsulfone (PPSU);|
|Polycarbonate (PC)||Polypropylene (PP);|
|Polyetheretherketone (PEEK)||Polyurethane (PU);|
|Polyether imide (PEI)||Silicone|
|Polyurethane fabrics, including Lycra|
|Polyamide fabrics, including nylon;|
The FDA also provided the exclusions to this policy, such as the devices that have components in contact with intact skin that were fabricated from materials that are not stated in the above list including novel materials and bulk metals such as titanium, stainless steel, nitinol and gold. The agency excluded these because there are known risks, or there is no adequate experience with these materials that may introduce toxicity risks. Biocompatibility testing or detailed rationales for the omission of this testing could address these concerns.
Similarly, the devices stored in or containing fluids or creams were excluded due to an increased risk that leachables can be transferred into the fluid or cream. There is an increased risk that polymerization or degradation products can change over time. Hence, products fabricated from in-situ polymerizing materials, absorbable materials, or hydrogels are also excluded.
There is an exclusion for breached or compromised surface due to the increased risk that leachables can be transferred through breached or compromised skin. Also, the exclusion list includes reprocessed single-use devices and adhesives to attach a device directly to the skin, e.g., electrode pads, on-body pump attachment systems.
The agency recommended the list of all materials used to fabricate the device with direct or indirect skin contact, a statement confirming that the listed materials have a documented history of safe use in legally U.S.-marketed medical devices in contact with intact skin, e.g.,
Medical Device Regulation (MDR) analysis, literature search; and a statement confirming that none of the above-listed exclusions apply information to be included in the premarket submission for device types within the scope of the policy outlined in this guidance.
The draft guidance recommends certain labeling information when the device is intended for use in a patient population that may not have the ability to identify adverse biological reactions related to cytotoxicity, irritation or sensitization, e.g., patients with epilepsy or dementia; and also recommends that manufacturers using this policy inform caretakers in the labeling by including a precaution discussing common adverse skin reactions.
The FDA intends to redesign Attachment G in the 2016 Biocompatibility Guidance to Attachment H to accommodate the new Attachment proposed in this guidance.
This approach will be helpful to the manufacturer in terms of time as well as resources. Furthermore, this guidance is excellent for reducing animal usage in skin contact medical devices biocompatibility evaluation.
Dr. Sairam Kishore Arava, Toxicology subject matter expert, UL India.
Draft Guidance for Industry and Food and Drug Administration Staff; Select Updates for
Biocompatibility of Certain Devices in Contact with Intact Skin Document. Issued on October 15, 2020. https://www.fda.gov/media/142959/download