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Today’s Topic: 

Biocompatibility Guidance Update: Certain Devices in 

Contact with Intact Skin 

October 12, 2023
Biocompatibility Guidance Update: Certain 

Devices in Contact with Intact Skin

Center for Devices and Radiological Health 

U.S. Food and Drug Administration

Jennifer Goode 

Biocompatibility Program Advisor 

Clinical and Scientific Policy Staff 

Immediate Office 

Office of Product Evaluation and Quality
Final Guidance

• Attachment G: Biocompatibility of Certain Devices in Contact 

with Intact Skin in the Use of International Standard ISO 

10993 - 1, "Biological evaluation of medical devices - Part 1: 

Evaluation and testing within a risk management process“, 

issued on September 8, 2023 

– www.fda.gov/regulatory-information/search-fda-guidance-documents/useinternational-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-

evaluation-and

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Learning Objectives

• Describe purpose of this FDA Biocompatibility Guidance update 

• Identify devices, components and materials included in and excluded 

from this update 

• Describe information and labeling needed for a premarket submission 

• Describe changes made to electronic Submission Template and 

Resource (eSTAR) form 

• Describe additional minor revisions to guidance to match the current 

recognized versions of relevant consensus standards 

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Purpose of Guidance Update

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Background

• Many devices have intact skin contacting materials made from synthetic 

polymers and natural fabrics 

• These materials pose a very low biocompatibility risk because they have a 

long history of safe use in legally marketed medical devices that contact 

intact skin 

• Attachment G describes a least burdensome approach for these devices that 

recommends specific material information to be included in a premarket 

submission in lieu of biocompatibility testing 

• This approach supports the principles of the “3Rs,” to replace, reduce, 

and/or refine animal use in testing when feasible

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Included Devices, Components, 

and Materials

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Which Types of Devices Are Included? 

(Section A)

Devices that meet all of the following characteristics: 

• Medical devices or components that contact intact skin surfaces only, as 

described in section 5.2.2 (a) of International Standards Organization (ISO) 

10993 - 1:2018: Biological evaluation of medical devices – Part 1: Evaluation 

and testing within a risk management process 

– EXAMPLE: Does NOT include mucous membranes or open or healing wounds 

• Limited (≤24 hour), prolonged (>24 hours to 30 days), and long term (>30 

days) durations of contact, including repeat use devices, AND 

• Composed of a single material or multiple materials outlined in Section B of 

Attachment G

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What Materials Are Included?

(Section B)

Synthetic Polymers

Acrylonitrile-butadiene-styrene plastic (ABS) Polychloroprene, such as neoprene

Cellulose Acetate Polyetheretherketone (PEEK)

Cured epoxy adhesives Polyetherketoneketone (PEKK)

Fluoropolymers, including PTFE, ePTFE, PVDF, FEP Polyether block amide (PEBA), such as PEBAX®

Nitrile Butadiene Rubber (NBR) Polyether imide (PEI)

Parylene Polyethylenes, including LDPE and HDPE

Polyamides (PA), such as nylon and Velcro® Poly(ethylene terephthalate) (PET), such as Velcro®

Poly(butylene terephthalate) (PBT) Poly(methyl methacrylate) (PMMA)

Polycarbonate (PC) Polyoxymethylene (POM)

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What Materials Are Included? 

(Section B)

Synthetic Polymers (Cont.)

Poly(phenylene sulfone) (PPSU) Polyurethanes (PUR), such as Lycra®

Polypropylene (PP) Polyvinyl alcohol (PVA)

Polystyrene (PS), including HIPS Silicone

Natural Fabrics

Cotton fabrics Silk fabrics

Rayon fabrics

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Examples: Devices and Components

Example 1 

• Device Type: Biomicroscope 

• Regulation: 21 CFR 886.1850 

• Product Code: HJO 

• Description: Device used in the ophthalmologist office for 

microscopic assessments of your eye 

• Intact Skin Contacting Components: Head rest, chin rest

CFR = Code of Federal Regulations 11
Examples: Devices and Components

Example 2 

• Device Type: Oximeter 

• Regulation: 21 CFR 870.2700 

• Product Code: DQA 

• Description: Small device that slides over your fingertip to 

measure your blood oxygen levels 

• Intact Skin Contacting Components: Finger cushion, external 

case and interactive components 

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Examples: Devices and Components

Example 3 

• Device Type: Blood Pressure Cuff 

• Regulation: 21 CFR 870.1120 

• Product Code: DXQ 

• Description: Inflatable sleeve wrapped around your arm for 

measuring your blood pressure by another device 

• Intact Skin Contacting Component: Entire device 

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Examples: Devices and Components

Example 4 

• Device Type: Powered Inflatable Tube Massager 

• Regulation: 21 CFR 890.5650 

• Product Code: IRP 

• Description: Device that uses air compression to help relieve 

minor muscle aches and pains and to increase circulation of 

your legs 

• Intact Skin Contacting Components: Leg wraps 

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Situations to Discuss in a Q-Submission

• If legally marketed device* made from same material: 

‒ Was found to be toxic in previous testing, OR 

‒ Resulted in adverse clinical findings after marketing that may 

be related to cytotoxicity, irritation, or sensitization, such as: 

• Redness (erythema), swelling (edema), allergy, and immune response 

or other reactions on the skin where the device has contact 

*For the purposes of this guidance, “legally marketed devices” are limited to devices marketed in the U.S.

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Situations to Discuss in a Q-Submission

• If proposed device is: 

‒ Indicated for use with neonates, 

‒ Indicated for use in pregnant women, OR 

‒ A device - led combination product, or a device comprised of 

biologically - derived material, such as tissues derived from 

animal or plant material 

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Excluded Devices, Components, 

and Materials

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Which Types of Devices Are Excluded? 

(Section C)

Medical Device Characteristic Reason for exclusion

Intact skin contacting components fabricated from 

materials that are not explicitly included in the above 

list, including novel materials and bulk metals, such 

as titanium, stainless steel, nickel, nitinol, gold, 

cobalt, chrome

• These materials may introduce toxicity risks

Stored in or containing fluids or creams • Increased risk that leachables can be transferred 

into the fluid or cream and then absorbed 

through the skin

Fabricated from in - situ polymerizing materials, 

absorbable materials, or hydrogels

• Increased risk that polymerization or 

degradation products can change over time. 

• Manufacturing process can impact the type and 

quantity of intermediate and final chemicals, 

which could introduce a toxicity risk

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Which Types of Devices Are Excluded? 

(Section C)

Medical Device Characteristic Reason for exclusion

Contacts breached or compromised surfaces, such as 

open or healing wounds

• Increased risk that leachables can be transferred 

through breached or compromised skin

Reprocessed single-use devices • Reprocessing can cause adverse biological 

responses, such as irritation

Adhesives used to attach a device directly to the skin, 

such as electrode pads, on - body pump attachment 

systems

• Can cause adverse biological responses, such as 

irritation

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Information and Labeling 

for a Premarket Submission

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Biocompatibility Information Needed

(Section D)

1. For all premarket submissions (PMA, HDE, IDE, 510(k), De Novo): 

• List all materials (including color additives) used to fabricate device or 

component with only direct or indirect skin contact; 

• Provide statement confirming that device materials are listed in Section B, and 

have a documented history of safe use in legally marketed medical devices in 

contact with intact skin, such as through Medical Device Reporting (MDR) 

analysis, literature search; and 

• Provide statement confirming that none of exclusions listed in Section C apply.

PMA = Premarket Approval Application 

HDE = Humanitarian Device Exemption 

IDE = Investigational Device Exemption

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Biocompatibility Information Needed

(Section D)

2. Additional recommendations for IDE applications: 

• Discuss any adverse biological responses from devices within this intact skin 

policy in IDE progress reports submitted pursuant to 21 CFR 812.150(b)(5). 

• Specifically describe any redness (erythema), swelling (edema), irritation, 

sensitization (delayed Type IV hypersensitivity), allergy, immune response, or 

other reactions observed by investigators during course of a clinical study with 

observations attributed to a specific device, if relevant.

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Biocompatibility Information Needed

(Section D)

3. Additional recommendations for marketing submissions (PMA, HDE, 

510(k), De Novo): 

• Include a statement that the manufacturer has documented in their Device 

Master Record (DMR) how they have determined that biocompatibility risks for 

their device are addressed such that biocompatibility testing, and a detailed 

rationale regarding manufacturing, is not necessary to include in a premarket 

submission.

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Biocompatibility Information Needed

(Section D)

Example Statement:

“We have documented in the Device Master Record (DMR) that we have addressed any 

concerns that have been identified through biocompatibility testing (i.e., cytotoxicity, 

irritation, and sensitization), manufacturing information (based on the type of materials, 

formulation (if available) and nature of contact) and/or relevant quality system 

requirements and postmarket controls related to: 

• Purchasing controls (21 CFR 820.50) of device materials, 

• Production and process controls (21 CFR 820.70) for manufacturing materials, 

• Acceptance activities (21 CFR 820.80) for component and manufacturing materials, 

• Corrective and preventative action (21 CFR 820.100), 

• Complaint files (21 CFR 820.198), and 

• Medical device reporting (MDR) (21 CFR 803).”

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Certain Labeling Information

(Section E)

• When 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, such as patients with epilepsy or dementia, or the vision impaired 

• FDA recommends that manufacturers inform caretakers in labeling by including a 

precaution discussing common adverse skin reactions 

Example Statement: 

“Caretakers should assess patients for adverse reactions on the skin where the device has 

contact, such as redness (erythema), swelling (edema), irritation, sensitization (delayed 

Type IV hypersensitivity), allergy, immune response, or other reactions.” 

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Revisions in eSTAR Form

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eSTAR Changes

Newly Added

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eSTAR Changes (cont.)

Click to open

Intact skin specific 

instructions

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eSTAR Changes (cont.)

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Some Additional Revisions

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Some Additional Revisions

• Minor revisions for clarity and consistency within guidance and 

with currently recognized versions of consensus standards 

• Update of links in footnotes, including currently recognized 

consensus standards and FDA guidances 

• Inclusion of language about Accreditation Scheme for 

Conformity Assessment (ASCA) Program 

• Update on recommendations about studies not in compliance 

with the FDA Good Laboratory Practice Regulations 

• Attachment A: Updated to be consistent with recommendations 

in ISO 10993 - 1:2018 

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Additional Resource

• Biocompatibility Assessment Resource Center 

‒

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www.fda.gov/medical-devices/premarket-submissionsselecting-and-preparing-correct-submission/biocompatibilityassessment-resource-center
Summary

• Some synthetic polymers and natural fabrics pose a very low 

biocompatibility risk 

– because they have a long history of safe use in legally marketed medical devices that 

contact intact skin 

• Attachment G of updated guidance includes a least burdensome approach 

for certain devices or components in contact with intact skin 

– that allows sponsors to include specific material information and certain labeling 

information in a premarket submission in lieu of biocompatibility testing or rationales 

• eSTAR form has been updated to include this policy 

• Minor revisions have been made to the main Biocompatibility Guidance

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Additional Panelists

Simona Bancos, Ph.D. 

Biologist 

Division of Health Technology 1A 

(Ophthalmic Devices) 

Office of Health Technology 1 

(Ophthalmic, Anesthesia, Respiratory, ENT 

and Dental Devices)

Molly Ghosh, Ph.D., DABT 

Pharmacologist 

Division of Health Technology 5B 

(Neuromodulation & Rehabilitation Devices) 

Office of Health Technology 5 

(Neurological and Physical Medicine Devices)

Jinny (Jinrong) Liu, Ph.D. 

Lead Chemist 

Division of Health Technology 1A 

(Ophthalmic Devices) 

Office of Health Technology 1 

(Ophthalmic, Anesthesia, Respiratory, ENT 

and Dental Devices)

Office of Product Evaluation and Quality 

Center for Devices and Radiological Health 

U.S. Food and Drug Administration
Let’s Take Your Questions

• To Ask a Question: 

1. Raise your hand in Zoom 

2. Moderator will announce your name and invite you to ask your question 

3. Unmute yourself when prompted in Zoom to ask your question 

• When Asking a Question: 

• Ask one question only 

• Keep question short 

• No questions about specific submissions 

• After Question is Answered: 

• Mute yourself and lower your hand 

• If you have more questions - raise your hand again
Thanks for Joining Today!

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• www.fda.gov/Training/CDRHLearn

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