Labeling Claims for Natural Rubber Medical Devices with Reduced Potential for Chemical Sensitization
This guidance provides recommendations for manufacturers and FDA personnel regarding 510(k) submissions for natural rubber (NR) medical devices with labeling claims related to: - Reduced potential for sensitizing users to rubber chemical additives - Reduced potential for causing reaction in individuals sensitized to rubber chemical additives
What You Need to Know? 👇
What are the specific labeling claims allowed for natural rubber medical devices regarding chemical sensitization?
Two claims are permitted: “Low Dermatitis Potential” for products with reduced sensitization potential to chemical additives, and “Low Thiuram/Carbamate/Thiazole” for products with reduced reaction potential in sensitized individuals. Both require specific testing and warning labels.
How many subjects are required for the Modified Draize-95 test to support sensitization claims?
A minimum of 200 nonsensitized adult human subjects must complete the Modified Draize-95 test. This sample size provides 95% confidence that chemical sensitization potential is less than 1.5% in the user population.
What is the difference between Type I and Type IV allergic reactions to natural rubber products?
Type I allergy is an immediate antibody-mediated reaction to natural rubber proteins, potentially life-threatening. Type IV allergy is a delayed cell-mediated reaction to chemical additives (thiazoles, thiurams, carbamates), causing contact dermatitis 1-4 days after exposure.
When is a new 510(k) submission required for natural rubber devices with reduced sensitization claims?
A new 510(k) is required for new devices with these claims, or existing “hypoallergenic” devices switching to Claim 2. Devices switching from “hypoallergenic” to Claim 1 don’t need new 510(k) if supporting data exists.
What scoring criteria determine a negative result in sensitization testing?
For the Modified Draize-95 test, all 200 subjects must score ≤1.5. For sensitized individual testing, all 25 subjects must score <1.0. Scoring ranges from 0 (no reaction) to 3.0+ (strong erythema with possible supplemental symptoms).
Are these human sensitization studies considered significant risk under IDE regulations?
No, these are considered nonsignificant risk studies because devices must first pass animal irritation/sensitization tests and undergo manufacturing processes to reduce chemical additives. They require IRB approval and informed consent but not full IDE submission.
What You Need to Do 👇
Recommended Actions
- Determine which claim is desired (Claim 1 or 2)
- Conduct required biocompatibility testing
- Perform Modified Draize-95 Test on 200 non-sensitized subjects
- For Claim 2, conduct additional patch testing on 25 sensitized individuals
- Prepare detailed documentation of test results
- Remove any “hypoallergenic” claims from existing products
- Submit new 510(k) if required based on claim type
- Ensure proper IRB approval and informed consent procedures
- Implement required warning statements in labeling
- Maintain complete test documentation on file
Key Considerations
Clinical testing
- Modified Draize-95 Test required on minimum 200 non-sensitized human subjects
- Patch test required on minimum 25 individuals allergic to specific chemical sensitizers for Claim 2
- Specific inclusion/exclusion criteria for test subjects provided
- Detailed scoring criteria and evaluation procedures defined
Non-clinical testing
- Basic biocompatibility tests including skin irritation and dermal sensitization studies in animals required
Labelling
- Term “hypoallergenic” prohibited on NR containing medical devices
- Two specific claims allowed with precise wording:
- “Low Dermatitis Potential” claim
- “Low Thiuram/Carbamate/Thiazole” claim
- Warning statements required for both claims
Biocompatibility
- Basic biocompatibility testing required as per FDA manual “Guidance for Medical Gloves: A Workshop Manual”
Safety
- Studies considered “nonsignificant risk” under IDE regulations
- IRB approval and informed consent required
- Compliance with Helsinki Declaration for foreign studies
Other considerations
- Detailed documentation of test results required
- Statistical requirements specified for test results interpretation
- Specific requirements for handling pre-sensitized individuals during testing
Relevant Guidances đź”—
- Medical Gloves - Premarket Notification, Quality System, Labeling and Compliance Requirements
- Device Labeling Requirements and Content for Premarket Approval Applications
- Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures
- Biological Evaluation of Medical Devices Standards in the Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program