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U.S. Department of Health and Human Services

Medical Devices

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3. Biocompatibility

INTRODUCTION

SKIN IRRITATION AND DERMAL SENSITIZATION STUDIES

COLOR AND FLAVOR ADDITIVES

LAB DIRECTORY

INTRODUCTION

We recommend that you conduct biocompatibility testing as described in the guidance entitled, “ Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing,” on finished gloves. You should select biocompatibility tests appropriate for both surface and external communicating devices with limited duration (24 hours) of contact. Because medical gloves are in direct contact with skin, a primary skin irritation study and a dermal sensitization study are appropriate.

You should perform biocompatibility tests on finished gloves. The gloves used for biocompatibility studies should contain the same colorants, fragrances, flavors, powders, lubricants, and processing chemicals. You should test gloves that have been processed, packaged, and if appropriate, sterilized by the same methods as the gloves you will distribute. You should consider the need to repeat biocompatibility studies if you make subsequent changes in glove composition, manufacturing materials, or processing.

The 510(k) submission should include biocompatibility test results and other information and data described in this manual as an attached report for each major study or test program. You should identify all reports or attachments with the manufacturer’s name, number the pages, and list the reports or attachments in the table of contents. For sterile devices, test data should include the results of tests performed using the finished sterilized devices.

You and the contract laboratory, if used, should check the: 

  • logical presentation of the biocompatibility data,
  • scientific soundness of the test method and data analysis,
  • relevance of the test program to the device and the intended use, and
  • completeness of the summary report of the tests or studies.

We recommend that you present the summary of test results in a table formatin each report whenever possible. Each study or test attachment report should contain sufficient and well-organized information in reasonable detail so that the FDA reviewer can determine:

  • what exact material or device was tested,
  • what tests were performed,
  • how the tests were performed, and
  • what were the test results.

We recommend that you submit reasonable and sufficient details of all test procedures and results to FDA. For biocompatibility studies, you should use a standard scoring system for each test method, if a standard scoring system exists. We recommend each test report include the following: 

  • name and address of the manufacturer of the item tested,
  • name and technical description of the item tested,
  • name and address of the laboratory where the tests were conducted,
  • test methods, including the scoring method,
  • number of samples and replicates tested,
  • control data needed to establish the validity of the test,
  • date when the tests were conducted,
  • summary report(s) of results obtained, and
  • analysis, interpretation of results, and conclusions.

You should keep the original records of the study on file. For surgeon’s gloves, the records should be maintained as part of your design verification records in the design history file. You should also maintain the original records when a study, such as a biocompatibility study, is conducted by a contract laboratory to establish a device specification and/or to obtain data for a submission to FDA. The original document should include the name and address of the laboratory and device manufacturer, the device identity, and dates of testing. You should not submit the original records to FDA. During factory inspections, FDA investigators may ask to see these original records.

SKIN IRRITATION AND DERMAL SENSITIZATION STUDIES

The following is a general discussion of how to conduct the skin irritation and dermal sensitization studies. Because methods may vary from laboratory to laboratory, the test data you submit to FDA should contain a brief description of the test protocol, scoring criteria used, and the method used for rating skin responses.

Primary Skin Irritation Test (Animal Study)

Performing skin irritation testing demonstrates the irritation potential of the gloves, i.e., for initiating or aggravating damage through its contact with the skin. We recommend that you perform the primary skin irritation testing according to the regulations of the Consumer Product Safety Commission ( 16 CFR 1500.41). We recommend that you identify the inside and outside of the gloves so that both sides are tested, i.e., approximately half of the test articles expose opposite sides of the glove to the subject.

Dermal Sensitization Study (Animal Study)

The purpose of performing dermal sensitization is to demonstrate the potential of the device for eliciting a delayed hypersensitivity (Type IV) immunologic response through its contact with the skin. This reaction is due primarily to substances which could leach out of a material. Guinea pigs are used because they have been shown to be the best animal model for human allergic contact dermatitis. We recommend the method described in ASTM

standard F720-86, Standard Practice for Testing Guinea Pigs for Contact Allergens, Guinea Pig Maximization Test, for the study. Laboratories may also use the method of Buehler, as reported in Archives of Dermatology (1965). Dermal sensitization studies use two tests or phases: the induction phase and challenge phase. You should identify the inside and outside of the gloves so that both sides are tested, i.e., approximately half of the test articles expose opposite sides of the glove to the subject.

Testing for Skin Sensitization to Chemicals

Your labeling may include special claims regarding reduced potential chemical sensitization in a 510(k), such as:

  • reduced potential for sensitizing users to rubber chemical additives or,
  • reduced potential for causing reaction in individuals sensitized to rubber chemical additives.

You should support these claims by data from human testing. Additional guidance on testing for skin sensitization to chemicals in latex products is available in the following guidance document:

Premarket Notification [510(k)] Submissions for Testing for Skin Sensitization to Chemicals in Natural Rubber Products

If you have already conducted a Modified Draize Test (MDT) on a minimum of 200 human subjects to support a reduced sensitization claim, you may use the MDT data instead of the primary skin irritation test (animal) and dermal sensitization study (animal) typically used to support the general biocompatibility of medical gloves.

 

COLOR AND FLAVOR ADDITIVES

You should show that any substance added to the gloves, including color, flavor, and/or scent additives, does not adversely affect the safety or effectiveness of the gloves. Therefore, if a device contains a color or other chemical additive and the device is intended to be in contact with the skin or other parts of the body, you should submit biocompatibility data to demonstrate the safety of the additives, unless you can establish that the additives would not leach and contact the body.

FDA considers the addition of color, flavor, or any chemical to a medical glove to be a significant change that should have a new 510(k) submission (21 CFR 807.81(a)(3)).You should provide full characterization and chemical identity of the color, flavor, or scent additives. You may submit a 510(k) submission for a modification to an existing glove as a “Special 510(k).” 

 

You can find color additive and flavor additive regulations in 21 CFR parts 70 to 82 and 21 CFR part 172, Subpart F, respectively. Note that color and flavor additives contained in these regulations are specific to foods, drugs, and cosmetics. The color additive regulations should not be confused with the general 510(k) requirements, which are independent of the color additive listing and certification mentioned above. You should show that any color or flavor substance added to a device does not adversely affect the safety or effectiveness of the device. Gloves that contain FDA-approved color or flavor additives for foods, drugs, or cosmetics should undergo biocompatibility testing to demonstrate the safety of the additives in the device. We may accept other color or flavor additives not contained in these regulations with appropriate biocompatibility testing.

Medical device labeling requirements do not require the glove box or carton to have an "ingredient statement" listing the flavor agent, colorant, or other additives used in the manufacture of the glove. However, manufacturers may do so voluntarily.

See Chapter 4 for labeling considerations for medical gloves with color and flavor additives.

LAB DIRECTORY

The websites below may be helpful in finding a testing laboratory. FDA does not certify testing laboratories. As with any supplier of services, you should verify the adequacy of the services offered (21 CFR 820.50(a)).

The American Association for Laboratory Accreditation

American Council for Independent Laboratories

ASTM International Directory of Testing Laboratories

Canon Communications

Consultants Directory on Medical Device Link: Biocompatibility/Toxicology
North American Suppliers Directory: Testing Equipment and Services

Thomas Register

Search categories include:

Testing Services: Safety
Testing Services: Latex
Testing Services: Medical Equipment
Testing Services: Medical Device
International Testing & Compliance Services
Product Safety Testing Services