Contains Nonbinding Recommendations 
 
Guidance for Industry 
 
User Labeling for Devices that 
Contain Natural Rubber (21 CFR 
801.437); Small Entity Compliance 
Guide; Guidance for Industry  
 
 
 
 
 
Document issued on:  April 1, 2003 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Office of Compliance  Contains Nonbinding Recommendations 
 
Preface 
 
 
Public Comment 
 
Comments and suggestions may be submitted at any time for Agency consideration to Dockets 
Management Branch, Division of Management Systems and Policy, Office of Human Resources 
and Management Services, Food and Drug Administration, 5630 Fishers Lane, Room 1061, 
(HFA-305), Rockville, MD, 20852.  When submitting comments, please refer to the exact title of 
this guidance document.  Comments may not be acted upon by the Agency until the document is 
next revised or updated.   
 
For questions regarding the use or interpretation of this guidance contact John J. Farnham,  Office 
of Compliance, Center for Devices and Radiological Health (HFZ-332), Food and Drug 
Administration, 2098 Gaither Rd., Rockville, MD 20850, 301-594-4616. 
 
 
Additional Copies 
 
Additional copies are available from the Internet at:  
http://www.fda.gov/cdrh/comp/guidance/1212.pdf, or    
To receive this document via your fax machine, call the CDRH Facts-On-Demand system 
at 800-899-0381 or 301-827-0111 from a touch-tone telephone.  Press 1 to enter the 
system.  At the second voice prompt, press 1 to order a document.  Enter the document 
number 1212 followed by the pound sign (#).  Follow the remaining voice prompts to 
complete your request.   
 
  2  Contains Nonbinding Recommendations 
 
User Labeling for Devices that Contain 
Natural Rubber (21 CFR 801.437); Small 
Entity Compliance Guide; Guidance for 
Industry   
 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking 
on this topic.  It does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public.  You can use an alternative approach if the approach 
satisfies the requirements of the applicable statutes and regulations. If you want to discuss 
an alternative approach, contact the FDA staff responsible for implementing this 
guidance.  If you cannot identify the appropriate FDA staff, call the appropriate number 
listed on the title page of this guidance.  
 
 
 
Introduction 
This guidance is intended to help manufacturers of medical products that contain natural rubber 
latex, the majority of whom are small businesses.  This guidance addresses specific federal 
regulations for labeling medical products that contain natural rubber latex.  This guidance does not 
apply to products made from synthetic latex or synthetic rubber that do not include natural rubber in 
their formulations. 
 
FDA has noted an increase in the number of deaths reported to the agency that are associated with 
an apparent sensitivity to natural latex proteins contained in medical devices. FDAs initial focus 
involved deaths following barium enema procedures that were associated with anaphylactic 
reactions to the natural rubber latex cuff used on the tip of barium enema catheters. Scientific studies 
and case reports have documented sensitivity to natural latex proteins found in a wide range of 
medical devices. In order to protect the public health and minimize the risks associated with the use 
of natural latex protein sensitivity, FDA has developed a labeling regulation that provides important 
information to individuals who are sensitive to natural latex proteins. This rule was published in the 
Federal Register of September 30, 1997 (62 FR 51029). This rule was codified in Title 21 of the 
Code of Federal Regulations (21 CFR 801.437) and became effective on September 30, 1998. 
 
  Contains Nonbinding Recommendations 
 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  
The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required. 
 
 
The Least Burdensome Approach 
 
The issues identified in this guidance document represent those that we believe need to be addressed 
before your device can be marketed.  In developing the guidance, we carefully considered the 
relevant statutory criteria for Agency decision-making.  We also considered the burden that may be 
incurred in your attempt to comply with the guidance and address the issues we have identified.  We 
believe that we have considered the least burdensome approach to resolving the issues presented in 
the guidance document.  If, however, you believe that there is a less burdensome way to address the 
issues, you should follow the procedures outlined in the A Suggested Approach to Resolving Least 
Burdensome Issues document.  It is available on our Center web page at:   
http://www.fda.gov/cdrh/modact/leastburdensome.html 
 
 
Summary of the Regulation
 
 
The final rule identifies specific labeling statements for use on medical devices and device packaging 
when they contain natural rubber that contacts humans. The kind of latex and use of the latex, either 
for a device or for packaging, is associated with specific labeling information, as follows:   
 
  labeling of medical devices containing natural rubber latex that contacts humans should state: 
Caution: This Product Contains Natural Rubber Latex Which May Cause Allergic 
Reactions.; 
   labeling of medical devices containing dry natural rubber that contacts humans should state: 
This Product Contains Dry Natural Rubber.;  
  labeling of medical devices containing natural rubber latex in their packaging that contacts 
humans should state: Caution: The Packaging of This Product Contains Natural Rubber 
Latex Which May Cause Allergic Reactions.;  
  labeling of medical devices containing dry natural rubber in their packaging that contacts 
humans should state: The Packaging of This Product Contains Dry Natural Rubber.;  
  and the claim of hypoallergenicity should be removed from the labeling of medical devices 
that contain natural rubber.  
 
 
 
  2  Contains Nonbinding Recommendations 
 
 
Questions and Answers on the Rule 
 
1.  To which devices does this rule apply? 
 
The rule applies to all medical devices composed of or containing, or having packaging or 
components that are composed of, or contain, natural rubber that contacts humans. The term 
natural rubber includes natural rubber latex, dry natural rubber, and synthetic latex or synthetic 
rubber that contains natural rubber in its formulation. 
 
2.  What is natural latex? 
 
Natural latex, for the purposes of this rule, is defined as a milky fluid that consists of extremely 
small particles of rubber obtained from plants, principally from the H. brasiliensis (rubber) tree, 
dispersed in an aqueous medium. It contains a variety of  
naturally occurring substances, including cis-1,4-polyisoprene in a colloidal suspension  and 
plant proteins, which are believed to be the primary allergen. 
 
 
3.  What is natural rubber? 
 
Natural rubber, for the purposes of this rule, includes all materials made from or containing 
natural latex. Products that contain natural rubber are made using two commonly employed 
manufacturing processes, the natural rubber latex (NRL) process, and the dry natural rubber 
(DNR) process. 
 
 
4.  What is the NRL manufacturing process? 
 
The NRL manufacturing process involves the use of natural latex in a concentrated colloidal 
suspension. Products are formed from natural rubber latex by dipping, extruding, or coating, and 
are typically referred to as containing or made of natural rubber latex. Examples of products 
that may contain natural rubber latex include medical gloves, catheters, tracheostomy tubes, and 
condoms. 
 
 
5.  What is the DNR manufacturing process? 
 
The DNR manufacturing process involves the use of coagulated natural latex in the form of dried 
or milled sheets. Products are formed from dry natural rubber by compression molding, 
extrusion, or by converting the sheets into a solution for dipping. These products are typically 
referred to as containing or made of dry natural rubber or ``crepe'' rubber.  Examples of 
  3  Contains Nonbinding Recommendations 
 
products that may contain dry natural rubber include syringe plungers, vial stoppers, and injection 
ports on intravascular tubing. 
 
 
6.  What does the phrase contains natural rubber mean in this rule? 
 
A device contains natural rubber, for the purposes of this rule, when the device is composed of 
natural rubber or the device contains components formulate from natural rubber.  The phrase, 
contains natural rubber, as used herein, also includes products described as made of  synthetic 
latex or synthetic rubber that include natural rubber in their formulations. Synthetic latex or 
synthetic rubber that does not include natural rubber in its formulation is not subject to this rule. 
 
7. What does the phrase contacts humans mean for the purpose of this rule? 
 
Contacts humans, for the purposes of this rule, means that the natural rubber contained in a 
medical device is intended to contact or is likely to contact the user or patient.  This includes 
contact when the natural rubber containing device is connected to the patient by a liquid path or 
an enclosed gas path; or the natural rubber containing device is powdered, and the powder may 
carry natural latex proteins that may contaminate the environment of the user or patient. 
 
     
8.  What labeling statements does the rule specify? 
 
The device may bear one or more of four labeling statements depending on the type of natural 
rubber in the device and depending on whether the natural rubber is in the device itself or in its 
packaging.  
 
 
 
(a) Medical devices containing rubber produced by the NRL process that  
contacts humans should bear labeling with the following statement in bold print:  
 
Caution: This Product Contains Natural Rubber Latex Which May Cause 
Allergic Reactions. 
 
Representative examples of devices that contain NRL include: Cuffed enema/enterolysis 
catheters, latex condoms (with or without spermicidal lubricant), wound drains, cuffed airways, 
latex surgical gloves, and latex examination gloves. 
 
 
  
(b)Medical devices containing rubber produced by the DNR process that contacts 
humans should include the following statement in bold print in their labeling:  
 
This Product Contains Dry Natural Rubber. 
  4  Contains Nonbinding Recommendations 
 
 
Representative examples of devices that contain DNR include: Anesthesia masks, electrode 
pads, contraceptive diaphragms, crutch pads and tips, wheelchair tires, elastic components of 
bandages, face masks, syringe plungers, parenteral drug vial stoppers, and intravenous injection 
ports. 
 
     
(c)Medical devices having packaging that contains natural rubber that contacts humans 
should bear labeling with one of the following statements as appropriate in bold print:  
 
Caution: The Packaging of This Product Contains Natural Rubber Latex Which 
May Cause Allergic Reactions. 
 
OR 
 
The Packaging of This Product Contains Dry Natural Rubber. 
 
The purpose of such statements is to inform individuals who are sensitive to natural rubber about 
the presence of natural rubber in the packaging of devices that may be, by themselves, natural 
rubber-free. 
 
 
 
(d)  Medical devices containing natural rubber latex should be labeled with the following 
statement in bold print:  
 
 
Caution: This Product Contains Natural Rubber Latex Which May Cause Allergic 
Reactions. 
 
This statement is also identified for use if a device contains both natural rubber latex and dry 
natural rubber that may contact humans. In this instance, the single statement will serve to advise 
a person who may not be aware that natural rubber may cause reactions and provide notice to a 
person who is aware of his or her sensitivity to natural rubber contained in the product. 
 
 
9.  Is there a labeling statement that may not be acceptable under this rule? 
 
Devices containing natural rubber that contact humans should not contain the term 
hypoallergenic' on their labeling.  FDA has determined that the term hypoallergenic on 
products containing natural rubber would likely mislead consumers to conclude erroneously that 
the product may not cause latex protein allergic reactions. 
 
 
  5  Contains Nonbinding Recommendations 
 
10.  How should this information be displayed in the labeling? 
 
Because of the importance of the labeling information for those individuals sensitive to natural 
latex proteins, the inclusion of the latex labeling information on each level of labeling increases the 
likelihood that consumers will be aware of the risks posed by the natural rubber in the product.  
This means that the latex labeling information should be prominently and legibly displayed on all 
device labeling; the principal display panel of the device packaging; the outside package; the 
container or wrapper; the immediate device package; the container or wrapper; and the device 
label.   
 
For example, the labeling statement for adhesive bandages that are individually wrapped and sold 
in a box would appear on each individually wrapped bandage, on the box, and on any individual 
pieces of labeling, such as an instructions for use sheet included in the box. Devices packaged 
and sold in bulk dispensing containers would display the appropriate statement on the dispensing 
container, as it is the immediate device container or package. 
 
 
11.  May I request an exemption or variance from this rule? 
 
Any affected person may request an exemption or variance from the requirements of this section 
by submitting a citizen petition in accordance with federal regulations that explain the citizen 
petition procedures in Title 21 CFR Sec. 10.30 of this chapter. 
 
 
12.  Who may I contact for further information on this rule? 
 
You may contact John J. Farnham, Center for Devices and Radiological Health (HFZ-332), 
Food and Drug Administration, 2098 Gaither Rd., Rockville, MD 20850, 301-594-4616. 
 
 
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