May 1, 1991


The Food and Drug Administration (FDA) has become aware of an increase in the number of reported adverse reactions and deaths associated with the use of one brand of enema devices with cuffs made of latex. During its investigation of enema devices, the FDA also reviewed the medical literature, data in FDA files, and other sources. Information about reactions to latex devices were found in these various sources. As a result of this review, the FDA is concerned that deficiencies in the manufacturing process for latex devices could be a contributing factor for some of these adverse events. That is, insufficient leaching or insufficient surface treatment by some manufacturers will not remove leachable proteins that are associated with these reactions.

The concern by the FDA is not meant to be an implication of the latex device industry. The FDA is, however, aware that the latex industry is always interested in meeting emerging health care needs. Consequently, the following advice has been developed by FDA in an effort to minimize the possibility that latex contaminants are either a source or a contributing factor in the adverse reactions attributed to various type of latex devices.

FDA's advice is as follows:


Current investigations and conventional manufacturing techniques indicate that one way of minimizing reactions is to remove as much of the water soluble proteins as possible from the latex devices. This removal is primarily done by: controlling the leaching process; assuring that the leach tanks contain hot water that is continually refreshed; and, immersing the devices in the leaching tanks for an appropriate time.


Depending on the nature of the latex device, manufacturing process and intended use, some latex devices may also need off-line washing with hot water after completion of the curing process. Also, surface treatment of the cured latex device with chlorine or other agents may denature surface constituents, such as water soluble proteins.


When establishing the design requirements for any device, the components used must be evaluated to assure that they are safe and effective for their intended application. Where feasible, manufacturers should specify components that do not contain ingredients which are known to present a hazard to health.

If such components are not available, then all constituents in the components or in compounding materials which could present a hazard to health must be removed from the devices or limited to an amount that will not present such a hazard.

The content of water soluble proteins in raw latex can be reduced by centrifugation and other techniques. Thus, a finished latex device manufacturer may deem it appropriate to specify the water soluble protein content of the raw latex to be purchased. Then, there should be adequate assurance that each lot of latex received meets the protein content specification.

However, unless the raw latex is completely deproteinized, further processing of the resulting devices may be needed to remove or reduce the residual water soluble proteins.


To meet good manufacturing practices requirements, the processes used to control water soluble proteins must be developed, evaluated (validated), documented and, thereafter, controlled. Likewise, the process for measuring proteins must be validated and documented. Data from validation of the testing method for proteins must assure that the leaching, cleaning or treating processes being used adequately reduce water soluble proteins to or below the level in the company's specification.

If you have any questions about these procedures, please contact:

Andrew Lowery, Chief, Technical Assistance Branch, at 800-638-2041 or, if you are located in Maryland, at 301-443-6597. Our FAX is 301-443-8818.

Sincerely yours,

John Stigi
Division of Small Manufacturers
Assistance, HFZ-220
Office of Training and Assistance
Center for Devices and Radiological Health