[Federal Register: October 15, 2008 (Volume 73, Number 200)]
[Page 61135-61136]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. FDA-2008-N-0523]

FDA-Regulated Products that Contain Bisphenol-A; Request for 

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for information.


SUMMARY: The Food and Drug Administration (FDA) is requesting 
assistance in the identification of types of FDA-regulated products 
that contain Bisphenol A (BPA), whether as a component of the product 
or its packaging, and any information relating to the leaching of BPA 
from the packaging to the product and/or from the product from the 
product following human administration.

DATES: Submit written or electronic comments and information by 
December 29, 2008.

ADDRESSES: Submit written comments and information to the Division of 
Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
and information to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov. Information submitted 
will be reviewed by the FDA BPA Task Force.

FOR FURTHER INFORMATION CONTACT: Norris Alderson, Office of Science and 
Health Coordination (HF-32), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-827-3340, FAX 301-827-3042, e-mail: 


I. Background

    BPA is a chemical commodity used primarily in the production of 
polycarbonate plastics and epoxy resins. Such plastics and resins have 
many applications including as components of packaging for food and 
drink, and as components of certain medical products and their 
packaging. Consequently, low levels of residual BPA may be present in 
such products. On April 14, 2008, the National Toxicology Program (NTP) 
released a draft brief on BPA for public comment and peer review. The 
NTP draft brief raises concerns that exposure to BPA could be linked to 
developmental problems of the endocrine system in infants and young 
children. The NTP draft brief also contains an exposure estimate to BPA 
for infants and young children due to leaching of BPA to food from 
plastic baby bottles and the linings of certain baby food containers. 
NTP has subsequently released a final report on BPA on September 3, 
    In response to the NTP draft brief, Commissioner von Eschenbach has 
convened an agency-wide task force to facilitate cross-agency review of 
current research and new information on BPA for all FDA-regulated 
products. The review will include the NTP brief and all other available 
information on the exposure of US consumers to BPA from FDA-regulated 
    During the course of this process the task force has been making an 
inventory of all FDA-regulated products that are known to contain BPA. 
The task force has already completed a thorough assessment of the 
potential exposure to BPA due to leaching from food-contact materials 
and is now interested in additional information on other types of 
products, specifically medical devices, biological products (including 
blood, blood products, vaccines, and cell and gene therapies, and 
    To ensure that we have current information to support our review of 
issues related to BPA risks, we are requesting information on the 
presence and levels of BPA for products with either direct or indirect 
patient contact. This would include situations where the BPA is a 
component of the product or its packaging. Information relating to the 
leaching of BPA from the packaging to the product and/or from the 
product to patients is also of interest.
    At this time, exposure to BPA from the use of the following BPA-
related materials provides an initial basis for the agency's query:
     Polyether sulfone.
     Polycarbonate/siloxane co-polymer.
     Biostable polyurethanes.
     Epoxy resin.
    The agency's query also extends to products that contain certain 
bisphenol acrylic oligomers, such as the following:
     Bisphenol A diglycidylether methacrylate (BIS-GMA).
     Bisphenol A diglycidylether (BADGE).
     Bisphenol A dimethacrylate (BIS-DMA).
     Ethoxylated bisphenol A diacrylates.

II. Information Requested for FDA-Regulated Products

A. Medical Devices and Articles Used in Product Manufacturing

    Direct contact devices would include, but not be limited to, those 
with direct contact with tissue, blood, other fluids, such as 
cerebrospinal fluid, and skin. Implants, catheters, and most dental 
devices are additional examples of devices with direct patient contact.
    Indirect patient contact or external communicating devices would 
include, but are not limited to the following:
     Components of blood pathway circuits, (e.g., hemodialysis, 
apheresis, and cardiopulmonary bypass).
     Respiratory tubing circuits.
     Blood and parenteral solution administration sets.
     Apheresis instrument harnesses including separation bowls 
and break away closures.
     Hard casing for leukocyte reduction filters.
     Platelet rich plasma preparation devices including tubes 
for centrifugation of blood.
     Tops for vials or other container closures.
     Large volume containers used in preparation of raw 
materials for biological products production when lined with epoxy 
material that contains BPA.
     Materials used for preparation of cell/tissue/gene 
therapies, including: T-flasks, roller bottles, cell factories, cell 
culture beads, hard conical tubes, and disposable plastic pipettes.
    In submitting your comments, we ask you to provide information with 
respect to any Class I, Class II, and Class III medical device that has 
direct or indirect patient contact. Whenever possible, include a 
description of the analytical method used to develop the submitted data 
and information.
    If the device contains polycarbonate or BPA, we request the 
submission of data concerning the following:

[[Page 61136]]

     The rate and extent of BPA release from devices under 
clinically relevant extraction conditions.
     What conditions affect the release and leaching of BPA?
     Estimates of patient exposure to BPA from use of the 
    FDA is interested in possible alternatives to BPA.
     Are you aware of available alternatives to the use of BPA 
in certain medical devices? Provide information concerning the 
alternative material and any associated risks.
    FDA is interested in receiving information concerning devices that 
have been shown to release BPA, including cardiopulmonary bypass 
circuits, hemodialysis circuits and certain dental devices. For these 
devices provide the following information:
     Describe the device type and intended use.
     Describe how the device directly or indirectly contacts a 
     Describe whether, and how, the device is used in pediatric 
patients, and describe the pediatric population by age and gender.
     Identify and attach any study reports related to BPA 
release from this device type.

B. Human-Use Biological Products and Drugs (Including Protein Drugs)

    For products that are: (1) Formulated with BPA-containing 
components or (2) liquid-based dosage forms [including solutions, 
suspensions, semisolids (cream, lotion, ointment, foam, gel etc.)] and 
packaged in plastic containers or in metal canisters with plastic 
lining or coating (e.g., epoxy) if either the container or the coating 
have been made by using BPA, please provide the following information:
     NDA/ANDA/BLA number.
     Drug product name, dosage form and route of 
     Components and composition of the formulation.
     Container closure system (CCS) and components in direct 
contact with the formulation.
     Drug Master File number(s) for the CCS, if applicable.
     Levels of BPA found either as an extractable (in model 
solvents from the CCS) or a leachable (in the formulation) through 
expiry, if known.
     Identify the analytical method(s) for quantitation of BPA.
     Acceptance criteria either as an extractable or leachable, 
if established.
    Please also provide summary reports from any studies that you may 
have performed to evaluate the toxicity and to justify the safety of 
BPA in these products.

C. Other FDA-Regulated Products

    We are also soliciting any relevant information on the use of, and 
potential exposure to, BPA from any other FDA-regulated products, 
including cosmetics, that have not been discussed in the above 
    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments and information. Submit 
a single copy of electronic comments and information or two paper 
copies of any mailed comments and information, except that individuals 
may submit one paper copy. Comments and information are to be 
identified with the name of the technology and the docket number found 
in brackets in the heading of this document. A copy of this notice and 
received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: October 3, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-24506 Filed 10-14-08; 8:45 am]