NAMPA News

Message from the Chairman

By John M. Rost, Ph.D.

Over the past few years, we have discussed certain trends companies working within the U.S. Food and Drug Administration (FDA) regulated industries find troubling.  These industries, including those represented by the North American Metal Packaging Alliance, Inc. (NAMPA) member companies, rely on the safety of products reviewed and approved by FDA, and believe FDA’s approval process should be respected.  We all know that science is evolving, that there are few things in science that are certain, and that there are few things that should not be challenged.  That said, it is troubling that certain third-party groups assert challenges to well-recognized FDA scientific practices and hasten to impugn FDA’s work before those challenges are fully and fairly considered and resolved.

The current FDA regulatory framework is based on well established principles of traditional risk assessment.  Risk assessments are a fundamental process in safety evaluations where the entire body of science around an issue is evaluated and the determination of the assessment is based on the preponderance of evidence.  Under this review, all relevant studies are considered and evaluated for scientific merit and application to real world situations, including human health.  No study is dismissed without consideration. Even those that are not used to determine appropriate safety levels are considered as part of a weight of evidence review.

What is most concerning in connection with the FDA review of bisphenol A (BPA) is the demise in the confidence of this tested and trusted system.  The risk assessment process must adhere to fundamental principles, the first of which is that not all studies deserve the same scientific weight as studies vary with respect to quality and detail.  For example, Good Laboratory Practice (GLP) studies that are designed to look at a particular toxicological endpoint or endpoints are audited and validated and are designed to have sufficient statistical relevance.  This is not to say that all GLP studies are designed properly.  In fact, FDA routinely dismisses certain GLP studies for their failure to adhere to certain study design and execution formalities.  But what is clear with properly designed GLP studies is that the data generated can be relied upon, verified, and validated.  These studies are used by FDA in risk assessments only when the full data package is presented for review and interpretation.  Other non-GLP studies are also useful in the risk assessment process, but often raise more questions than provide answers.  The data generated in these “mechanistic” type studies are extremely useful for the review process, but must be considered appropriately and given the weight they deserve in light of their quality and study scope.  Also, for non-GLP studies to be fully and fairly considered, FDA needs to review thoroughly sufficient underlying data supporting whatever conclusion the study authors have elicited from the data.

Without consumer trust in FDA’s review and approval system, the public suffers.  New and innovative products cannot be made available if there is no agreed-upon standard of safety.  Historically, the FDA approval process has served as the standard bearer, and without it, FDA, consumers, and regulated industries all suffer.  The current system has served us well in ensuring the safety of our food and approving the best medicines and medical devices available.  Of course, all systems and processes can be improved, but the current attack on the integrity of the FDA approval system will continue to cause irreparable harm to all constituencies.  NAMPA will continue to work with aligned stakeholders to blunt this erosion of confidence, and seek to restore the trust in the systems that have served us well in the past.

NAMPA Communications and Outreach

By Stanton Communications, Inc.

A series of important developments in recent weeks -- both good and bad -- have kept BPA in the headlines and on the minds of consumers, making an already challenging policy environment even more difficult for NAMPA and its members as more and more attention is focused on metal packaging.  While polycarbonate plastic baby bottles have garnered the bulk of the attention, media interest in the use of BPA in epoxy resin coatings for metal packaged foods and beverages is on the rise.  In response, NAMPA has aggressively pursued the media with statements coinciding with each event, and with direct outreach to reporters, an approach that will continue through the end of this year and into 2009.

In late August, following weeks of intense advocacy efforts on the part of NAMPA and several allied organizations, including the American Chemistry Council (ACC), the Grocery Manufacturers Association, the Infant Formula Council (IFC), and others, a bill to ban BPA from children’s products in California was defeated by the state assembly.  As an active member of an industry coalition focused on defeating SB 1713, NAMPA created key messages to counter opponents’ claims about BPA alternatives, Japan’s action on BPA, and more, while remaining actively engaged with legislators to educate them about the shortcomings of the proposed legislation.  Despite this victory, proponents of SB 1713 are expected to re-introduce the bill in California in 2009, and similar measures are expected in approximately 15 to 20 additional states.

September proved equally active on the BPA front with the publication of a new study and a public hearing by an FDA panel on BPA.  The Journal of the American Medical Association (JAMA) published new research results that purported to find a link between exposure to BPA and chronic diseases, including diabetes and heart disease.  NAMPA responded aggressively with direct outreach to major reporters and the issuance of a statement in advance of the official JAMA release.  As a result, NAMPA’s position -- that the study provided no scientifically defensible basis for its conclusion -- was included in numerous articles.  The JAMA study release was timed to coincide with a formal meeting of the FDA expert panel charged with assessing the science on BPA.  While FDA articulated the expert analysis that led them to their draft assessment that BPA was in fact safe at existing human exposure limits, only two individuals (ACC and NAMPA) of 19 spoke in defense of the National Toxicology Program (NTP) and FDA conclusions on the safety of BPA during the public comment period.

Also in September, the German Federal Institute for Risk Assessment (BfR) affirmed the safety of BPA following its evaluation of the JAMA study and another new BPA study.  The German BfR reviewed the two newest studies to determine if the new findings required an adjustment to the tolerable daily intake (TDI) of 0.5 milligrams BPA per kilogram body weight per day.  Based on its review, the BfR determined that the studies provided no valid basis for any change to the present risk assessment for BPA, a position once again brought to the attention of the media thanks to NAMPA.

In early October, Health Canada took center stage with the issuance of its official decision to ban BPA in polycarbonate plastic baby bottles.  The Canadian government also released several proposed risk management measures, among them the application of the ALARA principle or “as low as reasonably achievable” levels, of BPA in infant formula products for newborns and children up to 18 months.  Health Canada announced that it is continuing its efforts to work cooperatively with industry to develop a code of practice to evaluate infant formula.  Again, NAMPA issued a statement indicating it has been working cooperatively with Health Canada since April and is committed to continuing those efforts to reduce further migration levels wherever technology permits.  Activist groups, buoyed by their success in getting plastic baby bottles banned in Canada, have already indicated publicly their intent to go after metal packaging next.

Attention on BPA will continue into the foreseeable future, as a result of the most recent FDA meeting in late October, where the FDA Science Board voted to accept and submit the BPA Subcommittee’s report on the shortcomings of the initial FDA assessment of BPA.  This particular meeting attracted even more media scrutiny than usual, thanks to allegations raised by the Milwaukee Journal Sentinel about the head of FDA’s BPA review panel, Dr. Martin Philbert.  In its story, the Sentinel claimed that Dr. Philbert failed to disclose a financial conflict of interest regarding a donation made to the University of Michigan by a businessman who has voiced his support for the safety of BPA.  The Sentinel, along with other advocacy groups, subsequently called on Dr. Philbert to resign from the FDA panel.  At the same time, Representative John Dingell indicated his intention to expand his Committee’s investigation into Dr. Philbert’s role and the integrity of the FDA review of BPA.  Finally, the Natural Resources Defense Council (NRDC) announced in advance of the hearing that it had filed a citizen’s petition with the FDA seeking to remove BPA from all food packaging applications.  See related article in this Newsletter.

The BPA Subcommittee’s report on the original FDA assessment was issued two days prior to the October 31 meeting.  In its report, the Subcommittee concluded that FDA did not articulate reasonable support for criteria used to deselect a group of studies purportedly conducted utilizing recognized research methodology.  The BPA Subcommittee advised reconsideration of these same studies, which FDA had previously rejected citing flawed research design and procedure.  Due to the inclusion of these studies, the Subcommittee concluded that the initial assessment failed properly to assess potential health risks posed by BPA to human health.

Despite their previous criticism in advance of the report, environmental groups and legislators hailed the report as a victory and urged FDA immediately to take steps to remove BPA from food and beverage packaging, particularly those for infants and young children.  Industry groups, including NAMPA, ACC, and IFC presented oral testimony at the meeting to reiterate the concerns over yielding scientific analysis to fear, as well as the market implications of immediately removing BPA from food and beverage packaging.  FDA is currently considering the Subcommittee’s report and will issue its final assessment before the next meeting of the Science Board now scheduled for February 2009.

FEDERAL ISSUES

FDA Requests Information Regarding FDA-Regulated Products Containing BPA

On October 15, 2008, FDA published a Federal Register notice requesting assistance in identifying the types of FDA-regulated products that contain 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.  FDA is requesting information on the presence and levels of BPA for products with either direct or indirect patient contact, including “situations where the BPA is a component of the product or its packaging.”  FDA states that information relating to the leaching of BPA from the packaging to the product and/or from the product to patients is also of interest, as well as exposure to BPA from the use of the following BPA-related materials:

• Polycarbonate;
• Polyether sulfone;
• Polycarbonate/siloxane co-polymer;
• Biostable polyurethanes; and
• Epoxy resin.

FDA’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 (BISDMA); and
• Ethoxylated bisphenol A diacrylates.

Information is due December 29, 2008.  NAMPA intends to respond to the request for information.

 NIEHS and NTP Request Information Concerning Ongoing Research and Research Needs for Biological Effects of Exposure to BPA

In an October 21, 2008, Federal Register notice, the National Institute of Environmental Health Sciences (NIEHS) Division of Extramural Research and Training (DERT) and NTP published a Request for Information (RFI), seeking input on a number of key research areas that have been identified in recent evaluations of BPA.  The notice states that NIEHS and NTP will use information provided to help focus future research and testing activities on BPA.  NIEHS and NTP “welcome input from the lay public, environmental health researchers, healthcare professionals, educators, policy makers, industry, and others with an interest in BPA.”

According to the notice, NTP is currently pursuing studies of absorption, distribution, metabolism, and excretion (ADME) in experimental animals (rodents and non-human primates), as well as the kinetics associated with these processes, following exposures to BPA from the perinatal period through adulthood, over a wide range of doses, by multiple routes of administration.  In addition to ADME studies, other areas of research have been suggested to better characterize possible hazards associated with BPA exposures in humans, including studies to:  (1) examine pathways of human exposures; (2) identify cellular targets for BPA at low and high doses for consistency with an estrogenic mechanism of action; (3) identify interactions with other estrogenic substances, including naturally occurring hormones; and (4) investigate further the “low” dose effects reported in experimental animals.

NTP and NIEHS will analyze and consider the findings from the ADME studies and the information collected as a result of the RFI for use in the further development of NTP and NIEHS/DERT research and testing programs on BPA.  NTP and NIEHS/DERT request information on the following:

• Ongoing or planned research activities related to the RFI;
• Specific data needs for any or all of the priority areas identified below; and
• Suggestions for beneficial research collaborations.

To aid in the development of a listing of prioritized data needs, the notice provides the following summary listing of the research needs identified in the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) evaluation, the NIEHS co-sponsored workshop, or the draft FDA assessment:

1.         Studies of the concentrations of BPA and metabolites in human blood, urine, breast milk, amniotic fluid, placenta and other tissues, particularly in infants and young children, where appropriate;

 2.         More complete assessment of sources of human exposure to BPA;

 3.         In vitro studies examining interactions of BPA with multiple cellular targets (toxicity pathways) across a range of concentrations, and comparing these results with similar studies of other known estrogenic agents and combinations of estrogenic agents with BPA;

 4.         Studies of gestational and lactational exposure of experimental animals to “low” doses of BPA regarding effects on development and onset of adult disease, including:

a.         The sensitivity of the developing brain to BPA induced structural, functional, and biochemical alterations;

 

b.         The relevance to primates of diminished estrogen-dependent brain and behavioral sexual dimorphisms in rodents exposed to BPA during development;

c.         Confirmation of rodent studies reporting behavioral effects following BPA exposure during development related to the dopaminergic systems such as novelty-seeking, socio-sexual behaviors, and response to addictive drugs;

 

d.         The susceptibility of the mammary gland and prostate gland to alterations in development from exposures to BPA; and

 

e.         The predilection of BPA-induced changes in mammary gland and prostate gland development to neoplasia later in life.

5.         The robustness and biologic basis for altered puberty following BPA exposure in multiple species;

6.         The potential for effects on the immune system;

7.         The potential for metabolic disruptions leading to obesity, diabetes, or other metabolic diseases;

8.         The potential for disruptions to the male reproductive tract, including effects on sperm quantity and quality;

9.         The potential for aneuploidy or chromosomal disruption to female germ cells and for proliferative and/or cystic changes to the ovary and uterus later in life; and

10.        Other areas not previously identified.

 Responses are due December 1, 2008.

NRDC Files Citizen Petition with FDA

NRDC submitted a Citizen Petition to FDA on October 31, 2008, requesting that FDA prohibit the use of BPA in human food.  NRDC also requested FDA to “revoke all regulations permitting the use of a food additive that results in BPA becoming a component of food.”

NRDC asserts that FDA had approved the use of BPA in food packaging, and that this approval has resulted in significant human exposure, and adversely impacts human health.  NRDC cited evidence of early life exposure as being particularly troublesome because it occurred during critical periods of organ development.  NRDC also pointed to a growing body of literature that it claims links exposure with breast cancer and diabetes.  The specific action requested by NRDC is to establish the following regulation, pursuant to 21 C.F.R. § 189.1:  21 C.F.R. § 189.2XX (BPA):

(a)  BPA is the chemical 4-4’-isopropylidenediphenol ((CH3)2C(C6H4OH)2, CAS Reg. No. 80-05-7).  It is a synthetic chemical not found in natural products and has been used in the production of epoxy resins, polyester resins, polysulfone resins, polyacrylate resins, and polycarbonate plastics.

(b)  Food containing any added BPA is deemed to be adulterated in violation of the Federal Food, Drug, and Cosmetic Act based upon an order published in the FEDERAL REGISTER of [DATE].

NRDC also petitions the Commissioner to revoke all regulations permitting the use of a food additive that results in BPA becoming a component of food, pursuant to 21 C.F.R. § 171.130.

To support its request, NRDC sets out a variety of data that it believes show that BPA is not safe, and can cause serious adverse health effects.

Under the controlling rules, the FDA Commissioner is required to rule on a citizen petition within 180 days of the date that it is filed.  The regulation provides, however, that the Commissioner may issue a tentative response, stating that the agency has not reached a decision due to the existence of other priorities.  Most petitions receive a tentative response, and there is no reliable way to estimate when a decision might be reached, although it is likely to be out in the future.

NAMPA Chairman Rost Urges FDA Science Board to Review All Relevant Studies and Data

NAMPA Chairman Dr. John M. Rost spoke before the FDA Science Board during its October 31, 2008, meeting, during which it discussed the BPA Subcommittee’s review of FDA’s draft assessment of BPA for use in food contact applications.  Rost stated that NAMPA urges FDA to base its final safety assessment on a full and robust review of the relevant studies and their underlying data.  NAMPA fully supports the Subcommittee’s recommendation that the FDA review should include examination of the studies that FDA originally rejected based on its determination that the studies are materially flawed.  NAMPA encourages FDA to call on the authors of the research in question to submit to FDA all information required for a full review, which should include all raw data and related information.  Additionally, all pertinent information to other experiments from the authors that may not have been included in the published reports should be requested.  NAMPA also suggested the Science Board consider the positions on data assessment taken by other international regulatory bodies, including the European Food Safety Authority (EFSA), Germany, Japan, Canada, and the United Kingdom.

STATE ISSUES

California

Update on Prop 65 Activities

On January 18, 2008, the California Office of Environmental Health Hazard Assessment (OEHHA) announced the selection of BPA for review by the Developmental and Reproductive Toxicant Identification Committee (DARTIC) for possible listing under Proposition 65, as well as a 60-day data call-in for information relevant to the assessment of the evidence of the developmental and reproductive toxicity of BPA.  NAMPA submitted comments in response to the January 18 notice, as did other industry stakeholders.

In NAMPA’s April 17, 2008, response to OEHHA, NAMPA urged OEHHA to review the final report by the NTP CERHR, which provides a scientifically sound basis for assessment of the potential reproductive and developmental effects of BPA.  Because the CERHR Panel Report is balanced and authoritative, NAMPA recommended it be used as the foundation for any assessment of these issues that DARTIC performs.  NAMPA noted that the findings of the CERHR Panel are also supported by another recent evaluation of BPA prepared by EFSA.

As reported in the last NAMPA News, we expected BPA to be considered at the November 20, 2008, meeting of the DARTIC.  The agenda for the next DARTIC meeting in November has been published, however, and nothing is mentioned about BPA.  It is anticipated that BPA will be considered at a spring DARTIC meeting.  Since the Hazard Identification Document (HID), in which OEHHA explains its assessment of BPA for Prop 65 listing purposes, is expected to be available for a 60-day comment period prior to the DARTIC meeting, it is expected the HID will not be available until early 2009.

It will be important for entities wishing to oppose listing to provide a comprehensive and scientifically compelling response to the HID.  NAMPA continues to coordinate closely and regularly with representatives from the Grocery Manufacturers Association and the American Chemistry Council, and each organization’s lawyer, to ensure each organization’s advocacy is consistent, effective, and efficient.

INTERNATIONAL ISSUES

Health Canada Issues Final Action on BPA under CEPA

On October 18, 2008, Health Canada published in the Canada Gazette its final screening assessment report and announced the release of the proposed risk management approach document for BPA, according to the procedures set forth in the Canadian Environmental Protection Act (CEPA).  As stated in the Gazette, there will be a 60-day comment period, ending December 17, 2008.  Typically, Health Canada proceeds with the action it proposes absent convincing public response.  In the case of BPA, action can be assumed.  On the day before the notice was placed in the Canadian Gazette, Health Canada published the following:

OTTAWA - The Government of Canada today announced it will immediately proceed with drafting regulations to prohibit the importation, sale and advertising of polycarbonate baby bottles that contain bisphenol A (BPA).  The Government will also take action to limit the amount of bisphenol A that is being released into the environment.

The specific actions the government is discussing are summarized in a fact sheet posted when the other documents described above were posted:

Therefore, the Government of Canada will continue to ensure that levels of BPA in infant formula are kept at the lowest levels achievable by carefully reviewing pre-market submissions of infant formula and continuing to work with the food packaging industry to reduce levels of BPA in infant formula to the lowest levels possible.  We will also evaluate alternatives to BPA for infant formula can linings on a priority basis.

The Government of Canada is also moving forward with legislation to ban the importation, sale and advertising of polycarbonate baby bottles.

Environmental Concerns

Science shows that bisphenol A is entering the environment through wastewaters, washing residues and has been found in some leachate from landfills. It also breaks down slowly in the environment when there is a lack of oxygen. The combination of the slow break down of bisphenol A and its wide use in Canada means that over time, this chemical could build up in our waters and harm fish and other organisms.

As a precautionary measure, Environment Canada is considering a regulation that would set a limit for the maximum concentration of bisphenol A that can be released in effluent to the environment. The regulation would also require facilities using bisphenol A to implement best management practices to ensure that it is handled and disposed of safely.  These actions will keep the levels of bisphenol A being released to the environment at safe concentrations for fish and other aquatic life.

Health Canada is accepting comment on the risk management decision until December 17, 2008.  NAMPA will submit comments.

Health Canada Clarifies Position on Safety of BPA-Based Epoxy Materials

In an October 31, 2008, letter to NAMPA Chairman Dr. John M. Rost, Health Canada clarified the current status of its position on the safety of BPA-based epoxy materials used in conjunction with metal to package food and beverages.  The letter states that Canada’s final risk assessment “confirmed earlier results, which indicated that the general public need not be concerned by the potential exposure to BPA resulting from its use in food packaging applications including can lining.”  According to the letter, based on all information available to date, Canada has “concluded that the potential exposure to BPA from food packaging applications is extremely low and does not represent a health risk to consumers.”  Canada wants to be “prudent,” however, “and further reduce exposures of newborns and infants under 18 months.”

Melamine and Metal Packaging

The issue of melamine and food contamination has cropped up again.  Recent reports from China involving melamine in milk and infant formula have inspired a new round of media attention and government inquiries. In response to this challenge, NAMPA created a Melamine Task Group to prepare an information sheet that NAMPA members could use with their customers and other interested parties.  The document was approved on October 2.