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 May 29, 2002
(202) 434-4120 The Society of the Plastics Industry, Inc. Food, Drug, and Cosmetic Packaging Materials Committee Dear Ladies and Gentlemen: In this letter, we report on SPI's success in documenting that some of the more onerous provisions of the bioterrorism prevention legislation recently passed by Congress are not intended to apply to food packaging or other food-contact materials. In addition, we report on the Food and Drug Administration's (FDA) promulgation of the final rule for the Food-Contact Notification (FCN) program, as well as the release of revised versions of its chemistry and toxicology recommendations and administrative guidance for FCNs. We also provide information on the Agency's move toward electronic submissions. Further, we discuss the provision of the Farm Bill that recently was signed into law by President Bush which opens up the possibility of using the term "pasteurization" to describe irradiation of food. Recent developments in state legislation are discussed, including the addition of naphthalene and pyridine to California's Proposition 65 and the container deposit legislation passed by Hawaii. Finally, we discuss recent developments in the European Union (EU), including the issuance of a new draft Eighth Amendment to the Monomers Directive and opinions on bisphenol A and ethylene oxide released by the EU's Scientific Committee on Food, and other matters of interest to the Committee. Table of Contents
1. SPI Obtains Statements of Congressional Intent that the Full Scope of Expanded FDA Authority under the Bioterrorism Prevention Legislation Passed by the House and Senate Does Not Apply to Food-Contact Materials 2. FDA Publishes Final Rule for FCN Program A final rule amending the food additive regulations to specify the requirements and procedures applicable to the FCN program was released by the U.S. Food and Drug Administration and published in the Federal Register on May 21, 2002 (see 67 Fed. Reg. 35,724). Although FDA has been accepting FCNs under the program since January 2000, the program will be officially implemented when the final rule becomes effective on June 20. The final rule makes few substantive changes to the version issued as a proposed rule on July 13, 2000 (see 65 Fed. Reg. 43,269). The Agency did make some modifications in response to comments submitted on the proposed version by this Committee. Among the more notable changes is a revision of 21 C.F.R. § 170.104(b) to clarify that, provided a filing is complete when received, the 120-day review period begins upon receipt by FDA of the FCN, not the date FDA "accepts" the notification as FDA originally proposed. In addition, the Agency revised Section 170.101(c) to clarify that the Agency's good laboratory practice regulations do not apply to migration studies or other non-clinical laboratory studies. One significant aspect of the final rule is that each notification filed after June 20 must be accompanied by FDA Form 3480. According to FDA, the form has been revised to minimize duplication of information required elsewhere in a notification in response to industry comments; however, FDA retained the form as a required element of a complete FCN. Thus, the final rule apparently will allow FDA to reject a notification for failure to include the form, even if the required information appears elsewhere in the notification. In the preamble to the final rule, FDA notes that the guidance documents have been revised to provide cross-references to the form, in order to assist manufacturers and suppliers in completing FDA Form 3480. Although not specifically addressed in the preamble, a completed FDA Form 3479 also is mandatory for notifications for food-contact substance formulations under Section 170.106. It is also notable that FDA refused to include a provision in the final rule assuring that the Agency will continue to provide letters confirming that notifications have become effective. FDA noted that, under the Federal Food, Drug, and Cosmetic Act, no Agency action is required for a notification to become effective. The Agency recognized that such letters have value to industry, but was concerned that issuance of such letters could potentially consume limited resources that may otherwise be used to complete timely reviews of FCNs. In practice, FDA has consistently issued final letters for effective notifications; accordingly, it is likely that FDA will continue to do so. In fact, FDA acknowledged in the preamble of the rule that, as long as there are necessary resources to do so, the Agency will provide letters indicating that its review of a notification is complete and that the notification is effective. Comments Sought on FCN Licensing In addition to the final rule, FDA published an advance notice of proposed rulemaking, seeking input on whether the Agency should establish regulations permitting the licensing of the rights to manufacture and market a food-contact substance for the use that is the subject of an effective FCN (see 67 Fed. Reg. 35,764 (May 21, 2002)). The request stems from a comment, submitted by the American Plastics Council (APC), requesting that FDA issue regulations permitting manufacturers to transfer or license their rights under an FCN to third parties. Because FDA deemed this comment to be outside the scope of the proposed rules on the FCN program, the Agency did not address the APC comment in the final rule. Currently, notifications are effective for only those manufacturers and/or suppliers identified in the notification. Customers of any manufacturer or supplier identified in the notification may also rely on the effective notification. However, other manufacturers of similar or identical food-contact substances that are not covered by the effective FCN must submit their own notification and wait 120 days for the FCN to become effective before marketing the substance. FDA has requested comments on the proposal by Aug. 5, 2002, and is particularly interested in answers to the following questions:
On the surface, one might conclude that the ability to license or transfer the rights to other companies obviously is a benefit to industry. Ultimately, that may be the consensus; but we feel that the issue merits careful consideration. First, we note that transferability may not be that significant a benefit. It is already clear that FCNs can be "transferred" to successor corporations in the context of a merger or acquisition. This can be accomplished merely by means of a letter to FDA. We consider it equally clear that an effective FCN may be relied upon by the notifier's corporate parents, subsidiaries, and other corporate affiliates. Furthermore, third parties can obtain all of the non-confidential documentation supporting an effective FCN, and can use the information to obtain their own FCN for the same food-contact substance. If the "me too" FCN is well-constructed, it is likely to become effective 120 days after receipt by FDA. Thus, the right to transfer or license may not have great significance. In addition, we consider it to be inevitable that FDA will feel the need to establish rules and procedures for a transfer and licensing system. As with legislation, regulation always involves the risk of unintended consequences. We will not speculate at this time as to the possible nature of such consequences in this case, but we strongly recommend that industry consider the possibility of regulatory action that would adversely affect the existing FCN program. We look forward to discussing this matter with you at the upcoming June meeting of the Committee. In the meantime, we would be happy to receive any thoughts you may have. 3. FDA Issues Final Guidance on Chemistry and Toxicology Recommendations and Administrative Guidance for FCNs In April and May, FDA released revised versions of the chemistry and toxicology guidelines and administrative guidance for FCNs, respectively. The recommendations are fundamentally unchanged from the last versions of the documents, but the Agency has clarified and updated some of the information found in the guidelines. With regard to the toxicology guideline, the discussion in Section II ("Exposure Estimates") now makes it clear that toxicology data are not needed at a dietary level of 0.5 part per billion (ppb) or lower not only for the use of a new food-contact substance, but also for incremental exposures for substances for which there are existing clearances, i.e., in effect, an incremental change of 0.5 ppb is effectively no change. In Section IV ("Safety Testing"), FDA still indicates a preference for the mouse lymphoma tk± assay (as compared to in vitro chromosomal damage) (although this is not a change, we felt it was noteworthy.) Also, there is now a separate section that states explicitly that the dietary exposure thresholds for the various categories of toxicology test requirements for biocides are 1/5 those for other types of food-contact substances. In Section V ("Organization of the Safety Information"), FDA now is more explicit in the recommended organization of safety information, which is as follows: Section I - Comprehensive Toxicology Profile; Section II - Original Reports of Safety Studies; Section III - Published Literature; and Section IV - Appendices ("other information" and literature searches). Section VII ("Comprehensive Toxicology Profile") of the guidance no longer contains, with regard to risk assessments for carcinogenic constituents, FDA's previous reference indicating that the risk needs to be below 10-8; there is no reference at all now specifying what a safe level needs to be. Hopefully, this indicates that FDA will continue to assess carcinogenic constituents on a case-by-case basis. Further, FDA now clarifies in Section VIII ("FDA's Views of the Relevance of Various Types of Safety Studies in Notifications") that only studies relevant to the safety assessment of a substance in food need to be discussed, i.e., data from studies using routes of administration other than oral are not of value unless effects at distill sites are observed. Finally, there is now a (little) bit more guidance regarding the significance of the results of genetic toxicity tests. FDA explains that factors that should be considered in determining whether results of genetic toxicity studies indicate a potential safety concern for a food-contact substance include (1) other available safety data such as bioassays; (2) the quality of the genetic toxicity studies; (3) the array of positive and negative genetic toxicity test results; and (4) the chemical structure of the substance. The chemistry guideline now contains a new introductory section providing background information on food-contact substances. Section II ("Chemistry Data") also has a new introduction, focusing on uses resulting in exposures <0.5 ppb. There also are some clarifications in the appendices of the chemistry guidance. Appendix II ("Selected Migration Testing Protocols") of the guideline that discusses Condition of Use C testing conditions now clarifies that testing using Condition of Use C conditions covers Condition of Use C through G and not C through H. Item 2 of Appendix II contains the advice found in the previous version of the guidance on the use of low density polyethylene (LDPE) in migration testing for a new adjuvant to cover use of the adjuvant in all polymers, but now contains additional advice on selection of appropriate polyolefins for testing the migration of a new adjuvant, reflecting input from the Committee. Finally, in Appendix IV, Table I ("Consumption Factors"), the new consumption factor for polyethylene terephthalate (PET) is now included, and the consumption factors for polystyrene are broken out further than they were in the previous guidance. With regard to the administrative guidance, the revised guidelines are substantially the same as the draft version, but there are several notable differences. First, the definition of the term "supplier" in Section II ("Scope of the FCN Program") now includes "any person supplying the [food-contact substance] FCS, including companies supplying the FCS to themselves for manufacture of a food contact material." Thus, FDA recognizes that a company may submit a notification as the "supplier" of a substance, even if it does not manufacture the substance. The administrative guidance clarifies that providing a comprehensive summary -- one of the required elements under 21 C.F.R. § 170.101 -- may be accomplished by the proper completion of FDA's Form 3480 (located in Section III ("Format of an FCN for an FCS")). Finally, the administrative guidance adds language regarding situations in which FDA believes any component of the notification under Section 170.101 is missing. FDA states that, in most cases, the notifier will be provided with a brief opportunity to supply the missing information. If the information is submitted in a timely manner, the 120-day review period begins on the date of receipt of the missing information. If the data is not submitted, FDA will issue a non- acceptance letter. Our experience indicates that, in practice, this refers to major items of missing information, not to FDA questions about details, which should not require "restarting the clock" if the answers can be provided quickly (within ten working days) and can be reviewed quickly by FDA (within one day). The toxicology guidance, entitled "Guidance for Industry (Final): Preparation of Food Contact Notifications for Food Contact Substances: Toxicology Recommendations," can be found on the Agency's website at http://www.cfsan.fda.gov/~dms/opa2pmnt.html; the chemistry guidelines, entitled "Guidance for Industry (Final): Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact Substances: Chemistry Recommendations," can be found at http://www.cfsan.fda.gov/~dms/opa2pmnc.html. Finally, the administrative guidance, entitled "Guidance for Industry (Final): Preparation of Food Contact Notifications: Administrative," can be found on FDA's website at http://vm.cfsan.fda.gov/~dms/opa2pmna.html. 4. FDA Moves Toward Electronic Submissions FDA has issued a proposed rule that, when finalized, will be the first FDA regulation to require submission of information by electronic means. The rule, proposed on May 3, 2002, relates to labeling submitted for review with new drug applications (NDAs), certain biological license applications (BLAs), abbreviated new drug applications (ANDAs), and supplements. HHS Secretary Tommy Thompson says that this proposed rule is part of a larger initiative President Bush has ordered to use electronic data technologies to improve the federal government's efficiency. FDA has worked since 1997 to enable submission of information via electronic means, but previously has not required electronic submission. At this time, the Agency does not yet have the technology in place to allow the electronic submission of food-contact notifications (although CD-ROMs may be submitted in addition to hard copies). FDA intends, however, that Form 3480 relating to FCNs eventually will form the basis for electronic submission. 5. President Bush Signs Farm Bill into Law Authorizing "Pasteurization" to Describe Food Irradiation On May 13, 2002, President Bush signed into law the Farm Bill that was passed by Congress earlier in the month. Despite strong opposition from consumer interest groups, the final version of the bill does contain a section allowing use of the term "pasteurization" for any treatment or process, including a series of treatments or controls, that achieves the same food safety effect as currently recognized pasteurization methods. This sets the stage for description of irradiated food as "pasteurized," which has been the goal of some companies interested in using irradiation to enhance food safety. As we have explained in previous letters, some in the food industry would prefer to use terms such as "electronically pasteurized," rather than those containing the word "irradiation," due to concerns that the latter term unnecessarily alarms consumers. On the other hand, consumer interest groups such as Public Citizen feel that use of any term other than "irradiation" is misleading to consumers. The final version of the bill providing a definition of pasteurization to include methods other than traditional pasteurization processes differed in several respects from the previous version. Rather than amending Federal law generally, the final legislation specifically amends Section 403 of the Federal Food, Drug, and Cosmetic Act. The law also allows for the submission of premarket notifications to FDA to allow use of certain processes or treatments that have a food safety effect. The bill directs FDA to revise its irradiation labeling regulations. This is necessary because the regulations still require use of the descriptor "treated with radiation" and the radura symbol. 6. EPA Will Not Require Testing of Chemicals for Endocrine-Disrupting Effects The U.S. Environmental Protection Agency (EPA) has decided not to require testing of chemicals that are alleged to disrupt endocrine function at low levels. In a March 26, 2002 statement, the Agency explained that, until there is an improved understanding of the subject, "it would be premature to require routine testing of substances for low-dose effects." In making the announcement, EPA cited the results of the May 2001 National Toxicology Program's (NTP) report on alleged endocrine disruptors, which failed to resolve conclusively the issues regarding the health effects of the chemicals1. You may recall from our previous reports that, at the behest of EPA and the National Institute of Environmental Health Sciences at the National Institutes of Health, NTP conducted a scientific peer review of information relevant to the hypothesis that the standard toxicological testing paradigm may be inadequate for detecting and characterizing the effects of potential endocrine disruptors in the low-dose range. The NTP panel concluded that, while there is "credible evidence" that low doses of some compounds can have an effect upon test animals, other "credible studies" failed to observe similar low-dose effects. Thus, they concluded, the chemicals should be the subject of additional research. In its March 26 statement, EPA acknowledged that "additional research is needed to better understand the low-dose hypothesis. An improved understanding of the mechanisms of action by which hormonally-active agents exert their effects will allow EPA to modify testing protocols as necessary to detect potential effects at low doses." According to the Agency, its Office of Research and Development (ORD) is already conducting research in this area, and will take into consideration the research recommendations identified in the NTP report. ORD also will issue a solicitation for research proposals through its Science to Achieve Results (STAR) extramural program, and will monitor the outputs of ongoing research for applicability to the Endocrine Disruptor Screening Program. If future relevant information on specific chemicals becomes available, this information may support testing for low-dose effects on a case-by-case basis. 7. Naphthalene and Pyridine Added to California's Prop. 65 California's Office of Environmental Health Hazard Assessment (OEHHA) has added naphthalene (CAS Reg. No. 91-20-3) and pyridine (CAS Reg. No. 110-86-1) to its list of chemicals known to the state to cause cancer under the Safe Drinking Water and Toxic Enforcement Act of 1986 (Prop. 65); the naphthalene and pyridine listings became effective April 19, 2002 and May 17, 2002, respectively. Naphthalene was added to the list based on an NTP inhalation study in rats2, and pyridine was added based on NTP drinking water studies in rats and mice3. As you may know, Prop. 65 requires the Governor of California to publish a list of chemicals that are known to the state to cause cancer, birth defects or other reproductive harm. Prop. 65 imposes certain controls that apply to chemicals that appear on this list. These controls are designed to limit exposures from drinking water, consumer products, and the work environment. Prop. 65 also includes a right for private parties (read plaintiffs' lawyers) to file lawsuits and collect some of any financial penalty imposed. For further information on California's Prop. 65, you may want to read the current articles on the subject in the Monthly Focus section of our website, www.packaginglaw.com. 8. Hawaii Passes Container Deposit Legislation Hawaii has become the first U.S. state since 1982 to pass container deposit legislation. The bill, which will take effect in 2005, involves a five cent per container redeemable deposit paid by the consumer to the producer/distributor of the product, and an advance disposal fee paid to the state by the producer/distributor of the product. Specifically, starting January 1, 2005, a refundable five cent deposit will be added to the purchase price of all beer, wine coolers, tea, coffee, soft drinks, non-carbonated water and all non-alcoholic drinks (liquid form) sold in glass, metal, polyethylene terephthalate (PET) and high density polyethylene (HDPE) containers with a volume of sixty-four fluid ounces or less. This fee will be paid by the consumer at the time of purchase. Producers and distributors of the products in turn will pay the five cent deposit fee directly to the state. Exempted from the law are liquids such as syrups, concentrates, flavorings, drugs, infant formula, and products frozen at the time of sale to the consumer. Consumers will redeem the deposits primarily at the point of retail via in-store redemption, on-site redemption operated by a third party, or reverse vending machine. Urban areas must have a redemption location within two miles of any place that sells beverages, while rural areas have the leeway to place container redemption centers and machines at centralized locations, rather than keeping them near places where beverages are sold. The state will pay all redemption centers the five cent deposit, who in turn will pay the consumers for any beverage containers that they return for redemption. In addition to the refundable deposit, producers and distributors of the products listed above also will begin paying an Advance Disposal Fee (ADF) on October 1, 2002. The initial rate of the ADF will be 0.5 cent per container; this will increase to one cent per container by October 1, 2004. The ADF will be paid directly to the state and is to be used as a handling fee for businesses that redeem containers. 9. EC Issues New Draft Eighth Amendment to the Monomers Directive The European Commission (EC) has issued a new draft proposal to amend the Monomers Directive (90/128/EEC) for the eighth time. The latest document contains several items that may be of interest to members of the FDCPMC. It is important to keep in mind that these proposed amendments will affect only food-contact materials that fall within the scope of the Monomers Directive, i.e., only those materials that are made entirely of plastic. The Eight Amendment is scheduled to become effective as of January 1, 2005. The official deadline for comments on this draft was May 15, 2002, but we understand that Dr. Rossi will entertain comments for some period after May 15th. At this time, we do not have issues on which we recommend comments, but Committee members may have interests affected by the draft amendment. Highlights of the proposed amendments are as follows.
10. EU's Scientific Committee on Food Releases Opinions on Bisphenol A and Ethylene Oxide On April 17, 2002, the EU's Scientific Committee on Food (SCF) released opinions on Bisphenol A (BPA) and ethylene oxide (EO). With regard to BPA, the Committee analyzed all of the available data and concluded that, in essence, what FDA might call the "acceptable daily intake" for BPA is at least at the 600 ppb in the diet level (0.01 mg/kg bw TDI). The currently estimated worst case dietary exposure is more than an order of magnitude below this level. In sum, it is clear that all of the known uses are quite safe, especially since BPA is not a carcinogen, or a teratogen. It also is interesting to note that the report gives no credibility to the so-called "low dose" theory so widely touted by Dr. Fred vom Saal and his followers. The opinion on EO recommends that specifications for additives manufactured with the substance be revised to restrict EO to below its current limit of detection. As noted in the opinion, the best achievable analytical sensitivity for EO, in this case in a cellulose matrix, is 0.2 mg/kg. If 5% of the diet contained EO at this level, and assuming a daily diet of 3 kg, the resulting exposure to EO would be 30 µg/p/d. Given that FDA's virtually safe dose (VSD)4 for EO is 0.5 µg/p/d (see 63 Fed. Reg. 29548), the best available analytical methodology is still far (a factor of 60) from being useful in assessing exposure at a meaningful level. 11. European Food Safety Authority Recruits Board Members The EU has actively been recruiting personnel for the new European Food Safety Authority (EFSA). The European Council soon will nominate Members of the Management Board. Candidates' applications were evaluated for skills and experience that would benefit the EFSA. The short list includes internationally renowned food safety experts, managers, and scientists. Each Board member will serve a four-year term which may be renewed once. One of the first tasks of the Management Board will be to select an Executive Director based on a list of suitable candidates provided by the EC. The EC has renewed their call for applications for the position of Executive Director. They originally asked candidates to apply before March 27, 2002, but they have extended the deadline until June 7, 2002 to attract additional high-level candidates. As we have been reporting to you, as of February 21, 2002, the SCF officially was replaced by the EFSA, as stipulated in the regulation establishing the EFSA. However, in accordance with the regulation, until the Scientific Committee and Scientific Panels of EFSA are established, scientific advice on matters falling within the competence of the EFSA will continue to be provided by the existing Scientific Committees. Thus, as of this date, and throughout this transition period, the SCF continues its activity. 12. Swedish Researchers Find Elevated Levels of Acrylamide in Food Recent reports prepared by the Swedish National Food Administration (NFA) show elevated levels of acrylamide in certain food products. Analytical chemists at the NFA reported the results from the analysis of over 100 samples of food. Fried and oven-baked potato and cereal products contained the highest levels. No acrylamide was detected in boiled foods or uncooked products. Apparently, the studies were prompted by an incidental discovery of acrylamide "adducts" in humans and later in test animals fed fried animal feed (it is not clear yet, but the humans found to contain acrylamide may have been controls in a separate monitoring project). There was no explanation of how the acrylamide could be generated. The acrylamide levels found in the foods were highly variable among different food products. Based on a national Swedish food intake survey, the average intake of acrylamide per day from the foods was reported as 35-40 micrograms (mcg) per day. Based on this intake estimate, NFA indicated that several hundred cases of cancer could possibly be attributed to acrylamide, based on the specific analytical results reported to date. FDA's VSD of acrylamide is 0.085 mcg/day. Thus, the mean intake level estimated by NFA for Swedish consumers is almost 500 times higher than the VSD. On May 17, Britain's Food Standards Agency (FSA) announced that it had replicated the findings of the Swedish study that showed acrylamide is present in a wide range of foods. The FSA found that acrylamide appears to be formed naturally in the cooking process, but did not recommend that people change their diet on the basis of this evidence. The Central Science Laboratory (an Executive Agency of the UK Government) tested french fries, potato chips, and cereal and found significant levels of acrylamide in a range of commonly-consumed foods as a result of frying or baking, either at home or in mass production. No significant levels of acrylamide, however, were found in raw or boiled food. The FSA also is continuing to carry out a survey to test whether residual acrylamide is present in retail paper and packaging materials for food and, if so, whether there is any detectable migration to foodstuffs. The results so far indicate that, if there is any residual acrylamide in such paper or board, it is present in only a few samples and the levels there are generally much lower than those produced by cooking food. Work continues on the survey, which will be completed and reported as soon as practicable. 13. Japan Considers New Food Safety Agency Recent food safety crises in Japan have spurred Japanese Prime Minister Junichiro Koizumi to call for the formation of a food safety agency. Koizumi has suggested that a new agency be formed by the reorganization and consolidation of the various ministry and agency sections currently responsible for food safety. Recent food safety crises that have eroded consumer confidence in Japan's current regulatory scheme include the bureaucratic mishandling of a mad cow disease outbreak and Snow Brand Foods Company's deliberate misidentification of their beef's place of origin. 14. ISRTP to Hold Workshop on the Precautionary Principle The International Society of Regulatory Toxicology and Pharmacology (ISRTP) will hold a workshop on the precautionary principle June 20-21, 2002 at The Hilton Crystal City in Arlington, Virginia. This controversial principle, which has been promoted by environmental and consumer groups and some European government authorities, basically stands for the proposition that it is better to require a full set of toxicology data and a complete assessment of all possible risks before allowing new technology or products on the market. The workshop will include speakers from both sides of the debate. Further information on the workshop can be found on ISRTP's website at http://www.isrtp.org/. * * * As always, if you have any questions on the above, or if we can be of assistance in any other way, please do not hesitate to contact me, Jerry Heckman or Deborah Ziffer. Cordially yours, Ralph A. Simmons * * *
1. NTP's report can be found on its website at
http://ntp-server.niehs.nih.gov/htdocs/liason/LowDosePeerFinalRpt.pdf.
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