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 August 31, 1999 The Society of the Plastics Industry, Inc. Food, Drug, and Cosmetic Packaging Materials Committee Dear Ladies and Gentlemen: In this letter we provide you with a more detailed discussion of FDA’s recently released guidance document on drug packaging, and call your attention to FDA’s proposal to amend Section 314.70 of its New Drug Regulations regarding changes, including packaging changes, to approved new drugs. In addition, we bring you up-to-date on NSF International’s proposed standard for meat and poultry processing, further discussions on creating a single food safety agency, pending federal legislation to preempt inconsistent state labeling laws, such as California’s Proposition 65, and other matters of interest to the Committee. Table of Contents
1. FDA Issues Final Guidance Document on Container and Closure Systems for Packaging Human Drugs and Biologics; Chemistry, Manufacturing, and Controls Documentation As reported in our July 19, 1999 letter, the Food and Drug Administration (FDA) has now published in final form its guidance document on the information about container and closure systems that applicants should provide to the Agency in support of new drug and biologics submissions. The final guidance, dated May, 1999, follows a draft version, which was made available on July 15, 1997. We submitted comments on the draft document in 1997 on behalf of the Committee. We have now completed a detailed review of the final guidance and are pleased to report that it has been clarified in several areas consistent with our comments. In addition, although the guidance has not been modified to incorporate all of our suggested changes and continues to suggest including more information in a Drug Master File (DMF) than we would advise, the document explicitly states that DMF holders may include in their files "as much or as little information as they choose." Thus, FDA acknowledges that there is no legal obligation to include in a DMF the detailed information mentioned in the guidance. We continue to recommend including in a DMF on a packaging material only the information that is needed to establish the safety and suitability of the material for use in packaging drugs. With respect to beneficial changes to the guidance, the following have been made:
On the other hand, FDA has failed to address our comments in some areas. For example, the guidance makes the following statements, with which we disagree:
Historically, the Agency has not required this level of detail in a DMF. Indeed, with respect to the latter, compatibility information for a particular drug does not make sense in the context of a DMF, which may be used to support new drug applications for several different drugs; rather, this is the type of information that would belong in the drug application, itself. As indicated above, however, the guidance continues to state that DMF holders may include in their files as much or as little information as they choose. This being the case, we would continue to recommend that detailed information, such as raw material supplier names and manufacturing descriptions, should not be included in an initial DMF filing. If FDA has a legitimate need for the information in the context of its evaluation of a specific drug application, then the information can be provided at that time. We note that FDA has removed from this guidance document most of the discussion that appeared in the draft version regarding notification requirements as they apply to changes in container closure systems. As you may recall, we had suggested some significant changes to this section. Instead of modifying the section, the Agency has indicated that it will provide additional guidance on post-approval packaging changes "in the future." As indicated in the article below on FDA's proposal to amend Section 314.70 of the new drug regulations, this guidance is now provided in a document entitled "Changes to an Approved NDA or ANDA," which currently is available in draft form. This draft guidance document contains a section on the reporting requirements that arise as a result of various types of changes to packaging materials. FDA officials also have indicated to us that they plan to develop an additional guidance document focusing solely on post-approval changes to packaging materials (this document is being referred to by FDA as the "PAC PAC" document). The "PAC PAC" guidance, however, is not expected to be completed for at least two years. Guidance documents, such as this one on drug containers and closures, are considered "living" documents, open to public comment and amendment by FDA at any time. Therefore, the Committee could submit additional comments requesting FDA to reconsider the changes that we recommended but the Agency did not accept. We believe it is unlikely, however, that FDA would make further changes at this time in the absence of a clear error (which we have not detected), as opposed to a matter of policy or interpretation. 2. FDA Proposes to Amend Section 314.70 of its New Drug Regulations Regarding Changes, Including Packaging Changes, to Approved New Drugs FDA is proposing to amend Section 314.70 of its new drug regulations (21 C.F.R. § 314.70, "Supplements and other changes to an approved application") to implement provisions of the Food and Drug Administration Modernization Act of 1997 (FDAMA) with respect to manufacturing changes to approved new drugs. (See 64 Fed. Reg. 34608 (June 28, 1999).) As you may know, Section 314.70 sets forth the criteria for determining when a change, including a packaging change, to an approved new drug requires the filing of a supplemental new drug application (SNDA), when FDA prior approval is needed, and when notice in an annual report is sufficient. The proposed amendment to Section 314.70 updates and slightly modifies these requirements. FDA also has announced the availability of a draft guidance document entitled "Guidance for Industry: Changes to an Approved NDA or ANDA" (June 1999), which provides recommendations on the types of information that should be developed in connection with a change to an approved application, and which reporting category to use. Currently, Section 314.70 provides for three separate reporting categories for changes to an approved new drug application: (1) changes that must be reported in an SNDA and approved before the change is made; (2) changes that must be reported in an SNDA, but which may be made before FDA approval; and (3) changes that do not require FDA approval and that may simply be reported in the applicant's annual report. Changes of material type for a container and closure system for a drug product (for example, from glass to high density polyethylene (HDPE) or from HDPE to polyvinyl chloride) require the submission of an SNDA and FDA prior approval, while changes within a container and closure system (for example a change from one HDPE to another HDPE) based upon a showing of equivalency to the approved system under a protocol approved in the application or published in an official compendium (for example, the United States Pharmacopeia (USP)) do not require FDA prior approval and are simply described in the annual report. The proposed amendment to Section 314.70 slightly modifies these categories. Specifically, the proposed amendment to Section 314.70 provides four reporting categories for changes: (1) changes that must be reported in a supplement requiring FDA prior approval ("major changes"); (2) changes that require a supplement submission at least 30 days prior to distribution of the drug product made with the change ("moderate changes"); (3) changes that may be implemented when FDA receives a supplement (also considered "moderate changes"); and (4) changes that may be described in the next annual report ("minor changes"). Under the proposed rule, changes to a container and closure system "that may affect the impurity profile of the drug product" are considered major changes requiring a submission of an SNDA and prior FDA approval. Changes in a container and closure system that are not expected to affect the quality of the final drug product will fall within the category of moderate changes requiring submission of an SNDA at least 30 days prior to making the change, unless they are specifically covered by another category. This represents some relaxation in the current rule, which requires prior FDA approval of an SNDA for all changes in material type for containers and closures. Examples of other types of changes are: (1) changes in the size and/or shape of a container for a nonsterile liquid drug product without a change in the labeled amount of product or the type of container or closure (moderate change; a supplement may be filed at the time the change is made); (2) changes in the size and/or shape of a container for a nonsterile solid dosage form without a change in the number of dosage units or the type of container or closure (minor change which may be reported in the annual update); and (3) changes within the container or closure system for any nonsterile drug product (liquid or solid) based upon a showing of equivalency to the approved system under a protocol approved in the application or published in an official compendium (minor change which may be reported in the annual update). FDA has defined the categories of changes broadly in the proposed rule to allow itself flexibility in modifying the reporting requirements for various types of changes with increased knowledge and experience. Consequently, the Agency has indicated that it will provide information on its current thinking with respect to the scope of the reporting categories through guidance documents. In this regard, the currently available draft guidance on "Changes to an Approved NDA or ANDA" contains a section on packaging changes, which helps interpret the proposed changes to Section 314.70. The new draft guidance indicates that FDA has heightened its reporting requirements with respect to changes within container and closure systems for sterile liquid drugs, and relaxed somewhat its reporting requirements for changes to container and closure systems for nonsterile liquid and solid dosage forms. The new guidance indicates that FDA will continue to consider a change within a container closure system (for example, from one HDPE to another HDPE) based upon a showing of equivalency to the approved system under a protocol in an approved application or published in an official compendium to be a minor change for which notification in the annual report is adequate only if the packaged drug is a nonsterile drug product, liquid or solid. Presently, the regulations allow notification in the annual report for changes within the existing container and closure system (with the proper showing of equivalency) for any liquid or solid dosage form, except a change in container size for liquids. With respect to solid oral dosage forms, the guidance document suggests a further liberalization of the notice requirements beyond the explicit provisions of the proposed amendments to Section 314.70. Specifically, FDA indicates in the new guidance that changes within container and closure systems for solid drugs need not be based upon a showing of equivalency to the approved system based on a protocol in the application or in an official compendium, provided that any new component materials have been used in contact with other approved solid oral dosage forms. FDA is accepting comments on the proposed changes to Section 314.70 through September 13, 1999, and we are interested in hearing from Committee members as to whether you see any issues on which the Committee should submit comments. 3. Senate Passes FDA’s Fiscal 2000 Budget; Includes $6 Million for Food-Contact Notification On August 4, 1999, the Senate passed its version of the FY 2000 agriculture appropriations bill, giving FDA $264.8 million in FY 2000, up from $231.5 million in FY 99. Included is $6,000,000 for implementation of the Food Contact Notification (FCN) program. The House version of the bill still contains no appropriations for implementation of the FCN program. The FDA budget will be taken up by a House/Senate conference committee when Congress returns from its Labor Day recess. 4. Food Irradiation Coalition Submits Petition Urging FDA to Extend Irradiation to Ready-to-Eat Meats, Prepared Fruits and Vegetables As discussed in our most recent letters, industry groups are becoming increasingly frustrated with the regulatory hurdles surrounding the approval process for irradiation of food. Irradiation is considered the most effective method for protecting certain foods against contamination with pathogens that can threaten the health of consumers. As part of the push to expand the permitted uses of irradiation, on August 23, the Food Irradiation Coalition submitted a petition to FDA to approve irradiation for protecting ready-to-eat (frozen, refrigerated, and dried) meat, poultry, fruit, and vegetable products. FDA has indicated that this petition is likely to qualify for expedited review under the policy applicable to petitions that involve technology for enhancing food safety. In addition to submitting this petition, the Coalition is promoting other changes in the irradiation review process, including (1) concurrent FDA and U. S. Department of Agriculture (USDA) review of direct food additives, including radiation, for meat and poultry; and (2) legislative reclassification of irradiation as a "process," which would subject new uses of irradiation to a notification process rather than the lengthy rulemaking procedure now in place. In a related matter, the House Commerce Committee has asked the General Accounting Office (GAO) to conduct a study on the benefits and risks associated with food irradiation. The letter asks GAO to examine (1) the extent that food irradiation is being used and for what purposes; (2) the risks and benefits of food irradiation that can be supported by scientific evidence; and (3) the food safety laws and regulations that apply to food irradiation. 5. USDA Issues Notice and Holds Meeting on Voluntary Certification Program for Meat and Poultry Processing Equipment; NSF Announces Draft Standard for Certifying Equipment As we have been reporting to you in previous letters, the USDA eliminated its program of prior approval of equipment used in meat and poultry plants. In response to concerns expressed by the meat and poultry industries regarding the need for a new certification program, Congress, in the 1999 Omnibus Appropriations Bill, directed USDA to develop a new approach for evaluating the suitability of equipment and materials used in meat and poultry processing plants. USDA’s Agricultural Marketing Service (AMS) responded to the Congressional directive by publishing an advanced notice of proposed rulemaking (ANPR) in the July 16, 1999 Federal Register, announcing its intent to develop a voluntary user-fee funded certification program for processing equipment. Comments on this proposed program may be submitted to the AMS until September 14, 1999, although no details about the program are available yet. At this early stage, we suggest that the Committee may want to file comments urging the AMS to ensure that its certification allows adequate flexibility with respect to the basis for establishing the FDA compliance of materials for the food-contact surfaces of equipment. Specifically, as we did in the comments filed on behalf of the Committee concerning the draft Underwriters laboratories (UL) standard for meat and poultry processing equipment, we believe it would be a good idea to make certain the AMS is aware that food-contact materials do not always need to be the subject of a food additive regulation to have FDA compliance. In addition, the AMS held a public meeting on August 10, 1999 to discuss development of its certification program as well as current industry efforts to develop a sanitary standard for meat and poultry processing equipment. The meeting provided a forum for equipment manufacturers to present their concerns about the need to develop, through consensus building, a workable, flexible certification program and accompanying sanitary standard to promote public health and uniform industry practice. Representatives from NSF International, 3-A (the dairy standards organization), and UL also made presentations about their proposed draft sanitary standards. Overall, most participants were in favor of a voluntary certification program and supported the efforts of AMS. In addition to the draft UL standard on which we filed Comments for the Committee, NSF and 3-A have developed a proposed standard to cover all meat and poultry plant equipment except for modular belts and hand-held equipment (which will be addressed in separate standards). The standard is based on a draft international standard on hygiene requirements for the design of machinery (ISO/DIS Standard 14159); however the NSF/3-A standard includes additional requirements specific to meat and poultry processing equipment. The NSF/3-A standard will be open for public comment for a period of one year, during which it is contemplated that industry will use the standard on a trial basis to certify meat and poultry plant equipment. If you would like a copy of the draft standard to review, you may contact Ms. Marie K. Whybark at NSF by telephone at (734) 827-6824. We recommend the filing of comments on behalf of the Committee proposing that the NSF/3-A standard, like the draft UL standard, be revised to clarify the acceptability of supplier determinations of FDA compliance in addition to explicit listings in the food additive regulations. We will file such comments unless we have heard to the contrary from Committee members by September 17. Suggestions of additional subjects for comment also are welcome; of course, with a comment period extending for a year, we do not need to receive all your ideas by September 17. 6. California Recycling Bill Appears Dead for This Year In our last letter, we provided you with an update on California S.B. 1110, which would amend the state’s current plastics recycling rate and content law to phase in increases in the required recycling rates for rigid plastic containers covered by the law, calling for an increase to 30% by January 1, 2001, and to 35% by January 1, 2003. The bill proposes elimination of the present exemption of food and cosmetic packaging from application of the law, calling for mandatory recycling rates for these containers of 20% by 2001, 25% by 2003, and 35% by 2005. In the event that these recycling rates are not met for all food and cosmetic packaging on the market in California, the bill further directs the California Integrated Waste Management Board to implement a process to certify that each manufacturer has reduced packaging waste by the same target percentages through use of recycled content (by the manufacturer itself or through credits purchased from others) or source reduction or reuse. As of our last letter, the bill was awaiting a hearing by the Consumer Protection Committee, which postponed a scheduled July 13, 1999 hearing at the request of the Californians Against Waste. After the Assembly returned from its summer recess, the bill’s sponsor, Senator Chesbro, proposed amendments to the bill which would have effectively bypassed consideration of the bill by the Committee and allowed the bill to go directly to floor vote. At the request of Assembly leadership, the Chairpersons of the Consumer Protection Committee and Rules Committee considered the situation and ultimately refused to let the bill proceed without consideration by the Consumer Protection Committee. Since all bills still needing a policy committee hearing had to meet a hearing deadline of August 19, 1999 in order to remain in consideration this term, we understand that S.B. 1110 is not expected to move forward this year. We caution, however, that, since S.B. 1110 was not heard fully by the relevant Committees this session, it is eligible to be considered again next year. 7. Food Safety Council Solicits Comments on Strategic Plan; Opposes Single Food Safety Agency On July 15, 1999 the President’s Council on Food Safety held a public meeting to discuss a national strategic plan for improving food safety. Agriculture Secretary Dan Glickman, Health and Human Services Secretary Donna Shalala and other leading officials were in attendance. The meeting focused specifically on five broad goals which were outlined in full in the June 17, 1999 Federal Register: 1. Ensure the development and use of a comprehensive scientific and technological food safety knowledge base to support prevention, regulation, inspection, surveillance, and education programs; 2. Improve the effectiveness of surveillance, outbreak investigation and response; 3. Identify and manage food safety risks through protective standards, inspection, and enforcement from farm to table; 4. Ensure that all people who come into contact with food from farm to table are fully informed of the risks and measures to prevent or reduce foodborne illness; 5. Create a national and, to the extent possible, an international seamless food safety system from farm to table. The Food Safety Council intends to hold another public meeting on the strategic plan in October, and intends to submit a final version of the plan to President Clinton in July 2000. The Council is maintaining an open docket between now and March, and summaries of public meetings can be found at the following Internet site: www.foodsafety.gov. One of the issues debated at this public meeting was the creation of a single food safety agency. Although some members of the Council and industry groups expressed opposition to development of a single regulatory body, there were a number of participants that favored addressing food safety issues with a single voice. As we reported to you in our last letter, Senator Richard Durbin (D-Ill) and Rep. Rosa DeLauro (D-CT) introduced on June 24 the "Safe Food Act of 1999" which proposes to consolidate in a single agency all the food safety, labeling, and inspection functions currently performed by FDA, USDA, and the Department of Commerce. The Senate Government Affairs Committee Subcommittee on Oversight of Government, Restructuring, and the District of Columbia held a hearing on Wednesday, August 4 to discuss the merits of creating a single food safety agency. At the August 4 hearing, Dr. Jane Henney, FDA Commissioner, and Dr. Catherine Woteki, Undersecretary for Food Safety of USDA, cited a number of Clinton Administration campaigns and programs, such as Food Net, Pulse Net, and "Fight BAC!," that have been established over the past three years to better coordinate federal and state agency regulation of food safety and raise consumer awareness and education of food safety issues. Both Henney and Woteki oppose a single food safety agency because, in their view, it would cost too much money and would be too disruptive for both industry and consumers. There were, however, supporters of the Durbin legislation that argued a single food safety agency is not only necessary to simplify the currently fractured system, but a way in which to focus Congressional appropriations for food safety efforts. With only 3 cosponsors signed on to the bill at this time, there does not appear to be any significant momentum building in the Senate for passage of Durbin’s legislation. 8. Bills to Preempt Inconsistent State Labeling Laws Are Stalled in Congress Two bills that would preempt inconsistent state labeling laws for food (and, in one bill, food packaging), such as California’s Proposition 65, are held up in Congress awaiting hearings. The National Uniformity for Food Act, recently re-introduced into the Senate by Sen. Pat Roberts (R-KS), would restrict states from imposing labeling laws that are more stringent than federal requirements. This bill is held up in the Senate awaiting a hearing in the Committee on Agriculture. An identical bill introduced in the House by Rep. Richard Burr (R-NC) is awaiting a hearing in the House Committee on Commerce. The National Uniform Food Safety Labeling Act, introduced by Rep. Frank Pallone (D-NJ), seeks to establish national food labeling standards. It also is awaiting a hearing in the House Committee on Commerce. The National Uniformity for Food Act would prohibit a state or political subdivision of a state from directly or indirectly establishing or continuing to implement "any notification requirement for a food that provides for a warning concerning the safety of the food, or any component or package of the food, unless such notification requirement has been prescribed under the authority of this Act and the State or political subdivision notification requirement is identical to the notification requirement prescribed under the authority of this Act." The bill provides that the Secretary may grant state petitions for exemptions from federal notification requirements, provided the exemption (1) would serve to protect an important public interest that is otherwise unprotected in the absence of the exemption; (2) would not cause a food to be in violation of federal law; and (3) would not unduly burden interstate commerce. Rep. Pallone’s National Uniform Food Safety Labeling Act focuses only on labeling of food products, not packaging. Industry groups such as the National Food Processors Association strongly support the Burr/Roberts National Uniformity for Food Act and argue that national uniformity would ultimately lower the cost of the product for the consumer. On the other hand, consumer groups such as the Center for Science in the Public Interest would like to see the national regulations provide minimum labeling standards while allowing states to regulate beyond the national criterion. In our opinion, the National Uniformity for Food Act, if passed, would be helpful for the packaging industry because it would preempt California’s Proposition 65 and any similar state labeling or warning laws, such as the two bills introduced in Massachusetts this year, with respect to additional warnings on food packaging materials that meet FDA requirements. Fortunately, the Massachusetts bills were effectively killed by being sent back for further study. 9. NRC Releases Report Evaluating Data on Endocrine Disruptors The National Research Council (NRC) recently released an extensive report evaluating available scientific data on substances that have been identified by some as "endocrine disruptors." As you know, these substances, termed "hormonally active agents (HAAs)" by the NRC, are chemicals found in various products, including packaging, which have been claimed by some to cause adverse health effects in wildlife and humans. The study was initiated in July, 1995 by the Environmental Protection Agency, Department of the Interior, Centers for Disease Control and Prevention, and Congress. NRC assembled a panel of scientists, the Committee on Hormonally Active Agents, who approached their task by (1) identifying chemicals with alleged hormonal or antihormonal activity; (2) evaluating available scientific literature discussing the effects of such chemicals on humans, laboratory animals, and wildlife; and (3) considering whether the effects of the chemicals can be attributed to the hormonal properties of the chemicals and environmental exposure to them. While this review found some laboratory and wildlife studies which seemed to indicate an association between exposure to large amounts of particular chemicals and adverse health effects, the committee found no persuasive evidence that exposure to low doses of environmental contaminants is disrupting hormonal processes in humans or wildlife. According to the committee, a limiting factor in the analysis was the difficulty in extrapolating laboratory findings to humans. Lack of evidence as to the actual level of these chemicals in the environment also hampered the evaluation. Thus, a recurring theme in the report was the committee’s recommendation of extensive, long-term research to determine the effects of these chemicals on humans. 10. FDA Scientist Says NTP Report on Carcinogens Not Useful to FDA Bernard Schwetz, one of FDA’s top scientists, told the Toxicology Forum that FDA has little use for the National Toxicology Program’s (NTP) Report on Carcinogens, as the chemicals discussed in the Report have already been subjected to FDA’s lengthy premarket-review process. According to Dr. Schwetz, the report, published biennially since mandated by Congress in 1978, also wastes precious agency resources and complicates ongoing regulatory procedures. Dr. Schwetz further argued that the Report is not a useful reference for consumers, and that the listing of certain chemicals often serves to confuse the public. As an example, he cited the anticipated listing of tomoxifen, a drug shown to be effective in reducing future occurrence of breast cancer in women already diagnosed with the disease, as "known to be a human carcinogen" in the Ninth Report, which is due to be published late this year.
* * * As always, if you have any comments or if we can provide further information on any of the issues discussed above, please do not hesitate to contact me, Jerry Heckman or Deborah Ziffer. Cordially yours, Ralph A. Simmons More About SPI: Vision and Mission . Membership . Business Units . Regional Offices . News and Publications . Calendar of Events . Terms and Conditions of Use |
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 © Copyright 2005 The Society of the Plastics Industry.
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