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 October 1, 2001
(202) 434-4120 The Society of the Plastics Industry, Inc. Food, Drug, and Cosmetic Packaging Materials Committee Dear Ladies and Gentlemen: We hope that this letter finds you, your families, colleagues, and friends safe and well after the recent terrorist attacks on our country. To all who have suffered from these tragic events, you are in our thoughts and prayers. This situation brings a new perspective to our usual daily activities, but, along with the rest of the nation, we are making our best efforts to conduct "business as usual." In that vein, we are continuing to represent the Committee as we always have, monitoring legal and regulatory developments at the Food and Drug Administration (FDA) and around the world that affect packaging and issuing these reports to the Committee. We trust that you will continue to find that these letters help your businesses grow and prosper in what we hope along with you will be a safer, more secure world. In this letter we discuss FDA's safety assessment of di-(2-ethylhexyl)phthalate (DEHP) in polyvinyl chloride (PVC) medical devices in which the Agency concludes, with respect to adults, that there is little or no risk posed by exposure to the amount of DEHP released from PVC medical devices. While FDA did indicate that neonates may be at increased risk from exposure to DEHP, the Agency also stressed that, in developing a risk management strategy, other factors, such as the availability and safety of alternatives to DEHP and PVC, must also be considered. We also discuss the effect that the terrorist attack may have on Congressional action on FDA's FY 2002 budget, and bring you up-to-date on the United States Pharmacopeia's (USP) review of proposals that we submitted, on behalf of the Committee, recommending procedures for the interchangeability of polypropylene and low density polyethylene containers. Finally, we report that drug company executive Michael Astrue appears to be President Bush's top choice for FDA Commissioner, on the status of the Office of Food Additive Safety's (OFAS) move from Washington, D.C., to College Park, Maryland, and on other matters of interest to the Committee. Table of Contents
1. FDA Issues Safety Assessment of DEHP in PVC Medical Devices Now, the Center for Devices and Radiological Health (CDRH) at FDA has completed its safety assessment of DEHP in PVC medical devices. CDRH's assessment involved the comparison of the doses of DEHP received by patients undergoing various procedures to "Tolerable Intake" (TI) values for DEHP to develop a general index of safety or risk with regard to patient exposure to DEHP. FDA noted that the TI/dose comparisons derived for many clinical scenarios were likely to overestimate the risk to the majority of the exposed patient population, since worst-case estimates of dose typically are compared to TI values intended to be protective for even sensitive individuals in the population. In estimating the dose of DEHP received by patients undergoing various procedures, and to identify the critical effects of DEHP in exposed experimental animals, FDA conducted a comprehensive review of the literature on point; thus, no new information was brought to bear in FDA's risk assessment. In comparing the dose of DEHP received by patients undergoing various medical procedures to the TI value for oral or parenteral exposure, CDRH concluded that there is little or no risk to adults exposed to DEHP released from PVC medical devices in most applications. However, small segments of the population, such as premature babies undergoing multiple procedures during their stay in the neonatal intensive care unit, may be at heightened risk for the adverse effects of DEHP, compared to average adults, due to their increased exposure to the chemical and/or their increased sensitivity to the effects of the chemical. Thus, the FDA assessment confirms what previous assessments of alleged endocrine disruptors by various organizations have concluded: that there is minimal concern about the risk of adult exposure to low doses of these chemicals. While the neonate may be more vulnerable to chemical insults than the adult, FDA appropriately stresses in the DEHP risk assessment that "[o]ther factors, such as the availability and safety of alternatives to DEHP and PVC, must also be considered in developing a risk management strategy" to address the issue of the safety of DEHP. Indeed, technically feasible alternatives to DEHP-plasticized vinyl medical products often do not exist. FDA's risk assessment can be viewed on their website at http://www.fda.gov/cdrh/ost/dehp-pvc.pdf. 2. Terrorist Attack Delays Senate FDA Spending Bill for FY 2002 The terrorist attack and President Bush's subsequent pursuit of emergency money to counter terrorist activities have delayed Senate floor action on the agriculture-spending bill, which includes FDA funding for fiscal year 2002. However, on September 25th, Congress passed emergency legislation to keep the Agency funded at current levels for the first two weeks of fiscal year 2002, which began October 1st. The bill was signed by the President on September 28th. This measure will keep the government operating until October 16th while Congress continues to consider Agency appropriations for 2002. In addition to the delay on the agriculture spending bill, there is speculation that the President's quest for emergency money to fight terrorism could affect the level of financial support for domestic programs, including FDA funding, if the Administration feels pressured to not exceed the budget cap. However, President Bush has promised that he would only exceed the cap if there was a national emergency or a war - and the terrorist attack arguably qualifies as both. Congressional follow-up to the terrorist attack also is likely to delay action on other issues, such as stem cell research and a Medicare prescription drug benefit, that previously were on the front burner. 3. Update on USP Review of Recommended Procedures for Interchangeability of Polypropylene and Low Density Polyethylene Containers In early 2000, we submitted, on behalf of SPI, two proposals and supporting round robin test data to the United States Pharmacopeia (USP): one regarding the establishment of an interchangeability protocol for polypropylene (PP) containers for solid and liquid dosage forms, the other regarding an amendment to an existing polyethylene containers monograph to allow the interchangeability of low density polyethylene (LDPE) containers for liquid dosage forms (both sterile and non-sterile). The Packaging, Storage and Distribution Subcommittee of the USP Committee on Revision met in October of last year to discuss these proposals, and since that time we have been waiting for their response. With regard to the proposal to establish a PP containers monograph, you may recall that, subsequent to our submission, we commented on a few of the recommended procedures proposed by Mr. Clyde Erskine, a USP consultant. These procedures were outlined in the Pharmacopeial Forum in-process revision article on polypropylene containers published last year, and again this year. In a May 22, 2000 letter we submitted to USP, we generally expressed our support for an interchangeability protocol, as well as our views that the residue on ignition standard should remain, and that the specification limits for the water transmission and non-volatile extractives should cover the entire range of results obtained in the round robin study. We also diverged slightly from our proposal in expressing our agreement with Mr. Erskine that the thermal analysis testing should include two different reference standards for polypropylene homopolymer and polypropylene copolymer. We have now been informed by our contact at USP that the SPI proposal for a recommended interchangeability procedure for polypropylene containers for solid and liquid dosage forms will not be submitted to a vote for approval. Rather, the USP Committee on Revision is intending to meet in November 2001 to vote on approving the recommended procedure that has appeared in the Pharmacopeial Forum (i.e., Clyde Erskine's recommended procedure) for inclusion in Supplement 1 of USP 25. We also were told that FDA has expressed disagreement with the polypropylene interchangeability monograph as it relates to liquid dosage forms. We have long known that it is the view of the FDA staff that an interchangeability protocol for liquid dosage forms is inappropriate due to the safety/stability concerns attendant to liquid drugs (as opposed to solid dosage forms). As you may know, FDA believes that a case-by-case analysis of resin changes in containers for liquid dosage forms is required to ensure safety, and, consequently, has proposed changes to 21 C.F.R.§ 314.70 to require drug manufactures to submit supplemental new drug applications for such changes. USP believes that the data they have (and which was relied upon by Clyde Erskine in proposing his recommended procedure) fully supports inclusion of liquid dosage forms and, thus, is intending to move forward. In light of FDA's proposed amendment to 21 C.F.R. § 314.70, and its attitude on post-approval changes to container/closure systems for liquid drugs, it does not appear that the establishment of a final USP monograph on the interchangeability of polypropylene containers will effectively reduce the regulatory burden applicable to manufacturers of sterile liquid drugs. Stated another way, should FDA finalize the proposed rule in its current form, a manufacturer of a sterile liquid drug product will be required to report a resin change to FDA in a supplemental new drug application (instead of in an annual report), regardless of whether or not interchangeability between the resins can be demonstrated according to the procedures set forth in the USP polypropylene containers monograph. We will know more about the relationship between the USP polypropylene monograph and FDA's regulation of post-approval changes for sterile liquid dosage forms once FDA finalizes its rule and accompanying guidance in the upcoming year. In the meantime, we will attempt to obtain clarification from the Agency on this point. With regard to the LDPE monograph, we have been informed that the USP Packaging, Storage and Distribution Subcommittee has decided not to update the LDPE containers monograph to include liquid dosage forms at this time. Our contact was unable to provide the rationale for this decision, but did verify that the Subcommittee reviewed the SPI proposal and round robin data. We will continue to monitor USP's activities with regard to interchangeability protocols for PP and LDPE containers and, of course, will keep you abreast of any further developments. 4. Astrue, Crawford Rumored to Be Top Choices for FDA Commissioner In the latest round of rumors regarding the Bush Administration's top picks for FDA Commissioner, the two names at the top of the list appear to be Michael Astrue and Lester Crawford. One report stated that President Bush, apparently unconcerned that Democratic Senators have cautioned him against nominating an industry insider to serve as Commissioner of the FDA, appears to be poised to announce drug company executive Michael Astrue as his nominee to head FDA. Astrue is an attorney who serves as senior vice president and general counsel of Transkaryotic Therapies Inc., a biopharmaceutical company based in Cambridge, Massachusetts. Astrue also is a former general counsel with the Department of Health and Human Services, FDA's parent agency, and once served as a legal adviser to the first President George Bush. As we have been reporting to you, a coalition of seven Democratic senators voiced their general opposition to an industry insider in a strongly worded July 13th letter to the President, claiming that such an appointment would "raise irresolvable conflicts of interest, undercut public confidence, and undermine the agency's worldwide reputation as the gold standard of public health regulators." The letter also urged the appointment of an individual with a strong scientific or medical background. All of the senators who signed the letter sit on the Senate Committee on Health, Education, Labor, and Pensions, which is chaired by Sen. Edward M. Kennedy (D-MA) and will oversee confirmation of the new commissioner. We have seen conflicting reports regarding Lester Crawford, D.V.M., Ph.D. The most recent report claims that Health and Human Services Secretary Tommy Thompson told a Bear Sterns investor conference that Dr. Crawford is the top candidate for FDA Commissioner. According to the report, Thompson also indicated that Sen. Kennedy approves of the selection. Dr. Crawford currently is the head of The Center for Food and Nutrition Policy, which was most recently affiliated with Georgetown University. However, it was announced in mid-September that the group will soon become part of Virginia Tech's College of Agriculture and Life Sciences, calling into question whether Dr. Crawford is still a top candidate for FDA Commissioner. It is uncertain whether Dr. Crawford would be considering the Commissioner post after accepting the new position at Virginia Tech. Nonetheless, Dr. Crawford would likely be the more appealing candidate to the Senate Committee on Health, Education, Labor, and Pensions, due to his strong scientific, medical, and regulatory background (prior to working at The Center for Food and Nutrition Policy, Dr. Crawford formerly was Administrator of the U. S. Department of Agriculture Food Safety and Inspection Service and Director of the Center for Veterinary Medicine at the Food and Drug Administration). However, Transkaryotic Therapies, the company Astrue works for, is based in Kennedy's home state and, should Astrue reach the confirmation stage, there is speculation that the senator might find it difficult to vote against a corporate constituent. 5. FDA's OFAS Gearing Up for Move to College Park As we have been reporting to you, FDA's Office of Food Additive Safety (OFAS), formerly the Office of Premarket Approval, is planning to move from its C Street and Vermont Avenue locations in Washington, D.C. to more modern facilities in College Park, Maryland, near the University of Maryland. Starting in October, a small group within OFAS will make the move, but it is still unclear when the rest of the OFAS staff will follow. A new building intended to house the majority of the staff is still under construction with no immediate completion date in sight; however, it is our understanding that FDA is searching for nearby space that could be leased to house the rest of the staff until the building is completed. If the lease space can be found, OFAS will move to that space until the new building is completed. Otherwise, they will remain at the Vermont Avenue location. It is our expectation that there will be logistical issues with the handling of mail destined for OFAS staff as the office moves to College Park. Currently, mail destined for OFAS staff at the Vermont Avenue location is sent to a location on C Street to be screened for security purposes before being forwarded to Vermont Avenue. For now, this system will remain in place. However, as the move to College Park progresses, the mail will be sent from C Street to what FDA refers to as the "Paint Branch" facility in College Park, then to Vermont Avenue. As most of the staff leave C Street, all mail will be received at the Paint Branch facility for screening, then sent to Vermont Avenue. Since there is no precise timetable dictating when mail will be routed to different facilities, there is likely to be some confusion within the Agency that may cause some delay. We will continue to monitor this situation and notify the committee of any changes to the mail delivery system as we are made aware of them. 6. FDA to Hold Webcast on Draft Guidances on Electronic Submission of Food and Color Additive Petitions In our September 6, 2001 letter to the Committee, we discussed two draft guidances recently issued by FDA, entitled "Providing Regulatory Submissions to Office of Food Additive Safety in Electronic Format - General Considerations" and "Providing Regulatory Submissions to Office of Food Additive Safety in Electronic Format for Food Additive and Color Additive Petitions." See 66 Fed. Reg. 39517 (July 31, 2001). Now, FDA's OFAS has announced that it will present a webcast for industry to discuss electronic submissions and the guidance documents. The webcast will be held on October 10, 2001 at 2:00 p.m. EST. Details for viewing the webcast will be posted on FDA's website at http://www.cfsan.fda.gov/~dms/opaesub.html when available. For submitting questions during and after the webcast, the e-mail address is electronic_submissions@cfsan.fda.gov. Copies of the guidance documents also can be found on FDA's website at http://www.cfsan.fda.gov/~dms/opa-toc.html. 7. ACGIH Postpones Finalizing TLV for Mineral Oil Mists The American Conference of Governmental Industrial Hygienists (ACGIH) has announced that it will not be finalizing this year action on its proposal to change the carcinogenicity status and lower the permissible occupational exposure TLV (Threshold Limit Value) of mineral oil mists. ACGIH also indicated that it will discuss the issue during its February, 2002 meeting before further action is taken. You may recall that the TLV Committee of the ACGIH recently proposed that mineral oil mists be assigned an "A2 Suspected Human Carcinogen" status, and that the permissible occupational exposure TLV be lowered to 0.2 mg/m3. Currently, acute and chronic exposure to mineral oil mists is regulated by an Occupational Safety and Health Administration (OSHA) permissible exposure limit of 5 mg/m3 as an 8-hour time-weighted average concentration. ACGIH, as well as OSHA, currently includes in the definition of mineral oils and their mists the following substances: white mineral oil (considered food-grade), paraffin oil, cutting oil, hydraulic oil, transformer oil, lubricating oil, and others. Some plastics applications associated with potential generation of oil mists include metalworking and mold making, mist lubrication, mold release agents, oil-lubricating tools, and printing inks. 8. Keller and Heckman LLP to Hold Seminar on Regulation of Packaging Keller and Heckman LLP will present a seminar, titled FDA 101: An Introduction to the Food and Drug Administration's Regulation of Packaging Materials, on October 22, 2001 near our offices in Washington, D.C. Over the years, we have presented this seminar to many individual companies and at meetings of the Committee, and now are offering a chance for our clients and other interested individuals to attend the first of what we hope will be a regularly scheduled series of such programs. The program will include presentations from Keller and Heckman lawyers and scientists. A general question and answer session will follow the presentations. As many of you know, despite its title, FDA 101 is not just an introduction to FDA regulation, it is a comprehensive explanation of the legal/regulatory and technical aspects of the way the Agency clears packaging materials and the ways to avoid FDA when Agency clearance is not required. For more information on the specific topics to be discussed, please visit our special packaging website at www.packaginglaw.com. The conference, which will be held at The Grand Hyatt at Washington Center, is scheduled to run from 8:30 a.m. to 5:00 p.m., and includes a continental breakfast and lunch. Seating for the conference is limited, and reservations must be made by contacting Jolana Roberts at roberts@khlaw.com or 202-434-4270 by October 8th. The fee for the program is $250. * * * 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 Back to TopMore 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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