Document o9OpjvxqgK5Jx319vmrQeGOOX

THE SOCIETY OF THE PLASTICS INDUSTRY, INC. 250 PARK AVENUE NEW YORK, NEW YORK 10017 212/687-2675 MINUTES MEETING OF SPI FOOD, DRUG AND COSMETIC PACKAGING MATERIALS COMMITTEE Summit Hotel of New York New York, N. Y. June 19, 1969 9:40 a.m. Present Robert M. Miller, Chairman, Hercules, Inc., 910 Market St., Delaware Trust Bldg., Wilmington, Del. 19898 Taylor W. Hanavan, Vice Chairman, E. I. du Pont de Nemours & Co., Inc., 1007 Market St., Film Dept., Wilmington, Del. 19898 W. B. Ackart, Union Carbide Corp., Chemicals & Plastics, One River Road, Bound Brook, N. J. 08805 R, Arnold, M & T Chemicals Inc., Woodbridge Ave., Rahway, N. J. 07065 R. C. Asam, The Goodyear Tire & Rubber Co., Chemical Materials Dept., Dept. 480D, 1485 E. Archwood Ave., Akron, Ohio 44316 W. M. Atkinson, Nopco Chemical, 60 Park Place, Newark, New Jersey N. D. Bornstein, W. R. Grace & Co., Cryovac Div., Duncan, S. C. 29334 K. C. Conley, Development Div,, Borg-Warner Corp,, Washington, W. Va. 26181 P. F. Gundy, American Can Co., Research & Development Dept., Box 702, Neenah, Wis. 54956 R. A. Dannells, Dart Industries, Inc., P. 0. Box 37, Paramus, N. J. 07652 L. J. DeCorte, Sinclair-Koppers Co., Product Development, Frankfort Rd., Monaca, Pa. 15061 H. R, Dittmar, Imco Container Co., Div. Ethyl Corp., 75th & Cleveland Sts., Kansas City, Mo. 64132 D. S. Dixler, AIRCO, Air Reduction Co., Inc., Central Research Laboratory, Murray Hill, N. J. 07971 R. J. Dowling, Uniroyal Chemical, Div. of Uniroyal, Inc., Elm St., Naugatuck, Connecticut 06770 G. W. Ferner, The Goodyear Tire & Rubber Co., Research Div., 1144 East Market St. Akron, Ohio 44316 A. B. Finestone, Foster-Grant Company, Inc., 289 North Main St., Leominster, Mass S. W. Foulkrod, III, Law Division, Scott Paper Co., Research Div., Philadelphia, Pennsylvania 19113 L. J. Friedman, Ruco Division, Hooker Chemical Corp., New South Rd., Hicksville, New York 11802 B. J. Garceau, ICI America, Inc., P. 0. Box 1274, 151 South St., Stamford, Conn. Jerome H. Heckman, Keller & Heckman, 1712 "N" St., N, W., Washington, D.C. 20036 P. L. Henry, Esquire, Allied Chemical Corp., P. 0. Box 405, Morristown, N. J. ASI 00000821 2- - K. A. Hochschwender, American Hoechst Corp., P. 0. Box 2500, Somerville, N, J. T. J. Hughes, Esquire, Keller & Heckman, 1712 "N" St,, N. W., Washington, D. C. D. H. Hunter, Stauffer Chemical Co., Plastics Div*, P. 0. Box 320, Delaware City, OUaware 19706 G. W. Ingle, Monsanto Co., 1101 - 17th St., N. W., Suite 604, Washington, D. C. N. A. Jappe,Scott Paper Co., Philadelphia, Pennsylvania 19113 J. F. Jones, The Standard Oil Co. (Ohio), Midland Bldg., Cleveland, Ohio 44115 W. A. Knapp, Allied Chemical Corp,, Bad. Cliemiuwl Sfer., P, 0. Box 405, Morristown, N. J. 07960 F. S. Landers, Owens-Illinois, Lily Tulip Div., 500 Cotanack, N. Y. 11725 W. A. Larkin, M & T Chemicals, Inc., Rahway, New Jersey 07065 J. R. S. McCartney, Standard Packaging Corp., Ill Prospect St., Stamford, Conn. J. McDermott, SPI, 250 Park Ave., New York, New York 10017 G. L. McIntyre, Columbian Carbon Co., P. 0. Box 975, Princeton, N. J. 08540 K. Morgareidge, Food & Drug Research Laboratories, Inc., Maurice Ave. and 58th St., Maspeth, N. Y. 11378 P. Morison, Eastman Chemical Products, Inc., Chemical Sales Dev. & Technical Service, Kingsport, Tenn. 37662 W. P. Munro, American Cyanamid Co., Bound Brook, New Jersey 08805 B. G. Ikirray, Ferro Corporation, Color Division, 4150 E. 56th St., Cleveland,Ohio S. Nesmith, USI Chemicals Co., P. 0. Box 218, Tuscola, 111. 61953 A. S. Nyquist, American Cyanamid Co., P. 0. Box 425, South Cherry St., Wallingford, Conn. 06492 J. N. O'Connor, The Dow Chemical Co., Legal Dept., 47 Bldg., Midland, Mich. 4S640 B. N. Olson, Reynolds Metals Co., 10th & Byrd Sts., Richmond, Va. 23219 I. F. Peake, E. I. du Pont de Nemours & Co., Inc,, Film Dept., 1007 Market St., Wilmington, Del. 19898 G. A. Richter, Jr., Rohm & Haas Co., Independence Mall West, Philadelphia, Pa. A. M. Schnitzer, Phillips Petroleum Co., Research & Development Dept., 356 Chemical Laboratories, Bartlesville, Okla. 74003 W. W. Sederlund, National Starch & Chemical Corp., 1700 West Front St., Plainfield, N. J. 07063 M. E. Smith, Owens-Illinois, Plastic Products Div., Adams & 14th Sts., Toledo,Ohio C. J. Spiegl, Continental Can Co., Inc., 7622 South Racine Ave., Chicago, 111. M. C. Stone, Eastman Chemical Products, Inc., P. 0. Box 431, Kingsport, Tenn. V. R. Struber, Argus Chemical Corp., 633 Court St., Brooklyn, N. Y. 11131 M. F. Tietze, Airco Chemical & Plastics Div., Air Reduction Co., Inc., Murray Hill, N. J. 07971 H. Turpack, Diamond Shamrock Corp., P. 0. Box 191, Painesvllle, Ohio 44077 W. M. Westveer, The Dow Chemical Co., 433 Bldg., Midland, Mich. 48640 A. G. Whitney, W. R. Grace & Co., Research Div., Clarksville, Md. 21029 Charles L. Condit, Secretary. SPI, 250 Park Ave., New York, N. Y. 10017 Robert M. Miller, Hercules, Inc., Chairman of the Committee, called the business session to order at 9:40 a.m. He then referred ta a detailed agenda circulated with the Secretary's meeting announcement and, as a first order of business, asked for the usual self-introductions. ASI 00000822 3 Minutes Last Meeting Approved In the absence of comments as to corrections or additions to the Minutes of the last meeting held on November 7, 1968, Mr. Miller declared them approved as written and distributed by the Secretary. Remarks of Conmittee Chairman Mr. Miller then dealt briefly with several items of general interest to the Committee. He, firstly, announced that James A. Mitchell, Film Department, E. I. du Pont de Nemours & Co., Inc., has within recent weeks retired from the company and then asked that the Secretary place in the records a statement of deep apprecia tion to Mr. Mitchell for the time and effort that he has expended during some ten years of membership on the Committee. Mr. Miller next reported that within recent weeks, the American Society of Mechanical Engineers has organized a Food, Drug and Beverage Equipment Committee; that in this regard, SPI was invited to be represented on the Committee if it felt that it could contribute to the activities of the group. Continuing, Mr. Miller said that, essentially the purpose of the new committee, as presently defined at least, is to study the possibility of developing a safety code on food, drug and beverage equipment and practices. Mr. Miller then said that he Instructed the Secretary to advise ASME that, at present, the SPI Conmittee is not immediately interested In equipment per se, but that the Society would indeed like to be on the mailing list of the ASME Committee so that we can be aware of its activities and perhaps take an active part in its future work if there are indications that this would be mutually beneficial. The Secretary has taken this step and the Society is now on the ASME group's list. Continuing, Mr. Miller reminded that, under date of January 3, 1969, Jerome H. Heckman, Esquire, Keller and Heckman, had advised all members of the Committee about a communication received from Dr. Maurice Green of the American National Red Cross relative to a proposed protocol for a plastics evaluation program to be conducted by the Red Cross, the said program being designed to evaluate plastic materials suitable for the fabrication of containers for blood and related substances. In Mr. Heckman's letter to the members of the Committee, he pointed out, on Mr. Miller's instructions, that the distribution of this material would serve as a sufficient catalyst for those who were interested in the program so that they could proceed individually to contact Dr. Green directly. Mr. Miller announced, at the day's sessions, his belief that SPI has been of immeasurable help to Dr. Green in this particular project in view of the fact that Dr. Green has informed him that he has received some very promising leads from a number of companies represented on our Conmittee. Mr. Miller then asked the Secretary to attach to the Minutes of the day's session the new protocol for the "plastics evaluation program" developed by the American National Red Cross so that ail interested members of the Committee may study it. (Please Note; Attached hereto as Exhibit A is the March 1, 1969 draft of the new "protocol.") ASI 00000823 -6 - instances, it is not possible to identify a questioner or commenter. In such cases, the transcript simply indicates that the question or comment did come from the floor and was made the subject of appropriate discussion. At the conclusion of the wide-ranging discussion reflected in the transcript, the Chairman of the Committee, Mr. Miller, asked for a vote from the floor to approve the action being taken on behalf of SPI in conjunction with the so-called Inter industry Committee to bring about desired changes in the Ramsey proposal. The Committee then approved the action as requested by Chairman Miller unanimously. Report of Food Additives Petition Manual Subcommittee The Committee was reminded that, at the last meeting, an ad hoc Subcommittee was appointed to begin preparing a Manual on Food Additive Petitions. Or. Karl A. Hochschwender, American Hoechst Corporation, was appointed Chairman of this particular Subcommittee. Dr, Hochschwender then delivered the following status report: "Those of you who were in attendance at the Coanittee1s last meeting on November 7, 1968, will recall the discussion which centered on the desirability and feasibility of establishing a subcommittee of this Committee to undertake the drafting of what would ultimately amount to an SPI Food Additives Petition Manual. It was thought that such a Manual would be most helpful for technical, administrative and legal corporate personnel in the drafting of food additives petitions for incidental additives. "At the November meeting, a resolution approving the project was adopted and a Subconmittee is now comprised of Messrs. Asam, Goodyear Tire and Rubber Company; Conley, Borg-Wamer; Garceau, IC1 America Inc.; McCartney, Standard Packaging Corporation; Morrison, Eastman Chemical Products, Inc.; Nesmith, U. S. Industrial Chemicals Company; Peake, E. I. du Pont de Nemours and Co., Inc.; Smith, Owens-Illinois; and Dr. Kenneth Morgareidge, Food and Drug Research Laboratories, Inc. The Subcommittee was also promised the assistance of SPI Legal Counsel. "As matters developed, the Subcommittee convened its first meeting at the offices of Keller and Heckman on January 9, 1969. The meeting lasted several hours, and I think all who were there will agree that it was most fruitful in terms of laying the necessary foundation work for the proposed Manual. A first draft outline of the proposed Manual was drawn up at the meeting. The outline provided that, tentatively, the Manual shall be divided into the following seven parts: "Part I "Part II "Part III - Purposes and Objectives General and Background Information How to Approach a Potential Indirect Food Additive Problem at the Outset - continued - ASI 00000824 7 "Part IV "Part V "Part VI "Part VII How Petition* Are Processed at FDA Importance of Developing Analytical Data Toxicology-Protocols and Reports Sample Petitions (To Be Used As Appendices to the Manual) "Members of the Subconmittee were assigned to work on one or more of the various sections of the Manual, and it was hoped that a 'first draft* of part of the Manual could be prepared and distributed to Subcommittee members prior to this Meeting. "Unfortunately, the actual preparation of such a first draft has been delayed partly because the press of other urgent business has prevented Counsel, and several other members of the Subcom mittee from being able to complete their respective assignments; and, perhaps more Importantly, because of the recent significant developments at the Food and Drug Administration (namely, the now "semi-official" FDA proposal to amend Part 121.2SOO of the Food Additive Regulations) which could have great impact on the way in which the subject matter of our Manual will be presented. "These latest developments at FDA will necessitate some further thinking and possible reevaluation of the type and extent of information that should be included in any proposed Food Additive Petitions Manual. "We do Intend to go forward with this project diligently, however, so I urge those members of the Subconmittee who have not, as yet, completed their first assignments to do so at the earliest possible time. I believe I can feel quite safe in assuring the full Com mittee that we shall have more tangible results to report by the time of the next meeting. "Thank you." Reports on Liaison with Other Organizations Mr. Miller pointed out that, by tradition, the Committee hears at each of its meetings general reports on the Interests and activities of other associatl ns and groups vis a vis FDA activities. Synthetic Organic Chemical Manufacturers Association (SOCMA) W. P. Munro, American Cyanamid Company, delivered the following status report: "Since the last meeting of the SPI Food, Drug and Cosmetic Packaging Materials Committee, the members of the SOCMA Dyes Additives Cosmlttee have been supplied with the text of the - continued - ASI 00000825 -8- Ramsey proposal. No further action has been reported. It Is believed that the liberalized features of the Ramsey proposal will not greatly affect the position of dyes as indirect food additives. "It is suspected that Food Additives Petition 367 will be delayed further, while the Ramsey proposal is being considered." In addition to his prepared report, Mr. Munro commented in response to a question that the long pending SOCMA petition to clear organic dyes for use with paper products remains pending and that no immediate action is anticipated despite the long delay. The general feeling of SOCMA is that the Food and Drug Administration may well await some final action on the Ramsey proposal before acting on the petition since the two subjects could have some interrelation. Pharmaceutical Manufacturers Association SPI Liaison Group Chairman Miller called upon Watt Ackart, Union Carbide Corp., and Chairman of the liaison group between SPI and the Pharmaceutical Manufacturers Association, who presented the following report: "You will recall that the joint PMA-SPI study of methodology for testing polyolefin containers for tablets, capsules, oral powders, granules and ophthalmic pharmaceutical products has been the main concern of this group since Its reactivation in 1967. At the November 1968 meeting of this committee we reported that the Quality Control Section of the PMA had agreed to publish the methodology in the National Formulary but for ophthalmic products only and that opposition had developed regarding publication of the method as applied to dry products. At the last meeting we were instructed to pursue this further and expedite, if possible, the dry products publication. "Last March, Matt Smith and I met in Detroit with representa tives of the PMA and learned that the reluctance on the part of the PMA Quality Control Section was due to a feeling that the tests without numerical limits were of little value and represented only additional testing requirements which should not be encouraged. At this Detroit meeting, the concept was developed that the test procedures might be acceptable to the PMA if the resin and/or container suppliers accepted the responsibility for carrying them out. To sell this idea, the SPI was invited to send two speakers to address the spring meeting of the PMA. We made no formal commitment pending instructions from our Steering Conmittee, "Last April, at a joint meeting of our Liaison Group with the Steering Committee of the SPI FD & C Packaging Materials Committee, this proposal was discussed and it was agreed that - continued - 00000826 ASX the PMA Invitation should be declined with thanks since SPI member companies could not be committed to conducting such a testing program without discussion in the full committee. We subsequently advised the PMA of this position. It was further agreed that the whole question of the regulation of drug packaging was both unclear and unrealistic and that the SPI might well spearhead an attempt at simplification starting with polyolefin containers for dry pharmaceuticals. The PMA Liaison Group was instructed to prepare a proposal for a simplified procedure. A draft of such a procedure has been prepared and circulated for comments among members of the PMA Liaison Group. There have been no major objections which cannot be reconciled and it is hoped that a consensus draft can be prepared and circulated to this full committee either as an appendix to the minutes or as a separate mailing. We would then hope that our proposal meets with the approval of this committee and with the SPI as a whole. We expect then to approach the PMA and with their approval then to discuss our proposal with FDA in the hope that it can be incorporated into their Drug Regulations. "Meanwhile, the methodology will appear in the National Formulary without numerical limits and applied to ophthalmic products only. Our friends in the PMA will continue to try for extension of the methodology to dry products but they are not hopeful of much success without our active support." During the course of the day's meeting it was agreed among the members of Dr. Ackart's group that a meeting would be held in Detroit, Michigan, towards the end of July to go over the draft document prepared for ultimate presentation to the Pharmaceutical Manufacturers Association, and perhaps thereafter to the Food and Drug Administration. After the group meets in Detroit as planned, it is likely that the draft will be placed in final draft form. At this point, it will be circulated to the full Food, Drug and Cosmetic Packaging Materials Committee of the Society for conanents, after which appropriate meetings will be arranged with representatives of the Pharmaceutical Manufacturers Association to discuss the SPI concept. Depending on the outcome of such sessions, further action will be taken appropriate to the circumstances and the full Committee will be kept advised of all developments.*/ */ This group met on August 6 In Detroit and decided that rather extensive revisions to its first draft will be necessary prior to its circulation to the full Committee for review. Dr. Ackart is presently revising the material for additional consideration by the group. ASI 00000827 10 - Manufacturing Chemists' Association (Food Drug and Cosmetic Chemicals Committee) Taylor W. Hanavan, E. I. du Pont d^ Nemours & Co., Inc., delivered the following report on activities within MCA of interest to the Committee: "The Manufacturing Chemists' Association met on April 2, 1969. Very little was discussed of direct interest to the plastics industry. One arpect of discussion though is directly perti nent. The U. S. Food and Drug Administration did not accept the MCA request, and the requests of many others, that food chemical plants be exempt from the new Good Manufacturing Practices Regulations for food plants. Final regulations have been issued without any exception for such plants. "There was some discussion at the MCA meeting as to what the regulations will mean to the food chemical industry,which, I think, would have equal application to the food packaging industry. It was the consensus of the people present - not, I hasten to make clear, the official consensus of the commit tee - that a "wait and see" attitude would be appropriate; that is, wait and see how FDA will attempt to implement the regulations in connection with the food chemical plants or food packaging operations. "In this regard, the Food Chemical News issue of June 16, contains some fairly interesting conmentary excerpted from a presentation given by Alfred Bernard, Associate Director of FDA's Bureau of Compliance, at a meeting of the Federal Bar Association on June 12. As reported In FCN: "Bernard said that 'FDAers on the administrative side have been uncertain for some time just to what extent the Good Manufacturing Practice Regulations have the force and effect of law.' Bernard conceded that when work started on the Good Manufacturing Practice Regu lations five years ago 'they were regarded by us and by the industry generally as interpretive regulations' which 'merely expressed FDA's views as to what pro cedures would constitute compliance, and that there was ample latitude for industry to use other methods or techniques which might be equally or more effective in achieving compliance with the law itself.' More recently, Bernard continued, HEW Counsel William W. Goodrich 'has apprized us that these regulations have essentially the full force and effect of law.' Bernard noted disagreement with the staff by industry lawyers. "The FDAer expressed doubt that FDA 'will get a court interpretation of the question as a result of direct enforcement action,' He explained: 'The problem is - continued - ASI 00000828 11 - that FDA Is quite unlikely to bring a legal action for violation of Good Manufacturing Practice Regula tions unless the conditions are so bad that they either totally discourage vigorous defense or so surely constitute a violation of the law per se as to be independent of these regulations.'" American Paper Institute James R. S. McCartney, Standard Packaging Corp., reported that he had nothing more to relate on activities within the American Paper Institute than the information Mr. Heckman was covering in his report on the work of SPI in connection with the Ramsey proposal. Can Manufacturers Institute Charles J. Spiegl, Continental Can Co., Inc., also indicated that he had no further report to deliver at the day's meeting other than to point out that the Can Manu facturers Institute is participating in the Inter-Industry Committee dealing with FDA and that the Institute is taking no other independent action of any sort. SPI Food and Drug Bottling Committee of the Flastic Bottle Division M. E. Smith, Owens-Illinois, delivered the following report: "The Food and Drug Bottling Conmittee is working with the Mayonnaise Salad Dressing Institute to develop test pro cedures and performance data for three types of dressings packaged in different plastic containers. The task group will use standard formulae for three dressings consisting of: 1. Non-separating French 2. Separating French 3. Spoonable Salad Dressing "Two size containers, an 8 oz. and 16 oz. will be used. Approximately 2300 containers for each material will be required. "PVC and XT resins are to be tested. The task force has decided not to work with Barex at this time since it has not yet been approved for food use by FDA. They will not test polyethylene since its gas barrier properties are so much poorer than either PVC or XT. "The Food and Drug Bottling Comnittee at their next meeting on July 10th, will decide what PVC types will be used. The testing program will be run for six months at which time a final report will be written. - continued - ASI 00000829 T - 12 - "Bill Cummings of Creative Packaging Company will be the new Food Bottling Subcommittee Chairman. This Subcommittee is still working on putting together a "Primer for Food Bottling." Report of Technical Information Subcommittee Chairman Miller next called for a report from the Technical Information Subcom-' mittee, to which, from time-to-time, the overall Committee refers technical problems for handling. One of the continuing services of the Technical Information Subcommittee has been to provide at each session a listing of recently promulgated Food Additive Regula tions of interest. Thus, Mr. Willard M. Westveer, The Dow Chemical Company, pre sented such a listing and highlighted the issued regulations which he felt of particular significance. (Please Note: Attached hereto as Exhibit C is Mr. Westveer's report on recently promulgated Food Additive Regulations.) Status Report - Activities of SPI Plastics Waste Disposal Committee George W. Ingle, Monsanto Company, and Chairman of a recently formed SPI committee dealing with plastics waste disposal delivered the following status report: "This Committee is completing its organization with emphasis so far on clarifying its mission and objectives. "Mission is to study the problems associated with the disposal of plastics within the framework of present and future systems for solid waste management; to provide positive information to the public, and responsible leadership in implementing these solutions toward better management of our environment. "This mission has been analyzed in terms of a series of specific objectives. These will be implemented by a limited Committee organization via two subcommittees. I - Communications (Publications and Public Relations) and II - Technical Liaison (Information Sources, and Inter-Group Liaison), additional subcommittees may later be necessary. "Chief among the twenty odd objectives is for the Communications Subcommittee to prepare an in-depth document 'Proposals for Disposal of Plastic's Waste', by composition, product, end-use, origin, distribution by volume, in residential, municipal and industrial categories (present and future) by disposal routes new and old. "Preparation of this document will require parallel effort by the Technical Liaison Subcommittee. This will encourage compi lation from member companies, of data on identity, corrosivity, and toxicity of combustion products, distribution by volumes of all types of plastics, specific ingredients of concern (Cl, Br, Se) etc. - continued - ASI 00000830 13 "This first project for the Plastic's Waste Disposal Comnittee is very specific but also large and important. Volunteers from member companies will be needed to staff the two Subcommittees if this needed SPI program is to be successful. "To identify such volunteers, and their preferred areas of activity, an organization meeting of the full Committee, and of the two Subcommittees is being scheduled for July 31. "In the miscellaneous department: "1) Eastman Kodak has received B. P. 1,128,793 claiming a U.V. - light disintegratable packaging material comprising a copolymer of ethylene and carbon monoxide. "2) In a recent speech, BTC Commissioner J. M. Nicholson said 'If the price of packaging is out of proportion to the value of the product, or if the result of packaging innovation is the creation of new social problems or the aggravation of existing ones, then a more militant generation of consumers may exert massive pressures for change.' "3) Senator Muskle's recently introduced bill (S.2005 Resource Recovery Act of 1969) amends and extends The Solid Waste Disposal Act of 1965, aims to recover useful materials from solid waste, recom mends incentives to solve SWD problems, and proposes changes in production and packaging practices to reduce solid wastes, and finally, "4) We note an increasing number of new uses of plastics in solid waste disposal equipment. "5) This week, New York City begins large-scale trial of polyethylene garbage bags." Report of Lawyers' Advisory Subcommittee Chairman Miller next called on Taylor W. Hanavan, DuPont, who presented the following report: "At our last meeting, we noted the establishment of the National Commission on Product Safety and the fact that this organization would be conducting hearings throughout the country during the course of 1969 on household products other than foods and drugs. Since the first hearing, a hearing was held in Boston, Massachusetts, dealing with various statutory and common law legal liability problems connected with the marketing, sale and use of household products, and additional hearings have been held in - continued - ASI 00000831 14 - Washington and Chicago. A series of hearings on the West Coast are now being held on various aspects of the product safety area. "As a result of these hearings, one piece of federal legisla tion has been proposed - Senate Bill 1639 to amend the Federal Hazardous Substances Act to protect children from toys and other articles intended for use by cnildren which are hazardous due to the presence of electrical, mechanical or thermal hazards. I I I "Another piece of federal legislation that has been introduced in the House is H.R. 6180, which would give the Commissioner of FDA authority to set up standard packaging requirements for toxic household substances. Presumably, such standards would require producers to package products designated by the Commis sioner as toxic household substances in such a way as to deny access to them by children. This would be somewhat similar to the safety closure specification for aspirin bottles that FDA and industry have jointly developed. Again this bill is pending. No committee hearings have been set. "We pointed out at the last meeting a series of bills in Congress relative to occupational health and safety. We were then talking about 1968 bills authorizing the Secretary of Labor to set up industrial hygiene safety standards for all manufacturers operating in interstate commerce. Essen tially similar bills have been introduced again in this session of Congress authorizing the Secretary of Labor to set up standards and to appoint a national advisory committee to make safety standard recommendations to the Secretary. "Actually, the bill in this area that probably will be of most interest has not yet been introduced; it will be a socalled administration bill. From what we are able to gather, the administration bill presently being contemplated would provide for a council of advisors who would be permanent federal employees responsible for the development of standards of industrial safety and recommending same to the Secretary of Labor. If the Secretary did not like a recommendation, he would have a veto power except that, if the Council of Advisors four out of the five members as presently constituted in the proposed legislation - were to reaffirm the standard, the Secretary of Labor would have no choice but to promulgate it. The whole question of industrial safety standards is now wrapped up in a tremendous battle as to which federal agency should have complete responsibility in this area. Should it be HEW or the Department of Labor? "We also mentioned at the previous meeting regulatory proposals by the Secretary of Labor (Willard Wirtz at that time) under - continued - ASI 00000832 15 - the Walsh-Healey Act dealing with safety procedures In production facilities of federal government contractors. The procedures proposed excessively stringent safety standards in several areas. Notwithstanding protests and requested modifications, Mr. Wirtz, as one of his last contributions to the Johnson Administration, finalized I his Walsh-Healey Act proposals without substantial change I in the Federal Register of January 17, 1.969. "The new Administration, under Mr. Schultz, appointed a tri-partite National Safety Advisory Committee to conduct a careful review of the Regulations, at the same time post poning the effective date until May 17, 1969. "The Advisory Committee recommended that the Secretary adopt a modified set of safety regulations which would, among other things, incorporate by reference consensus safety standards, such as those promulgated by USASI, NFFA, ASMS, and ASTM, wherever possible, "The regulations which became effective upon their publica tion in the Federal Register on May 20, 1969, provide for a range of permissible noise levels of from 90 decibels for an eight hour day to 115 decibels for a quarter of an hour or less, "I might also note in passing that the regulations provide that compliance with applicable state safety, sanitary and factory inspection laws shall be deoned to be prima facie evidence of compliance with the federal regulations. However, because of the evident mandatory fashion in which government representatives are instructed to apply federal standards, any effect compliance with state laws might have is, at best, somewhat vague. "There are two recent cases of interest I would like to men tion. In deference to our sister corporation, which lost the case, I won't go into detail on the first of these - Neville < Chemical v. Union Carbide, found in paragraphs 6121 of the | CCH Products Liability Reports, However, I commend it to any attorney here, and suggest that non-attorneys here comj mend it to their attorney advisors to read. It deals with the very important issues of disclaimers of warranty, notice of limitation of claims and the time within which claims must be received. "What I do want to discuss in some detail is the case of United States (Petitioner) v. An Article of Drug...BactoUnidisk,..(Difco Laboratories. Inc.. Claimant), 37 Law Week 4382, which I think is of considerable significance to the plastics industry in that it bears directly on an area that heretofore we all hoped might go away - that is, the area - continued - ASI 00000833 16 - of surgical use of plastic products. This case involved a disc to test the sensitivity of antibiotics. I'm sure moat of you are familiar with the fact that the disc itself is used as a diagnostic aid, usually by outside laboratories. The U. S. Supreme Court in a logical extension of its decision in Amp v. Gardner had little difficulty in ruling that this diagnostic aid was a 'drug.' "A few words from the Supreme Court's opinion might illustrate the broad scope of the Court's interpretation of the meaning of the word 'drug' as defined in Section 201 (g) of the Act. '(T)he legislative history, read in light of the statute's remedial purpose directs us to read the classification 'drug' broadly, and to confine the device exception as nearly as is possible to the types of Items Congress suggested in the debates, such as electric belts, quack diagnostic scales, and therapeutic lamps, as well as bathroom weight scales, shoulder braces, air conditioning units and crutches.... We need only point out that the (device) exception was created primarily for the purpose of avoiding the semantic incongruity of classifying as drugs (1) certain quack contraptions and (2) basic aid used in the routine operation of a hospital, items characterized more by their purely mechanical nature than by the fact that they are composed of complex chemical compounds or biological substances.* "I think it is safe to say that with the. exception of bandages, surgical swabs, sponges, sutures and possibly a few other surgically related products, industry has generally classified all surgical implant uses of plastic products as devices. The Food and Drug Administration, of course, has been attempting for a number of years to get device legislation requiring premarket approval ostensibly to go after the quack devices, 'cancer cure' products and so forth but, nevertheless, also to get statutory control over many items used for surgical applications. The Bacto-Unidi3k decision now provides FDA with ample authority in the surgical use area. "Since the Bacto-Unidlsk decision, it has been reported that FDA bed been in the process of developing a policy statement as to what device products the agency was now going to consider to be 'drugs.' However, we now understand that no such policy statement will be issued, at least in the near future. Regardless, it will be hard to ignore the drug implications of the Supreme Court's decision with respect to surgical implant materials. "Assuming surgical implant materials may be classified as drugs, as plastics suppliers, consideration should be given to your company's handling of Inquiries from the medical profession for - continued - ASI 00000834 17 samples of these materials. If drug use Is Involved, then the sample provided may be a drug component. Depending on the circumstances, and always after having checked quite carefully with your company counsel, you may then have to consider the need for special investigational drug labeling or for registering your facility as a drug production facility with the Food and Drug Administration. "In any event, and in all cases, I strongly urge that you consult and work closely with your own company counsel on questions of this type." Following Mr. Hanavan's report, there was a rather wide-ranging discussion among those present relative to such matters as the distinctions between drugs and devices, the regulatory ramifications of this distinction, and the precautionary steps that companies in the plastics industry should take when they supply materials to doctors, for example, for experimental work. It was strongly sug gested that company officials should consult with their own counsel regarding such activities sc as to avoid the possibility that, by cooperating with those in the medical profession, their companies will be subjected to unanticipated regulation by the Food and Drug Administration. Some such activity could, for example, necessitate the registering of an installation as a drug plant without any true intent or desire of management to maintain a drug plant. International Developments In introducing Thomas J. Hughes, Keller and Heckman, Chairman Miller said that of continuing interest to the Committee within the past several years have been developments abroad in the regulatory area. Thomas Hughes then delivered a detailed status report on regulatory matters in the United Kingdom, the Netherlands, the activities of Codex Alimentarius Commission, and, recent contacts with other European countries. (Due to the length of Mr. Hughes' report, it is being attached hereto as Exhibit D.) Consideration of Committee Bylaws vis a vis New SPI Bylaws By way of reminder, Mr. Miller noted that the SPI Board of Directors has, within recent months, developed a new "plan for Growth" in order to assure that the Society's services to its members keep abreast with the growth of the plastics industry. In this regard, the membership of the Society overwhelmingly approved new Bylaws composed around the "Plan for Growth." In this connection, the Steering Committee, with the help of Jerome Heckman, has reviewed the Bylaws of the SPI Food, Drug and Cosmetic Packaging Materials Committee, finding that, fortunately, there will be no need to change them in order to assure their compliance with the new Bylaws of SPI. ASI 00000835 18 - t New Business There was no further business offered for discussion at the day's meeting. Next Meeting Mr. Miller announced that, as usual, the date and site for the next meeting of the full Committee will be left up to the Steering Conmittee. The day's session was adjourned at 3:00 p.m. Respectfully submitted, Charles L. Condit Secretary CLC:vw Enclosures (4) ASI 00000836 Cn3 U THE AMERICAN NATIONAL RED CROSS EXHIBIT A PLASTICS EVALUATION PROGRAM PROTOCOL MARCH 1, 1969 AS I OOO00837  TABLE OF CONTENTS Pagg SECTION 1 - INTRODUCTION 1.1 Purpose 1.2 Participation 1.3 Definitions 1.4 Subcontracts SECTION 2 - PROTOTYPE CONTAINERS 2.1 Acceptable Materials 2.2 Preliminary Evaluation 2.3 Acceptance and Classification of Materials 2.4 Test Lots of Prototype Containers 2.5 Single Class Evaluation 2.6 Multiple Class Evaluation 2.10 Container Construction 2.11 Container Dimensions 2.12 Container Volume 2.13 Ports 2.14 Pilot Tubes 2.15 Suspension System 2.20 Solutions and Filling 2.21 Schedule for Filling 2.22 Addition or Deletion of Solutions 2.25 Sterilization 2.26 Non-Sterile Containers 2.27 Labels 2.28 Boxes 2.29 Additional Containers 2.30 Test Lot Data 2.31 Divided Responsibility 2.32 Additional Data 2.33 Limited Responsibility 2.34 Delivery of Test Lot SECTION 3 - TEST PROCEDURES 3.1 3.2 3.10 3.11 3.12 3.13 3.14 Tests to be Performed Sampling of Test Lots Initial Sterility, PyTogenicity and Safety Tests Unfilled Containers Sodium Chloride Solution Glycerol-Mannitol Solution Anticoagulant Solutions 1 1 1 2 3 3 3 3 4 4 4 4 5 5 5 6 6 7 7 8 8 8 8 9 9 9 9 10 10 11 11 11 11 11 11 12 ASI 00000838 TASTE ny reENTS (Continued) J.20 3.21 3-25 3*30 3.31 3.32 3.33 3.34 3-40 3.41 3.45 3.46 3.47 3.4R 3.49 3*50 3.55 3.56 3.57 3.60 Initial Biological Tests U.G.l'. CpouificationG for Toxicity Tissue Culture Testa Physical-Chemical Analysis Spectral Analysis of Containers Spectral Analysis of Contents Thermogravinetrie Analysis Chemical Extraction Mechanical Tests Inspection Tests of Plastic Materials Impact Brittleness Tear Resistance Tensile Strength Transparency Water Absorption Tests on Containers Rupture Test Drop Impact Test Accelerated Service Tests . SECTION 4 - LONG-TERM STORAGE 4.1 Sampling for Storage 4.2 Storage Temperatures 4.3 Storage Periods 4.4 Weight Loss 4.5 Testing of Stored Containers 4.6 Toxicity Tests on Contents 4.7 Toxicity Tests on Containers 4.3 Mechanical Tests 4-9 Additional Tests on Unfilled Containers SECTION 5 - CLINICAL TRIALS 5.1 In Vitro Tests 5.2 Packed Red Blood Cells - Class A/B 5.10 Acceptance for Clinical Studies SECTION 6 - GENERAL CONDITIONS 6.1 Modifications of Protocol 6.2 Test Results 6.3 Final Evaluation 6.4 Reports to Participants 1 6.5 Reports to NIH 6.6 Other Reports 6.7 Non-Endorsement of Products 6.8 Termination of Tests ASI 00000839 Pare 12 12 12 12 13 13 13 13 13 13 14 14 14 14 14 14 14 14 15 15 16 16 16 16 17 17 17 17 17 18 18 18 19 19 19 19 19 20 20 20 SECTION 1 - INTRODUCTION 1.1 PURPOSE The American National Red Cross (ANRC) is currently investigating new methods for the processing and preservation of blood and blood products. This research is being conducted by the ANRC Blood Research Laboratory under a contract with the National Heart Institute of the National Insti tutes of Health. As a part of this program, the ANRC is conducting an evaluation of plas tic materials suitable for the fabrication of blood and blood product containers to be used at temperatures from +40 to -196cC. This evalua tion will consist of toxicological, chemical, mechanical and clinical tests to be performed on test lots of prototype containers submitted by participating plastics and/or container manufacturers. A basic goal of this effort is to provide a cooperative evaluation pro gram between the ANRC and industry which will (l) identify new plastics which are potentially suitable for blood containers, (2) provide a care fully controlled comparative evaluation of these materials, and (3) pro vide the manufacturer with an independent set of data which may be used for license application for suitable materials. This, in turn, will serve the public interest by expediting the establishment of new improv ed methods of processing and preservation to insure an adequate supply of blood and blood products. It should be noted that although this will be a comparative evaluation, it will not be competitive in the sense that any one material or contain er must be recommended to the exclusion of others. 1.2 PARTICIPATION Participation in this program is open to manufacturers of plastics mat erials and to fabricators of plastic containers. Organizations having materials or containers which appear suitable for the uses described in Section 2.3 are invited to submit samples to the ANRC, but the ANRC re serves the right to limit the number of participants and/or materials tested. In general, only one source will be accepted for prototype con tainers of any given material. 1.3 DEFINITIONS As used in this protocol or subsequent amendments thereof, the term: (a) "American National Red Cross" or "ANRC" means the American National Red Cross, its chapters and subsidiaries, including the Blood Re search Laboratory, and its subcontractors under this protocol. (b) "Manufacturer" means an organization responsible for the production of a plastics material and/or container. Asi 00000840 (c) "Supplier" means an organization responsible for the sale and/or distribution of a material or container. (d) "Container^)" means a device, including all appendages and attach ments thereto, for containing blood or blood products. (e) "Material(s)" means the polymer plastics and/or resins employed in the fabrication of the container. (f) "Protocol" means this document and any subsequent amendments and the test procedures or other documents referenced therein. (;) "Test Result(a)" means the data and/or interpretations thereof ob tained as a result of tests performed according to this protocol. 1.4 ONHCUNTRACTS The ANRC may, as il rh.cms Uf'cersary and with the consent of the National Heart, Institute, contract, other persona or organizations to perform one or more of the teats prescribed in this protocol. Except that no parti cipating manufacturer or supplier or other organization engaged in the manufacture or fabrication of plastics materials or containers may per form such tests without prior written consent of the manufacturerCs) or supplier whose material or container is to be tested, the selection of peruons or organizations to perform such tests shall be the sole respon sibility of the ANRC. ASI 00000841 -2- t SECTION 2 - PROTOTYPE CONTAINERS 2.1 ACCEPTABLE MATERIALS The containers shall be fabricated from flexible polymeric materials (plastics) or combinations thereof. The use of pure polymeric mater ials, free of plasticizers, antioxidants, or other additives, is recom mended. Adequate data with regard to generic name, constituents, manu facturer, and lot number shall be provided for all materials employed in fabrication of the container. 2.2 PRELIMINARY EVALUATION Suitable samples of the candidate material(s) and data describing it3 general chemical and physical properties shall be submitted to the ANRC for preliminary evaluation- Evaluation of a material for prototype con tainers shall be based ;.pon the data received, the results of such tests as may be deemed appropriate by the ANRC, and the opinion of the ANRC review committee, consistent with the aims and requirements of the evalu ation program. 2.3 ACCEPTANCE AND CLASSIFICATION 0? MATERIALS The manufacturer or supplier of'a candidate material shall be notified in writing of the decision of the review committee to accept or reject that material for further evaluation in the program. For those mater ials which are accepted by the committee, one or more of the following classifications will be assigned, indicating the ultimate U3e for which evaluation is recommended; Class Ai For storage of packed red cells, platelets and other blood pro ducts in the presence of a cryoprotective agent in the tempera ture range of -100 to -I96C (-143 to -365F). Class B: For storage of packed red cells, platelets and other blood pro ducts in the presence of a cryoprotective agent in the tempera ture range of 0 to -100C (+32 to 14SF). Class C: For collection and storage of blood and blood products in the presence of an anticoagulant solution in the temperature range of +37 to -7S.5C (+100 to -U0F). The manufacturer or supplier may request a change in classification where additional information can be submitted to ANRC to support such a change. 2.4 TEST LOTS OF PROTOTYPE CONTAINERS Following notification of acceptance of a candidate material for the evaluation program, the manufacturer or supplier of the candidate mat erial shall submit to the ANRC written notice of intent to participate -3- ASI 00000842 In the evaluation program indicating (a) Name of candidate material (b) Classification (of those recommended) for which prototype contain ers will be submitted and solutions with which they will be filled (see Section 2.21). (c) Name and address of manufacturer(s) or supplier responsible for sut>mission of containers and to whom evaluation reports should be sent. 2.5 SINGLE CUSS EVALUATION A single lot of prototype containers of each candidate material fabricat ed in accordance with Sections 2.10 - 2.15 of this protocol and filled in accordance with the schedules provided in Sections 2.20 - 2.22 shall be supplied to the ANRC in sealed, sterile, pyrogen-free condition except as provided in Section 2.26. The number of prototype containers required for the test lot shall be determined by the classification and appropri ate schedule of solutions required. 2.6 MULTIPLE CLASS EVALUATION For materials rated for two or more evaluation classifications, test lota will be submitted as follows: Class AB: Class AC: Class SC: Class ABC: Submit one (1) lot as per Class A. Submit two (2) lots as per Classes A and C. Submit two (2) lots as per Claeses B and C. Submit two (2) lots as per Classes A and C. 2.10 CONTAINER CONSTRUCTION The container shall consist of a main body or bag to which are attached ports, pilot tubes, and other appendages as described below. The main body of the container may be fabricated by heat or impulse sealing of flat film or extruded tubing, by molding, or by other methods consistent with the production of high quality plastic containers. The ports, pilot tubes and other appendages may be fabricated as an integral part of the main body or may be attached separately, but the use of cements or other chemical bonding agents to attach these appendages is not acceptable. 2.11 CONTAINER DIMENSIONS The dimensions of the main body of the container, exclusive of append ages, 3hall be ae follows: For Class A and Class B containers: (a) Length: 30.5 11.3 cm (120.5 in.) (b) Width: 22.9 11.3 cm (910.5 ip.) (c) Wall thickness: 0.127 0.051 mm (0.005 0.002 in.) (d) Internal surface area: 129Q* 130 sq.cm (200 + 20 sq. in.) ASI 00000843 -4- C: (a) Length: 17,15 + 0.64 cm (6.75 1 0.4? in.) (i) WLUt.h: 17.70 1 0.64 cm (5.0 + 0.25 in.) (r) Wall thickness: 0.15 i 0.076 mm (O.UOo + 0.003 in.) id) Internal surface area: 435 20 sq.cm (67.5 + 3.0 sq.in.) The overall nimensionc of the container, including all appendages, shall be as follows: (a) For Clans A ar.d Clans H containers - The containers, when filled according to Section 2.21, shall fit securely within a box having inside dimensions of 22.9 cm x 35*6 cm x 1 cm (9 in. x 14 in. x 3/8 in.) without undue distortion of either the box or the container. (b) For Clare- C '-onaniners - The container, when filled according to Section 2.21, .-hnli fit securely within a boxhaving insidedimen sions. of 12.7 cm x 30.5 cm x 1.3 cm (5 in. x12 in.x in.) with out undue distortion of either the box or the container. 2.12 CONTAINER VOLUME The volume contained within the main body of the container shall be as follows: For Class A and Class 8 containers: 675 i 25 ml when constrained to a uniform thickness of 1 cm (0.4 in.) and a minimum of 2000 ml when unconstrained. For Class C containers: 550 + 50 ml. 2.13 PORTS K.-c'h container shall have at least two (2) ports or tubes provided for filling and/or draining of the container in an ascept-ic manner. These ports shall be permanently attached to the edge of the bag along its width and shall extend a minimum of 2.0 cm (0.8 in.) from the edge of the main body of the container. The internal diameter of the port tube shall be such as to fit the stylet (bottle needle) of a common admini stration net (nominally 0.20 - 0.22 in.). Provision shall be made for a sterile hermetic closure of each port, either by heat sealing or by means of a closure device. 2.14 PILOT TUBES Bach container shall have provision for obtaining at least two (2) samples of the contents for cross-matching. These appendages shall be attached to the same edge of the bag as the ports described above. Provision shall be made for obtaining independent samples of 0-5 ml each in a sterile manner. A precalibrated pilot tube i3 highly de sirable. Provision for an independent tamperproof identification system for the pilot tubes and container is highly desirable to insure correct identi fication of blood unit3 for cross-matching. - 5- ASI 00000844 NOTE: The same basic device may be employed to serve as either port or pilot tube in which case a minimum of four (4) such devices shall be required. 2.15 SUSPENSION SYSTEM Provision shall be made for securely suspending the container from hooks along either the length or width of the container as may be desired. 2.20 SOLUTIONS FOR FILLING The following solutions will be used to fill the prototype containers according to the schedules given in Section 2.4: r.(a) Anticoagulant Acid Citrate Dextrose Solution (AGP) (N Tri-sodium citrate (Na^C^jOyZHaO) Citric acid (C^H^O-y -1 f ^0) ^ fi_jl * 8.0 gm. Dextrose (C^H]_26'H2'; Water for injecMon (us?) to make 24.5 gm. 1000 ml. (b) Anticoagulant Acid Citrate Dextrose Solution plus Adenine (AAGD): Tri-sodium citrate (Na3C6H507*2H20) Citric acid (C^Hg07*H20) Dextrose (C^H^O^HjO) Adenine* (C^H^N^) Water for injection (USP) to make 22.0 gm. 8.0 gm. 24.5 gm. 0.52 gm. 1000 ml. (c) Anticoagulant Citrate Phosphate Dextrose Solution (CPD): Tri-a.di on citrate (Na'?ClH<j07i2H20) Ci^.r_s '-.rid (C^Hg07-H2Q) Dc;:tr: n \l.'uii206*H20) Monobasic sodium phosphate(Na r^PO^'f^O) Water for injection (USP) to make 26.3 gm. 3.27 gm. 25*5 gm. 2.22 gm, 1000 ml. (d) Anticoagulant Citrate Phosphate Dextrose Solution plus Adenine (ACPD)t Tri-sodium citrate (Na3C^H507*2H20) Citric acid (C6Hg07'H20) Dej.trose (C^H^O^l^O) Monobasic sodium phosphate (Na^PO^^O) Adenine* (C5H5N5) Water for injection (USP) to make 26.3 gm. 3.27 gm. ' 25-5 gm. 2.22 gm. 0.52 gm. 1000 ml. ASI 00000845 "^ (e) Glycerol Mannitol Dextrose Solution (GMD) : Glycerol (C^IIgO^) Mannitol (C^H^O^) Godium chloride (NaCl) Monobasic potassium phosphate (KH2PO4) Dextrose Water for injection (USP) to make 571-0 gm. 30.0 gm. 4.38 gm. 1.36 gra. 2.75 gm. 1000. ml. (f) Sodium chloride, isotonic (SCI): Sodium chloride (NaCl) Water for injection (USP) to make 9-0 gm. 1000' ml. NOTE: Current source of supply for adenine is from: Dr. Grant H- Dartlet-t Laboratory i>r Comparative Biccnemistry Gan Diego, California 2.21 sckei i'Cf? I .IDG The folio1.r-r v-_h :r lcs shall be used to determine the solutions, volume of solution pa:- ^ roirr.r, and number of containers required for each of the designated ol; ifcations; Container Class Solution Code Volume to be Filled No. of Containers Required GMD sex Unfilled 400 ml 400 ml - 150 150 500. GMD SCI Unfilled 40C ml 400 ml - 100 100 500 r. r -> , * rtD C; P : "D 13 ml/100 ml* 13 ml/100 ml 12.3 ml/100 ml 12.3 mi/lOO ml 100 100 ICO 100 '-.filled 13 ml/lOQ ml - r/-:> 200 f' 'n the nominal design volume of the container. containers rated for both Class A and B use Class A. i DELETION OF SOLUTIONS The cohed ..; i.t filling given in Section 2.21 may be modified by nrutui ' ;y,;.r.'uo of the ANEC and the manufacturer (s) or supplier to pf-mit the tasting of additional solutions or to obtain a limit ed evaluation of a given container with a lesser number of solutions. - 7- AS1 00000846 2.25 STERILIZATION Where practical the container and contents shall be steam or dry-heat at. -ilized after filling. For those plastic materials which will not withstand ateom or dry-heat sterilisation, the empty container may be gas sterilised with ethylene oxide and then filled asceptlcally with sterile bulk solutions. 2.26 NON-STERILE CONTAINERS Prior to sterilisation a number of containers shall be removed from the test lot as follows: 5 each of those filled with ACD, AACD, CPD, ACPD, and GMD 10 each of those filled with SCI 20 each unfilled These shall be sealed and clearly labeled "Non-Sterile". For those containers vhich would be sterilised with ethylene oxide, the sterile solutions will be filled into the non-sterile containers. 2.27 LABELS A label of approximately 10 x 10 cm (4 x 4 in.) shall be affixed to one side of the main body of the container. This label shall include the following: (a) Name and address of the primary manufacturer(s) or supplier. (b) Lot number. (c) Code designation of solution with which filled. (d) Evaluation classification code, as assigned. (e) The legend "Prototype Container for Investigational Use Only", (f) A blank space approximately 5 x 10 cm (2x4 in.), for recording laboratory data. 2.28 BOXES Each prototype container shall be enclosed in an individual plain white cardboard box of the following size: Class A or B: Inside dimensions: 22.9 x 35.6 x 1.0 cm (9 x 14 x 3/6 inchea) Wall thickness; 0.5 mm (0.02 in.) Class C: Inside dimensions: 12.7 x 30.5 x 1.3 cm (5 x 12 x Wall thickness: 0.5 mm (0.02 in.) in.) The information required in Section 2.27 shall appear on the outside of each box, either printed directly on the box or on a label affixed to it. i ASI 00000847 -$-  ADDITIONAL CONTAINER.! A ' Utionnl test loir, of prototype containers may be requested by ilio ANRG for the purpose of further evaluation. A reasonable ef fort ali.-Gil be nwde to supply these additional test lots identical in all specifications to the original test lot unless a modifica tion of the specifications is requested by the ANRC. 2.30 TECT IDT DATA The following information shall be supplied in writing with each tent lot of prototype containers: (") None and address of primary manufacturer(s) or supplier. (b) i n number. (c) Trade name of material (main bag) (d) Generic name of material. (e) Evaluation classification code Container (f) List of plastic materials used for fabrication of each part of container, by part, name of material, and source. (g) List of constituents of each plastic material, including plasticisers, antioxidants, and other additives, which are present or likely to be present in the finished container. (h) Dnfco(s) of fabrication Golutionri (i) Gohodulc of solutions filled (.i) Conroe of solutions (k) Dnl.c(c) of filling Lt.rril i ration (l) Method used (m) Date of sterilization 2.31 DIVIDED RESPONSIBILITY Where two or more establishments participate in the manufacture of the materials and the fabrication, filling and sterilization of the prototype containers, then each establishment shall be identified to the ANRC by name, address, and nature of participation. 2.32 ADDITIONAL DATA Further information concerning the materials or containers may be requested from the manufacturer(s) or supplier when such information is deemed by the ANRC to be necessary for this evaluation. The de cision to provide any or ail of such information shall be at the sole discretion of the manufacturer or supplier. However, such information shall not be unreasonably withheld. The information so disclosed, un less previously published by the manufacturer or supplier, shall be considered as privileged information and shall not be disclosed by the ANRC to any other party except as provided for in this protocol or by prior written permission of the manufacturer or supplier. - 9- ASI 00000848 2.33 LIMITED RESPONSIBILITY Where the primary mnnuf'> ; turer(s) or supplier fabricates or fills prototype containers from materials of commerce or other materials ;nii. of !i.ia own manufacture, and data on these materials (e.g. con stituents) is not available to him by virtue of its being proprie tary or otherwise restricted, there shall be no penalty or prejudice for failure to submit this data. 2.34 DELIVERY OF TEST LOT A reasonable period of time, mutually agreeable to the ANRC and the manufacturer or supplier, shall be allowed for the fabrication, filling, sterilization and delivery of the test lot{s) of prototype container to the ANRC. Asr 00000849 - 10 - SECTION 3 - TEST PROCEDURES 3.1 TESTS TO BE PERFORMED Each tent lot of prototype containers shall be tested to determine the suitability of the containers for use in aach of the assigned evaluation classifications. Tests shall be performed for: (a) Sterility and pyrogenicity. <b) Toxicity (c) Physical-chemical properties. (d) Mechanical properties. (e) Effects of storage at various temperatures on container mater- L-iIa and contents. 3.2 SAMPLING OF TEST IGTS Upon receipt of each tost, lot ox' prototype containers, a set of conse cutive serial numbers shall be assigned and affixed to the containers for purposes of sampling and recording tost data. For the purpose of sampling, each subgroup consisting of all containers of a given test lot filled with a given solution or 'infilled shall be considered to be separate lots. Samples shall be selected at random from these lots. 3*10 INITIAL STERILITY, PYROGENICITY AND SAFETY TESTS Upon receipt of each test lot of prototype containers, a sample of 20 containers or 10 percent of the lot, whichever is the smaller number, shall be selected for sterility, pyrogenicity and safety tests. 3.11 UNFILLED CONTAINERS Unfilled containers shall be tested for sterility, pyrogenicity and safety in accordance with the methods prescribed for "Transfusion and Infusion Assemblies" in U.S.P, XVII. 3.12 -SODIUM CHLORIDE SOLUTION The contents of containers filled with SCI solution shall bo tested for sterility and pyrogenicity in accordance with the requirements of Section 73.73, Title L2 (PHS). 3.13 GLYCEROL-MANNITOL SOLUTION The contents of containers filled with GMD solution shall be tested for sterility. Samples from each of these containers shall be diluted with pyrogen-free saline T.3. to a final concentration shown by previous control experiments to be non-toxic to the test animals and shall be tested for pyrogenicity. * - 11 - ASI 00000850 3.14 ANT1C0AG1 NT SOLUTIONS Tho contents of coni,miners filled with ACD, AACD, CPD, or ACPD solui-U'nn shall lie tested for sterility. Samples from each of these coni-liner:', shall be diluted with pyrogen-free saline T.S. to a final con cent,ration of 0.5 percent sodium citrate ird shall be tested for pyrogoriicity. 3.40 INITIAL BIOLOGICAL TESTS Ilium receipt uf each tost lot, a cample of 20 containers or 10 percent v i' thu 'Joi,, whichever in tho lonr.or number, shall be selected at ranO'Hi. i'or toxicity tost:; (3.21), tissue culture tests (3-25) and physicalduuiLc.'il analysis (3.30). 3.21 U.S.P. SPECI IT CATIONS FOR TOXICITY The containers shall be sampled and tested for toxic materials in accoraanco with the methods proscribed in U.S.P. XVII for C^ass VI plas tic containers. The extractions shall be performed at 50 u for all materials and at 121C for those containers which are sterilized by steam or dry-heat. 3.25 TISSUE CULTURE TESTS The container materials and contents and extracts thereof shall be test ed by the method of Guess, et al [J. Pharro. Sci., 1545 (1965)J using mouse fibroblast cell (Strain L-929) in tissue culture, (a) Samples of the plastic materials from various parts of the contain er shall be tested directly in contact with the tissue culture. (b) The various parts of the containers shall be sampled, the samples extracted with 95$ ethyl alcohol for 24 hours in a Soxhlet appara tus and tho eluate evaporated to dryness. The weight of residue old,ained shall be recorded. One half of the residue shall be dis solved in 95$ ethyl alcohol to a final volume of 50 ml and the re mainder of the residue shall be dissolved in cottonseed oil to a final volume of 50 ml. The two solutions thus obtained shall be tested for cytotoxic reactions. (c) The contents of the filled containers shall be sampled and tested directly for cytotoxic reactions. (d) The contents of the filled containers shall be sampled and the samples set aside for physical-chemical tests (3.30). (e) The reminder of the contents of the filled containers shall be extracted with chloroform and the chloroform fraction tested for cytotoxic reactions. 3-30 PHYSICAL-CHEMICAL ANALYSIS The containers obtained in Section 3.20 shall be used for physical- ehondeal analyses, including chemical extraction tests, infra-red (IR) arid ultra-violet (UV) spectral analysis and theraogravimetric analysis (TGA) . fcSl 00000851 - 12 - 3.31 SPECTRAL ANALYSIS OF CONTAINERS (a) The variou:: pur is of the container shall be sampled, the samples extracted with carbon tetrachloride, and the IR and UV spectra of the extract determined using a pure solvent blank. A second set of spectra on these extracts shall be measured using the ex tract from a non-sterile unfilled container of the same lot as the blank. (b) The IR and UV spectra of the ethanolic solution of the residue obtained in 3.25 (b) shali be recorded as in (a) above, (c) A portion of the ethanolic solution of the residue obtained in 3.25 (b) shall be evaporated to dryness, the residue redissolved in carbon tetrachloride, and the IR and UV spectra recorded as in (a) above. 3.32 SPECTRAL ANALYSIS OF CONTENTS (a) The UV spectra of the samples obtained in 3.25 (d) shall be re corded. (b) The IR and UV spectra of the chloroform extract obtained in 3.25(e) shall be recorded. 3.33 THERMOGRAVIMETRIC ANALYSIS The various parts of the containers shali be sampled and analyzed by TGA to establish a "fingerprint" for the material. 3.34 CHEMICAL EXTRACTION Determination of the effects of various chemical agents on the contain er materials may be made, as necessary, according to the methods of ASTM D3239-55 (1965) and D543-65. 3.40 MECHANICAL TESTS The plastic materials and containers will be tested for various mechani cal properties and the effects of temperature and solutions upon these properties. Where applicable, these tests shall be conducted using standard methods of the American Society for Testing and Materials (ASTM) and in accordance with the principles established for sampling (ASTM D1898-16T), conditioning (ASTM D618-61) and low temperature testing (ASTM D759-66;. 3.41 INSPECTION Upon receipt of the test lot of prototype containers, a' 5 percent sample shall be selected at random and inspected to determine that the contain ers and contents conform to the requirements of Section 2 of this proto col. - 13 - ASl 000008S2 3./,5 test:; ok plagtic materials Upon receipt of l.lic tent lot, a cample of 5 containers or 5 percent of the lot, whichever ,ic the lesser number, shall be selected at ran dom in accordance with Section' 3.2 The various parts of the contain er:-. shall be campled and tested as follows: 3.4o IMPACT BRITTLENESS Samples of the material in the main body of the container will be test ed according to the method of ASTM D1790-62. Tests shall be conducted at the lowest service temperature for the rated container class(A:-196C; B:-100C; C:-78.5C). 3-47 TEAR RESISTANCE Samples of the material in the main body of the container shall be test ed at 23C in accordance with the methods for initial tear resistance (ASTM D1Q04-66) and propagating tear resistance (ASTM D1922-67 or D193862T). 3.48 TENSILE STRENGTH The tensile strength of the material in the main body of the container shall be determined at 23C in accordance with ASTM D882-64T. 3.49 TRANSPARENCY The transparency of the material in the main body of the container shall be determined by measurement of the absorption spectrum in the region of 350 to 700 nm. or by means of ASTM D1746-62T. 3.50 WATER ABSORPTION The water absorption of the material in the various parts of the contain er shall be measured in accordance with ASTM D570-63. 3.55 TESTS ON CONTAINERS Upon receipt of the test lot, a sample of 10 containers or 10 percent of the lot, whichever is the lesser number, shall be selected at random from each of the subgroups and tested in accordance with 3.56 - 3.60. 3.56 RUPTURE TEST (a) Samples of the filled containers shall be placed in a non-restrict ing thin plastic overbag and placed on the platen of a hydraulic laboratory press. The pressure required to rupture the bag shall be recorded. Duplicate tests shall be run. If 'failure occurs at the closure device, the test 3hall be repeated using new sample containers on which the port tubes have been heat sealed close to the main body of the container. (b) Samples of the unfilled containers shall be filled to nominal volume ASI 00000853 - 14 - I (Class A or D : 675 +Z5 ml; Class C : 550 +50 ml) and tested as in part (a). 3.^7 DROP IMPACT TEST * Duplicate samples of unfilled containers shall be filled with water to nominal maximum volume (Class A or B: 2000 ml; Class C: 550 ml) and tested for drop impact resistance by a modification of ASTM D2463-65T. Filled containers shall be tested as received. 3.dO ACCELERATED SERVICE TESTS The remaining samples from each subcroup shall be subjected to ten (10) freeze-thaw cycles consislinc of freezing at the lowest service temper ature for the rated container class (A; -196C, B: -10QC, C: -78.5C) for 4^ hours, thawing at +40C and holding at room temperature (+25C) for 24 hours before refreezing. Following the final holding period the containers shall be sampled and tested according to Sections 3.45 - 3.50. - 15 - ASI 00000854 SECTION 4 - LONG-TERM STORAGE 4.1 SAMPLING FOR STORAGE Upon receipt of the test lot of prototype containers, samples shall be selected at random according to the following schedule: Class A: 75 filled containers from each solution group 90 unfilled containers Class B: 60 filled containers from each solution group 75 unfilled containers Class C: Same as Class B. NOTE: For containers rated for both Class A and B evaluation, use Class A schedule. The containers shall be removed from their boxes, weighed and return ed to the box. The weight and date of initial weighing shall be re corded on the label. 4.2 STORAGE TEMPERATURES (a) Fifteen (15) containers from each solution group and 15 unfilled containers shall be placed in storage at the following temperatures Class A: '*50, +25, +5, -85, and -170C. Class B: +50, +25, +5, and -85C. Class C: +50, +25, +5, and -25C. (b) Five (5) additional unfilled containers shall be placed in storage at each of the following temperatures; Class A: +50, -85, and -170C. Class B: +50, -25, and -85C. Class C: +50, +5, and -25C. 4.3 STORAGE PERIODS (a) Three (3) containers from each group of the filled containers and 3 unfilled containers shall be selected at random and removed from storage at each storage temperature after each of the following in tervals of storage time: 21 days, 3 months, 6 months, 12 months, and 24 months. (b) The additional 15 unfilled containers placed in storage according to Section 4.2 (b) above shall be removed from storage after 12 months. 4.4- WEIGHT LOSS Upon removal from storage, each container shall be allowed to attain ASI 00855 - 16 - <..iL.-r.Tiai ot4ui.iiorium at room temperature for 12-24 nours. Eacn contain er shall then be removed from its box, reweighed and the new weight and veii'ht change, if any, recorded. 4.0 TOTING OF STORED CONTAINERS E'ch sri of three (3) containers removed from storage shall be retested for toxicity and changes in the mechanical properties of the materials. 4.6 TOXICITY TESTS ON CONTENTS (a) The contents of 2 containers from each set of three filled contain-, ers shall be sampled and screened for cytotoxic reactions according to Section 3.25 (c-e). (b) If the tests in (a) are positive, the results shall be confirmed using the contents of the third container, and the spectral analy sis of 3.32 performed. (c) If (a) and (b) boun yield positive tests for toxicity, then three additional containers shall be withdrawn from storage and the con tents tested for sterility and pyrogenicity according to Sections 3.12 - 3.14. 4.7 TOXICITY TESTS ON CONTAINERS (a) Samples of the plastic materials from various parts of the contain ers shall be tested for toxicity according to Section 3-25 (a). (b) If the tests in (a) are positive, the containers snail ce tested for tcxicity in accordance with Section 3.21 and the IR and UV spectra (3-31 a) and TGA fingerprint (3.33) recorded. 4.3 MECHANICAL TESTS (a) Samples of the materials in the main body of the containers shall be tested for impact brittleness (3.46) and transparencey (3*49) and the results compared with the results obtained initially. (b) If significant changes are noted in (a), then the materials shall be tested by spectral analysis (3-31 a) and by TGA (3-33). 4.9 ADDITIONAL TESTS ON UNFILLED CONTAINERS The additional unfilled containers stored according to Section 4.2 (b) shall be tested for alterations in tear resistance (3.47), tensile strength (3*48) and drop impact strength (3.57). - 17 - ASI 00000856 SECTION 5 - CLINICAL TRIALS 5.1 IN VITRO TESTS iijior, .-.uoceojful completion of all initial tests up to and including the si-Jay storage period, the prototype containers will be tested for de leterious effects on blood and/or blood products by in vitro measure ments. 5.2 PACKED RED BLOOD CELLS - CLASS A/B (a) Five (5) sterile unfilled containers will be selected at random and filled with GMD-treated packed red blood cells (human). (b) Two (2) sterile GMD-filled containers will be selected at random and filled with packed red blood cells (human). (c) The filled containers will be stored for various periods of time up to 6 months at the appropriate service temperature as follows: Class A: 7 containers at -170C. Class D: 7 containers at -85C. Class AB: 3 containers at -170C and 4 containers at -85C. (d) Following storage the containers will be thawed at +40C and the red cells deglycerolized by continuous-flow centrifugal washing according to the current methods for frozen red cells. (e) Measurements of supernatant hemoglobin and intracellular potas sium will be made throughout the above procedures and the percent recovery of red cells calculated. 5.10 ACCEPTANCE FOR CLINICAL STUDIES Upon completion of all initial tests, in vitro tests and storage tests up to and including the 6 month period, the results of thesi tests will be evaluated by the ANRC Review Committee. At this time one of three (3) ratings will be assigned for each evaluation class: 1 - "Acceptable for Clinical Trials11 2 ~ ''Continued Evaluation Recommended" - Not acceptable for clinical testing at this time. Re-evaluate in 6 months. 3 - "Not Recommended" Prototype containers receiving a rating of "1" will be .submitted for in vivo clinical trials in humans under an I.N.D. issued to the ANRC. ASI 00000857 - 13 - SECTION 6 - GENERAL CONDITIONS 6.1 MODIFICATIONS OF PROTOCOL This protocol may be modified or amended as may be deemed necessary or desirable by the ANRC. Where feasible, notice of such amendments or modifications shall be submitted in writing to all participants prior to the effective date of change. However, the ANRC reserves the right to add, delete or alter test procedures or conditions for tests per formed on any or all prototype containers or materials in a test lot ana any or all test lots without prior notification. 6.2 TEST RESULTS Results of all tests conducted under this protocol shall be submitted in writing to the Director of Research, ANRC Blood Research Laboratory or to such other personnel of this laboratory as may be designated by him. 6.3 PINAL EVALUATION At the completion of the evaluation program or at the termination of testing of a given prototype test lot for any reason, the test results obtained to that date will be evaluated by the ANRC Review Committee and one of the following ratings assinged for each evaluation classi fication : 1 - "Acceptable for Use. Class __ n 2 - "Acceptable for Restricted Use. Class __ " 3 - "Not Acceptable - Re-Evaluation Recommended11 4 - "Not Acceptable" 6.4 REPORTS TO PARTICIPANTS Reports of the test results obtained on each plastic material and/or prototype container shall be submitted by the ANRC to the primary manu facturer (s) or supplier of that material or container as indicated in Section 2.4. Interim reports shall be submitted at the completion of each test phase and/or storage period. A final summary report, includ ing the evaluation and recommendations of the ANRC Review Committee shall be submitted at the end of the program or upon termination of testing of a given prototype lot for any reason. Submission of such reports shall constitute the full responsibility or obligation of the ANRC to that manufacturer or supplier. 6.5 REPORTS TO NIH In accordance with the terras of a contract between the ANRC and the National Heart Institute, National Institutes of Health, reports of - 19 - ASI 00000858 I.lu t.i'iiL rosulIs ;md Lhc interpretations and evaluations thereof shall i`> nub 1.,oci by the ANRC to the NIH. 6.6 OTHER REPORTS ii.-''ort;3 of I.he tent resplto, interpretations and evaluations thereof, ni.d data, and ether technical information concerning the plastic mater ial r. and/or prototype containers which may be submitted to the ANRC by the manufacturer(s) or supplier shall be considered as privileged in formal ion and shall not be transmitted to any other persons except as provided for in this protocol or by prior written consent of both the ANRC ar.d the manufacturer(s) or. supplier of the plastic material and/or container in question. 6.7 NGN-ENDORSEMENT OF PRODUCTS Acceptance of a plastic material and/or prototype container for testing by the ANRC or the result,;; of such tests shall under no circumstances be construed a3 an endorsement of said plastic material and/or container by the American National Red Crocs or the National Institutes of Health. 6.8 TERMINATION OF TESTS (a) Under normal circumstances, the evaluation will commence on the date of receipt of the test lot of prototype containers by the ANRC and shall continue for a period of 24 months unless terminated for other reasons. (b) The ANRC reserver, the right to discontinue testing any or all plas tic materials and/or prototype containers or to terminate the eval uation program at any time. In the event such action is necessary, a written statement of intent and the reasons for such action shall be sent to the participants. (c) The right to withdraw from this evaluation program at any time is reserved to the manufacturer(s) or supplier upon written notice of intent to the ANRC indicating the reasons for 3uch withdrawal. (d) Upon premature termination of the evaluation program or withdrawal by the participants, the ANRC shall, upon request, destroy or re turn to the manufacture(s) or supplier all existing prototype con tainers received therefrom. ASI 00000859 20 - PLASTICS EVALUATION PROGRAM PROTOCOL SUPPLEMENT NUMBER 1 APRIL 1, 1969 i Blood Research Laboratory 9312 Old Georgetown Road Bethesda, Maryland 20014 ASX 00000860 iff. -!, 1 v Apr LI .1, '969, the foil owing amendments to the ANRC Plastics i'.v.i ir.ih'-.r, '''mgr-am Protocol of March ], 1969 are hereby adopted, as pia.vi.l.M i'' t in section 6.1 of the protocol. I. Tin. Table of Contents is AMENDED by deletion of the following section: 3.33 THERMO CHAV IMETRIC ANALYSIS The Table of Contents is AMENDED by addition of the following sections: .1.16 DONOR TUBE 2.23 CONTROL SAMPLES 3. Section 2.10 is AMENDED to read as follows: 2.10 CONTAINER CONSTRUCTION The container shall ccnr.i.:,t of a main body or bag to which are attached ports, pilot tubes, and wtl.ur appendages as described below. The main body of the container may be fabricated by heat or impulse sealing of flat film or extruded tubing, by molding, or by other methods consistent with the production of high quality plastic containers. The ports, pilot tubes, and other appendages may be fabricated as an integral part of the main body or may be attached separately. Solvent welding or similar techniques may be employed, but the use of cements or other chemical bonding agents which are not subsequently removed or dissi pated from the container is not acceptable. 4. Section 2.11 is AMENDED to read as follows: For Class A and Class B containers: (c) Nominal wall thickness: 0.076 to 0.178 mm (0.003 to 0.007 in.) with normal manufacturing tolerances. For Class C containers: (c) Nominal wall thickness: 0.076 to 0.226 mm (0.003 to 0.009 in.) with normal manufacturing tolerance. 5. Section 2.16 is ADDED as follows: 2.16 DONOR TUBE Class C containers shall be provided with a length of flexible plastic tubing of approximately 91 cm (36 in.) in length for the collection of blood from the donor. This tube shall be attached to the same edge of the bag as the ports and shall have a 15 or 17 gauge needle with sterile cover attached to the distal end of the tubing. -1- ASI 0000861 o. Section .2.23 is ADDED as follows: 2.23 CONTROL SAMPLES' Two (2) separate samples of 25 ml each of each of the bulk solutions filled into the prototype containers shall be supplied to the ANRC in scaled glass vials or ampoules. These samples shall have been sterilized in a manner identical to that employed for the prototype containers- 7. Section 2.27 is AMENDED to read as follows: (e) The legend "Prototype container manufactured for the American National led Cross Plastics Evaluation Program. CAUTION: New Drug - limited by United States law to investigational use." 8. Section 3.25 is AMENDED to read as follows: (b) Samples of the solution obtained from the extractions performed in section 3.21 for the U.S.P. tests shall be tested for cytotoxic reactions in tissue culture. (e) The remainder of the contents of the filled containers shall be extracted with carbon tetrachloride (CCl^) and the organic phase tested for cytotoxic reactions. 9. Section 3.30 is AMENDED by deletion of the words "and thermogravimetric analysis (TCA)". 10. Section 3-31 is AMENDED by deletion of parts (b) and (c). 11. Section 3-32 is AMENDED to read as follows: (b) The IR and UV spectra of the carbon tetrachloride extract obtained in 3-25 (e) shall be recorded. 12. Section 3*33 is DELETED. 13- Section 3-46 is AMENDED to read as follows: 3.46 IMPACT BRITTLENESS Samples of the material in the main body of the container will be tested according to the method of ASTM D1790-62 or by use of a calibrated air impact hammer. Tests shall be conducted at the lowest normal service temperature for the rated container class (A: -180C; B: -85C; C: -78.5C). The tests will be repeated after conditioning of e second set of test samples for 48 hours at the test temperature. ASI 00000862 -2- I i"w e-4S L; AMENDED to road as follows: . -4o vi-jn.-.; i.r.-i ctuKngtj! '*11 ' strength of the material in the main body of the container shall bo determined at 23C in accordance with ASTM D682-64T (Method A). Section 4-7 :s AMENDED as follows: (b) DELETE the words "and TGA fingerprint (3-33)". Section 4.8 is AMENDED as follows: (b) DELETE the words "and by TGA (3.33)". -3- ASI 00000863