■ ’*"* //s' -iF~e- c*l, T^ac^We, r<=L/ AS I 00001729 Food, Drug, and Cork tic Chemicals The B.F.Goodrich Co. 500 S. Main St. Akron, Ohio 44318 December 8, 1967 Mr. Morgan M. Hoover Manufacturing Chemists' Association, Inc. 1825 Connecticut Avenue, N.W. Washington, D.C. 20009 Dear Morgan: In response to your latter of December 4, 1967, with respect to the carcinogenic question, I am in agreement with your thinking to leave the matter rest on the basis of our November 3 statement. Very truly yours, W.E. McCormick mj Knapps cc: W.A. V.H. Kaeep A$I 00001730 lElErHONL HUDSON 3G)fl> Manufacturing Chemists’ Association, Inc. (FOUNDED IT. 72) 1825 CONNECTICUT AVENUE, N. W. Washington, D. C. 20009 Dec or.her 4, Hr. V7. E. 1957 ICcOo:.;1deb TVig Vt V. C>oo.:'ric'i Company 500 3. Main Street Akron, Ohio 443.10 Dear Kill: In answer to your Jotter of Hovembor 24 re the? separate statement endorsing Jack Frawley’s specific proposal, Bill Knapp caliod after receiving his copy of my November 3 7 letter to you to cay that, he is v;iXliny to withdraw his request for the separate statemeat because the MCA statement to the lit’7 Hearing Clerk, dated Move Tiber 3 accomplishes the objective in large measure. Your suggestion that I or r.iy source contact Jack Frawley to discuss the carcinogenicity Question raises a problem because the source wishes to remain anonymous and I do not have the necessary detailed background. I do not think that this is worth spending much more time on since we already have gotten the main point acrofjc in the Hove Tribe- 3 statement, the proponent is now satisfied without tee separata statement, and there were three negative votes anyway. Do you agree? Sincerely yours. Morgan M. Hoover MMii: a jg / cc: VV7. A. Knapp V. H. Knoop 00001731 AS I Food, Drug, and Cosmetic Chemicals The B.F.Goodrich Co. 500 S. Mala St. Akron, Ohio 443X8 November 24, 1967 Mr. Morgan M, Hoover Manufacturing Chemists' Aaaoclatloo, Inc. 1825 Connecticut Avenue, N.W. Washington, D.C. 20009 Dear Morgan! This refers to your letter of November 17. X an still la favor of the MCA's endorsing Fravley's stateaant and It appears as If the majority of the ConsIttee feel likewise. 1, of course, do not know the basis for your source's coment re* gardlng the carclnogenclty question, and It nay be that the results are equivocal. 1 feel that you and/or your source should Immediately contact Jack Fravley and discuss it before making the final presen* tatloo. If for any reason after your discussion It appears undesirable to do so, then we should not. Very truly yours. w.g. McCormick ■J ect V.H. Knoop , W.A. Knapp^ ASI 00001732 TELEPHONE HUDSON 3-6126 Manufacturing Chemists’ Association, Inc. (FOUNDED 1872) 1825 Connecticut Avenue, N. W, Washington, D. C. 20009 November 17, 1957 Mr. 17, The B. 500 3. Akron, 3. McCormick F. Goodrich Company Main street Ohio 44313 Dear Bill: The replies to my letter of November 2 to the FDCCC re­ questing advice re MCA's support of Dr. Frawley's specific proposal show eight in favor, three not in favor, one no objection, one not involved. Most of tho replies did not go into any detail. However, one set of comments in particular makes me question the advise ability of our going beyond what we submitted on November 3 in support of Dr. Frawley's concept. This particular set of comments 3ays that even at 0.2% evidence of carcinogenicity has kaen detected. Why this apparently wa3 not reported before is a mystery to me. The come source said LD-5C' s and 30-day feeding studies ere needed for new compounds. T>1 , ivx: a: to :.ow you :o handle this matter. Sincerely yours, Morgan M. Hoover cc: yz. H. Xnoop v/W, A. Knapp ASI 00001733 November 13, 1967 Mr. Morgen M. Hoover Manufacturing Chemist*1 Association, Inc. 1825 Connecticut Avenue, N.V. Washington, D.C. 20009 Dear Mr. Hoover: Pursuant to letter ballot requested in letter of November 2, I wish to east my vote in favor of endorse­ ment of the Frawley proposal. This would not eliminate difficulties in compliance where petition is required but it would eliminate the necessity for petitions on a substantial number of substances. It appears to be a move in the right direction. Sincerely yours. Original Signed I. A. Knapp W. A. Knapp VAKtdek ee: Mr* William X. McCormick, The B.F. Goodrich Company, 500 8* Main Street, Akron, Ohio 44318 ASI 00001734 / ATLAS CHEMICAL INDUSTRIES, WILMINGTON. DELAWARE I N C. 10899 November 3, 1967 Hearing Clerk Department of Health, Education and Welfare Room 5440 330 Independence Avenue, S.W. Washington, D.C.20201 Dear Sir: Comments on Proposed Rule-making 21 C.F.R., Part 121, Federal Register Volume 32, No. 152, Pages 11443 - 6 Atlas Chemical Industries,. Inc., hereinafter referred to as Atlas, is a manufacturer of food additives and has in the past filed many food additive petitions for both direct and indirect additives. Atlas expects to file additional food additive petitions and hence is an interested person. Atlas supports the comments filed or about to be filed by the Manufacturing Chemists Association. In addition, Atlas makes the following comments with respect to the proposed regulation. Section 121.50(e)!, B, 2 and 5, and Section 121.50(e) II, B, 1st paragraph and subparagraph 2, require an estimate of the maximum as well as the average quantity of the food additive to be expected in the total daily diet of the consumer. It is respectfully submitted that estimates of the maximum quantity, for both direct and indirect food additives, will be relatively meaningless and that this requirement should be deleted. The meaningful figures and the Department of Agriculture tables are average consumption figures and, where feasible, these have been used in the Atlas petitions that establish the average Quantity of the food additive to be expected from all of the approved uses. The safety factor of 100 is designed not only to take care of the species difference between animals and humans, but also to take care of the different dietary patterns of humans. In ASI 00001735 some cases, of course, as, for example, infants, it may well be that the average will also be the maximum in the sense that the infant may only be, consuming one food. A discussion of the safety factor of 100 and its applicability is more fully set forth in the comments filed by the Manufacturing Chemists' Association and will not be repeated here. Section 121.50(e) II, A, 1, b, Description of the additive, subparagraphs iv, v, vi, and vii, regarding manufacturing processes, specifications, reproducibility and stability data are objectionable in that they do not exclude this type of data where this data is unnecessary for one reason or another. For example, present regu­ lation 121.51(c) A, in the second paragraph, says some of these types of information shall be supplied "When the chemical identity and composition is not known,". It is suggested that this qualifi­ cation be applied to all these subparagraphs. Examples would be petitions for new uses for additives already included in the Food Additive Regulations, Food Chemicals Codex, U.S.P., N.F., etc.) Section 121.50(e) II, A, 2, a, relates to indirect additives and recognizes two types, namely those added for fiinctional use in production and those in food contact surfaces. This comment relates to the latter. As a practical matter and for purposes of clarity, the petition framework should recognize that there are at least two aspects of food contact surfaces which are not necessarily amenable to uniform treatment. The first of these is the basic substrate of the contact surface, such as cellophane, polyethylene, etc., and the ingredients used in making it. The second constitutes the large group of adjuvants used in or on the basic substrate. In existing food additives Subpart F relating to food additives resulting from contact with containers or equipment, these two types of additives from food contact surfaces are treated in at least three different manners. Some of the regulations define only the basic substrate leaving the definition of suitable adjuncts to other regulations in Subpart F. Examples, of such regulations are 121.2510 Polyethylene and 121.2521 Vinyl Chloride-Propylene Copolymer. A second type of regulation defines the composition of the basic substrate and also in the same regulation lists optional adjuvants that may be incorporated in or added to the basic substrate. An example of this type of regulation is 121.2522 Polyurethane Resins. Or such a regulation may list the adjuvants and also provide for the use of other adjuvants included in any other regulation as safe for use as a component. Such a regulation is 121.2507 Cellophane. See 121.2507(b)(3). ASI 00001736 3 A third type of regulation lists classes of adjuvants that may be in or on any of the approved food contact surfaces. Such a regulation is 121.2541 Emulsifiers and/or Surface Active Agents. Section II, A, 2, b, and particularly portions of subparagraphs iii, iv and v are confusing and inapt in that they tend to treat the adjuvants for food contact surfaces in terms of the food contact surfaces. For example, subparagraph iii requires "Manufacturing process, including for food contact surfaces the raw materials and their specifications that encompass the basic resin polymer and the adjuvants (such as plasticizers, stabilizers, preservatives, fillers, colorants, catalysts, etc.) along with the analytical technique used to check the specifi­ cations***." If it be assumed that the basic substrate is an approved food contact surface, as it will be in many instances where a new adjuvant is proposed, it is not believed that this information should be required for the basic food contact surface or substrate. If it can be said that subparagraph iii is not applicable to a new adjuvant, we then turn to subparagraph iv which reads in part, "Specifications for the additive(s) in food contact surfaces, including their identities, the minimum content of the desired component(s), and the limitations or impurities including total heavy metals, monomers, catalyst residues, etc.**** Data from a suitable number of representative production batches of the food contact surfaces shall be included ~to establish"'the range of impurities and by-products to be expected and to show that the proposed specifications can be met." (Emphasis ours.) It is submitted that data from representative pro­ duction batches of the food contact surfaces are not appropriate to show that the specification for the adjunct additive can be met. If the requirement that data from a suitable number of representative production batches is kept (see above comment regarding subparagraphs iv, v, vi and vii under A, Identity, 1, Direct Additive (b) Description of the Additive), it would seem that this should be "representative batches of the additive(s)" • It is noted in this connection that Atlas also supports the Manufacturing Chemists' Association position that at the time a food additive petition is filed, there may not have been any "production" batches of the additive and that the word "production" should be deleted. Again in subparagraph v. we find the requirement "Reproducibility of the food contact surfaces including the production controls and tests employed to assure that a reproducible product will be manufactured." ASX 00001737 4 If this requirement is to be retained (see above comment regard­ ing subparagraphs iv, v, vi, and vii under A, Identity, 1, Direct Additive (b) Description of the Additive), it should not be applicable to adjuvants particularly for adjuvants for substrata food contact surfaces that have already been approved in the regulations. In Section 121.50(e) II, D, Methods, subparagraph 4 it appears that the specifications for food contact surfaces referred to are no different than those referred to in A, 2, b, iii, and iv, which require the analytical methods for each specification. This would appear to be duplication of information on the "tests" or "analytical methods." Respectfully submitted ATLAS CHEMICAL INDUSTRIES, INC. By Assistant to the President KEMtHP Submitted in Quintuplicate CERTIFIED MAIL RETURN RECEIPT REQUESTED CC; .'r. Morgan t, fi^rver :*r. Jare# Hulse nr. C. T». Vincent Dr. w. a. Knapp ASI 00001738 TELEPHONE HUDSON 3-6126 Manufacturing Chemists’ Association, Inc (FOUNDED 1872) 1825 Connecticut Avenue, N. W. Washington, D. C. 20009 November 2, 1967 TO: Pood, Drug, and Cosmetic Chemicals Committee SUBJECT t MCA Support of Dr. Frawley's Proposal re Indirect Pood Additives Gentlemen: Your chairman requests that you advise me by November 15 whether or not you favor MCA support of Dr. Prawley's specific proposal as submitted to HEW in his letter of October 23. A copy of this letter was mailed to you from this office on October 30. The MCA statement regarding FDA's proposed food additives procedural regulations as prepared by Dr. Knapp's task group, to be filed by November 6, endorses Dr. Frawley's concept only, not the specific proposal. If you are willing to support the specific proposal, a supplemental communication to the hearing clerk can be made. Please be sure to reply one way or the other. Sincerely yours MMHssjg ASX 00001739 HOFFMANN- LA ROCHE N UTLEY * NEW JERSEY • INC. 07110 October 30, 1967 Dr. william A. Knapp Allied Chemical Corporation P. O. Box 405 Morristown, New Jersey 07960 Dear Doctor Knapp: I have received Mr. Hoover's letter dated October 23, 1967, enclosing a copy of the comments which MCA has pre­ pared for filing with FDA with respect to the Food Additives Procedural Pegulations. The time and work on the part of the committee that obviously went into the drafting of these comments is certainly appreciated. As Mr. Hoover requested, we have reviewed the draft of the MCA position and have set forth our comments below. We have added several ideas which were not contained in the letter to you of September 25th. We would appreciate your considering these for incorporation into the final MCA comments filed with FDA. The comments are as follows: (1) With respect to Section 121.7 (a) We suggest the addition of a new subsection (4) as follows: "Where the conditions of use or characteristics of a new drug or antibiotic drug which substance is also a food additive provide adequate protection of the public, such conditions or characteristics may be considered as being acceptable, practical regulatory methods." PHARMACEUTICALS • CHEMICALS * VITAMINS • AROMATICS ASI 00001740 HOFFMANN -LA ROCHE INC Dr. William A. Knapp • NUTLEY - 2 - • NEW JERSEY October 30, 1967 We believe the addition of this paragraph is essential to provide in the regulations the flexibility necessary to permit the approval of a New Drug Application and promulga­ tion of a regulation without requiring assay methodology in those cases where assay methodology will not contribute further to the protection of the public. An example of when such flexibility would be needed is when the drug is used on animals at a time when the animals are at a stage of life or in a condition which is not suitable for the production of food. Another example would be when the drug substance itself consists of several components, one of which is metabolized more rapidly than the other. To be an effective regulatory method in this case, regulatory methodology would be needed only for that component which is present for the longest J period of time. Still another example might be in cases where a substance is to be given to animals as an antidote. In7 Such cases usage and distribution would be limited. Alpo, in these cases the animals would not likely be fit for food production and potential hazards to the public would be strictly limited. To require methodology in such cases would impose undue burdens upon the industry and restrict the development of substances for these uses, thereby adversely affecting the public interest. (2) With respect to Section 121.50(f) We suggest that there may be an internal incon­ sistency between the wording of the proposed revision of this regulation and the discussion of that wording immediately following. In the proposed rewording of this section it is stated that a general summary of the toxicological basis on which the Food Regulation is based is "not considered ASI 00001741 MVNN-LA ROCHE INC A. Knapp • NUTLEY • NEW JERSEY 3 October 30, 1967 1 or entitled to protection" as a trade secret. the last sentence on page 17 it is stated that ary of the toxicological data is not necessary ment purposes and "should not under any circumreleased as public information unless the petisnts". We agree with the general intent of the .snce. ition, we suggest that it may be unadviseable to : alternative you suggest on page 18 permitting ;wal of the petition prior to publication. We do -hat it would be desirable to provide the Agency eans of forcing the petitioner to withdraw his . consent to have the information published. Very truly yours. General Attorney P. Vincent riathieson Chemical Corp.) aorge ames Hulse . Pfizer & Co.) organ M. Hoover facturing Chemists' Assn., Inc.) ASI 00001742 TELEPHONE HUDSON 3-612G Manufacturing Chemists’ Association, Inc. (FOUNDED 1872) 1825 Connecticut Avenue, N. W. Washington, D. C. 20009 October 30, TO: 1967 Members of the Food, Drug, and Cosmetic Chemicals Committee SUBJECT: Dr. Frawley's Proposal re Indirect Food Additives Gentlemen: I am enclosing a copy of Dr. Frawley's letter of October 23, 1967 to the HEW Hearing Cleric (along with a copy of his BIBRA talk) for your information in the event you intend to submit an individual company set of comments re FDA's proposed changes to the Food Additives Procedural Regulations. Dr. Knapp's task group has referred to Dr. Frawley's proposal in its draft sent to you with my covering letter of October 23. This draft also mentions "it is expected that many of these (MCA) companies will also submit their comments directly to the Food and Drug Administration." The task group plans to reference the BIBRA paper. Sincerely yours. Morgan M. Hoover MMH:sjg Enclosures Copy to: Dr. J. P. Frawley ASI 00001743 296 J. T. IRAWLKY States, the term toxicological insignificance has real meaning and significance. I believe it is a sound scientific principle which must be preserved and eventually 1 hope will be restored in my country. It is this principle which I believe is the very crux of intelligent common* sense regulation of food-packaging materials. Let us take stock. Experience has taught us that most uses of food-packaging materials arc safe beyond any reasonable doubt'. Experience has also taught, at lc;wt in the United States, that an “omnibus” permissive list not only diverts the energies of our corporations, government and universities into predictably unprofitable research, but can lead to some, if not general disregard for the law. This leaves us with the conclusion that some mechanism should be found for subjecting to a permissive list only those uses of packaging materials which pose a potential hazard to health; that is, constructing a “non de minimis list" or “relevant” list. Here is where I invite each and everyone of you to sit down and define those uses which can be assumed to be safe. As I stated earlier this exercise sounds like fun, but it is just plain hard work. I am not certain that my solution is the best, but I assure you it is the result of many hours of reflection and analysis. Tn its briefest form, 1 believe that any chemical suitable for use in food-packaging is safe for man at a level of 01 ppm in the total diet. Extrapolating this dietary concentration to a practical and meaningful guideline for regulatory purposes, use of a chemical in a container at a level of 0-2 % or less will contribute less than 0-1 ppm to man’s diet. On the surface, this may not appear to propose a major improvement, but application of this guideline would permit deletion of 75% of the citations in the United States regula­ tions and I am certain would permit more efficient use of manpower, in establishing permissive lists in other countries. I do not ask that you accept this conclusion oil faith. So, as briefly as possible, I should like to review the scientific basis for this conclusion. First of all, what level of a compound, which is suitable for use in food packaging, but of unknown toxicity, can be assumed to be safe in the human diet? I know of no better approach to answering this question than to examine our toxicological experience and tabulate the experimentally determined safe level for all the compounds which have been studied. Because 90-day toxicity studies are generally considered inadequate for calculation of safe levels and because only a small number of these are published, I decided to review as many 2-yr chronic toxicity studies as I could find and to tabulate the “no-effect” level confirmed for each. I can make no claim that T have found every 2-yr chronic toxicity study which has been conducted. I can only claim that I have tabulated the “no-efTect” levels from every chronic study which I could find, without any selection or rejection except irradiated foods. In total, I was able to locate 2-yr chronic toxicity studies on 220 different substances (see Appendix), and although this may seem like a modest number, it represents between 4 and 7 million pounds in toxicological research. Last September I had been able to locate only 143 such studies, but with the co-operation of many of my colleagues in the field of toxicology, I estimate that I now have collected about 90% of all such studies which have been conducted. Table 1 presents the distribution of “no-effect” levels for all of the 220 compounds. It is apparent from Tabic 1 that a small percentage of compounds w ill be extremely toxic—having a “no-cffect” level in experimental animals below 1 ppm, but that the majority will exhibit no toxic effect even at 100 ppm. Only 19 of the 220 compounds demonstrated ASI 00001744 HERCULES INCORPORATED MEDICAL DEPARTMENT October 23, 1967 Hearing Clerk Department of Health, Education, and Welfare Room 5440 33Q Independence Avenue, S. W. Washington, D. C. 20201 Re: Food and Drug Administrations' Proposed Food Additives Procedural Regulations (32 Fed. Reg. 152, p. 11443) Dear Sir: I wish to concur with the stated objective of the Food and Drug Administration that the Procedural Food Additive Regulations should be revised "to expedite their scientific review," and to reduce the "unnecessary burden that wastes the time and efforts of both Administration and industry scientists." Having been a scientist in the Administration, as well as in industry, I share the concern of the Administration over the increasing use of your experts on nonproductive assignments. This concern is one which scientists inside and outside government consider to be a major threat to a continued unblemished record of consumer health protection currently shared by the Administration and the industry. However, after careful review of the proposed changes in the procedural regulations for food additives, I have concluded that the Administration has overlooked one of the major obstacles to efficient and effective use of industry and Administration scientists, because no recognition has been given to the inherent safety of certain uses of incidental food additives and no procedure has been provided to eliminate such uses from the same exhaustive scieptific evaluation and administrative review required of more hazardous applications. If we are to provide the public the degree of protection to health which we are morally and legally dictated to provide, we must find some mechanism for expending our limited resources, both manpower and finances, in a manner appropriate to the relative risk. Under the current regulations and the proposed revisions, no opportunity is provided for this. In the field of food packaging I do not think we should direct any criticism toward any individual or group for failure to incorporate such provisions into the existing regulations adopted in 1959. At that time the potential health h'azard from food packaging was poorly defined and scientists in industry and government, including myself, were unwilling to assign a lower risk to any use of a food packaging component. However, after many years and ASI 00001745 298 J. P. FRAWLEY Therefore, if we exclude heavy metals and pesticides from our consideration, experience has indicated that only a very occasional (fewer than 1 out of 100) commercial compound will have a “no-effect" level below 100 ppm and that an infinitely small number will exhibit any toxicity at 10 ppm. or less. ' Dietary no-eiiect level, ppm Fig. 1. Tfi'toprnm showing distribution of “no-c(Tcct" levels in 2-yr chronic studies on 2.10 compounds. Shaded mens denote pesticides and heavy metals, and blank spaces other chemicals. Now if we apply the conventional 100-fold margin of safety to these experimentally determined “no-cffcct” levels, all 132 of the non-pcsticidal chemicals me safe for man’s diet at a dietary concentration of 0-1 ppm or higher. Many of these materials are used at much higher levels in food, but had we assumed that they were all safe at 0-1 ppm and permitted their use up to that level without toxicity studies, we would have been correct in 100% of the eases and would not have exposed the public to any health hazard. Tor accuracy, l should point out that in the above calculation 1 have dealt only in orders of magnitude. If these “no-cffect” levels arc subdivided into small groups as 10, 30, 100 or 300 ppm, it can be concluded that all were safe to animals at 30 ppm. Moreover, I did not take into consideration the larger food consumption per kg of body weight of rats and dogs versus man. Combined, these additional calculations show that the 0-1 ppm level in the human diet provides less than 1 /1000th the mg/kg/day intake of the most toxic of the 132 compounds. Some may argue that I have been unnecessarily conservative, and perhaps I have been. Now let me consider briefly the other aspect of our problem—migration to food—and attempt to develop some guidelines which will tell us which uses may contribute more than 0-1 ppm to the diet of man, and which uses cannot. First of all, it is obvious to everyone that any major component of a food container must be assumed to possess the capability of migrating to food at a level in excess of 0-1 ppm, unless proven otherwise. However, it is equally obvious, that some uses will not contribute 0-1 ppm to the diet. Our problem is to find this dividing line. Undoubtedly, this dividing line is different for each type of substrate. It will be different for films than for bottles. It will be different for one polymer than for another. V/c could establish a whole series of levels for each food-packaging substrate and its intended use, but most of these differences are not sufficient to justify complication of regulations. Therefore, in order to determine the level of addition which would contribute less than 0-1 ppm to the diet with all types of substrates, I selected the substrate which is the most permeable and susceptible to extraction by food, namely, papei. In addition 1 have selected ASI 00001746 Hearing Clerk Page 3 October 23, 1967 (4) Substances permitted for use by regulations in this Subpart F. (5) Substances used at a level of no more than 0.2% by weight of the container or no more tKan 0.2% by weight of the coating or other surface treatment, provided these substances are not heavy metals, as defined in Food Chemicals Codex,or pesticides, as defined in the Federal Insecticide, Uodcnticide ■ ind Fungicide Act. Addition of this new subparagraph to regulation 121.2500 appears logical because it automatically incorporates the other restrictions of good manufacturing practice to the food packaging uses of these trace components; for example, that the amount used in the container shall not exceed that which is "reasonably required to accomplish the intended physical or technical effect," that the purity shall be "suitable for its intended use" and that the uses shall not violate any other provision of the Federal Food, Drug and Cosmetic Act. I submit this proposal for your careful study and consideration and recommend its adoption. Sincerely, John P. Frawley, Ph.D. Chief Toxicologist JPF/eaw Attachments ♦HERCULES ASI 00001747 J. P. mAWLKY 300 food, sugar, doughnuts, ground beef, butter, bacon, sausage, to name just a few) ami anal­ ysed each sample at several different storage intervals and temperatures. For our purposes, T hare selected only the uncoatcd and -it n waxed paper and only the maximum migration levels obtained for the 13 commodities packaged in these uncoatcd papers under typical commercial storage conditions. Admittedly this gives unrealistically high values for rosin size which arc not typical of industry practice, but for our present purposes, the worst case must be presented. Table 4. Calculation of maximum migration of rosin size* to total diet Commodity group Milk products Vegetables Meats Fruits Grain products Supar Rutter, oils Percentage of diet Average migration (ppm) 31 20 18 13 10 5 3 31 20 38-2 OS 35 02 328 Contribution to total diet (ppm) 10 04 69 01 04 00 09 Total ... 9-7 *4% in paper. Table 3 shows the maximum migration value for IS food commodities at various typical storage times and temperatures when exposed to paper containing an average of 4% rosin size. It is obvious from some of these values that hig.h levels of migration can occur with some foods, whereas other foods contain much less rosin si/e. The data in Table 3 can be tpii'chly considered since the individual values arc of no great significance, but the com­ posite of these values can be helpful. Table 4 shows the average consumption of these various commodity groups in the USf, the average migration to that commodity group and a calculation of the maximum level of rosin size in the average total diet, if 100% of the diet were packaged in uncoatcd paper containing 4% rosin size. Undoubtedly there arc some differences in dietary habits between our count!ies, but 1 doubt that they would significantly niter the calculation. As T mentioned previously, three different sizing levels were used in these studies. Table 5 shows the final dietary calculations for the same foods, under the same conditions for paper containing 2 or I % rosin size. The extrapolation is remarkably good, 'lbe but column shows the migration in ppm expressed on the basis of a unit of 1 % rosin si/e in the paper or container. For each per cent addition to the container, man’s diet would contain a maximum of 2 ppm of the additive, if the entire diet was. in contact with that container. One further calculation is necessary in order to arrive at a realistic d.tenninatiim of the Table 5. Maximum n.igraf'on of rosin size to diet Level of size in paper (%) 4 2 1 Migration (ppm) 9-7 4-4 19 ppm/ % 2-4 2*2 1-9 tU.S. Department of Agriculture Dietary Evaluation of Fond Used in Households in U.S., 1961. ASI 00001748 Fd Cos-net. Toxicol, Vol. 5, pp. 293-30S. Pcrgamon Press 1967. Printed in Great Britain BIBRA Annual Scientific Meeting* Scientific Evidence and Common Sense as a Basis for rood-Pncltagiiig Regulations J. P. Fra.wi.ly Hercules Incorporated, IVihnington, Delaware 19399, USA 1 am honoured by your invitation to meet with you tonight and to discuss with you some of the problems associated with assuring the safety of food-packaging materials. However, 1 am equally humbled by my own inadequacies to discuss our subject matter as expertly as it deserves. Unfortunately for all of us, there is no individual who can be considered an expert on all aspects of food packaging. Although essentially all of the individual components used in food packaging originate in a chemical plant, the technology for formulating and converting these materials into useful containers varies with every substrate, whether it is plastics, paper or metal. Moreover, the marketing relationship between producer, formulator, con­ verter and the food industry is notably different for each segment of this complex industry. Consequently, it is a formidable task to become an expert for even one aspect. Each of you here tie's evening possesses expert knowledge in one or more aspects which I wish 1 had. It is unfortunate that telepathic communication has not reached my level of intellectual development, so I could benefit from your experience. In fact, the only thought waves reaching me suggest that many of you should be delivering this lecture rather than I. Therefore, if you wilt consider me to be a substitute speaker, you may be a little more tolerant towards my remarks. When was the last time you sat down in the solitude of your study and attempted to write out a geometrical proof that the shortest distance between two points is a straight line? Most of us would have a difficult time doing it today because, as you recall, it is not sus­ ceptible to proof. It must be accepted. Indeed, some of the most difficult things in life to prove are the obvious ones. A number of months age, I sat down to try to prove something which was obvious to me—that there are some uses of food-packaging materials which cannot involve any hazard to health of the consumer of food. I had no preconceived idea of tire end point I would reach, but it seemed like it would be fun. Sometimes now I wish I had resisted the temptation and invested my time in some other form of recreation. My main exercise was to try to determine a level of use of an> food-packaging component which could be considered safe regardless of its degree of toxicity. Many of you know the conclusion I reached; namely, that any component of a food container or coating which is •Editor's note: This paper was delivered to the Fifth Annual Scientific Meeting of the British Industrial Biological Research Association (BJBR.A), held in London on 2$ January 1067. 'the Annual Scientific Meeting, instituted m 1962, provides an opportunity for members and guests of the Association to receive an address from an eminent toxicologist on atopic related to BJRRA's field of interest. Previous speakers have been Professor IJ.C. Hodge, Or, A. J. Lehman, Professor L. J. Go'dwatcr and Dr. J, M. Barn.s. 253 ASI 00001749 302 J. P, FRAWLEY The most frequent comment is a concern that despite our toxicological experience to date, we cannot assume that the next compound will not be toxic at 0.1 ppm. The same basic concern has been expressed in another way, by expressing doubt that toxicity data from 2-yr chronic studies represent a valid cross-section of chemicals, since some of the more toxic ones are rejected by short-term toxicity tests. It is, of course, possible that sonic chemical may be synthesized at some lime in the future which would be tov'c at 0-1 ppm in the diet. However, it is almost impossible for such a compound to become an intentional component of a food container, lor a compound to ^e toxic for man at 0-1 ppm presumes that it will be as toxic or more toxic than any commercial pesticide. For it to be used as a component of a food container presumes that it must be manufactured, packaged, distributed, and in other ways handled several times before contacting the food. It is inconceivable that a compound as toxic as this could pass through so many hands, in an industry not accustomed to handling highly toxic substances, without revealing its toxicity through injury to personnel. Once recognized, safe handling of such a compound would require such extreme industrial hygiene precautions as to bo incompatible with converting operations and food-packaging practices. It seems to me that in order to produce an unsafe food package, due to incorporation of a toxic ingredient at a level of 0-2% or less, it would require a deliberate or intentional act on the part of a manu­ facturer to poison the public, without at the same time poisoning his own workers. No amount of legislation or regulation, can protect against such insanity. It has been suggested by a few of my colleagues that the extreme toxicity of such materials as allatoxin rules out an assumption that any chemical is safe at even one part in a thousand million unless it has been te-'.ed. 1 believe that such an assumption is valid, if we limit our discussion to certain uses or industries. Again, I believe common sense tells us that it is inconceivable that anyone could manufacture millions of pounds of nflnto.xin, or any substance of extreme toxicity and distribute it for use as a stabilizer in plastics or wetstrength resins for paper without finding out that it was too toxic for that industry. No company can afford to lose customers that way. Accidental contamination with aflatoxin or other extremely toxic substances is another matter, but this is outside the considerations of a permissive list. Whether a permissive list contains 200 or 20,000 suit it -.nccs, accidental contamination is no more or less likely. Quality control, inspection, .-.:t.! personal attention to details in manufacture are nil necessary ingredients to the prevention of contamination of any product. A few individuals have questioned the validity of my estimate that no mojc than 25% of the diet will be in contact w ith the same packaging substrate or chemical. In rare circum­ stances, of course, some individuals may eat canned foods almost exclusively and some may cat fresh or unpackaged food almost exclusively. These vacations in dietary habits, along with other intraspecies differences have been taken into consideration as pait of the basic concept of our 100-fold margin of safety. Moreover, as mentioned above, the conservative calculations used above provide a 1000-fold margin of safety. The principal objection to this proposal in the United States has been administrative. Adoption of this proposal w ould obviate the need for many of our packaging regulations and would suggest a complete rewriting of Subpart F. For example, the "general adhesives” and “defoamer in paper manufacture" regulations would be replaced by a statement of * good manufacturing practice that adhesives should not contact the food (as is already provided despite the fact that thousands of chemicals are enumerated) and that defoamers may be used only prior to aid during sheet-forming process (as is also already provided). ASI 00001750 FOOD-PACKAGING CONTROL 295 common-scnsc approach to allow us to concern ourselves with potential hazards and not with predictably safe practices. It is to this assignment that I applied myself last summer—to try to develop a scientific basis for a start, and only a start, towards a common-sense approach to food-packaging regulation. However, before proceeding with the scientific evidence I have collected and the conclusions T have drawn, I have made two statements which require documentation. First, that the return on our investment has been negligible and second, that our regulatory scheme has been too complex to serve its intended purpose. f ollowing enactment of our law, the major task facing the industry was evaluation of current industry practices. Many of you are familiar with some of the larger research progiammcs undertaken by different segments of the industry, for example, the petroleum wax studies by the American Petroleum Institute, the can enamel studies by the can pro­ ducers and the rosin product studies by Hercules. Many other programmes which received less publicity were conducted on regenerated cellulose, polyethylene and other polymers, paper coatings and wet strength resins, to mention only a few. The net result of this invest­ ment of millions of pounds has been that more than 90% of the prior industry practices have been confirmed as safe, through a combination of low toxicity and low migration, and have been endorsed by our Food and Drug Administration (FDA), by inclusion on our permissive list. This general endorsement of the vast majority of industry practices testifies to the fact that most uses of packaging materials arc inherently safe. However, before sufficient facts were accumulated to confirm the low degree of hazard associated with packaging materials, wc had committed ourselves to an “omnibus” per­ missive list, containing every conceivable chemical which might even remotely come in contact with food. We now have 94 separate food-packaging regulations or lists dealing with different uses of packaging chemicals, from 967 ingredients*' for adhesives to 8 ingre­ dients for zinc-silicon dioxide matrix coatings. These regulations contain over 43,000 w ords, about 10,000 words more than the regulations for all intentional food additives. In 1966 alone, the 8th yr of the law’s existence, over 200 new uses of packaging chemicals were approved and published in our Federal Register. Even a superficial examination of these regulations reveals that the vast majority of these words are devoted to the enumeration of thousands of chemicals for one or more specific uses under which most cannot migrate to food at an unsafe level, regardless of their degree of toxicity. Unless you work with these regulations on a daily basis, are familiar with the multiple cross-references and have sufficient technical training to understand what chemicals are covered by sonic of the vague generic terms, it is almost impossible to determine the approved uses of a given chemical. \Ve have created a complex maze of regulations, too lengthy and involved to be understood by most of the regulated industry, with the unanticipated result of a growing apathy towards ■ correct interpretation. I This type of “omnibus” permissive list came about in the United States at the insistence of some segments of industry, coupled with a change in interpretation of our laws by the FDA—a change which revoked the long-established principle of de minium non curat lex (the law does not concern itself with trifles) by claiming that the law does not recognize any level of a chemical as insignificant. This denial of the existence of a toxicologically-insignificant level or biological zero is analagous to a denial of the existence of night, on the grounds that you cannot prove the absence of light. In all countries outside the Unite.'. •967 dors not count the numerous reaction products cleared for one o; more of these chemicals. If these arc counted, the number exceeds 3800. ASI 00001751 J. P. FHAWLEY 304 Appendix (eontd) Crmpound No-cffect level (ppm) 2.4-Hu hloro 6 n-chlmonnilino-Stiiu.-inc (Gyrene)* 5000* 2.4-Oi .hlnioplv.noxycihj 1 sulphate, sodium salt* 200* 4l4'-ilifhl(iro-n-trich!oromethylhcn/h\ drol (Kclihanc)1 20* Dic\ 'mdiamidc3* 2500 Dic'drm1 0 5* 0,0-T3icthyl 0-3-chloro-4-mclhyI-l0X0-* IIA -benzopy ran-7-yl phuxphorothioatc (Co-Rat)1 2* Di(2-ctbyUie\yl) pluhalaic1' 1300 Di-»-he\yi a/elatc8* 50o0 rsi-ivobutyl adipate’ 5000 Dihuiyl (liiodipropinnic acid" 30,000 Dimethyl caibatc14 10,000 2.4-Dimethyl-2-mcthy!cnc*l,2,4tbi.'.diazolidinc-5-tbionc1 100* Dimethyl plilhalate'* 20,000 3.5-Oin iethyltctraliydfo-1,3,5,2//ihhdiarinr^-t’Mnnc' (Mylone)" <10* n,i > I )imi:tliyl-f)-(2,4,5-ti ichlnrophctiyl) phn'-pltou.thioatc (Ronnel)4 10* 3.5-l3'iiitrobcil/amido:,! xy ben/onte44 1500 1-[S*(3a.4,5.6,7,7,i-l lcxah\dro-4,7methanomdanyl)]-3,3-dimcth\'urca 500* (Heiban)* 10,000 H' di o\\ ethylccMulosc17 50,000 I hdiowpropi imethvlccllulosc1 Ilydroquinonc" lO.OOOr rf-Tsoascorbic acid" 10,000 2500 (/-rsonscorhy 1 palmifatc" Isopropyl ,V-(3 chlorophcnyl) carbaniatc 2000* 1c4 120* Mercurv acetate1 25* Mcthoxvchlor7'1* 200* 0-Meth\l-0-(!-/err-butyl-2-chlorophcnyl) mcthvlphosphoro.-.midothioatc 30* (Rucknc)1'1". 0-Methyl-0-(2.4-diehlorophcnyI) isopropy Iphosphoramidothioate’ 10* 20,000 Methvl p-hvdro.vylvn/oate" 100 Mcthvl metliaciylate34 Methyl napluhalcncacetic acid7 2500* Mcthylpolysiloxanc1 3000 Mcthvl salicylate'1 10,000 Monuron* 2J0* l-N:ipluhxI-.Y-meiliyl carhamalc’ 200* 50* NieOtinc* t>2 2500 Nordihs drtvpjaiarelic acid" 100,000 Nylon (Zytel)54 Octadeeyiamir.e'5 500 Octyl eallatc1* 350 p-h'tt- Octy Iphcnoxj -polyethoxy elhr.nols (Triton X-405)1* 14,000 Parathion1 1* Petrolatum'7 50,000 Petroleum wax no. 2'* 100,000 Petroleum wax no. S'* 100,000 Petroleum wax no. 12 100,000 Petroleum wax no. I S'* 100,000 Pe’troleum wax no. 20'* 100,000 Phcnacctin” 630 Phenol71 10,000 Phenvl mercuric acetate7 01* o-Phcny IphenoF* 2000* Pimaricin" 500 Piperonyl hutoxide4 700* 297 FOOD-PACKAGING CONTROL Tabic 1. Distribution of "no-effect" levels in 2-yr chronic studies “No-cffcct” level (ppm) All compounds (220) <1 <10 <100 <1000 <10,000 5 19 40 101 151 any toxic effect below 10 ppm, Wc might conclude that the odds of detecting a toxic effect at 10 ppm from any “unknown” compound are approximately 1 in 10. Let us now look at Table 1 a little more closely and examine the nature of these 19 compounds which had a “no-efTcct” level at 10 ppm or less. Table 2 shows the same in­ formation as Table 1, except two additional columns have been added which subdivide these 220 compounds into two categories: (1) a “heavy metals and pesticides” category and (2) an "all other compounds” category. I believe this breakdown is worthy of careful examination. The most apparent conclusion is that all 19 of the compounds, which were toxic below- 10 ppm, were pesticides and heavy metal compounds, Equally significant is the fact that 39 of the 40 compounds, which had “no-efTcct” levels below 100 ppm in experi­ mental animals, were also pesticides or heavy metal compounds. The only compound in the “all other compounds” category which was toxic below 100 ppm was acrylamide. Table 2. Distribution of "no-effect" levels in 2-yr chronic studies “No-effect” level (ppm) All compounds (220) Heavy metals and pesticides m Others (132) <1 <10 <100 <1000 <10,000 5 19 40 101 151 5 19 39 72 86 0 0 1 29 65 It is obvious that the degree of toxicity of pesticides and heavy metals (which were used as pesticides at one time) is quite different from that of other commercial chemicals. This should represent no surprise because pesticides are synthesized, screened and selected for their toxicity to one or more forms of life before becoming commercial products. This contrast is more clearly shown by Fig. 1 which depicts the distribution of “no-efTcct” levels for the two categories of chemicals. It is obvious that the average toxicity of a pesticide is about 100 times as great as the average for other chemicals. ASI 00001753 306 J. P. FRAWLEY Aof Food mid DrugOfiicials of the I hided Suites. 8. Ibkr. H. I .. Nies, P. O. A Dene, p. II. (1963), The loxieitv iT in ori'anic ar-vnical, 3 nitro-1hjdii'v pi: uyl.iironie acid. II. Chronic Toxicity. Toxic, appl. Pharmac. 5, 526. 9. rit/hugh, O. C. A Nelson, A. A. (1946). Subacute ami chronic toxicides of oscorbyl ;'..!mit.i(ss. Proc, Sac. e\p. Biol. Mat!, 6|, 195. Ki, Joint I VO/WIIO I'xpert Committee on Food AJJ.'tivcv Sixth Itip-it (1963). (’valuation of the "I oxicity of a Number of Antimiciohials ..!t A111i*>\nl;i11ts. B i ll, Bop, Aor. Il'ht Jfllh Or;:. 228. 11. Oxer, H. L., Or.cr. Mona & Morgarcidgc, K. (P65). Stud'cs of the safety of nzo'h'carbonnmidc as a flour-maturing agent. Toxic appl. Pharmac. 7, 445. 12. Deichmann, 3V. Jl., Clcrntner, J. J., Rakoczy, R. A f!tam.Iiine, .1. (1955). Toxicity of ditciti..ryiii.t>liiicthy'lphcnol. AM.A. Archs hiil. Ilhli 11,91. 13. Joint Iv'li Wilt) Fxjvit Committee on Food Additives Ninth Report (1966). Specifica­ tions for the Identity and Purity of rood Additives and their Toxicological Evaluation: Sonis Antimicrobials, Antioxidants, Emulsi­ fiers, Stabilizers, Hour-Treatment Agents, Acids and Bases, 7ir/i. Bop. Sir. 1 Phi llllh Or:;. 3J9. 14. I etimnn, A.J. (1955). Insect Repellents. Vol. 19. p. 87. The Association of Food and f)rug Oli-ciuls of the United States. 15. Scala, IF. A. A Pavnter, O. E. (1964). Safely evaluation studies on l,3-butv!ene glycol. Toxic, appl. Pharmac. 6, 358 !6. Oscr, B. L. A Oser, Mona (1962). 2-(p~tertPuiylphenoxyVi-opropvl 2-ch!oroethlvl sulfite (Aramite). II. Carcinogenicity. Toxic, appl. Pharmac. 4, 70. 17. Oxer, B. I , Oxer, Mona A Spencer, II. C. (1963). Sifcty c\ablation studies of calcium FDTA. Toxic, appl. Pharmac. S, 142. 18. Oscr, B. L., Morgareidgc, K., Weinberg, M. S. it Oser, Mona (1966). Carcinogenicity study of tarhirsonc. Toxic, appl. Pharmac. 9, 528, 19. Shclanski, II. A. & Clark, A. M. (1943). Physiological action of sodium carboxymithylcell.ilose on laboratory animals and humans. Til Res. 13, 29. 20. Bagdon, R. F., ^binden, G. & Studcr, A. (1960), Chronic toxicity studies of /(-carotene. Toxic, appl. Pharmac. 2, 225. 21. I chmnn, A. J., Fitzlntgh, O. G., Nelson, A. A. it Woodward, G. (1951). The pharmacological evaluation of antioxidants. Ailv. Fi! Res. 3,197. 22. Dehihunt, C. S., P'an, S. Y., Dardin, V. J. & Schneider, J. A. (I960). Prolonged administra­ tion studies with chlorpropamide. Toxic, appl, Pharmac. 2, 195. 23. Dessau, F. I. A Sullivan, W. J. (1961). A twoyear study of the toxicity of chlortctracycline hydrochloride in rats. Toxic, appl, rhnrmnc. 3, 654. 24. Dacic, J. C. (|96x), f'bionic toxicitv and me ia.yooity iliehcx on Cuius Red Nil. 2. Pi <■ Ut /r. <);.o-,• a:Silt. 13.31. 25. I lumen. W. 1! , n.ms, K. J. A I it/hug.h, O. G. (196?). Chronic U" icily c>f cube. Toxic, appl, Pha, mac. 7, 535. 26. Industrial Bio-Te-t 1 .sl-oratorics (Unpublished data), 27. n.ivis. K, J. .t I it/hiigh, cl. G. (1962). Pathologic chan.vs noicd m i.Us fed II A C Red No. 9 for t vo voais. Toxic, appl. Pharmac. 4, 2U0. 28. Davis, K. .1. A Fit/hugh, O. G. (1963). Pathologic dunces noted in rats fed D & C Red No. 10 [n-onofodium wait of 2 (2-hydroxy* 1-naphthy lace)-l-n.iph:halenesulfonic acid] for two years. Toxic, appl. Pharmac. 5, 728. 29. American Cynnamid Company (Unpublished data). 30. 1 lodge, II. C., Maynard. Is. A., Downs, W. L,, Salci no. I illi.m .9 t'.i- ’ , r, .1. T. (1967). Cbtoilic oral toxicity studies • >f di-n-hexyl a/e!ate in rats and dop.s. rove. appl. Pharmac. 4, 247. 31. Smyth, II. I7., Jr., Carpenter, C. P. & Weil, C. S. (1966). Toxicologic studies on 3,5dinic.hyhctr.ihy dro-1,3,5, 2 (C-thiadia.zinc-2tltionc, a soil fun ucide and slimicide. Toxic, appi. Pharmac, 9, 521. 32. Kerr, K. 11., Abmhnmsrn, p, R, A Ipson, J. R. (1965). Exahr.tion of the safety of 3,5-dinitroben /amide. Toxic, appl. Pharmac, 7, 488. 33. Ambiose, A. M., Pool'i, A. N., DeFds, F. A Cob, A. J., Jr, (I960). A toxicological study of biphonxl, a citrus fum-istat. Til Res. 25, 328. 24, Payntcr. O. E. A Weir, R. J„ Jr. (1960). Chronic toxicity of S.ntom.rse No. 3 from olefin (dodccyl binzenc sodium sulfonate). Toxic, appl. Pharmac. 2, 611. 35. I eviivk.'s, G. J,, Vidmie, t ma B., O'Grady, .1. J. A Sbaifer, f). (1961). ,\ ute and chronic toxicity ori,iodir': (s'-dodccyigii. midi;.c acetate). Toxic, appl. Phanauc. 3, 127. 36. I arsoi). P, S., Finrc.an, J. K., Haag, H. B., Suvth, P.. B., Jr.. A llcnnigar, G. R. (1960). Chronic toxicity studies on two epoxidi/cd soybean oils in ilie rat and dog. Toxic, appl. Thanrac. 2, 649. 37. Filzhugh, O. O.. Nelson, A. A. A Frnvvlcy, J. P. (1951). A comparison of the chronic toxicitics of sy mhetic sweetening agents. J. Ain. pharm. Ass. Sci Til. 40, 583. 3S. Doicclkva, J. F.. ( arson, P. S., Hennigar, G. R., Jr„ Jlu.T, F. G., Craw Ibid, E. M. & Smith, R. B„ Jr. (1951). Studies on the chronic i d toxicity of monomeric ethyl acrylate and .I'.eihvl r.-.clhaciylatc. Toxic, appl. pharmac, 6, 29.' 39. Troon, J. 1-’., Dutra, V. R. A Cleveland, F. P. (19*3). Toxicity of 2-eihylhe.xyl diphenyl phosphate. A.M.A. Archs ir.it. ttsg, 3, 170. 2 FOOD-PACKAGING CONTROL an additive which is very readily extracted from its substrate, namely, rosin size. This combination of substrate and additive, I believe, represents the most extreme case of migration and values determined from rosin sized paper should represent a maximum for any component of any packaging media. Indeed, such data would be excessive for most uses of packaging components. In our initial efforts to study the migration of rosin size from paper, wc used typical simulated solvents: various aqueous solutions, hexane, maize (or corn) oil, etc. This was wasted effort because, in water and oil, the extraction was a direct function of time and temperature and did not plateau until essentially 100% of the rosin size was extracted and the integrity of the paper sheet was destroyed. Nevertheless a century and a half of experience has shown paper to be a satisfactory packaging material. Although these studies clearly demonstrated that rosin sized paper would be an appropriate choice for developing maximum migration data, they contributed nothing to the evaluation of safety of rosin size which was our principal motive at that time. As a consequence of this failure of the simulated solvents test to help define the amount actually migrating to food, wc prepared radioactive samples of rosin size, incorporated them into typical commercial paper and paperboard at known levels, packaged a wide variety of food in contact with these paper samples at typical package ratios, stored them at typical storage temperatures for typical storage times and determined the rosin size content of each food by counting tbc radioactivity. The study was far more extensive than I shall describe, because wc used several types of paper (greaseproof, waxed, unwaxed, etc.), containing three different levels of rosin size, 24 different types of food (water, ice-cream, oysters, apricots, green beans, dry breakfast Tabic 3. Maximum migration af rosin size* from unrooted paper under typical storage conditions Food Milk products Water Icc-crcam Vegetables Green beans Green beans Lettuce Potatoes Merits Ground beef Chicken beefsteak Sausage. Fruits Apricots Apples' Grain products Puffed rice Whcaties Flour Doughnuts Others Sugar Putter Temperature CF) Time (days) Migration (Ppm) 34 10 14 28 5-9 03 34 72 34 72 7 14 7 28 1-3 41 2-4 02 34 34 34 34 5 3 7 5 8-7 7-2 4-9 1240 72 72 28 28 01 1-2 72 34 72 72 14 28 28 * 3 5-8 70 02 0-9 72 34 28 14 02 32-8 *4% in paper. ASI 00001755 J, P. FRAWLtY 308 69. riphmdt, O, C., I n ?. ■ "lov . Chemical Society^ ■ 'r .... 1— ■-% Draft Page 3 ih i",' fp< .f o~.^ A 1 In this he reaches the conclusion that 4 1 « "... any component of an article contacting food which is present in the article or its coating at a level not exceeding 0.2% by weight is generally recognized as safe provided it is not a heavy metal or pesticide." We submit that a practical solution might be to establish a realistic s .> level for the components of a packaging material below which / l €. ‘ f - , , t* - ' -* ^ there need be no concern with migration, provided, of course, • that the materials are known not to he-highly toxic. The purpose of this discussion is to urge that administ­ rative policy be established and regulatory provision made for^rapid acceptance of food additives which are present in packaging material in small quantity (e.g., <0.2%), or which would not be expected to be found in significant quantities (e.g., 0.1 ppm) in the daily diet. The comments submitted herewith represent, in substance, comments submitted to the Manufacturing Chemists * Association by many of its member companies. It is expected that many of these companies will also submit their comments directly to the Food and Drug Administration. respectfully urge the Commissioner to carefully evaluate our position on the proposed regulations and ask that appropriate changes be made in any final regulations that may issue. We strongly ASI 00001765 I Draft Page 4. urge that, in finalizing any regulations in this area and in evaluating the existing food additive regulations, especially those dealing with indirect food additives, that careful consideration be given to the substantive problems we have discussed regarding the administrative treatment and handling of these materials. } ASI 00001766 M*. JFACTURING CHEMISTS' ASSOC ,TION COMMENTS ON FDA PROPOSED FOOD ADDITIVES PROCEDURAL REGULATIONS (32 FR 11443) §121.7 P.l. Food additives for use in feed and drinking water of animals and food additives that are also new drugs, certifiable anti­ biotic drugs and/or pesticides. §121.7 (a) (3) We strongly urge that this Section be revised to delete the word "chemical." The limitation of acceptable assay methods to "chemical assays" is an unnecessary and illogical restriction as there may be practical biological physical, or other methods which technically cannot be defined as chemical assays. To limit acceptable assay methods to chemical assays would unduly restrict the constant search by quality control personnel for better and more practical methods of assay, some of which may be better than chemical methods. We point out that neither Sections 505 nor 409 of the Federal Food, Drug, and Cosmetic Act require that assay methods relating to food additives be limited to chemical assay methods. 121.9 Food additive master files. 121.9 (a) We request that the words "submitting or intending to submit a food additive petition" be deleted from the first sentence of this Section. In many instances, the person submitting a food additive master file is doing so for the benefit of another company or person; he, V himself, may not intend to submit a food additive petition The last sentence of this same paragraph appears to limit the use of these master files to use in food additive petitions. Many materials are used as adjuncts in connection with foods, drugs, colors and pesticides. ASI 00001767 P.2. In view of the voluminous nature of many of these master files, it is believed that one master file should suffice for all of these fields. §121.9 (c) We strongly urge that this subparagraph be deleted from the proposed regulation. Master files are submitted voluntarily and represent a confidential relationship between the Food and Drug Administration and industry. We believe that this relationship should remain* jexcept wherein parts t-fra- roastac- file a&e- incorporated rrr- finno—ky^r«fnvniii*n j For our comments on the confid­ entiality of analytical methods and toxicological data in a food additive petition, please refer to §121.50 (f). §121.50 Content and form of food additive petitions. §121.50 (a) It is requested that the third sentence of this Section be amended to read as follows: Any published information used in support of the petition shall be submitted in reprint form, if available, or other suitable photocopy, and, in the event that the published material is readily avail­ able to FDA, references can be made to the publications in lieu of furnishing reprints or photocopies. Under the existing regulation 121.51 "reprints or photostatic copies" of published information are permissible. We submit that the proposed regulations, restricting the petitioner to reprints is not practical and quite often will be impossible to meet. In some instances, reprints are not available for a number of reasons. We urge, therefore, that either reprints or ASI 00001768 P.3. other suitable photocopies be allowed to support the food additive petition. In addition, where the pub­ lished material is from a journal or other source readily available to FDA, the petitioner should be authorized to merely cite the journal or other source. This procedure is presently being used in the new drug and certifiable antibiotic areas (§130.37) and should also be adopted in connection with food additive petitions. It is also requested that the sixth sentence which refers to unpublished scientific studies be amended to read as follows: All original unpublished scientific studies supplied in the petition shall include identification and a descript­ ion of the qualifications including educational background and experience of the technical and professional personnel who are responsible for assuring the accuracy and reliability of such studies. This information need only be furnished for the person or persons who are the responsible head of the laboratory or scientific unit conducting the studies. We point out that in many instances, it would be imprac­ tical to list the identity and qualifications of all the various^chemists, toxicologists and other scientists or technical personnel who participated in the unpublished study presented in the petition. We point out that in regard to new drug applications §130.4 (c), subsection 2.8 (b) requires that the detailed educational and background information need only be given for the person responsible for assuring that the drug has the safety, ASI 00001769 P.4. identity, strength, etc., which is claimed by the application. We submit that this information should only be required for the person responsible for the scientific studies presented in support of the food additive petition. §121.50 (b) Section 121.50 (b) provides for the incorporation by reference of previous submissions where the previous submission ". . . is in a food additive master file kept current by the petitioner, or is in another form of submission not over 10 years old." We do not understand the intent or meaning of this 10 year limitation. By implication, one could conclude that any data over 10 years old is deemed to be unreliable unless in a master file kept current. We suggest that many submissions whether part of master files (formerly designated "master files" or now designated "food additive master files"), petitions, new drug applications, or data leading to prior sanctions or approvals are of permanent value regardless of age. For example, detailed toxicological studies submitted in 1950 which led to a prior sanction or approval are still valid in many cases and data in food additive petitions filed since the effective date of the Food Additives Amendment may still be valid although over 10 years old. The net effect of such a 10-year limit on submissions other than master file submissions is to force petitioners to establish master files for intentional or incidental food additive products. We see no justification for imposing this added burden on a petitioner whose formal petition filing should constitute an adequate file record. ASI 00001770 P.5. The only burden petitioner should have in connection with the reference to data already on file with FDA is a requirement of an accurate description in sufficient detail to provide adequate identification thereof and a .statement reaffirming the current validity of any con­ clusions therein. For the above reasons, we would suggest deletion of the 10-year limitation for submissions other than those in a "master file kept current." §121.50 (c) This section prescribes paper size, line spacing, typing margins, hole punchings, etc., which must be used in connection with petitions. There are many reasons which would make compliance difficult. Some are the following: (1) Except for legal purposes, the vast majority of U.S. business establishments use only 8-1/2" x 11" paper for correspondence, report writing, etc. It is difficult to obtain any other size from most stationers except on special order at extra cost. Carbon paper of different size presents similar difficulties. (2) Photoreproduction papers are likewise of 8-1/2" x 11" dimension requiring hand trimming to bring to size prescribed. (3) It is often desirable for the sake of com­ pleteness to include past studies rather than incorporate same by reference. The proposed regulation would require retyping of thousands of pages of text and photoreduction of graphs or pictures to bring to proper size. ASI 00001771 P.6. (4) As noted in comments on §121.50 (a) above, reprints or photoreproductions of journal articles are usually not of the prescribed size and would require photoreduction or enlargement at needless and great expense. (5) Similarly, reports of outside investigators (toxicologists, consultants, analysts, etc.,) are all on paper of 8-1/2" x 11" dimension and would require retyping or other reproduction to the size prescribed. (6) File cabinets, file folders, record boxes, ring binders, etc., are made to accommodate 8-1/2 x 11" paper. While 8" x 10-1/2" paper can be used in these storage containers, 10% of storage sp^ce therein is wasted. (7) To the best of our knowledge, the vast majority of prior submissions have been on 8-1/2" x 11" paper. If §120.9 (b) means that master files must be converted to 8" x 10-1/2" paper "as if it were a portion of a petition" the task would be an impossible burden. For the reasons stated above and probably additional complications not yet conceived, it is suggested that paper size requirement be deleted. Further, it is requested that double spacing be suggestive rather than obligatory or the requirement modified by "where practical." The retyping of large amounts of available material now in single space does not appear to be a reasonable requisite for food additive petitions. ASI 00001772 P.7 §121.50 (e) I.B.2. We request that this Section be amended to read as follows: USE. The purpose which the additive is to serve, including, if a direct additive, an estimate of the average quantity of the direct food additive to be expected in the total daily diet of the consumer, and where possible or practical, an estimate of the maximum quantity to be expected in the daily diet of the consumer. The bases for such estimates will be provided in this summary. The introductory summary of use information required in this Part B for both direct and indirect additives is not practical as applied to indirect additives. Incidental or indirect food additives, whether food packaging or processing materials, do not lend themselves to mean­ ingful estimates of either the average or the maximum levels that might be expected in the total daily diet. Food processing and packaging materials, unlike many direct food additives, generally can be used for acrossthe-board food contact use, thus coming into contact with countless types of foods under a variety of indus­ trial processing and packaging use situations. Indeed, the petitioner for an indirect food additive in most cases will have no way of knowing all of the many packaging uses that the additive could be used for. We submit, therefore, that estimates of either the average or maximum quantities that might become part of the total daily diet will always be relatively meaningless figures; as such, this information should not be required for indirect additives. ASI 00001773 P.8. , 7 We do not suggest the deletion of this requirement for indirect additives without pointing out that FDA has adopted and is presently following the philosophy that the 100-fold safety factor (100 times the no­ effect level found in animals) adequately ensures the safety of indirect food additives and can logically be relied upon to take care of multiple variables such as diverse use and consumption. The text "Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics," published by the Association of Food and Drug Officials of the United States in 1959, was written by FDA staff members. This publication relates the sensitivity of man to various species of animals and reports that the highest ratio is that man is ten times as sensitive as the rat or cat. The safety factor of 100, then, provides another multiple ten-fold difference to protect man from possible adverse effects of a food additive. The use of the factor of 100 was also endorsed by the Joint FAO/WHO Expert Committee on Food Additives. In the Second Report of this Committee, in the section entitled "Procedures for the Testing of Intentional Food Additives to Establish Their Safety for Use" (See WHO Technical Report Series No. 144, page 17,1958), the Committee concluded: "From these various investigations a dosage level can be established that causes no demonstrable effect in the animals used. In the extrapolation of this figure to man, some margin of safety is desirable to allow for any species difference in suscept­ ibility, the numerical differences ASI 00001774 P.9. between the test animals and the human population exposed to the hazard, the greater variety of complicating disease processes in the human population, the difficulty of estimating the human intake and the possibility of synergistic action among food additives. 'It will be useful to try to define here the standard daily dietary dose. This is taken to be the amount of the food additive that might be expected to be consumed by an average adult eating a normal diet as determined from some appropriate dietary survey. It should be assumed in these calculations that all the foods likely to be treated with the additive will contain it at the level proposed. 'It is inescapable that some arbitrary factor must be applied in order to provide an adequate margin of safety. Where the maximum ineffective dose in animals is calculated in g/kg body-weight, a margin of safety of the order of 100 has been widely used. In the absence of any evidence to the contrary, the Committee believes that this margin of safety is adequate." ^ In addition to the deletion of the requirement of an estimated quantity of daily consumption of an indirect additive, we urge that as to direct additives, a petitioner need only estimate the average quantity of the direct food additive to be expected in the total daily diet of the consumer. It should be realized that an estimate of the average quantity will be a somewhat arbitrary figure, but an estimate of the maximum anticipated consumption will be even less meaningful. Again, we point out that the safety factor of 100 in judging the safety of the ASI OOOOI775 P. 10. particular direct food additive on the basis of animal toxicity studies was designed to take care of the variations in consumption by individual consumers. §121.50 (e) I. B. 5. For consistency with this entire Section 121.50, we request that the phrase "daily diet” be used wherever ■ reference is made to the "diet of the consumer." In addition, we request that the reference to "several species of test animals" in the second sentence be amended to read "in test animals." As a practical matter, normally only two species of test animals are required by FDA. With respect to the third sentence of this Section, we strongly urge that it be amended to read: Thenargins of safety between the no-effect level in the most sensitive species of test animals and, with respect to direct food additives, the average level 1 as the maximum level, where practical to determine,, likely to occur in the total daily diet of the consumer should be stated, taking into consideration previously approved food addi­ tive uses for the substance and any toxicologically comparable substance. (Underlined language is new). To support our request that the requirement for estimating average and maximum quantities of food additives to be consumed in a daily diet be limited to direct additives we refer to our comments on Section 121.50 (e) I. B. 2. In addition, we urge that the consideration given to "comparable substances" be limited to those substances that are known to be "toxicologically comparable." ASI 00001776 p.ll. It is well known that many substances are comparable from the standpoint of their effect or use in food but are not comparable from a safety or toxicity or chemical viewpoint. §121.50 (e) II (A) (1) (b) We find this subsection confusing in that several terms used therein appear to be descriptive of the same thing, namely, the chemical specifications for the food additive. Thus, "complete quantitative composition" (b.i.), "food grade specifications" (b.v.), and "reproducibility" (b.vi), all, we believe, mean substantially the same thing and would be best covered by the term "food additive specifications" or "food grade specifications." We submit that either of these terms adequately describes 1 "complete quantitative composition" and "reproducibility" and request these items be deleted. c -v*V “..y^ v-v" a.* \ . 'v.’(V §121.50 (e) II. A. 1. b. iv. ^ It is requested that this subsection in describing food additives be amended to read: iv. Brief description of manufacturing process(es) and a listing of raw materials and their specifications. We believe that a "brief description" of manufacturing process(es) should suffice for the purposes of evaluating the safety of the food additive petition by FDA. Detailed processing information would serve no real purpose. We would point out that once a petition is approved and a food additive regulation Is published, any manufacturer may produce the additive using any manufacturing process ASI OOOO1777 1 known, so long as the food additive meets the product specifications established in the applicable regulation and the manufacturer adheres to good manufacturing practice. The question arises as to whether petitioner would be bound to the process described in his petition. If so, the developer of the new facet of food technology would be placed at a severe disadvantage. We believe that the structure of §409 (b) of the Act, which details the requirements for a petition, supports the argument that production process information should be required only in special situations and not as a matter of routine. In this regard, §409 (b) (2), subsections A through E thereof, lists the basic statutory requirements of data that must be included in a petition. No reference is made to production process information. A separate subsection of §409 (b), namely, (b) (3), deals with the problem of supplying, upon request of the Secretary, "a full description of the methods used in anr? the facilities and controls used for the production of such additive." Thus, we believe it was the intent of Congress to provide that the Secretary have the right to require such information where relevant because of special circumstances, but not merely as a matter of routine in every petition. Otherwise, a separate section (b) (3) would be meaningless since the require­ ment of production process information would have been listed in subsection (b)(2) of §409. Finally, we also urge that the proposed requirement in this subsection for detailing the analytical techniques used to check the raw material specifications be deleted. ASI 00001778 P.13. The important consideration is the final product specific­ ation and validation of the analytical methods used for the final product. In special situations, at the request of FDA, the description of specific analytical techniques could be provided to FDA but certainly they should not be required as a routine matter. 8121.50 (e) II. A. 1. b. v. We request that the third sentence in this section be revised to delete the word "production" prior to the word "batches." Very often, at the time that the food additive petition is submitted no production batches have been prepared. Thus, it would be impossible for a petitioner to submit data from production batches. Data from either laboratory batches or controlled pilot plant batches should be sufficient to show the range of impurities and by-products to be expected and to show that the pro­ posed specifications can be met. §121.50 (e) II. A. 2. a. vi. Deletion of this requirement is suggested. Methods presently available for determining molecular weight distribution of polymeric substances are generally complex and difficult to reproduce. We submit that extractive limitations for polymeric materials in selected solvents adequately reflect low molecular weight fractions which may be suspect toxicologically and that molecular weight distribution adds little to the appraisal of safety. ASI 00001779 P.14 §121.50 (e) II. A. 2. b. ili. , Please refer to our comments on §120.50 (e) II. A., b. iv. with respect to requirements for manufacturing processes and analytical techniques used to check raw material specifications. With respect to the specific wording of this para­ graph, it is presumed that "adjuvants" referred to ' therein refers only to such adjuvants as are incorporated in the basic polymer polymerization and not to adjuvants in a resin formulation. To our knowledge, the final resin formulation has not been the subject of a petition nor is it intended that they should be. Such formulations are comprised of the basic resin to which may be added GRAS materials, adjuvants listed under the basic resin regulation and adjuvants otherwise permitted under Subpart F. as in regulations of the types represented by 8121.2511, §121.2527 and §121.2541 as examples. §121.50 (e) II. A. 2. b. iv. As in 8121.50 (e) II. A. 1. v. we submit that prod­ uction batches are normally not available at the time of petitioning. Hence the word "production" should be deleted. §121.50 (e) II. A. 2. b. v. As in comment on §120.50 (e) II. A. 1. b, above, we submit that product specificationsas given in §121.50 (e) II. A. 2. b. iv. of the proposed regulation are the proper measure of reproducibility. ASI 00001780 P.15 §121.50 (e) II. B. For the reasons set forth in our comments under Section 121.50 (e) I. B. 2., we ask that the second sentence be amended to read: • The petitioner shall furnish, if a direct additive, an estimate of the average quantity of the direct food additive to be expected in the total daily diet of the consumer, and where possible or practical, an estimate of the maximum quantity to be expected in the daily dijet. §121.50 (e) II. B. 1. We strongly urge that the first sentence be amended so that the data required need only be given "if reasonably practical or possible to determine." This qualification should apply to all the data sought in this Section. We point out that the use information and specifications provided in the petition are designed •' ^ to ensure the expected tolerable and safe level of the V additive. The analytical methods are designed to t ■' measure the levels of the additive in a particular food or class of foods. The requirement in this proposed Section for showing the fate of the additive in food, conversion information, and possible reaction with other components of the food, is not necessary and very often, cannot be readily determined. As a practical matter, where final assays do not show an acceptable level of the direct additive, a petition is not likely to be approved by FDA. ASI 00001781 P.16 §121.50 (e) II. B. 2. Although migration data using actual and simulated foods will determine extent of transfer of a food additive in terms of milligrams per square inch of food contact surface under conditions of use, we submit that it will not provide information from which the average or maximum daily dietary intake can be calculated • for reasons stated in §121.50 (e) I. B. 2. above. Accordingly, comments there are equally applicable to this subsection. §121.50 (e) II. D, 2. This subsection requires that in the case of the food additive needing a tolerance the regulatory method (analytical procedure) . .be satisfactory for application to the raw, processed, and/or finished food." This requirement is presumably intended for direct additives or those substances incidentally present in a final food product because of addition for functional , use elsewhere in the production operation. We trust that this subsection is not intended to cover indirect addi­ tives as represented by extractives migrating from packaging materials. These extractives are multicomponent in character and in many cases it would be extremely difficult if not impossible to determine accurately amounts of individual components in food per se. Accord­ ingly, it is suggested that this requirement be limited to direct additives and incidental additives ( those substances incidentally present in a final food product because of addition for functional use elsewhere in the food production operation). ASl 00001782 P.17 §121.50 (f) For the reasons set forth below we request that this Section be amended to read: Data in a petition regarding any method or process entitled to protection as a trade secret will be held confidential and will not be revealed unless it is necessary to do so in a regulation, and the petitioner approves of such regulation or in the alternative chooses to withdraw his petition, or in an administration hearing preliminary to any , ‘ judicial proceedings under the Act. The r->, analytical methods which do not reveal con. >'} *4 * fidential processing information and the y ^ general summary of the toxicological basis iz1' on which a food additive regulation is based, as such general summary was presented and so designated in the petition, are not considered confidential or entitled to protection as trade secrets. Detailed descriptions of toxico­ logical studies and the raw data of such studies will be considered confidential and entitled to protection from general disclo­ sure. (Underlined language is new.) I It is our unified belief that |in-process^ analytical methods and toxicological' data should be entitled to protection as are trade secrets and remain confidentialThe development of toxicological data and analytical methods are two of the most costly aspects of food____ additive petitionS-j^While knowledge of Jfinal productjt ? analytical techniques may be necessary for enforcement purposes by FDA, and as such, ultimately disclosed in an enforcement action, no real need is seen for author­ izing general public disclosure of such knowledge. Toxicological data,* aad- even «—summary■'thepcof^is* not necessary for enforcement purposes and should not under any circumstances be released as public information, unless the petitioner consents to such release ASI 00001783 \ P.18 ;y aH/' non-J£©A > L,V^ata to ron as appeajj^ If it is deemed necessary to publish information concerning analytical methods in a regulation, the v petitioner should be given the opportunity, prior to V publication, to decide whether he wishes to have such information published or wishes to withdraw his petition. We take particular note of the fact that Section 301 (j) of the Federal Food, Drug, and Cosmetic Act makes it an offense for any person to use to his own advantage or reveal to other than the secretary officers or employees of the department or to courts under certain circumstances any information acquired under Sections 404, 409, 505, 506, 507, 704 or 706 concerning any method or process which as a trade secret is entitled to protection. We believe that the arbitrary designation of analytical methods and toxicology astt_, j . , vi aiLv tfcw W non-confidential re in f-aet -an attempt-to usurp-the-* ------- *) A. •■v*—•i **» function o the courts and _ goes beyond the authority V: granted to FDA by the legislature. J? j >■'/ r* t * We must strongly request that Section 121.9 (c) be / deleted, since the development of methodology may be a l major expense involved in the development of a marketable vJ food additive and in addition, we see no reason that the toxicological information in support of a food additive i petition, also developed at a major expense to the petitioner, be released for public disclosure. If this i v T \* request is not honored, we would ask that this Section be amended in accordance with the language set forth above. ASX 00001784 \4 * P.20. 1121.51 (c) If further information or sample is requested by FDA "a reasonable time in advance of 180 days, but is not submitted within such 180 days after filing the petition, the petition will be considered withdrawn without prejudice." It is suggested that "reasonable time in advance of 180 days" is too indefinite and that * "180 days" implies that if added data are required the petitioner has no hope for a regulation within the 90 days provided by Section 409 (c) (2) of the Food, Drug and Cosmetic Act and little hope of obtaining a regulation within the statutory limit of 180 days. While we would hope that request for sample and/or additional data be made within 45 days after date of filing,a limit of 90 days would appear equitable. It must be recognized that the time required to provide information or sample may vary from days to months depending upon nature of the request. The petitioner should not be penalized by withdrawal of petition when, in fact, notice in advance of 180 days is not adequate to fill request. 121.51 (d) It is respectfully requested that petitioner be , provided an opportunity to review language of a proposed j regulation prior to publication in the Federal Register 1 if it differs from that proposed by petitioner (§121.50(e)II.F.) i | and that this subsection be so revised. \ ASI 00001785 October 24f 1967 7DCC Subcommittee oa FDA Procedural Regulation* TO: Dr. George P. Vincent Mr. Jam* a V. Hulae Photoprint* of Eastman letter of October 11 and attachment thereto are encloaed. I do not believe consents of Mr. Bernard Aatill will affect our brief but believe you should have complete file of consent*. Original Signed I*j A„ Knapp W. A. Knapp VAK:dmk Enel. 00001786 ASI October 20, 1967 Mr. Morgan M. Hoover Food, Drug and Cosmetic Cbanlcalc Comittee Manufacturing Chemists' Association, Ine. 1625 Connectleut Avenue, H.W. Washington, D.C. 20009 Dear Morgan: Enclosed herewith are original and one copy of drafta of (1) contents on FDA proposed Procedural Regulations and (2) letter of trananlttel to Hearing Clerk. In the flnnl document we believe It nap be acre suitable to follow trananlttel era—senta with comenta on proposed regulation in letter proper rather than as attachment but to avoid re-typing and further delay we request that It be sent to the full coeeulttee in present form. To meet the deadline of Moveefeer 6 wa request that cownlttee review Immediately and return any further cements by Monday, October 30th, with copies to you and subccnadttee rathers. we assume that MCA staff reviaw can be nade simultanaously. We alao assume thet MCA office will type finel submis­ sion end, if neeessary, deliver to Hearing Clark unless you advise differently. Sincerely yours. Aa: jtnapp W. A. Knapp WAK:dmk Encls. cc: Dr. 0. P. Vincent Mr. J. W. Hulse 00001787 * x October 13, 1967 FDCC Subconsnlttee on FDA Procedural Regulations TO: Dr. George P. Vincent Mr. James W. Hulse Attached second draft of consnents on FDA Procedural Regulations Includes, 1 believe, all consnents not definitely deleted at our last meeting. 1 suggest a meeting In latter part of week of October 13th and that Dr, Vincent mention date which might coincide with his weekly visit to New York. Very truly yours. Original Signed I* A. Knapp W. A. Knapp WAR: dak Enel. cc: Mr. Morgan Hoover P.S: Mr, Hoover: These drafts to you to indicate we are working. Suggest they be destroyed whenever final draft is produced. ASI 00001788 October 4, 1967 FDCC Subcommittee on FDA Procedure! Regulations TO: Dr. George P. Vincent Mr. James W. Hulse The attached compilation of comments of FDA Procedural Regulations includes more points of discussion than were agreed to at our last meeting because on reconsideration I felt that the MCA commentary should include all questions we could not ourselves resolve. Also, I felt it would be easier to delete than to compose language at our next meeting now set for Wednesday, October 11 at Morristown if we find no opportunity to meet earlier. Will you please contemplate tone of introductory remarks to FDA. Very truly yours, W. A. Knapp WAKidmk Enel. cc; Mr. Morgan Hoover ASI 00001789 TELEPHONE HUDSON 3-8126 Manufacturing Chemists’ Association, Inc. (FOUNDED 1872) 1825 Connecticut Avenue, N. W. Washington, D. C. 20009 JAMES R. CARNES SECRETARY-TREASURER October 11, 1967 Mr. M. C. Stone Assistant Secretary Tennessee Eastman Company Kingsport, Tennessee 37662 Dear Mr. Stone; Thank you for your letter of October 6 which gives us your comments on the Proposed Food Additives Proce­ dural Regulations. These should be of considerable interest to the task group within the MCA Food, Drug, and Cosmetic Chemicals Committee which is preparing our comments. So X am sending them along to the chairman of this task group, Dr. William A. Knapp of Allied Chemical, along with his copy of this letter. As you probably know by now, the deadline for filing comments has been extended 30 days until November 5. Sincerely your3 JRCisjg ccj w. a. Knapp ASI 00001790 CCT 9 DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE FOOD AND DRUG ADMINISTRATION WASHINGTON. D.C. 20204 October 6, 1967 Mr. F. H. Carman Manufacturing Chemists' Association, Inc. 1825 Connecticut Avenue, N. W. Washington, D.C. 20009 Dear Mr. Carman: Dr. Goddard has asked uc to reply to your letter of September 18, 1967, which requests an extension of time for filing comments on the proposed food additive procedural regulations published in the FEDERAL REGISTER of August 7, 1967. We believe that the proposed revision v;ill aid in the preparation of petitions so that the resultant FD\ reviews can be completed more rap­ idly and with fewer requests to petitioners for clarification of submitted material. Comments so far received have responded favorably to the more detailed descriptions provided by the proposal. In order to permit your members additional time, we are extending the time for comments for another 30 days or until November 6, 1967. A notice to this effect will appear in the FEDERAL REGISTER shortly^___ Sincerely yours, ^Associate Commissioner for Compliance - V ASI 00001791 CHAS. PFIZER S CO, INC. ESTABLISHED 1849 235 EAST 4-2!Ld STREET NEW YORK, N Y. 10017 LEGAL DIVISION October Dr. William Knapp Allied Chemical Corporation P.0. Box 405 Morristown, New Jersey 07960 (<•' 1967 r . a'* Dear Dr. Knapp: As agreed upon at our recent meeting, I have drafted comments on numerous sections of the proposed food additive regulations which prompted comment from many member companies of the FDCC Committee. I have attempted to incorporate the comments of the member com­ panies, following the guidelines agreed upon at our meeting. On those sections where you agreed to draft comments, 1 have so indicated this fact. I think that one area we should take a further look at is the area dealing with indirect additives and the many requirements for same in the body of the petition. If at all possible prior to our next meet­ ing, you might discuss the quite detailed requirements for indirect additives with a member of the committee that is more directly concerned with indirect additives than are either your company. Dr. Vincent*s, or Pfizer. I hope this draft will be helpful to you and that we can soon put together a final draft. Very truly yours JWH:mw Enclosure cc : G. P. Vincent, Olin fcfethieson M. Hoover, MCA ASI 00001792 1 INDU TRIAL. CHEMICALS DIVISION. j Corporation-----------;-------------------- ----------- —............. -■■ — ----- ----- -- , i; h ■ -j —J RESEARCH LABORATORY • P. 0. BOX 405 • MORRISTOWN. NEW JERSEY 07960 TEL. (201) 538-8000 October 4, 1967 FDCC Subcommittee on FDA Procedural Regulations TO: Dr. George P. Vincent Mr. James W. Hulse The attached compilation of comments of FDA Procedural Regulations includes more points of discussion than were agreed to at our last meeting because on reconsideration I felt that the MCA commentary should include all questions we could not ourselves resolve. Also, X felt it would be easier to delete than to compose language at our next meeting now set for Wednesday, October 11 at Morristown if we find no opportunity to meet earlier. Will you please contemplate tone of Introductory remarks to FDA. Very truly yours, W. A. Knapp WAK:dmk Enel. cc: Mr. Morgan Hoover ASX 00001793 INDUSTRIAL CHEMICAL DIVI ION Corporation il RESEARCH LABORATORY . P. O. BOX 405 • MORRISTOWN, NEW JERSEY 07960 TEL. (201) 538-8000 September 18, 1967 TO: F.D.C.C. Sub-Committee on F.D.A. Procedural Regulations Gentlemen: Attached are comments submitted to S.P.I, Food Packaging Materials Committee for consideration in connection with new F.D.A. Procedural Regulations. The language therein is from one committee member to another and will require revision if presented to F.D.A. As I see our situation it will be very difficult, if not impossible, to submit comments by October 7 deadline, if they are to be approved by the full committee via letter ballot. As discussed with you, Jim, we will hold meeting in your office as shortly after September 26 as is convenient for Dr. Vincent, possibly September 28 or 29. This, of course, presumes that we will have some comments from members to discuss. Morgan Hoover expects to issue letters today: (1) to F.D.A. requesting extension and (2) to committee members requesting comments by September 25. Very truly yours W. A. Knapp WAK:dmk Attachment cc: Mr. M. Hoover,M.C.A.,1825 Connecticut Ave.N.W.Washington,D.C.200C Mr. J. W. Hulse, C.Pfizer & Co.,235 East 42nd.St.,N,Y. 10017 Dr. G.P. Vincent, Olin Mathieson Chem.Corp.1730 K.St.N.W. Washington, D.C. 20006 ASX 00001794 TELEPHONE HUDSON 3 6126 Manufacturing Chemists’ Association, Inc (FOUNDED 1872) 1825 Connecticut Avenue, N. W, Washington, D. C. 20009 September 18, 1967 TO: Members of the Food, SUBJECT: Drug, end Cosmetic Chemicals Committee Proposed Revised FDA Food Additives Procedural Regulations Gentlemen: At the September 12, 1967 meeting of the FDCC Committee, it was voted unanimously to prepare a recommendation as to what MCA should do regarding the notice of Proposed Rule Making sent to you on August 11 which appeared in the Federal Register, Vol. 32, Mo. 152 - August 8, 1967 (21 CFR Part 121). In line with this, your chairman requests that you review this notice immediately and mail your comments no later than Septemb r 25 (Monday) to the chairman of the task group appointed to handle this matter: Dr. William A. Knapp (Allied chemical Corporation, P.O. Box 405, Morristown, New Jersey 07960) with copies to task group members James Hulse (Chas. Pfizer & Co., 235 E. 42nd Street, New York, New York 10017) and Dr. George P. Vincent (Olin Mathieson Chemical Corporation, 1730 K Street, N.W., Washington, D. C. 20006). Please send a copy to me also. It is planned to send the recommendation of the task group to the full committee for letter ballot. It is most important that your comments be sent in promptly so as to give the task group time to prepare a recommendation and ballot the committee prior to the deadline of October 7. We are requesting an extension of time, but of course have no way of knowing whether or not it will be granted. As you can see, there is very little time for the task group to do its work and for a letter ballot to be made. Sincerely yours, MMHssjg ASI OOOOI795