Document yrbmEbgEDwL7xE3oXVxzbLj0d

\ September 19, 1966 % Page 15 FOOD CHEMICAL NEWS FQA GUIDELINES FOR CHEMISTRY AND TECHNOLOGY REQUIREMENTS OF FOOD AOOITIVE PETITIONS I. Protocol for Direct Additives A. Identity and composition - ~ Information satisfying 121.51 in this area may se furnished in the form of a cowrEhensivE monograph. 1. Name of the food additive: a. Common name: established or proposed, if any; s. Chemical name following the nomenclature of Chemical Abstracts'; c. Other names in use, including trade names. 2. Formula: a. Empirical formula; b. Structural formula, if known or proposed; c. Molecular weight. 3. Definition and description of the food additive, including its complete Quantitative composition: liquid, solid, crystalline, amorphous, color-, odor, taste, etc. Brief description of the manufacturing process, including A LIST OF ALL SUBSTANCES USED TOGETHER WITH THEIR SPECIFICATIONS AND THE EQUATIONS FOR ALL CHEMICAL REACTIONS INVOLVED* Any production controls employeo to assure a reproouoible product should be described. 4. Physical, chemical, and/or biological properties, specifically incluoing information or data on stability and also ALL OTHER PROPERTIES WHICH MAY BE APPROPRIATE, SUCH AS M.P., B.P., SOLUBILITY, SPECIFIC GRAVITY, REFRACTIVE INDEX, VISCOSITY, OPTICAL ROTATION, pH, ACIDITY, OR ALKANILITY, ASH, WATER CONTENT, IODINE NUMBER, SAPONIFICATION NUMBER, ALKOXYL CONTENT, VOLATILE MATTER, WATER-SOLUBLE MATTER, ETHER-EXTRACTABLES, BIOLOGICAL ACTIVITY, ABSORPTION SPECTRA IN THE ULTRAVIOLET AND INFRARED, FLUORESCENCE SPECTRA, READILY CARBON I ZABLE SUBSTANCES, REAOILY OXIOIZABLE SUBSTANCES, etc. Will also appear in 5U) or 5(c) when required. n 5. Specification for food grade: a. Identity - - include specifications useful in identifying the food adoitive AND METHODS FOR CHECKING THE SPECIFICATIONS; B. ASSAY - - SPECIFICATION PRESCRIBING THE MINIMUM CONTENT OF THE DESIRED COMPONENT(s). ASSAY PROCEDURE DESCRIBED IN FULL WITH VALIDATION DATA. DATA SHOWING THE RANGE OF ASSAYS ANO THAT THE ASSAY SPECIFICATION CAN BE MET; C. IMPURITIES - - SPECIFICATIONS LIMITING TOTAL HEAVY METALS (U.S.P. OR ACS TEST) AND SPEC IFICAEEY LIMITING ARSENIC AND LEAD ANO ALSO OTHER UNDESIRABLE IMPURITIES SUCH AS REACTION BY-PRODUCTS TO THE LOWEST LEVELS CONSISTENT WITH GOOD MANUFACTURING PRACTICE. DETAILS OF TESTS FOR CHECKING THE SPECIFICATIONS. DATA FROM A SUITABLE NUMBER OF REPRESENTATIVE BATCHES SHOWING THE RANGE OF IMPURITIES ANO THAT THE SPECIFICATIONS CAN BE MET; / Any other pertinent information. B. Usage ano Label Specimen - * Information should be furnisheo showing the quantity of the fooo additive proposed for use AND THE PURPOSE FOR WHICH IT IS PROPOSED, TOGETHER WITH ALL DIRECTIONS, RECOMMENDATIONS, ANO SUGGESTIONS REGARDING THE PRO POSED USE, ANO A SPECIMEN OF THE PROPOSED LABELING. The MAXIMUM AS WELL AS THE AVERAGE QUANTITY OF THE FOOD ADOITIVE TO BE EXPECTED IN INDIVIDUAL FOODS OR TYPES OF FOODS AND IN THE TOTAL DAILY OIET OF THE CONSUMER IS TO BE ESTIMATED FOR THE USAGE PROPOSED; ANO THE BASIS FOR THE ESTIMATION IS TO BE OESCRIBEO IN DETAIL INCLUDING ANY ASSUMPTIONS MADE AND THE ARITHMETICAL computations. Using adequate methodology, oata should be submitted showing the fate of the food additive in finished fooo READY-TO-EAT,. WHETHER THE FOOD ADDITIVE REMAINS UNCHANGED IN SUCH FOOD OR WHETHER IT IS CONVERTED TO ANOTHER SUBSTANCE BY REASON OF OXIDATION, DEGRADATION, OR REACTION WITH COMPONENTS OF THE FOOD, AND THE OEGREE OF ANY SUCH CONVERSION. C. Oata on intended effect in fooo * - Experimental data should be submitted showing that the food additive will produce the intended effect in food and that the usage level sought does not exceed the quantity of the additive reasonably requireo TO PRODUCE SUCH EFFECT. Data FROM CAREFULLY CONTROLLED EXPERIMENTS SHOWING THE DEGREE OF EFFECT ACCOMPLISHED BY THE ADDI TIVE AT GRADUATED LEVELS OF ADOITION TO FOOD MUST BE OBTAINED. The NUMBER OF GRADUATED LEVELS WILL OEPEND UPON A NUMBER OF FACTORS, SUCH AS THE TOXICITY OF THE ADOITIVE, THE PARTICULAR FOOOS INVOLVED, THE PROPOSED USAGE LEVEL, ANO THE INCREMENT OF THE AOOITIVE REQUIRED TO INDUCE ANY NOTICEABLE CHANGE IN THE EFFECT ON THE FOODS. IF THE LEVEL OF USAGE IS CONSIDERED BY THE PETITIONER TO BE SELF-LIMITING, THE REASONS SHOULD BE EXPLAINED AND DATA FURNISHED SHOWING WHAT EXCESSIVE LEVEL OF THE AOOITIVE WILL PRODUCE AN UNACCEPTABLE PROOUCT. Samples. To be furnished only on request. In order to assist us in evaluating the intended effect in food, WE SHALL usually require samples of the food additive ano samples of food reflecting usage of the adoitive, TOCETHER WITH APPROPRIATE CONTROL SAMPLES. ThE SAME SAMPLES MAY OCCASIONALLY SERVE BOTH THE PURPOSE OF METHOOOLOGY TESTING DISCUSSED BELOW AND OF DEMONSTRATING THE INTENDED TECHNICAL EFFECT IN FOOO. jw. 0. Methodology - - If usage of the fooo aooitive requires a tolerance for the fooo additive or for its conversion proouct(s) TO PROTECT THE PUBLIC HEALTH, A PRACTICABLE METHOD WILL HAVE TO BE FURNISHED TO ENFORCE THE TOLERANCE. IT MUST BE SATIS FACTORY FOR APPLICATION TO THE RAW, PROCESSED, AND/OR FINISHEO FOOD, ,I.E., GIVE CONSISTENT RESULTS, WHEN USED BY ANY PROPERLY EQUIPPED ANO TRAINED LABORATORY PERSONNEL. THE METHOO MUST BE CAPABLE 'OF QUANTITATIVELY DETERMINING THE FOOD ADOITIVE OR ITS CONVERSION PRODUCT(s) IN THE PRESENCE OF THE NORMAL COMPONENTS OF THE FOOO IN WHICH IT IS TO BE USED ANO IN THE PRESENCE OF Ilif :MER chemicals;, INCLUDING FOOD ADDITIVES, THAT CAN reasonably be EXPECTED TO BE PRESENT IN SUCH FOOO. VALIDATION DATA MUST BE INCLUOEO, I.E., BLANKS (UNTREATEO FOOD) ANO RECOVERIES (FOOO ANO AOOITIVE AT VARIOUS LEVELS, INCLUOING LEVEL OF USAGE), SUFFICIENT TO DEMONSTRATE THE ACCURACY AND REPRODUCIBILITY OF THE METHOD. ASI 00002351 Page 16 September 19, 1966 FOOD CHEMICAL NEWS 11. Protocol for Indirect Additives (migrants from fooo-packaging and food-processing equipment) A. Identity and composition: 1. Name of each substance in the food-contact surface, or likely to migrate to the food contact surface, including polymeric materials: a. Common name, if any; b. Chemical name following the nomenclature of Chemical Abstracts; c. Other names in use, including trade names. 2. Formula of each in A.l: a. Empirical formula; b. Structural formula, if known or proposed; c. Molecular WEIGHT: for POLYMERS, THE MOLECULAR WEIGHT DISTRIBUTION IN THE BASIC RESIN AND THE AVERAGE MOLECULAR WEIGHT, CITING METHOOS USED. 3. Quantitative composition of the food-contact surface of the packaging material (paper, cellophane, plastic film or sheet, rubber, and/or polymeric coating) or of the food-processing equipment: a. Basic resins polymers; b. Aojuvants: Plasticizers, stabilizers, preservatives, fillers, colorants, etc.; c. Impurities: heavy metals, MONOMER, CATALYST RESIDUES, ETC. 4. Description of the manufacturing process, including ano the equations for all chemical reactions involved. product should be described. a list of all substances used together with their specifications Any production controls employeo to assure a reproducible 5. Physical, chemical, and/or biological properties. Same as for direct additives. Applicable to each substance WHICH MIGRATES TO FOOD UNDER THE CONDITIONS OF USE. PROVIDE THE VAPOR PRESSURE OF EACH SUBSTANCE PROPOSED FOR USE IN THE PACKAGING OF ORY FOODS AND FOR ALL USES IN food-packaging adhesives. Will also appear in A.6 WHEN REQUIRED. 6. Specifications of ioentity and purity. Include specifications for each substance of the food-contact surface in the packaging material useful ini identifying it and assurinc it to be of suitable grade for the purpose. Always include the manufacturer's specifications for purposes of information, whether or not petitioner deems THEM NECESSARY IN THE REGULATION. PROCEDURES FOR CHECKING ANY NEEDED SPECIFICATIONS SHOULD BE FURNISHED; ANO DATA REFLECTING SAMPLES' FROM REPRESENTATIVE PRODUCTION LOTS SHOWING THAT SUCH SPECIFICATIONS CAN BE MET SHOULD ALSO BE FURNISHED. B. Usage - - Details of proposed food-packaging usage: Individual foods or types of foods (specific examples) to be PACKAGED, MAXIMUM TEMPERATURE OF PACKAGING, MAXIMUM TEMPERATURE ANO TIME OF STORAGE, MAXIMUM TEMPERATURE ANO TIME OF COOKING IF FOOD IS TO BE SUBSEQUENTLY COOKED OR PROCESSED IN THE PACKAGE OR CONTAINER, MINIMUM SIZE OF PACKAGE (WEIGHT OF FOOO) TO BE USED, ANO AREA ANO MIL THICKNESS (INCLUDING WEIGHT) OF FILM OR DITHER CONTAINER SUCH AS A BOTTLE OR COATING EXPOSED TO FOOD IN THE MINIMUM SIZE PACKAGE. SIMILAR DETAILS OF FOOD PROCESSING EQUIPMENT USAGE. C. -Intended technical effect - The intended effect of each substance in the food-contact surface is to be described with accompanying data showing the intended effect is accomplished; and if the migration to food is a function of the quantity of the substance present, data should be furnished showing that the.proposed level of the substance in the surface is IN AN AMOUNT NOT MORE THAN THAT REASONABLY REQUIRED TO ACCOMPLISH THE INTENDED EFFECT. IF THE FOOD A0DITIVE IS A COMPONENT OF A SINGLE SERVICE (ONE TIME USE) FOOD-PACKAGING CONTAINER, INFORMATION SHOULD BE FURNISHED TO SHOW WHETHER THE CONTAINER IS LIKELY TO BE REUSED BY THE CONSUMER FOR HOLDING OR STORING FOOD. Samples. To be furnished only on request. In oroer to assist us in evaluating the proposed use, we shall USUALLY REQUIRE SAMPLES OF THE FOOD-PACKAGING MATERIALS, OR COATED PANELS OR OTHER SUITABLE SPECIMENS OF FOOO-PROCESSING EQUIPMENT, REFLECTING THE PROPOSED USAGE. 0. Quantity of the indirect additive in food:- 1. Extraction data to show the likely degree of migration to food of all components of the finished formulated PACKAGING MATERIAL OR THE FOOO'PROCESS ING EQUIPMENT UNDER the MOST SEVERE CONDITIONS AS WELL AS UNDER THE-OSUAC ~ CONDITIONS OF PROPOSED USAGE. THE MAXIMUM AS WELL AS THE AVERAGE QUANTITY OF THE FOOO ADDITIVE-TO. BE EXPECTED IN INDIVIDUAL FOODS OR TYPES OF FOODS AND THE TOTAL DAILY DIET OF THE CONSUMER IS TO BE ESTIMATED ANO THE BASIS FOR THE ESTIMATION IS TO BE DESCRIBED IN DETAIL, INCLUOING ANY ASSUMPTIONS MADE ANO THE ARITHMETICAL COMPUTATIONS. Tests are to be performed on test specimens (films, bottles, panels, cans, or other .suitable samples) reflecting THE INTENDED CONDITIONS OF USE. THE MAXIMUM QUANTITY OF ANY COMPONENT, INCLUDING THE MAXIMUM THICKNESS OF THE film or container (bottle), that is likely to be used in practice should be in the test specimens. All famu_ies_ . OF POLYMERS THAT ARE to BE USED WITH A NEW AOJUVANT SHOULO BE TESTED. IF THE ADJUVANT'TE A CATALYST* AN^EXPLANA-* ' TION OF ITS NATURE ANO FATE IN THE PROCESSED ARTICLE SHOULD BE FURNISHED. "" -------- Comprehensive extraction data are usually required for food-packaging materials to show whether the practicable tests ano limitations of sec. 121.2514 or 121.2526, or ones similar thereto, are adequate for the new substance, OR WHETHER OTHER ENO-TESTS ANO UMITAUONSS ARE REQUIRED TO PROTECT THE PUBLIC HEALTH. FOR PURPOSES OF ADEQUATELY CHARACTERIZING THE FOOD-CONTACT SURFACE TO BE USED FOR AQUEOUS OR FATTY FOOOS, EXTRACTION TESTS MUST INCLUDE ALL THE FOLLOWING SOLVENTS EVEN THOUGH USAGE IS TO BE LIMITED TO ONLY ONE OF THESE TWO MAJOR TYPES OF FOOD: DISTILLED WATER, 3* ACETIC ACID, 50* ETHYL ALCOHOL, ANO HEPTANE. The EXPOSURE IS TO BE MADE AT 120 F IN EACH CASE UNTIL THE MAXIMA EXTRACTABILI-y ,V. iLIBRIUM) IS REACHED AS GAUGED BY AT LEAST THREE PERIODIC DETERMINATIONS. FOR AQUEOUS I SOLVENTS, THE EXPOSURE TIME MUST TOTAL AT LEAST 72 HOURS ANO FOR HEPTANE AT LEAST 6 HOURS. AS A GENERAL RULE, USE I 2 AN. SOLVENT PER SQUARE INCH OF AREA. SEE THE ASTM"AOAC METHOD, SEC. 7.034-7.039, METHODS OF ANALYSIS, A.O.A.C., | Tenth Ed., 1965. I 2)f one or more of the conditions of use (Table and the limitations together with the end-tests AST 00002352 September 19, 1966 Page 17 FOOD CHEMICAL NEWS in Sec. 121.2526 of the food additive regulations are applicable to the usage proposed, data must be provided TO SHOW the EXTRACTABILITY RELATIONSHIP BETWEEN THE EXPOSURE CONDITIONS OF TIME AND TEMPERATURE IN TABLE 2 REELECTING THE MOS' SEVERE CONDITIONS OE USAGE SOUOHT AND THE EXPOSURE CONDITIONS UNDER WHICH THE TEST IS CARRIED to equilibrium at the same temperature. Ie the limitations and enq-tests of sec. 121.251H or 121,2526 are proposed, oata reflecting samples from representative production lots should be furnished showing that these limitations CAN BE MET. For food processing and handling equipment and other repeated use articles the data must show the likely level of migratory adctives contributed to food during the first use of the articles and the level which will likely be adoed during their subsequent use. If the end-test and limitations of 121.2562 are proposed, data reflecting samples from representative production lots should be furnished showing that these limitations can be met. For usage in contact with certain foods, it is often desirable ano oepending upon the extractability data reflecting simulated food solvents, it may be necessary th determine the extractibility relationship between the solvents and foods such as eoible oil, milk, etc. Since analytical difficulties are often encountered here, it IS USUALLY ADVISABLE TO CONSULT WITH FDA AS to whether these extractability relationship data ARE NEEOEO. As A MINIMUM REQUIREMENT, ALL EXTRACTS USING FOOO SIMULANTS MUST BE CHARACTERIZED BY DETERMINING THE TOTAL non-volatile extractives ano by showing the distribution between the organic ano inorganic fractions Isee Regulation 121,2526 FOB mfThihiI. It MAY also be NECESSARY to ANALYZE THE EXTRACTS FOR THE SPECIFIC FOOD ADDI TIVES involveo, depending upon the circumstances. Details of the analytical procedures employed must be furnisheo. If computations show that no more than 0.01 ppm of a substance would be added to a food assuming it all migrated, the extracts usually need not be tested for such substance. If none is found in the extracts, the sensitivity of the method employed must be adequately validated. 2. Abrasion Data. For dry foods such as bulk grain, flour, salt, etc., in contact with coated surfaces, obtain abrasion data using the most abrasive food concerned or an acceptable substitute. MethAo 6191 in Federal Test Method Standard No. U1 is usually acceptable. It may be possible, in some instances, to incorporate a suitable TRACER in ThE COATINC FOR WHICH A SENSITIVE ANALYTICAL METHOD IS AVAILABLE. ALSO, INCLUDE PERFORMANCE OATA showing the coating's expected life and its resistance to flaking or peeling. o 3. End-test ano usuace specifications.7,for non-fooo articles to assure that the proposeo usage is safe. Men NECESSARY THE PETITIONER SHOULD PROPOSE MEANINGFUL SPECIFICATIONS FOR THE PURPOSE OF LIMITING TO SAFE AMOUNTS THE MIGRATION TO FOOO OF COMPONENTS OF THE FOOD-CONTACT SURFACE OF THE FINISHED NON-FOOO ART I OLE UNDER ITS PROPOSED conditions of use. The end-tests for checking such specifications should be described in detail ano shown to be valid ano reproducible. Data reflecting samples from representative production lots shoulo be furnished showing that the specifications can be met. 4. Results of food test packs. Any oata obtained in evaluating the utility or acceptability of a packaging material or other non-fooo article should be included in the petition submitted. E. Methodology - - Methods useful in checking on compliance with the regulation sought should be furnished and identified as such. See D above. A. Ioentitys III. Protocol for Radiation ano Radiation Sources 1. Radiation and radiation source proposed: a. if an isotope, identify it, and oescribe the type of encap sulation used; b. If a machine source, describe it. 2. Engineering oata providing complete information on the geometry of the radiating mechanism, including the SPEED OF MOVEMENT BY THE RAOIATING HEAD, THE RAOIOISOTOPE, AND THE HUMBER OP7 curies in the source used (if isotopes), the voltage and amperage used (if machine), ano the total time of exposure. A statement of THE RADIATION FLUX CALCULATED THEREFROM SHOULD BE INCLUDED. 3. Data providing complete information on the means to be useo to control the exposure: a. In the case of MACHINES, OATA SHOWING the SENSITIVITY OF THE MEANS OF CONTROLLING THE POWER SOURCES, AND THE WAY IN WHICH RECORDERS ARE COUPLED TO PRODUCE RECORDS OF THE OPERATING VOLTAGES AND AMPERAGES; B. IN THE CASE OF ISOTOPES ANO MACHINES, DESCRIBE THE NATURE OF THE DOSIMETER ANO THE FREQUENCY OF THE DOSIMETRY AND FURNISH OATACSHOWING THE DOSIMETRY ANO PHANTOMS TO BE USEO, INCLUDING THOSE WHICH SHOW THE DOSIMETRY READINGS WILL ADEQUATELY REFLECT THE OOSE ABSORBED BY THE FOOD DURING EXPOSURE. 8. Use - - This section should include information on the dose ranges TO BE USED and the purpose for which the radiation IS PROPOSED, TOGETHER WITH ALL DIRECTIONS, RECOMMENDATIONS, ANO SUGGESTIONS REGARDING THE PROPOSED USE. THIS SECTION SHOULO ALSO INCLUDE SPECIMENS OF LABELING TO BE USED ON THE RADIATION SOURCES ANO ANY LABELING TO BE USED ON THE TREATED FOOO. C. Technical effect: 1. Experimental data should be submitted showing that the radiation dose proposed accomplishes the intended TECHNICAL EFFEOT AND DOES NOT EXCEEO THE AMOUNT REASONABLY REQUIRED TO ACCOMPLISH THE INTENDED EFFECT. ASI 00002353 'Page 18 September 19, 1966 FOOD CHEMICAL NEWS 2. Information should be included showing that there is no inouceo radioactivity in the food or packaging MATERIAL. This CAN INCLUDE A THEORETICAL DISCUSSION BUT SOME ACTUAL EXPERIMENTATION DATA SHOULD BE PROVIDED TO SUPPORT THE THEORY ADVANCED. IF DIFFERENT RADIATION FLUXES ARE TO BE USED, THOSE MATERIALS SUBJECT TO THE highest flux and dose contemplated should be selecteo for testing for induced radioactivity. A description of the methodology and the sensitivity of the methods used to establish the absence of induced radioactivity IN THE TREATED FOODS DR PACKAGING MATERIAL SHOULD BE FURNISHED. 3. Data should be provided to establish the extent to which the nutritive composition of the irraoiated fooo HAS BEEN ALTflED BY EXPOSURE OF THE food to the highest dose and under the highest flux expected. If any such CHANGES ARE FELT TO BE INSIGNIFICANT, THESE SHOULD BE SO DESIGNATED AND THE REASONS DETAILED FOR THEIR CLAIMED INSIGNIFICANCE. THE METHODOLOGY EMPLOYED SHOULD BE FULLY DESCRIBED. it. Data should be provided to establish that the irradiateo fooo has not been significantly altered in ORGANOLEPTIC OR OTHER PHYSICAL CHARACTERISTICS SO AS TO RENDER THE MATERIAL OTHERWISE UNFIT FOR FOOD. WHERE a fresh food is ord.inarily stored for a period of time at particular temperatures, data should be includeo REFLECTING THE RESULTS WHEN THE IRRADIATED FOOD IS APPROPRIATELY STORED AND/oR SHIPPED. 0. Methods (See C). (Story continued from Page 14) Petition in the area of chemistry and technology. When a Petitioner omits any of the data and information sug gested by the guidelines or substitutes other types of data and information for those suggested by the guide lines, he should clearly explain the reason for the omission or how such substituted data and information fulfill the legal requirements of the regulations. "A general summary of the Petition should be supplied by the Petitioner. Among other things it should contain a statement with respect to the quantity of the food addi tive in individual foods or classes of foods, under the proposed conditions of use, and the maximum as well as the average quantity to be expected in the total daily diet of the consumer; and a statement with respect to the margin of safety provided by the animal feeding studies. The clearance sought should be~included and specifically stated. " _. ------ -- FDA-ers say the guidelines represent additions to the 1959 Ramsey document of material which has been disclosed over the years in papers, speeches, and in correspondence with industry. Protocols are included for direct food additives, indirect additives, and irradiation. Veterinary drugs and feed additives are not included, since they are now handled in FDA's Bureau of Veterinary Medicine, rather than in the Petitions Control Branch of the Bureau of Science. Washington Attorney Jerome H. Heckman, in a speech at last week's American Chemical Society meeting in New York, praised Ramsey and FDA Associate Commissioner Kirk for inspiring th new guid lines. He said, ''Although industry will certainly take exception to some of the requirements the 'Guidelines' set ASX 00002354