Document 326mXJDNXVv035YvpYVOXkeD

v,,- _ - .3/0 .JOSEPH E. KELLER JKHOMI'. II. HECKMAN CHARLES M MEEHAN WILLIAM U BOKtiHESANI. JU ROBERT H TI Eli NAN wayne v, black DAVIl) I,, HILL MARTIN W IJEECOVICI LELAN'D '7 BLAIR PETER M. N'EMKOV JOSEPH E HADLEY" CAROLE C HARRIS WILLIAM W. PUGH TO: 7,AW oPFICr.S KlZlA.KR AND IIkOLvMAn UNO 17T" STRI KT, N W SUTTE lOOO WASIlINcn ON, D C. 2003C) March 20, 1973 All Members of the SPI Food, Drug and Cosmetic Packaging Materials Committee TF.I F,PHON 1' 20^ IfDO-tilOO CAnu, ADDEI-.S*- KEI M W RE: The Food and Drug Administra tion's Environmental Impact Statements (38 F.R. 7001 et seq. ) Gentlemen: Reference is made to the Food and Drug Administration's July 12, 1972 proposal to amend its own regulations to include consideration of environmental impact factors pursuant to the Na tional Environmental Policy Act of 1969. After reviewing the comments submitted, FDA has, as of March 15, 1973, adopted in final form agency pro cedures regarding the preparation and filing of Environmental Impact Statements. A copy of these new FDA rules and regulations is enclosed herewith. The new regulations integrate the NEPA requirements into the already-established FDA procedures. One of the new requirements of special concern is the classification of food additive petition approvals, located at 6.1(b) (11), as a major agency action that significantly affects the quality of the human environment. Accordingly, a new item, H, has been added to the food additive petition form, as set forth in 121.51(c), re quiring that a food additive petition submit an environmental impact analysis report analyzing the environmental impact resulting from the manufac turing and consumption of the subject food additive. With regard to the filing of these en vironmental impact analysis reports, trade secret data are granted a protected status, as set forth ASI-PR 0001655 March 20, 1973 Page Two in 6.1(h). Thus trade secret data are not required in an environmental impact analysis report even though the sar.3 data must be included in the food additive petition. It is also implied in the rulemaking ^notice that following the NEPA proceedings may well !lead to even longer petition processing times, the 1180-day statutory time notwithstanding. In this iregard, it is noted on page 7002, paragraph D that, (regardless of any further delays, the NEPA proce- ` idures will, nonetheless, be followed. In short, as a result of the adoption of these new rules, FDA iprocedures will, in all probability, become more .complex and lead to even greater failure to meet (Statutory deadlines, a situation which we have janticipated in our earlier reports to you. While writing to inform you about the Environmental Impact Statement matter we thought we would also take this opportunity to supply you with the now finalized new Food and Drug Administra tion regulations relative to "in vitro diagnostic products for human use." The only reason we are bringing this matter to your special attention is because it was discussed at our last meeting and, in our opinion, continues to represent a situation where a sort of statutory authority "stretching" process has been used by FDA to bring its power to bear with the respect to items that many would consider not subject to FDA standardization or labeling prescription. In our opinion, this rulemaking does presage, however, the kind of statu tory authority FDA is seeking to obtain where devices are concerned. Should anyone have any questions or comments regarding these matters, please feel free to let us know. Cordially yours, v>' /^ Enclosure ASI-PR 0001656 RULES AND REGULATIONS 7001 (2) During La? open season, fishing shall bo poriau'-ul each day from 1 hoar before sr_nri e to 1 hour after run,-.:fi U.,e of artificial lights "111 not be per muted. Hart Mountain National Antelope Kefu ;e --(Ilradqu irters: Sholdon-Hnrt Mov.nl am Nat tonal Antelope Refuges, Po-t Ohio s Do1? 111, Luke view, Oil 975 '')!. IBamalh Fcrf'ot National Wildlife Refuge--'ilendquarterr,: Tula Lake Na tional Wiiduie Refuge, Route 1, Box 71, Tufifinke, CA 0513 D. Sprei.il condition: (1) Lfie of boats is not pc. milted. Malbiur National Wildlife Refuge, Pool Office Pox 112, Barns, OH. 97720. Special condition.-.: < 1) Refuge ve.tens, with the exception of iCrumbo Reservoir, aic doted to the/use of boats for fi.iiung purp.vev (2) The use of motors on boats Is not permitted on Krurrioo Reservoir. Upper Klamath National Wildlife Refuge--(Headquarters: Klamath Busin National wildlife Refuses, Route 1, Box 71, Tulelake, CA 95131). Special condition: (1) Speedboats shall not exceed 10 miles per hour an any stream, creek, or canal, and that por tion of Peiican Bay west of a line be ginning at a point cn the north, shore of Pelican Bay one-fourth mile e.ijt of Crystal Creek and extendin'; due scuff h to opposite shore of the lake. William L. Finley National Wil.Ulfe Refuse, Route 2, Box 203, Corvallis, OR 97330. Special conditions: (1) Use of boats is not permitted. (2) During the open season, fishing shall be permitted each day from ' ) 'W before sunrise to 1 hour after -et Use of artificial lights will not be per mitted. Cold Springs National Wildlife Ref use--(Headquarters: Umatilla National Wildlife Refuge, Post OflLce Box 233, Umatilla, OR 97883). Special conditions: (1) The refuge Is closed to sport fishing during the mi gratory waterfowl hunting season. (2) Boats without motors may be used for purpose of fishing. I.lcKay Creek National Wildlife Ref uge--(Headquarters: Umatilla National Wildlife Refuge, Post Office Box 233, Umatilla, OR 97S32). Special condition: (1) The refuge Is closed to sport fishing during the migra tory waterfowl hunting season. The provisions of these special regu lations supplement the regulations which govern fishing cn wildlife refuge areas generally, wliich are set forth in Title 90, Cede of Federal Regulations, Part 33, and arc effective through De cember 31, 1973. L. Eo-.vxr.o Perry, Aidit>y Regional Director, Bu reau at Sport Fisheries at'-d Wildlife. March 8, 1973. [ffR Poe.73 -3001 Flied 3-11-73:0.45 inn] PART 33--SPORT FISHING C2) The u.,e of boat,; is not perm!'.tort. Certain '.Vildt.fe Refuges in Washington Tile following s; eoi:J re gul.it'3n is is sued and L, elective ou March 3 5, 1373. 5 33.3 Fpcrbd r-:r.l uior^; ..p<->ri /filling; for i:t'l:s idu.d iMidniu t-rfi.g,* arras. (3) lisfifiag during dayfigut hours only. Hie pro'.fiuus of this specie! regu!:' fi,a supplement the rcpilatioui r.'filch, giyrn fishing on wildlife refuge areas g iiy which arc set forth In Title C9, Part Oener.d condnions. rL.hins shall be and ore effective through Se-ote.p-.e-m 15, in .'vcord.-.r.ce v. ff.h no; kcabie Slate reg 1973. ulations. Portions of she refuse which Kocsht G. Persovius. are open to fud r g are designated by liefuyManager, !falcon N".- signs and/or deluNated e.i maai. The t ion cl Wildfi/ti Belays, Mag me.ps are avalisole at the refuge head i'ills, Wis. quarters :nd from the office of the Re gional Director, Bureau of Sport Fish eries Mid WdcLifo, Post Ofice BOX 3 737, Alar.ci: 6, 1973. im Doc,7j-;t'ie Filed c-m-73,3.45 nm] .Portland, OH 97203. O.IcNary National V.fiJdLie Refuge, a Title 21--Food end Drugs Fort Office Box 13, Burbank. WA 99323. Special co di cions: (1> The refuge is closed to sport fishing during the mi gratory' waterfowl hunting season, (2) The use of boats or floating de vices of any description, is prohibited. CHAPTER I--FOOD AND DRUG ADMINIS TRATION, DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE ENVIRONMENTAL IMPACT STATEMENTS Procedures for Preparation Columbia National Wildlife Refuge, Post Office Drawer F, Othello, WA 99344. Special conditions: (1) Mallard Lake, Migraine Lake, Se&brock Lake, Roy el Lake, Crab Creek, Marsh Management Units I and in are ocen April 15 through August 15, 1973. (2) The use of boats and the use of outboard motors are prohibited on lakes so posted. The provisions of this special regula tion supplement the regulations which govern, fishing on wildlife refuge areas generally, which are set forth in Title 50, Code of Federal Regulations, Part 33, and are effective- through December 31. 1973. In the FdoESAL Regis~x of Jury 12, 1972 (37 FR 13536), tire Commissioner of Food and Drags published proposed pro cedures for consideration of environ mental impact factors pursuant to the National Environmental Policy Act of 1969 (Public Law 91-190; S3 Stat. 852 et sea.; 42 U S.C. 4321-4347). During the 60-day comment period, 15 comments were received on the pronot-al; from the Environmental Protec tion Agency, one college of agriculture, three trade associations, and regulated industries. The principal points raised arid the Commissioner's conclusions are as follows: A. Applicability. Seven comments ques 1. Nea'aho Pep.ry, tioned whether routine actions of the A.r.inj -1 Director, Food and Drug Administration, such as -/ Fisheries approval of new drug applications, new and- i/AdAfr. animal drug applications, antibiotic drug March 7.1973. [FR DOC.73-S00O Find 3-14-73:3:45 am] monographs, food additive petitions ana color additive petitions constitute major actions significantly affecting the quality of the human environment which would PART 33--SPORT FISHING Hcricon National Wildlife Refuge, Wis. require issuance of environmental impact statements. Two comments doubted that destruction of condemned, enjoined, de The following special regulation is is sued and is effective on March 15,1973, tained, or recalled articles would ever amount to a major agency action requir ing an environmental impact statement. 33.5 Special regulations; sport fishing, for individual wildlife refuse areas. W rs consist Five comments proposed establishing categories of animal drugs which would be excluded from environmental imoact consideration. The Commissioner con HOHICOM NATIONAL WILDEIrE REFUGE Sport fishing on the Horicon National Wildlife Refuge, Maj-vilie, Wis., is per mitted only on the areas designated by signs as open to fishing. These open areas are delineated on maps available at refuge headquarters and from the office of the Regional Director, Bureau of Sport Fisheries and Wildlife. Federal Building, Fort Sni-liir.g, Twin Cities, Mmn. 55111. Sport fishing shall be in accordance with all applicable State regulations subject to the following special conditions: fl) The open season for sport fishing on the refuge extends from May 15. 1573, through September 15, 1973, inclusive. cludes that the National Environmental Policy Act applies to the categories of agency action in 5 6.1(b) and that FDA shall therefore consider the need for preparing environmental impact state ments for them. No envim" mental im pact statement will be i uni if the egency action is not major ur it does not significantly affect the quality of the hu man environment. B. Environmental impact analysis re ports. Five comments stated that the FDA has no authority to require new drug applications, new animal drug ap plications, new antibiotic drug amplica tions. food additive petitions and color additive petitions to include environ- No. 5 0--Ft. 1- FEDERAL REGISTER, VOt. 33, NO. 50--THURSDAY, MARCH 15, 1973 ASI-PR 0001657 7002 RULE? AND REGULATIONS mi ntnl .unly. i-> reports, or to rcfu..o to arc pt or file such an an;:l'Cnt;on or pcti'ion for l.ukne to include sir.h a it-poit, or to rej.i t such cn ap plication or petition for fiuluie to include an adequate environmental impact cneljss report. Seven comments ob ject a ] tint the filing of environmental impact rmalj - ; repeats would cau-q lenaiav i! -1.in tire nroce'~:ur.'i of such npolrtaricn . mid petitions. rIhe Ccra;r,:> ,sinner cone'r.dei that the National Environineni i! Policy Act, as interpreted by the comic, amend.; tile Federal rated, Ping, and Cosmetic Amt to the e dent that rt require con.mdi itat.oii of rnt ;ron- naenta.l issues in the review by tine FDA of these applications nr.d petitions, and that the EDA therefore has the authority to require submission of adequate en vironin'- 1 tel data as a criterion for ac cepting, i.finq, and approving them. Five comments proposed that an ap plicant or a petitioner be required to filo an environmental imoact analysis report only when the FDA determines that a specific application, or petition constitutes a major agency action sig nificantly affecting the quality of the human environment. One comment sug gested that submission of an environ mental impact analysis report be re quired for destruction of condemned, enjoined, detained, or recalled articles only when the agency determines that destruction of an article constitutes a major FDA action significantly affect ing the quality of the human environ ment, The Commissioner concludes that environmental impact analysis reports are necessary for all applications and petitions submitted t-o FDA and for all destructions of condemned, enjoined, de tained, and recalled articles in order to provide sufficient environmental data and information to enable the agency to determine whether an environmental impact statement must be issued on the action involved. The amount and detail of the information provided in the en vironmental impact analysis report will be expected to vary depending upon the nature of the action inv; red. Three comments proposed prompt notification to an applicant if its en vironmental impact analysis report is inadequate. Three comments also rec ommended that notice be afforded an applicant when the FX)A deems the amendment to an existing regulation or the supplement to an existing approval is .substantial enough to require submis sion of an environmental impact analy sis report. Notice in both these instances will be given in accordance vvuh existing regulations of the FDA providing that an applicant will be notified if its ap plication is incomplete for filing. C. Trade secrets end confidential in formation. Twelve comments cxpiessed concern that submission of an environ mental impact anaivtus report by an ap plicant or petitioner would necessitate disclosure of trade seeieu and confiden tial information, particularly with re spect to a description of tlie manufac turing procy-ss nquiicd in Liio report. Seven common's proposed that appli cants and prt.d loners have the oppor tunity to ievjcw environmental impact sfiilemairis define they are made avadu'e'o to fine' pub', c to prevent disclosure of trade l curt'; and confidential infor mation by the statement.;. 'lire Commiesioiici com hides lint cl.d.i ard informa tion vhi'-h eoustiiute trade secret; or c-o rtbapirt infivru tion under 21 CFH 1A.VL T Lcmd-d net be submitted in an environment d impact aii.ily.jr; report, although ti.:.v are submitted as part of an application or petition itself. A new paragraph (h) i; therefore added to 5 6,1 to tins efi'ccf. The FDA is not precluded from coiiriderlfig trade secrets or con fidential information submitted by an applicant or petitioner m its c.vironir.ental assessment of an application or petition. However, no trade secrets or confidential liuormation submitted in the application or petition will bo dis closed in an environmental impact state ment circulated outside the Department. D. Time for consideration of environ mental impact statements. Nine com ments proposed time limitations for the preparation and review of envirf -.mental impact statements for food additive peti tions, new drug applications and new animal drug applications on the grounds that sections -iOOic), 505(c), and 512(0 of the Federal Food, Drug, and Cosmetic Act require th agency to act on such applications a: pennons within 100 days after filing. ' 'he Commissioner con cludes that the National Environment?-! Policy Act, as interpreted by the courts, amends the Federal Food, Drug, and Cosmetic Act to the extent that it re quires the FDA to give full consideration without restrictions of time to all en vironmental issues relevant to FDA ap proval of food additive petitions, new drugs and new animal drugs. Every effort will be made to stay within the statutory time periods and the regula tions so provide. E. Alleged regulatory duplication,. Seven comments contended that the re quirement to include a description of manufacturing processes m environ mental impact analysis reports unneces sarily duplicates regulatory activity since the Environmental Protection Agency and various State and local au thorities already administer air and water quality standards controlling the emission of pollutants. Two comments made an identical contention with re spect to the requirement of environ mental impact analysis reports for destruction of condemned, enjoined, de tained, or recalled articles. The Commis sioner finds that existing Federal, State, and local regulation of air and water pollution doas not eliminate the inde pendent statutory obligation of the FDA under NEPA to consider all relevant en vironmental factors in performing its regulatory activities. The Commissioner concludes that, to fulfill Its responsibili ties under the Nitional Environmental Policy Act, the FDA must require the submission of environmental data, and information on the discharge of pol- luLnu'ts In the manufacture of any dr;y, food r(Id:tive or color add;'i,e it :ev:c for mailietitig and In the destruction cl all article; removed from the imfig ,c; a result of legal action it initiates. O ` e a description of the pollutants e.xpe; d to lie discharged is included, a statcirans of other applicable Federal, S'.ate, and local requirement;, and mformarton showing tiii'.S they ora satisfied, will ordi narily be sufficient for this aspect of the environmental impact analysis report. F, Destruction of perishable artifice. One comment expressed concern that perLhnhle articles condemned, enjoined, detained, or recalled might create an en vironmental and health hazard while awaking environmental impact consid eration prior to dertruction. Section G.3 (c> of the regulation permits immediate destruction of such articles without en vironmental impact statement considera tion in order to protect the public health. - G. Direct solicitation of comnmnis from Federal agencies. The Environ mental Protection Agency proposed that comments on draft environmental im pact statements be directly solicited from those Federal agencies Concerned with the substance of the statements by rea son of jurisdiction by law or special ex pertise to insure maximum input to the aye-icy's environmental statement rsvnew process pursuant to the NEPA guidelines of the Council on Environ mental Quality. The Commissioner con curs with this proposal, and provision for direct solicitation is therefore included in 5 6.3(a) (3). II. Investigational new drugs. The Environmental Protection Agency ques tioned the exemption afforded investiga tional new dings from environmental impact statement consideration in 6 1 (d)(5) of the proposal. Since an inves tigational new drug is not permitted to be commercially marketed, the Commis sioner concludes that allowing limited in vestigation in most instances is not a major action and does not significantly affect the quality of the human environ- meat. In those instances where an en vironmental impact statement may be required, the applicant will be so noti fied and 6.1(d)(5) is amended to so provide. I. Additional changes. In addition to the amendments adopted on the basis of comments received, the Commissioner concludes that additional amendment^-be made to the regulation, as follows: 1. All provisions of the proposal gov erning hazardous substances are deleted since jurisdiction for such substances is- belng transferred from FDA to ihe Con sumer Product Safety Commission. 2. Sections 6.1(e) and 6.1(g) nramended to delete the provision reouir-' inq that an applicant in its environ- mental impact analysis report analyze" whether th; proposed action is a major Federal action significantly affecting the quality of the human environment. The National Environmental Policy Act re quires tlie FDA to make tills determina tion, and In any event an applicant may comment on this Issue in an enviror*- i KDERAL KECI3TEK, VOL 33, I.O. SO--THUSSDAY, MARCH 15, 1973 ASI-PR 0001658 RULES AND REGULATIONS 700.'! m mlal impact CUafi.is report If ha v. i :hi to do -so. 3, Pec; ion c,3ib) o' the pronc.-nl is -meruieT to rcficct the Commi ufioner's clu.-ion that eu\ Ironmcntul corisid- ..'.ion or con:: .-an"'!, erjoinro, or aiiiricj ara a.mo-irion cf lab- oratory a, a A: m '; should hr uridert-iieu on a. c,;. a-'.'.1.use bo.as and t,iat til- di.-i'a.- n.`'lwv, ron:i:h-raci ho o-r.s- i -1;'ll! via Ik.l:"vl. fitole, and local roci.! 11to . do .uord tho h"ir.an en viron.:,nut mill th.a nubile health. 4, Tho pre Moil for puollc hearings on final o.'.vtronirtoi'.'al impact state ment.; in ; fi tho'' (G> i. d ToLoJ from the lino.' order sin.?-' they are not required by Nl-VA nr by the Council cn Environ mental Quality. TTv'rafora, having considered the comruonk; rct.rio.'I ;,TM1 other relevant ma terial, the Coaurtr'icner concludes that tho propos'd, o.ith changes. should be adopted as set forth below. Accordingly, pursuant to the National Environmental Policy Act of lOCt) (sac. 102(2X0, 33 St at 853; 43 U S.C. -l-CCQ), and pursuant to the prevh.-ions of tho Federal P'ood, Drug, and Cosmetic Act (sees. 403. 505, 50 7, 513, 701, 700. 33 Stat. 1053 as a; mded, 1055-1050 as amended by 70 St it. 010 and 73 Stat. 043, 59 Stat. 403 as amended. 73 Stat. 1785-1733 as amended, 71 Stat. 300-4[14 as amended, 83 Stat, 343-331; 31 U S.C. 343, 355, 357, 3G0b. 371, 376), and under authority delegated to the Commissioner (31 CFR 2.130), title 21, Chapter I is amended: 1. By adding a new Part 6 as follows: PART 6--ENVIRONMENTAL IMPACT CONSIDERATIONS ec. 6.1 Applicability. 6.2 Content and format of environment,ol Impact statements. 6.3 Preparation rad. review procedures. 6.4 Responsible agency ofacials. 6.5 Submission of comments to other agenclfS. 6.6 Public availability of environmental Im pact statements. Autiioiuty: Sec. 701, 52 Stat. 1055-56 aa amended by 70 Stat. 019 and 72 Stat. 946, 21 C.EC. 371; roc. 10. 74 Stat. 373, 15 U.S C. 1260; sec. 102(2) (C). 83 Stat. 853, 42 U S C. 4332; thB Guidelines Issued by the Council on Environmental Quality (36 FR 7724): Ex ecutive Order 11514 of March 4, 1370 (35 PR 4247). 6.7 Applicability. (a) (1) An environmental impact statement shall be prepared, circulated, and filed puri-iiont to section 103(3) (C) of the Natioml Environmental Policy Act of i'jj.l for every major agency action that significantly .affects the quality of the human environment. (2) Agency decisions shall include a careful consideration of all environ mental eifects of proposed actions. (b) Tho need for preparing an envi ronmental impact statement shall be considered for the following r.-g ncy ac tions pursuant to environmental criteria established by tho agency and the department: (1) Pa.;:ii;.:;ads .ions or report > made to Cosuvs on prop pais for 1' palntion in hi -..ii...; v.Iim" th.e rascy ha; pri mary re-ysr,iO.,.fy fas the subject mat ter invol, ea; (2) If' >h. ir.tbin -f ratifies condemned after s'-kure or '.'.joined; (3) f)1.tr.,e't..j,e of aitides f.rilsuin3 dcLc.it.on or r-cfil a: a ,cncy rerp" -t: (4) D. g'L'.'.he.i of Food end 1).'..: Ad ministration hi a am.tory waste matiriods; (.j) lss.iun.ee ol Iieeimes for bid: ,1c,d prefix ts; (G) rfiabTclament by rcrrr'nt'.on of label!:.j or other requirement for mrrkctd'.j articles; (7) E^tubh-iimen; by regulation of standards for articles (except food standards); (8) Approval of now drug and abbrev iated new drug applications and old drug monographs; (3) Approval of new animal drug and abbreviated hew animal drug aplieotlons and old animal drug monographs; (10) Approval of antibiotic drug monographs: (11; Approval of food additive petitions; (12) Approval of color additive peti tions; and (13) Policy, regulations, and procedure making which significantly affect the quality of the human environment. (c) An environmental impact state ment will not be requ.r -tl for amend ments to existing regu_ ..ions and ap provals of supplements ,j existing ap provals unless tne change is substantial. (d) The agency has carefully consid ered the environmental effects of tile fol lowing types of actions and has con cluded that since they are not major agency actions significantly affecting the quality of the human env ironment, en vironmental impact statements are not required for them: (1) Recommendations for court action concerning foods, drugs, devices, cos metics, and electronic products; (2) Factory inspections; (3) Seafood inspections; (4) Issuance or amendment of food standards: and (5) Investigational new drug applica tions and investigational new animal drug applications, unless the agency no tifies the applicant that one is required. (e) Whenever a person submits any application or petition requesting action b7 the agency (except action specified In paragraph (d) of this section), he shall Include an environmental Impact anal ysis report on the requested action. Failure to include an aaequate environ mental imoact analysis report in an ap plication or petition shall be sufficient grounds to refuse to accept or file the application or petition. (f) Whenever a manufacturer, distrib utor, or dealer proposes to destroy a food, drug, cosmetic, device, orelectronic prod uct which has been condemned, enjoined, detained, or banned by regulation, he shall submit to tire agency an environ mental Impact analysis report analyzing lh: c-nvi ronra.c ml u.'p.'-.t of the fit .co sh .os of such a rt:-i 'S. (g) A/t environmental impart ar. w : ; report 'hr.il be i_ub~ul`.ed to fine rvei.ay in the following format: Eh,vit.o.nt'l Ii-aver Avua'm P...m -t Date: cl __________ 1. De.orib"! the pr?\;c j*ici Jiotlon: ___ 2, tbe pro'.Mblrt impact of th-s :ic- tion or bo o'!, r.rr.^ r. t (incluclicg primary ad coo. , >) : __________ 3, DinCU'o tlic* jixtverJe o'lviro'i-* irierL^u'l ellocts Tv^.icb. crvimot ^ a\o de-:'.: 4. Evaluate nlt?rr.ati7cs to the prerroseti acticn: __________________________ 5. Dozcrihe the relationship between local short-term 1:^3 of the en.v:"on.n'.r;nt with r^p^ct to the proposed action and the maintenance and enhancement of lon^-temi productivity; *___________ ____________ 6. Descr any irrever ule and 'JtT'" ..eva* b'e conm.ntfnt of resources which wild involved in tho proposed action should it bo Implemented: _________________________________ __ 7. Discuss the objections raised by other agencies, organisations, or individuals which are 'mown to the applicant; ___________________ B. If proposed action should be taken prior to 90 daya from the circulation of a drafs environmental Impact statement or 30 days from the filing of % dna! environmental im pact statement, explain why:___ _____ ____ Or Analyze whether th& benefit U> the pub lic of the proposed action will outweign the action's potential risks to the environment: (Date) (Signature of responsible official) (h) Data and information which, con stitute trade secrets or confidential in formation under Part 4 of this chapter shall not be submitted in an environ mental impact analysis report. (i) Upon receipt of an environmental impact analysis report, the responsible agency official shall make an independ ent assessment as to whether an en vironmental impact statement shall be prspared for the proposed action. 6.2 Content ami format of environ mental impart statements. (a) When is is determined that an environmental impact statement is re quired. draft and final environmen'al impact statements shall cover the fol lowing points: (1) There shall be a description of the proposed action including adequate in formation and technical data to permit a careful assessment of the environmen tal impact. Where relevant, exhibits should be provided. f2> The probable impact that the pro posed action will have on the envlron- FEDE2AL REGISTER, VOL 33, NO. 5d--THURSDAY, MARCH 15, 1973 ASI-PR 0001659 7001 RULES AND REGULATIONS mont shell be r inly zed and .-bull include the inpac t oh ecolo, li_.il sy' tenia such as wildlife, ball, unci other me, line 11. e. Roth pi inun y .mil secondary significant roii- Ecqucuc. for lb,e environment should pe included in i he nnolyIs. (3) 'ihi 'v; oh--,]! ho a n- .cripMen nf yr,y pnuj.i'j'e e.d,ev.n c:n irminento.l effects v.l.r il cannot be cvuidcd Cmi'-Ii ns water Oi e.r pcilii, b.n, u:ua.-i:abl . lunc! lire pat tern", il 'me u> hie s> biir.t, throat:', to health, or other con 'oh', 11 cos adverse to tiio env n oniuer.kd . o":i : Cl 'forth ::i sec tion 101 (b) of tiio f,at:o)uil Enviro.imcgi- te.i Poiicy Act). (4) At'ornaiivos to tiic proposed fic tion mii.-t be cie-ciioc-d, in a'-ecrdance with section 1021 2)01) of th .Motional Environnii-ntul Policy A.ct, win, 1 requires the responsible agency to `ktudy, de velop, real Tieacnoe appropriate alterna tives to recommended courses of action in any proposal which involves unre solved conflicts concerning alternative uses of available resources." A rigorous exploration and objective assessment of alternative actions that might avoid some or all of the adverse environmental effects is essential. Sufficient analysis of alternatives and their costs and impact cn the environment should accompany the proposed action through the agency review process in order to avoid elimi nating prematurely options which might have fewer advet.se environmental effects. (5) The relationship between local short-term uses of men's environment and the maintenance r .id enhancement of long-term productivity must be dis cussed. Thus, realizing that each gener ation. is trustee oi tr.a environment for succeeding generations, the agency must assess the action for cumulative and long-term effects. (C) There must be a statement con cerning any irreversible and irretriev able commitments of resources which would be involt :-d in the prooosed action should it be Implemented. This requires the agency to identify the extent to which the act1 on curtails the range of beneficial ui , of the environment. (7) Where appropriate, there must be a discussion of the problems and ob jections raised by other Federal, State, anti local agencies and by private or ganizations and individuals, and a dis position of the issues raised by these problems and objections. This section may be added at the end of the review process in the final text of the environ mental statement. __ (b) When it is determined that an environmental impact statement is re quired, draff and final environmental impact statements shall be prepared in the following format: (`Di-.m-t" or 'Finv.' ) rsur.os'irsni T.mr.\CT Sr,vrn-,iEMT, Food a:-a Dace, Adv.i.-iihtraiioh (Uisro.'.nm Onr.uwc Divi sion-) 1, Indicate adminlsu-ntne action or legis lative action. 2. De,ci.bc the action, nidi'.iting any St.'.ie-j or coui'tio, pniticiUirlv it'fectcU. C. Analyse the oini:,o:mi"Mt;il impact ot the propo ,-U action. 4. Dc- 'i-iLo h:.>" una;reliable r-J-rcrce cnvlrontce--'. 1 c'-.cm c.f the fa-; jn, ,4. It 'r:i,e 1 t-__ u.te rmine cour. is Of C-C ' '-1 r r..Viler, (i. C. 1' . ,rr id.; r-ri imtrlev- lilii . ", '.Vs ri re:.-';.',: - Involved i:i Urv -n-n the ii't'ori. 7. o erv ;.p, r_--'I evcluote r.i.y c/ojec- tior : to t:.- ac .on ;'n,u by iulerevltcl pcL -onv, 5, (a) For mutt r, - o I. - - r, - n 11. rt.vte ti'.e date cc.d to.:.', cl I --r.tr'c ll-ia:,-;,", png: c:...,on by vU_._h i..,lit--il'" :v t'-vn rerj':c,.Lcd from nil Jnte-e.l.i pci .-.-.a and al-,.rn a coj>y oi th.e notice. (b) cor Sit! dv.pv"n.:.;, lut all p-rtons fcom vviih ii v.rPon con-.m.'.ctc have been rece.'.ed and at'ac': a co_.y ..- : a, 0 Give the nine; t'tat the drait or f.-al cta'cm-nt mas ir,-d.c av..liable to the Canned on Etivironmin. ,:I Quality and to tiic public. 6.3 Prepncaiion and review prov'-Jures. (a) V.'b.cn it is determined that an environmental impact statement is re quired, the statement shall be prepared as follows; (1) Preparation of draft environ mental impact statement. A draft en vironmental impact statement shall be prepared by tile rcopom. te agency c.fiicie.l ns designated in 5 6.4. Wncii p.upropriate during tire preparation o a draft environmental impact statement, ti'.e re sponsible agency official shall consult with Federal, State, and local officials and other interested persons. (2) Distribution of draft environ mental impact statementi. After tire responsible agency official has prepared a draft environmental impact statement;, he shr.ll forward 20 copies of the draft statement to the Office of the Secretary which shall thereupon forward 10 copies to the Council on Environmental Quality. At the same time the draft statement will be made available for public inspec tion by the Oulce of the Assistant Com missioner for Public Affairs and the Hearing Clerk, (3) Solicitation of comments, (i) After the preparation and distribution of a draft environmental impact statement, comments will be solicited from all in terested persons. Sixty days are allowed for reply, after which it is presumed that no comments will be made unless a specified extension of time is requested, (il) Where the subject of a draft en vironmental impact statement is also the subject of a notice of proposed rule making or a notice of filing published in the Federal Register, the Federal Rzcisizr notice shall state that the en vironmental impact analysis report and the drait cm ironmental impact state ment, are available upon request and shall solicit comments by all interested persons. (iii) Where the subject of a draft en vironmental impact statement is not also the subject of a notice published in the Federal Revisier, a notice wiil be pub lished m the Federal Register de scribing hie pioposed action, stating that the environmental impact analysis re port and the draft environmental im pact statement are available upon re quest, and soliciting comments by all interested Perrons. This notice may be published by the agency or th.e rh rtment, or the ay-mey or The d.-oar.ii: at may r?r,..e=t iuH, the Cngicd cn En vironmental Quality publl. h (iv) Cor.', men to shall be r;i.-d fiom Fccicivd a yens ichaving j u. h diet.on by law or special expei the v. fib rc-yect to the environmental impact of a per /j -,! action b:~ sending them a copy of a chafe environmental imp ict staTeiiicnt. (v) AH comments on dr 'c cn.vr,onmental impact statLincnts -hall be sub mitted in quintuph.cate to tiio Hearing Cici'k, Food and Drug Adiah.irf: ation. Depat tmcr.t of Health, Edu-, tticr., and V/elfaie, Room R-- .3, ildOc) Iuv-h a , Lana, Ihwhvillc, f.m 20 31'.', wiiare t!i sliail be available for pubhe ;nrp-ct,c,h. d'oring working hour..-, Monday hire ugh Friday. Cvi) When the reopc.'.:.i!ile agency offi cial concludes that no environmental impact statement is necessary and tr.3 proposed action is the .subject of a notice of proposed rule making or a notice of filing published in the Fzdor.il P-zclstlx, the Federal Regisi'er notice shall state that no environmental ifapact statement is necessary and, where applicable, that the environmental impact analysis re port is available upon request. (4) Tims for consideration prior to de cision.. Draft environmental impact state ments shall be prepaied, forwarded to tho Council on Environmental Quality, and made available to the public early enough in the consideration r: the pro posed action to permit meaningful re view Of the environmental issues in volved. To the maximum extent practi cable, no final action shah be taken on the proposal earlier than SO days ailcr a draft environmental impact statement has been prepared, forwarded to the Council, and made availaoie to the public. (5) Final environmental impact state ments. The final text of an environ mental impact statement shall be pre pared by the responsible agency official after comments on the draft statement have been reviewed and shall include an evaluation, of all comments. The final statement shall receive fuh considera tion in the agency's decisionmaking process. The responsible agency official shall forward 20 copies of the final state ment to the Office of the Secretary which shall thereupon forward L0 copies to the Council on Environmental Quality, and copies of the final statement shall be made available for public inspection by tile Office of the Assistant Commissioner for Public Affairs and the Hearing Clerk. To the maximum extent practicable, no agency action shall take place earlier than 30 days after ti'.e final statement lias been iorwarded to the Council on Environmental Quality and made avail able to tho public. fG) Where the subject of an environ mental impact statement is an agency action governed by specific time require ments under statute or regulation every effort shell be made to comply with the provisions of this part within the tune specified, and those time requnemenrs shall be extended only as long as it ab solutely ncceosary to permit tiio agency federal register, vol cs, mo. so--.Thursday, march IS, 1973 ASI~PR 0001660 RULES AND REGULATIONS TOO.', to coils"'.m or isMo: :i,_ environmental imp ,ci at of til'.' . c.hn. (b) When the pit, ,c ,cd action involves .tiuNi n of comb uiy. ,-d. enjoined, de- i .bird or iccadl'' 1 wliclcs or cL..position or Food a; d Drug /.diuir.Istiadiun labo- ird try vc..-.1? m it. ' d.;, the a eney shall nrlhei-i to cl..;" il "U.d, it" `-a ton. do to nr V. t [ 11 L 0 d ` I'll 1, 1, t Id'. It lid 1 Cf ? 1 1? -1 Ul'.i 10 tllS r'vilic.d I; on r. r r-i,y-o;:.,e brigs. Hi is shod 1:0 rod.'f in e-r.ju nm-mill im part ',t,,li.'ja v, no:1, they me t (l.d oil m: not mm. lc) 'Ido'.? aic Ci-.i'un io dd, \,:y ac- ti.?i',-', t.tiio.;, i-'t'o p'...e of their immediate Ir.ip r.ranee to ttio p idl'.c health, make adherence to tin; requireoi-nM of para graph (O' 11) U1 rough <7t) of thij section imp. a o' t hie. CcTinl.rnee with the re- ciuir, fit? fu iiTamnental analysis under t .ao lie; 'no1. Err.ironmeutnl Policy Act is inipo.- Me in instances wnlch re quire immecii. ` tul Mery action to safeguard Hie i hi-allh. The respon sible agency od.ond shall line written notice to die Council on Environmental Quality of those actions honing poten tially sigr.iiica.ri individual environ mental impact as to which no environ mental Impact statement n hied because public health considerations require im mediate action. 6,1 Ilespon-ildt* ngctlo.Y official*. (a) When environmental impact state ments are required, the following agency 0td.'ial3 are re-wonsible for preparing the statements as indicated; (1) The office of the Commissioner is -Csponslble for preparing a draft or final environmental imp.vet statement on ac tions not delegated by the Commissioner. (2) The director of each bureau Is re sponsible for preparing a draft or final environmental impact statement on ac tions delegated to that bureau by the Commissioner under 2.121 of this chapter. (3) The Executive Director for Re gional Operations is responsible for pre paring a draft or final environmental impact statement on the destruction of a; tides condemned after seizure, en joined, under import detention, or under detention or recalled at agency request, (b) Every action memorandum propos ing an agency action included under 5 tj.l(b) shall contain an evaluation of the environmental impact of the pro posed action and shall be accompanied by a draft or final environmental impact statement if one is required. (}.(> F'd.dir avail..bi'.itv of cuviiouniciu t.d i in pad v; Lu ..; ad,, ,, (a) AH draft and uivi environment 1 impact ..titt.'UdUv ana Mi c nvirounv iv.ul impact anelp ,i ; report: mall i ? available for public hc-nccdior throg"'.1. `he c'dce of tiro A;.nM'-int Co mmi_ doner lor Public Aifairs .it'd, the II, army cit.k. (b) Dralt P r,1i imal env ronment.A i,;))- pact s `11 .-j Vl, tj.i :j e av a liable im :nL`ai- y a 11 o ? Pi :;on . jVtl cm; 01- .1 nap let r r 1 3 re part ill be avail*: oh* at ih.e ton'? a d?aH cn-* <rcn- mi,-,it;';1 i noc.t_'.-" ?[1; ni X circulrit`d if no i nwroi i m c wt .M.uem e lit. is nexus.->1 j , the Fi ft C Li13 TiNG -_L. fim.e of: puhlicnti.on of no ice snnuunci the av ailaoii ity oi' the rt. PArtT S---COLOR ADDITIVES 2. In Part 3, by adding a new item J to tile form, in 5 3.4-(c), oa follows: 8.1 l'c-litltiis proposing regulations for color ad..'dive*. * * (c) * * * J, Tho petitioner is required to submit nn enviromimntaf Impact analysis report anslyzUi* the? manutaCvUrtnij process mid the ulti mate Uf-e or consump .on. o' the color addi tive purvo:uU to 5 3*1 ot ihl3 chapter. ***** PART 121--FOOD ADDITIVES 3. In Part 121: a. By adding a new item H to the form in j 121.31(c), as follows: 12 1.31 Petition proposing regulations for food additives, * ** (c) * * * fL The petitioner is required to submit an eTfi'onmeutal impact aitalj.,is report analys ing tbe environmental impact of the manu facturing process and the ultimate use or consumption of the food additive pursuant to S 6.1 of this chapter. ** * ** b. By adding the following sentence to J 121.53: 121.33 Substantive amendments to petitions. * * * Where the substantive amend ment proposes a substantial change to the petition which may affect the quality of the human environment, the peti tioner is required to submit an environ mental impact analysis report pursuant to 3 6.1 of this chapter. b. Seel! on 100. i li lltlU-i', ded by :. r,:: lt-.i 1 lo to Fie form in p? i (c) ( 2), m v\ by r.,d..Y. 'Yale ng par (f) (6, ;,.c POLY. *T a pit (f) ('V) ;'.n:I n tice.v ; ar ai'yaph (t> (G) r. ; folio.. 5 15 0. *, .Appl it *1 non-. (c) * * * (2) * * * 15. The rnpAvuv i -> regum-d, to ceY: a an C"r. ::: ; Y al c : v` or.-g eg; r*'pori On Y . h's the environ;:.-ndd impart, of vl'.e ma.aifact'inn-; pro<x-; and tun '.iHi.ra.'.; u_.e or c;a- un-.'j-.nn of tLe ding pa: a..a; to lot o! this chap .or, ***** (f) Abbreviated new drug applications. * * (S) All environmental impact analysis report analyzing the environmental im pact of the manufacturing process and ultimate use or consumption of the drug pursuant to 5 6.1 of this chapter. ***** C. By adding a new subparagraph (8) to 5 130.5(d), as follows: 130.3 Reasons for refusing to file ap plication*. (d) * * * (8) The applicant fad's to submit an environmental impact analysis report analyzing the environmental Impact of the manufscarring process and the ulti mate use or consumption, of the drug pursuant to 5 6.1 of this chapter. ***** d. By adding the following sentence to the end of 5 130.0(a) (1): 130.9 Supplemental applications. (a)(1) * * * A supplemental applica tion proposing substantial changes which may affect the quality of the human en vironment shall be accompanied by an environmental Impact analysis report pursuant to 6.1 of this chapter. ***** e. By adding a new subparagraph (7) to 130.12(a), as follows: 130.12 Refusal to approve the appli- cation. (a) * * * (7) The applicant fails to submit an environmental imnact analysis report analyzing the environmental impact of the manufacturing process and. the ulti mate use or consumption of the drug pursuant to 5 6.1 of tills chapter. ***** 6.5 SuTjml-Mori of riimmcnli in oilier uitriicics. When tlie Food and Drug Administra tion i,, requested by the O.Tice of the Sec retary to comment on environmental im pact statements prepared by other agen cies. the Commissi nor shall prepare such comments as lie deems appropriate and shall submit them to the OiTice of the Secietary, wiucli shall prepare an ap propriate response for submission to the requesting agency and the Council on Env ironmeiital Quality. PART 130--NEW DRUGS 4. In Fart 130: a. Bv adding a new item ly to the form In j 130.3(a) (2), as follows: 130,3 New drugs for in\r-tigatioiud u*e in human being*; exemptions from srelion 50.3(a). (a) * * * (2) * * * 15. When requested by the agency, na environmental impact analycLj report pur suant to i 6 1 of tills chanter. * PART 133--NEW ANIMAL DRUGS 5. In Part 135: a. By adding a new subparagraph (10) to s 135.3(b), as follows: 133,3 Now animal drugs for ime-iNa. tion.-d u-e: exemptions from section 312(a) of the Act. ***** (b) * * (10) When requested by the agency, the sponsor shall submit an environmen tal Impact analysis report pursuant to 5 6.1 of this chapter. ***** FEDERAL REGISTER VOL. 33, NO. 50--THU3S0AT, MAP.CH 15, 1973 ASI-PR 0001661 7Cr:f> rules and regulations b. In v 137 4..'.!)), by itdesign at an? sub- p.',:1.! H r':)h (13) A vm b'l.n bmiLimj Vic r.ppVcct or. , aubpara/raph (15) and adding a n.wv subparagraph (14) ns fol io*',(a iii'.v .'.li'ip.irr ;rnph (11) has re cently be.in proposed) : 1,1.", l,i fV'W ailut.il drui; njq.Ui'.iLion*. ***** (b) * * (111 Ed- :ra,inf'll1 ill iinncot a",C,l',sis repicV. Ti:,i appLas::!, i-> required to Mb- mit on umt-iilal Im.:l 7 mvl ;; rc-pTt rrhnq th; on; ,ro; . lentai .m- f,f iv mi'iiufactumv: process and the ultimate me or consmuphon. cf the now animal drug pui./.iaut to 5 0.1 of this chapter. ***** c. By adding a new subparagraph (9) to 5 137.12(a),, folio vs: 5 10.1.1- Iicfu?;il to .approve an applieslion* (a) * * * (9) The applicant fails to submit an environmental impact analysis report paralysing the environmental Impact of the manufacturing process and. the ulti mate use or consumption of the new animal drug pursuant to 5 6.1 of this chapter. ***** d. By adding the following senior :e to 5 135.13aU) (1) : 131.13j Supplemental new animal drug applications* (a) (1) * * * A supplemental appli cation proposing substantial changes which nay affect the qualify of the human environment shall be accom panied by an environmental Impact analysis report pursuant to 5 6.1 of this chapter. * * * * * e. E; elding a r.; ,v paragraph (d) to 5 135.13b, as follows: 135.13b Supplemental applications for animal feeds bearing or containing new animal drugs. ***** (d) A supplemental application pro posing substantial changes which may affect the quality of the human envi ronment shall be accompanied by an environmental impact analysis report pur aunt to G.l of this chapter. PART 115--ANTI3IOTIC DRUGS; PROCE DURAL AMO INTERPRETATIVE REGU LATIONS C. In Part 110. by adding a new para graph U) to 145.10, as follows: 115.10 New antibi,>lie arid anlihiniici on).lining products. ***** (;> An environmental impact analysis report analyzing the environmental im pact of the manufacturing process and the ulMm ite use or consumption of the antibiotic drug pursuant to 1 0.1 of this chapt-.r. VUcV.i'c dc;c. Tils or:', : shall fcoco.TT ; ifechve wh Mar. .i 1J, 1375, CS-t. i:a;.o (f) c-`>. si s/it, car", *2 un o. 4322; rcj-.. <!(.', COS, ;-J7, rig, 70i, 70S, C" L.r.t. 1`jj2 us I'.PI-.rC-HAS v> ra'icad-'1 by 70 ft'..it :>13 i 72 to -,t. uj. C3 fct it, 4,'W 1-1 i.T.i-".;! .n. 72 UUst. 17."i-17C3 at arr.sa i.a), 71 .3:: t. 3 j Ii rv-n.baiisd, be ta.it, 0:; : 11: 2i u./.c s-m, :iss. 3302, 37',, Mo) Da'cii: March 13, 1973. Sit a tv in G \ ?, e: rr.;, DepnVj ConunU doner of Food and Drags, [FT. Do:`i3-E0C3 Filc<l 3-14-73.5.45 m] PART 8--COLOR ADii HIVES Subpart--Provisional Regulations Postponement of Closing Dates of Pro; isio.vAL Listing Pursuant to the provisions of title II of the Color Additive Amendments of 1960 (sec. 305(a) (2), Public Law 86-613, 74 St at. 404; 21 U.S.C. 376, note) and under authority delegated to him (21 CFTt 2.120), the Commissioner oi Food and Drugs is authorised to postpone the closing date of a provisional listing of a color additive on ins own initiative or upon application of an interested person. He is also authorized to promulgate and keep current a list cr lists of the color additives and of the particular uses thereof, whenever in Ills judgment such action is consistent with the protection, oi the public health. Requests have been received to post pone the closing dates of provisional lut ings of the color additives in 5 S.591 of the color additive regulations. For those color additives listed in paragraphs (a) and (b) of 8.501 where the uses in products such as foods, drugs, and lip sticks involve ingestion, reports on teratological potentials have been submitted to the Food and Drug Administration, in accordance with the provisions of the no tice published In the Federal Register of September 11, 1971 (36 FR 18336). A notice was published In the Federal Register of January 31, 1973 (33 FR 2D96), to clarify the status of metallic salts and vegetable substances when used as color components in hair dye. The no tice stated that it was the intention of the Food and Drug Administration to provisionally list, on an Interim basis, metallic salts and vegetable substances for use as color components in hair clye. Any such substances will be removed from the provisional list, and thus dis approved for any further use, unless the requirements of that notice are satisfied. In addition, requests have been re ceived to restore the color additives, DEC Brown Mo. 1 ur.d External D&C Violet Mo. 2, for use in coloring externally applied cosmetics, to the provisional list. These color additives previously had been pro visionally listed for use in externally aupn'cd drugs and cosmetics. The closing dates of the provisional listing wcie ter minated boa.-onc the saoiiier no Lm.:.;r had any commcrciM l::Ure-.t in color rddhiva".. Sub -qu.-ntly, r"a.s were reciivccl fre.n otucr n.d i.er- tons, who had M-o been v.sieg ins colors and conduct., tost.,, to [.rn,::,, ally list each of tin zlor ud:-h. as it.r u. e m external!/ av.,coim-oller, and to ie- store them to the pro.nlo:::.: U,t pend ing the p.cee,-agrig of these petitions. In the light, of their previous pro'./ aon-i listing and the continuing sc;: .Litre :n- ve..ti':a;ioqs, the Comm:;,,oner 1 oiiclnds.; that the..c colons should be restored to the provisional hot. The Cca.inus donor of Food tuicl Ditto finds that postponem-nt of the closing date of the current!;/ pro'.ioiuually listed color additives is consistent with, the pro tection of the public health and with Lire objective of carrying to completion the 'cic-ntiuc invrofi atisiis. including muiti- 'neration, reproduction sm .es and . 'bility testings, and regulatory review tl, -eof, r .cessaiy for making a deiemri- nr.iion as :o the lifting of such color ad ditives, or specified uses thereof, under section. 705 of the act. These extensions are granted on condition, that, where applicable, progress reports on the re- imictive multigeneraticn reproduction, studios shall be received or. or befora July 1, 1973, by the Food and Drug Ad ministration. The Commissioner of Food and Druss also finds that the provisional listing oi metallic salts and vegetable substances for rise as color components In hair eye, and the restoring to the provisional list of D'.c Brown No. 1 and External D&C Violet No. 2 are consistent with the pro tection of the public health. Therefore, pursuant to authority of the Federal Food, Drug, and Cosmetic -Act (sec. 203 (a)(2) and (d)(1), Public Law 36-613; 74 Stat. 404-405; 21 U.S C. 376, note) and under authonrv delegated to the Commissioner (21 CPR 2.120), Part 8 of the color additive regulations is- amended as follows: 1. The closing dates for the color ad ditives listed In paragraphs (a), (b>, (c), (e). <f>, and (g) of 5 8.501 of the color- additive regulations are changed to readt "December 31, 1973, or until a new clos-- lng date is established". 2. Paragraph (b) is further amended by inserting therein the following itemr Clothuj date FiitT-.erM* ** DilC Brown No. 1. **> * DlC- 31, 1073, Or until a nssv cIumAJ d.ito Is eotiibhihed. *** * To- oo\Ar!r.!i Ai* CW'iliieUts* * - 3. Paragraph (c) Is further amended, by inserting the following item: Clown date EtfumM n.Ul Vlu'.sL No *L *** Dev, 31, I".`3. or until \ V cl jbSin* riAfo IJ ** *** jyar.ti.vnl * l'^r t*i- irrivui1 Citopn v. ** * FtDIRAL FJGISTfS, VOL. CO, MO. DC--THU710AY, MARCH IS, 197 3 ASI-PR 0001662 7C`1G BUIES AMO REGULATIONS Title 01--r*'-. ' oral Drugs CMAPTEf? I--FCCD AND D ,';!J 3 ADMINISTR.Mion, o;;j.r.~T\":r, r ct health, EDUCATION, AMD V.ELFARE r/.OT 1--r.TC.Ul-ATifi'N 3 TO:! THE ENfooct:-,:nt or i.-ie f^oeoal focj, DTHC, A NO cos:. ETIO ACT A'FJ THE f.m.i ,v.c;o\o:no ano lageuns act part 167--ri vr::o inm-mostic PRODUCTS EG,'. H'J' :.M I USE Ur>R-'quu t nve-fis and Procedures for Dcv-Mo;eilunt rfi f.i.-iivl.irdv for in Vitro D;.i-jnoslio f'.'l.'fiiv.ts for ilu.n.in UjU Id Mm .Tr.r-w. oil August 17, 1 07 i'!'< - Ll lGfilfi) a pr'.vxvgT v,n ; pub lished to eiti'-b'mil provs'ilMi", to d. . top stood H'd." for in vitio d:,, .r.osMc prod uct.,. Inter'':, ted p'.-'i. (Jtritj w-re invited to submit conn's ;-:i!. on the yiovoiol within 60 dots A total of '17 l-cponses was rccc-h-fi. The*-e included comments from i>i- uul u-turcr associations. user aczocia- tico.i, manufactureth of diagnostic sys tems, and comments fiom a consulting firm and an individual consumer. The Diagnostic Products Advisory Committee his met and has provided significant as sistance to the agency m the develop ment of this program. At their first meet-, ing the committee considered broad scientific questions concenur.; the propo .ed approach and aim commented on the question of priorities for the estabhshm-nt of product claw, standards. The-,e sources have provided useful in fo-motion for the development of reason able regulations governing the manu facture, labeling and performance of m vitro diagnostic products. The comments and concinsioi , of the Commissioner of Food and Drug's, based on his evalua tion, a"'* summarized as follows: 1. A . umber of comments state that the p;. 'sc-tl order purports to be au thorize'.. by sections 201. 501, 502. 505, 503, 510. or 701 of the Federal Food. Drug, and Cosmetic Act, and none of these sections explicitly authorizes the pro mulgation or in vitro diagnostic prod uct standards that con ititute substantive rules. Comments were made that the act contains no provision conferring author ity ou the Food and Drug Administration to determine the new-drug/old-dmg status of a product. It was also stated that tile FDA does not have authority to nm be substantive determinations of adul teration or misbranding, and it was Claimed that the fact that a product does not conform to an applicable standard does not cause the product to be mis branded or aduiteiatcd without regard to the adulteration or misbranding pro visions in tiie act. The question, of the authority of the FDA to promulgate regulations of this nature was previously raised and discussed in connection with establishing proceduies lor classification of over-the-counter drugs, published in the ID dural Rcc.isi'er of May ll, 1973 (37 Fit 01G4S, and the conch;: ions reached there are equally applicable here. T1 t standards to be established under tfiuse procedural re,'.illations, if upheld by tiie courts, will proscribe the condi tion,. which nr. in vino diagnostic prod uct must meet if it is not to be in viola tion of th.e u'kbiar.ding an 1 or adulter ation and/or ucv,-ding pro-,anus of the art. 2 Tn pome to other comment", the dcrn'Hpn 0f ''product close" has b.en ri'a'Ufivfi to PcTOuL the dev'-'ornm lit of p' c` (. stouiijrt.!" for '-cduc's, with common f,r re'iateii clie ter.pics or tiro, e ii.t"::.', i [or com: ; o: related u-e., i;: v;'/i ion to the for me for a prti i i-'livi ceti rnii.iatUjn or related gioup o; dot urm.rnt'i'.vns. 3. Sc."ini comments f.tatcd tied the Fc -rr.l Food, Drug, and Co hichc Act do .1 hot p-vmdo cutlioiiiy lor lor-by- lof ccr'.'.f. Cion Tim < ainmir - nor eon- (.ir..!.is t'.-o, Ml ni , .".Mon aurhmi- ireii only v,h?ie it is n ce-.-ary to asoiiie compliance v.i-.h the act, find the remla- ticm.s ivi-, r been revised to clarify th.s point. Such ceiLiflcation, '..here required, may be corr.iucfetl by ths FDA, by the Center for Dr case Control, by independ ent D.borato:ies. or by other organiza tions, as dOoi'-umted in tire standard. 4. Some of the comments objected to the handling of In vitro din-no.-Aic prod uces as a class, without any attempt to classify them as drugs or devices. It is the petition cf the FDA that as a matter of law it has the authority administra tively to determine whether products are dings or device.-.; it lias made dear its position that unul new device lc-.- iation is enacted and where the authority in herent m section 505 of the Federal Food, Drug, and Cc .meric Act is necessary to protect the public health, products will be regarded and classified as drugs under the Act. The FDA believes it is not In the public interest to spend time dwerminmg winch in vitro diagnostic pioducts arc drugs and winch are devices for the pur poses of this regulation. Such a determi nation will be made only when necessary to bring violative products into compli ance. 5. Rome comments stated that the FDA has no authority to impose the re quirements of the Federal Hazardous Substances Act (FHSA) on in vitro di agnostic products, whether or not they are intended or packaged for use in the household. The regulations do not un pose the requirements of the FHSA. The requirement of appropriate warnings is based upon section 503 of the Federal Food, Drug, and Cosmetic Act. The warnings prescribed in 21 CFP, Fart 101 are appropriate in many cases for in vitro diagnosin' products and therefore arc incorporated by reference. 6. The section of the proposal dealing with labeling drew the largest number of comments. Eeveial substantive objec tions to the wording of this section have been accommodated, and several items have been restated for clarification. Many Sims commented that specific items were not applicable to certain products; the regulation has been changed to allow flexibility and to per mit omi' .ions where certain items of information arc inapplicable. The re quirement for a fixed lormat and order for presentation of labeling information lie..; been retained in the interest of uni formity. 7. Th me was objection to ;v.j npy-Mw- nt'iit f i declaration of tee q-,, :ML_, prop.".-!,iun of each rcrcu'.a. ce or inactive ingredient in the labe..r.;; ,-c- tonw 'n: ins each product, luc.-c o.-ye'- tio;', v. ore baiocl prune ily on tun p,,. tiou that such dcrla;, tion v.oa'u e..-- cio:e v.-.l'.i bl-" trade secrets and piop::.,- ti".-y information. The FT' \ con-ia'M,, b.'.^ed in part on its evah: on. of th_ comment,; and in peat on ,.;e advice of the Diagnostic Products AuvAory Co:r.- mfitce, tiiat there is no dv.nomtri.iui net d. as a general requirement, for a dec1 v. a,lion of the or yororuon ol each cate.!, tic or inactive ingredient in tiie labeling accompan;, ::ig the-- products. Such requirernenrs may he cie- tcrmin.pd to be necessary for n parricuiar produ-t or class of producis as pan, of .specific promict class standards in t:;a future. TiU-rcfore, tins subpas:-graph has been amended to require the oc rati on of the established name (common or usual name), if any, and the quantity or proportion only of each reactive in gredient, iu'iss a standard requires ctherwr.e 1 -ept where such provision is coi fined m a standard, a general state;: nt indicating the presence of. and characterizing, any catalytic or nonrcactivo ingredients will be sufficient. 8. A significant number ot respondents objected to 5 167.2(a) (3) (21 CI-H 1*57.2> stating that, information including the quantity or proportion of reactive in gredients is not necessary for the user of these products and that the quanti tative description of the reactive ingredi ents on the label would constitute dis closure of trade secrets. It is lhe pov.uon of the FDA, after consultation wirh its Advisory Committee, that knowl-dge of this information is important as a part of adequate directions for use of these products. Therefore, no change has been made in this provision. 9. A large number of comments stated that tlie recuiirement that tile label bear a statement that the product is intended for in vitro diagnostic use only is unduly restrictive since many of these products are legitimately used for other purposes. This section has been revised to eliminate the word "only". There is nothing in this language that would preclude the use of the product for other legitim,.:e purposes. to. Several comments indicated con-- cern with the requirement of a state ment of the declaration of net quantity or contents in metric terms. Tnis provi sion has been revised to state a prefer ence, instead of a requirement, for this terminology. 11. Several respondents perceived end slated that the requirement tor a kit or control number on the label of products did not reflect an appreciation of the cu3- tinct problems associated with muihpl-e- unit products or instruments. This pro vision ns reworded provides for this distinction. 12. The provision relating to excep tions to requirements for certain infor mation on immediate container labels was the subject of many comments After discussion v.ith the Diagnostic Product Advisory Committee, J lC7,2m) (lOMii KOERAL register, vol. 3S, mo. so--Thursday, march 15, 1973 a$I~Pr 0001663 RULES AND REGULATIONS 7007 been nvK d to allow the can',; noil of for fine d``"> `A tbo lab.---Tinfiou on tin in'cr.dud i:.,.-; of stand:1 rd I. 7 ir O? pre.{- it cleoe 25. Mhny v ..vui,!f'n,s obliged to the V <1 J : )t i'h 1-1 ry i'c:oe.' * of l ir.M'.ion i* ca'- t'A ii-o.i'.'ct, a'.opciftion of re.-ciivo n- place hard -n:.- ru iiE'.Tr, upon, re -* of ill. 06 i.Cjii, j a * i t r,iv .i.'i ; gred.'-utnings, .el dr use condition.',, search.: ; or o m..1'-, ctor ,. A p.-nple r.'1 d bv ; a.-* ` \IV.v t\ Th.j L 'MS and r._l coufi-utreqiurcd by 5 107 2(a) form for pro .. :'L r. ol .IP',itier. v. Ill b-_- r-.i L<..>i" 'L he inp-'p.t: va OL lio ) IV- (2), (3>, ('. (.S'), and (7 >, final the imned:."fi- c 'fitain'T lcbel uncle:- certain riperifiod c- 'LLNjivj. IT. A 1:".' ,e number uf per -on,, cbiectr-d bo deiciopcd i' li t:ir' ;k!'. ice of fine .fid- visor/ Cji::.t.;'v. cud o`!vr inter.' m. d person1', r r.u nvi'D avefi . 1)1 - .\t a 1. dale. An ;adfiP-ioni'l u,e fo - e ' t-D tiAa: r l jo K : ri'.'A i .10:.'j. .V.io !'_for ti.e i! er o; : l'C( :oct. fi .1-3 i:\coi;pvhion is nc'cc :i: for toe ? -y rtll c.. fo ci:v ?':i; p product c!. a - o a'ld- to tv..1 ifingut in ; 107.2'b) (3> that if Uce p:s 11 c-c Isfiohug refer:, to ;-i/ other p:occ r'u the appro.)riaLe literature ccf etc ' i* Tc cli no ii.ci-iued, and La,- ir.Dci- tion pee.1-.d?d m tn.s no 4 if;:: a`;-in pro- ceil are is to ir.foim fi.i'-l [ u r.i*. of ti'.C agency concernrg the .`.-n.icy of products shipped w lrh 1 I:l s,\ fi;IL :xv do a r.pi'c for the mtev.d-^1 u.ovr. 21. The Diagnostic Products Advnoiy Com.mime noted thac. the provisions for too .usbiua.atn of information under iaU fipudl e gilum tan roe :o.t lor mid : aefi ir.y fi;oc;:o_; from the origi nal and their 0...1 t on die muT.,. oa die luoelm g rme! to miuimirc I- -li'y of th.c ut. n.ere^jary mit.rfi o. riy.r.,i''w mice nctivit.ee lor pro'' Lie.' P-`0r to 5 167 2(c) m. .lit im-n, ,e an un.uece.v.nry burden on u interested person who wnhed to pro ide comment more !muted be...is tluit thu icpiesen'ed comp ml ere m.irbchr.g'. Whim comnurcia: m iiketh' C than that called for in 5 167 3(c), Trie l.dmilU'. 'Ihere is no reTUiroiumt for is befpm. nor.fi.ciV fim to Ur., , kect will Commissioner agrees that a more in tonia ri .j'.iii oi one product with .mufhor be required as provided m fire procedures formal sulimimion should be acceptable in uio i-c';u!;i tion ;u, proponed or an f.nnl- for implementation of the Dru ; Listing and the regulation is revised accordingly. ined If -i manufacturer doer, make such n Act. 22. In response to comments that the compart,on, h.o.vever, it ir. incumbent 17, Several comments were addressed proposed n.-ual period of 69 days for upon nun to p.iituy it fully m hrs Label to tiie problem of including general pur submission of intormntion pertaining to ing. Ti;e requ-romont for an explanation pose laboratory reagents and other a. product standard requested under ol the reason tor the chan :e from r.n multiple-purpose materials in the re 5 157.3(c) was inadequate, this require orisin.il procedure has be-a deleted, nice quirement of 21 CZT'i Fart 137. The Com ment has been revised to allow a uniat little b.ueilt woidd accrue to the in missioner recognises that there are hun period of 00 days for these submissions. tended mer of these products from the dreds of common laboratory reagents However, thus will vary for Individual posoC-.-ioioti of thin information. and equipment (e.tp, hydrochloric acid product class standards. Ii- view of the 11. There (verb numerous comment.; and plass bearers), the use of which is notice given, in the August 17. 1372, pro received concerning the lequlrcmer.t un generally known by persons trained in. posal tnnt the first request for informa der 55 157.2(b) (T> (i) and 107.3 (e) (12) their use in laboratory procedures. Tire' tion would be for those products used (21 CFR 157 2 arid 1G7.LS> that nnv state inclusion in their labeling of nil of the in the determination of glucose, the tune ment on ".special preparation of the pa information required by 1 137 2 (a) and for submission of tins information will tient" involved an intrusion info the ..(b) is net feasible or necessary for the be CO days, practice of medicine. Tile FDA does not proper use of these general pu.po^e 23. Several comments objected to the believe that this provision represents tin laboratory art a -s. Therefore, the Com provision that after a standard is pro Intrusion into the practice of medicine, missioner has added a new 5 157.2(d) mulgated or amended the FDA will m-ke but rather is required for adequate direc to Ihe regulations to identify the infor data available to the public within 30 tions for use of the product. To further mation which must be included in days unless the submitter of the data can clarify the intent of f "'.,e two subpara the labeling for those products. New show that the data are con,,dent;.il. The graphs they have bc"n revised to Indi 5 167.2(d) is applicable to general pur applicable statutes (13 O.LC. 1395: 21 cate that such sp.cial prep iratien Is pose laboratory reagents and equip U.3 C. 33Ki)) provide for tile coniiden- needed as it bears oil the validity of the ment which may also be used as part tiaiitr of trade secrets obtained from a test. ol an in vitro diagnostic procedure. person. The FDA is bound by these 15. The same basic objection was raised with respect to tin* provisions in 55 167.2(b) (10) and lGT.Ihc) (15) which requested a statement that additional teats may be required in certain in stances. An example of the application of this provision would be to indicate the availability of a confirmatory procedure if the product in question is intended for Use as a screening determination. This requirement has been retained since it appears necessary that the user be pro vided adequate information concerning limitations of the procedure. 1G. Otner comments requested exclu sion of products intended for research and invo.fiir aional use. The Advisory Committee .,o made recommendations concerning exceptions from the label ing requirements when diagnostic prod ucts are shipped for investigational purpo .?s. The FDA recognises that adequate information to fulfill the requirements of 5 107.2 (a) and (b) may not be avail able at the time of the earliest testing, ft is a greed that a provi.don to cover the labeling of products prior to commercial muhsling is appropriate, and 5 107.2(c) has been added to cover tills matter. Notification piior to the time of com mercial marketing will be required In 18, Many comments expressed a need for a time period within which to de velop and effect the necessary labeling changes in order to avoid imposing an undue hardship on the affected Industry. Considering that these regulations re quire labeling revisions for all products and the development of data In many cases, a period of 12 months from the date of publication of this document w.ll be allowed for compliance with the general labeling requirements of 5 167.2 (a) and (b) for nil products. Since the problems of labeling for products subject to the requirements of 5 167.2(c) are of a lesser magnitude. t> months from the date of publication will be allowed for compliance. 19, A significant number of respond ents objected to the requirement for the disclosure of the complete product for mulation in the submission of data to establish a standard. This paralleled the objections to the dioClosure of certain formula information in product label ing. The FDA requires information of tills hind to establish standards Quanti tative formulae are recognised as valu able trade secrets and are protected from public disclosure by the FDA under tire statutes and will treat as confidential all information that has been demonstrated by the submitter as falling within the confidentiality provisions of one or more of those statutes. Information not ex empt from disclosure under the Free dom of Information Act (5 U.S.C, 552 (b)) may not be withheld from public disclosure. Section 167.4 (21 CFP. 167.4) of the regulation has been revised to clarify the position of the FDA with resnect to the confidentiality of sub mitted information. 24. Among the product groups con sidered by the Diagnostic Products Ad visory Committee to be o: the highest priority for developing product class standards were microbiological anti gens, antibodies, and adjuncts; transport and growth media; products for the measurement of immunoglobulins; cali bration, reference, and quality control materials: laboratory water: clinical chemistry products used m the deter mination of glucose, calcium, bilirubin, ennymes, sodium, potassium, chloride, urea, uric acid, cholesterol, and triglyc erides: and products mod in the deter mination of hemoglobin,. Fu: titer delib eration will be required m order to refine and designate or deliu vde product order to as list the agency in planning co.-.I'.dcntiai.ty statutes governing infor clas-cs and to place them u. appropriate its aeLiviiie.i and anticipating the needs mation obtained by the gos eminent. order according to priorities for cievelop- FEDERAL REGISTER, VOL. 33, NO. 50--THURSDAY, MA.1EH 15, 1973 ASI-PR 0001664 70H3 BULES AND KEG'JLATICNS in': and rrfiabhxhing product ciasi Standi1 rds. 25, Tut .o re 'illations do not pi-or'ude t;-" impo u'.mri of additional r> quircncnts ii11_I"the Act whan the Coinm.s.iio.i-r corn,'aides tit it such rcqniromnV ; a:e rei'1'' .-e::, to p:v,i'icl >'10 pybkc hulth. `J*;, E til a p:. , v.oii.s of Part 1 ft 7 apply to th ;.-e ppiP.uc:, si.-jr-ct to the - cw.yt'sn fro ;i the Fbvhng require- rrmT , o: soo'.vu f/F-i' t i 11 > of the Act pi 5 l.ldc.p, t'on'm.. loner :s r-ua.mg 1 10 J < J) to indicate that in Mtro clj;1. or-- jvi.'ic, piodivti su'd tut to ihc.i. .`.ecbou \\!. i'h are m rom-fi.ar.i'--' with the pro'.i- iai, of Part i<i7 > 11 be deemed to meet the li'ee'un.'rri quirtin'-nm of 5 FV.I < D (1). 27. The provisions of these re. via nous, in; hiding both 'he requirements for It.b.and development of standards, apply to ail in taro diagnostic products, including b'oiogics. All questions con- certury in vitro diagnostic products, ex cept for b'.olo.,icuds subiect to an existing license tinder section 271 of the Public Health Service Act, should be addressed to the Diagnostic Products Staff, Bureau of Drugs, BD-207, Existing licenses for biological products issued under section 211 of the Public Health Service Act vd> remain in effect until applicable star; _rds are picmul- nated pursuant to lb.,. 167. For in vitro diagnostic products whicn are .oloqics but which have not previously been licensed, compliance with the require ments of Part 167 shall be deemed to constitute compliance with section 351. Such unlicensed products need obtain a license under section 351 only if the Com missioner determines and so informs the manufacturer or distributor pursuant to 1G7.C that a license under section 351 is required in order to protect the pu. lie health. Therefore, pursuant to provisions of the Federal Food, Drug, and Cosmetic Act (secs. 201, 501, 50 ".. 505, 503, 510, 701, 52 Stat. 1010-1042, us amended, 1040- 1051, as amended, 1053. as amended, 1055, as amended, 1056, as amended; 21 U.S.C. 321, 351, 352, 355, ''53, 560, 571) and the Public Health Sc ice Act (sec. 331, 53 Stat. 702, as amended; 42 U.S.C. 262) and under authority delegated to the Commission (21 CFR 2.120), Chapter 1 is amended in Part 1 by tensing 51.106(j> and by adding a new Part 1Q7, as follows: 1. In Part 1 by revising 5 1.10S(j> to "read as follows: 1.106 Drug's a:ul devices; directions for use, ***** (j)Exemption for in vitro diegnostin products. A product intended for use m the diagnosis of disease and wluch is an in vitro diagnostic product as defined in -5 167.1va) ol tiiis chap'or ill all be deemed to lie in compliance v. :th the require ments of this section and section 502(f) (1) of the act if it marts the require ments of Part 107 of tide chapter. f* * 2. By adding a new Part 107, In Vitro Diagnostic Products For Human Use, to Eubchupter O ns follows: S'-c, i*? i 1U7.2 1S7.3 1C7 4 1ST 3 IV/ ; 10<\7 Subpart A--Procai.ijral r>' r` ` i :Pir. 'In Z tor In prO-A ' Ptoch v ;ro ;,'r cp* or r< vitro cll;'^r,r C o' ,.U' r,n t\ a:i* r.> a *"- , ry v{!o;i, C : . itqt.l.'u' in.-:'*.' i't C VI 1*. prc^'^ir; or i'j w"ro JI.f;no ; pr^ti'icts. At i liv"1! v: TM). Go,'!, C0:,( 303, .-110, 701. 52 Shu, -J, ic; i-lojt, anirne-gt, levy re, cm-.. 1 si, IC.sl, sc : '-.cl 'ft, 1 cIf. sc, :--.I; 21 L 6- C. LSI, LAI, Iic2, SSj, 35.., 3`XI, 371. lf>7.1 Definitions. (a) "In vitro diagnostic products" are t'uose reagents, instillment and systems intended for u..f; in trie d: no:B of dis ease or ;n th ueiermin :: > ; of the stare of health in order to cm mitigate, treat, or prevent disease or ir.3 stoueiae. Such products are intended for use in the col lection, pi aparafion arid examination of specimens taken from the human body. There products are drugs or devices as defined m section 201(g) and 201(h), re spective! v, of the , i deral Food, Dmg, and Cosmetic Act < the act) or are a combina tion of drugs and device-1, and may also be a biological precinct subject to section 351 of the Public Health Service Act. _ (b) A "product class" is all those prod ucts intended for use for a particular determination or for a related 1 roup of determinations or products wth common or related characteristics or those in tended for common or related uses. A class may be further divided into sub classes when appropriate. (c) A "product class standard" is a statement describing performance re quirements necessary to assure accuracy and reliability of results, specific labeling requirements necessary tor the proper use of ;* particular class, and procedures for testin'" the product to assure its satis factory performance. (d) "Act" means the Federal Food, Drug, and Cosmetic Act. 167.2 Igibrling for in vitro diagnostic products. (eh The label for an in vitro diagnostic product shall state the following infor mation, except where such information is not applicable, or as otherwise speci fied in a standard for a particular prod uct class. Section 20 Uk) of the act pro vides fi'-nt "a requirement made by or under authority of this act that any word, statement, or other information appear on the label shall not be con sul!, red to bt: complied with unless such word, statement, or other information aho appears on the outside container or wrapper, if any there be, of the retail package of such article, or is easily legi ble through the outside container or wrapper." (l) T'ne proprietary name and estab lished name (common or usual name), if any. (21 Tiic intended use or uses of the product. (3 Foi a reagent, a th duration of t.:c estr ' a fil'd name (Coma an or ham.), if any, nrd que.V"y. p.-cc rr; ;n or coi'c-.r.i ration cf each roic::'. a ir.g.-gdrinl; and for a re a unit d-ri.ed f:::u biological mat'Uiai, tuo ronree ard a. mciuuro of its activity. T:-.a quanuty, proportion, couce:itr. lion or aetivitv sirfil be stated m the ry.rtein ,g;;r.raiiy used ami recogr.i.'od by tiic m1---nd id imr (c.g.. metric, inn national utu: i, etc,). (4) A rt.aiem.'.r.t of warn.r.gs or pre caution-, for v- -rs as eswbl incn in the ivfiu'afioni co ..mod :n Part i;u of this chga'jr and a 1 other v,:irr..aa i.pprcpriafe to tin i.O-i'd picseiVeu by ihe pi'Oiiuct; and a stru; ment "Far In Vitro Diagnostic Ura1' ami fry other iamimg statements appropriate to the intriiu.-d ' >e of the product. (5) For a reagent, appropriate - torr.ge instruciioua adequale to prrFce: the sr.ability of the product. When apr'ic:.ble, these instructions shall include if.: in formation as conditions of temperature, light, humidity, and bther pertinent factors. lor products requiring manipu lation, such as reconstitution nna/or mixing before use, appropriate storage instructions shall be provided for the re constituted or mixed product which is to be stored in the original container. The basis for such instructions shall be determined by reliable, meaningful, and specific test methods such as these de scribed in 2 133.13 of this cbm uer. (6) For a reagent, a means by which the user may be assured that the prod uct meets appropriate standards of identity, strength, quality and purity et the time of use. Tins shall c; provided, both for the product as t v-.ded anti for any resultant reconstituted or mixed product, by including on the label one or more of the following: (i) An expiration date baaed upon the stated storage instructions. `(ii) A statement of an observable indi cation of an alteration of the product (e.g., turbidity, color change, precipi tate) beyond its appropriate standards. (in) Instructions for a simple method by which the user can reasonably de termine that the product meets its appropriate standards. (7) For a reagent, a declaration of the net auantity of contents, expressed in terms of weight or volume, numerical count, or any combination of these or other terms which accurately reflect the contents of the package. The use of met ric designations is encouraged, wherever appiopnate. If more than a single de termination my be performed using the product, any statement of the number of te-its ;hall be consistent with ir.simctions for use and amount of material provided. (8) Name and place of business of manufacturer, packer, or distributor. (0) A lot or control number, identi fied as such, from which it is pctsible to deteimine the complete manufactur ing history of the product. (i> If it is a multiple unit product, hke lot or control number shall permit trac ing the identity o* the individual ur-ts- FEDERAL IlGItTER, VOL 38, NO. 50--THURSDAY, MARCH 15, m3 ASI-PR 0001665 RULES AND REGULATION? (ii) For r' tl in.` i the lot nr unit.;, cV,), \ .,i it grignt ind.c hag tb" trot number . "'Ll w-. mt treeing the p. -J of ami eh irectcr; vug any idootilv of till iiir,' . ' m';, - on.Dies. <in) For mu'.:: /re unit prod"i.''. v. hi'di pr(i.ii-; th" u;e i. f inc 1'.deii ii;'.3-> tovtlier H,\ a all ill.he ..g'.iAl b...r the .`el 1 > hit nr tout nil niri'li-'i, if a//. n, ::i- ti,' ore,11' i uuifo.m identifica (_. i R or rare s. a ' a. e i - p pg , (' g,, bull 'l's, n P. v,11, at ".bp,: :ii. (ill A 3 it' '..e.:'.t of v.,,rui:` p r. ,iro- cau( reis inr (,,'... .a ret,/);: .hen . i The re ,e.h33in; car,hi n -! in Tni t 10! of tins cht ;1 cry o/g'g' v...:ui" ;pp:o- tion ' 'hi he w ',fi pi'iat'c to tat ha:.'Id peg ;3 ! D, the (tfn I,: ci ot t'h't :"'>r hi'irs in p.-re,- produc1'. ana a at agent "In' Ir Vi'i'Q ,.i 11.1 fli tni r,i ::i `9) oi t'-h.i .'or- Dp-puio./'c U ' rug any o'g a . : ,. ir.g li,i:h 11' In lilo r.i 1 oi i:;:l':i 'hall oo.l- a!r Lament'; n\ sar a.1; to ;: h'tem'ud t V111; 1.. tni iw'!; nr nth 'ih-'o un: big tire .>f ih" product. to ;lr`r"on Dll,1 11 l.'.ln'l l.l'll l i ' i ' 1C111 (ini A dequa'c nr ti u"fuv.is for re- . to 1 ir ill] .r.irh i1', ho in ' t-on i.i'.d rc:r f.t'Urvu, mixm ;, ddmioa, -to. i.il,,-|i i - I- ihirhn: '.hi iiihni mr otitor ron- (IV) An imp: .ate i/orr-e m. truci: to.iiev 111 111 . .i I, 1titty o.i ti oniiih - o - adaruste to pioiret ::v: at"b g;,v o: fine tile itihi! mat mo iI'I;trod !); nor-i- piu la't- \Vh:n apuhi.ab'e. t; -'-e m-truc- iih-tti'i i i > <'2). 13). 'll, ()). (O' <u > - oi) tions shall include .vicli infcnr. non as cmd t 7i oi tliiii ' -'rt'oM nr,:, ap/c u m tiro conditions oi lemn1'; are, lad'.f, humid oui`cRitahwr lihi-liith only. ity, and of'her per; .nAnt factors. For (u) [ii nny case m v.ii'.gh the pig ence products r'Taiinng pganiniduticn, sucii as or tin, ihto: .notion, on tore hrngd.aie reronstitg :o.u ami 'or iT nng bffore use, coi'.ta w i " 1`i h'llo: tore with the test, the appropriate storaco ;n.,t. uctiors sha'l be inform al'ori may appear on Hu; outoide provided :or the retonsotuted or mixed contain,::' or wrapper rut her tliun on the product. The basis for such ipjiruetions immediate container label. shall be determined by reliable, mean (ta) Labeling' accompanying each piod- ingful, and specific test methods such as uct (ceg , a pircht:t;e insert) snail stale those described in 133.13 of this i:i one place the lolk'Wir.g in to re-nation chapter. in the fo'inat anti order sp-cified below, except . ;cre such information is not applies or ns specified in a standard Tor a p.,.ticular product clans Tiie label ing for a multiple-purpose instrument used for diagnostic purposes, and not committed to specific diagnostic pro cedures or system . may bear only the in formation indicated m paragraph lb) (1), (2), (0). (14), and (15) of this sec tion. The labeling for a reagent intended for use as a replacement m a diagnostic system may be hrmted to that informa tion necessary to identify the reagent adequately and to describe its proper use in the system. (1) The proprietary name and estab lished name (common or usual name), if any. (2) The intended use or uses of the product and the type of procedure (e.g.R qualitative or quantitive). (3) Summary and explanation of the test. Include a short history of the meth odology. v.'ith pertinent references and a balanced statement of the specir.l merits and limitations of thus method or prod uct. If the product labeling refers to anv other procedure, appropriate literature citations shall be included and the label ing shall explain the nature of any dif ferences from the original and their ef fect on the results. (4) The chemical, physical, physiologi cal, or biological principles of the pro cedure. Explain concisely, with chemical reactions and techniques involved, if applicable. (5) Reagents, (i) A declaration of the established name (common or usual name), if any, and quantity, proportion or concent;ation or each itactile in gredient: and for biological material, tiie source and a measure of its activity. (v) A statement of any purification or treatment required for use. (vi) Physical, biological, or chemical indications of insiability or deter: on. (*3) Instruments; (l) Use or fiu . m. (ii) Ir donation procedures curd spe cial reqv i rients. u;i) i'. ''Spies of operation. Uv) P-r. rmance characteristics and spccificatiors. (v) Operating in-tructions. (ti) Calibration procedures including materials and/or euyipment to he used. (vii) Operational precautions and limitations. (viii) Hazards. (ix) Service and maintenance infor mation. (7> Specimen collection and prepara tion for analysis, including a description, of; (i> Special precautions regarding specimen collect'on including special preparation of the patient as it bears on the validity of the test. (ii) Additives, preservatives, etc., nec essary to maintain the integrity of the specimen. (iii) Kno-.vn interfering substances. (iv> Recommended storage, handling or shipping instructions for the protec tion and maintenance of stability of the specimen. (3) Procedure: A .step-by-step outline of recommended procedures from recep tion of the specimen to obtammg results. List any points that may be useful in improving precision and accuracy, (i) A list of all materials provided (e.g., reagents, instruments and equipment) with instructions for their use, (ii) A list of all materials required but not provided: Include such details as sizes, numbers, types, and quality. . The quantity, proportion, concentration (Hi) A description of the amounts of or activity shall be stated in the system reagents necessary, times required for generally used and recognized by the specific steps, propm- temperatures, intended user (e.g.. metric, international wavelengths, etc. CD A at 3 eA'lldc a, .buig the Dabil- i`y '3 the fi'.vi n.v r.i tvr..,i to bj me.a.iu.d r,"d `lie t'-gj uAhi.: v.hfh ,t sha'l be inch !- a -u:e accti n1- sub i <\> D.-l.-d", of c:3.iii'g' ion- I3.L".'ify ivf r"U'.v me'rg lei. D:. Cube piep l:g. -1 of refer'-:' e j (,), c e of iilauh ., nreparedirei of `i g d cuiie, e'e 'Ihe do""iip ion of Ire larDO of cedibr i- t:on sh.oeJu ir.cl'i.'j Ihe I'gji'es: and tl - iou.'-A lehic, measure.//;': ny th.o pro cedure (VP De",il' of *..i',rl; of '.lit;.' cc:.f:ul pioc.d'iPes end mate;;:/.:; re .Uirco, If there :s n '"d for !>o;,h rg-pgve a':'! r.i, g- ative cur/ rob-,, rb.., .'.3.0(da 1) ' r.t, ,:ed S' a' : what rro cng.mA-;-q sati-faetoi-y limit-, of performance. (9) Results: Exp win the procedure for calculating the value of tue unbn.v.vr.. C-r.e en e,.plan.it:o;i for each "-soa-ent of 1,1,e fvaT.if,, used for tae eidai.on of */'e ua'ar.O'VTi. Include a sssrih ealcu- laiion. si.';)-by-.3,V'p. explaining the an- er. The values shall be expre.sed to tha appropriate number of s:. .'ificant figures. If the test provides "other than quatitit.it:1, results, provide an adequ .e description o expe :ted results. (10) Limit..iion . : the procedure: In clude a stale went of hrmtations of the procedure. Stale known extrinsic fact, rs or interfering substances affecting re suits. If furti'.er testing, either more spe cific o" more sensitive, is indicated in all cases wh-Te certain results are obtained, the need for the additional test shall be stated. (11; Expected values: State the range(s) of expected values as obtained with the product from studies of various papulations. Indicate how the ranye(s) was established and identify the popula- tion(s) on which it was established. (12) Specific performance cv ...acter- istics: Include, as appropriate, informa tion describing such things as accuracy, precision, specir.city, and sensitivity. These shall be related to a generally ac cepted method using biological speci mens from normal and abnormal popula tions. Include a statement summarizing the data upon which the specific per formance characteristics are based. (13) .Bibliography: Include pertinent references keyed to the test. (14) Name and place of business of manufacturer, packer, or distributor. (13) Date of issuance of the last re vision of the labeling identified as such. (c) A shipment or other delivery of an in vitro diagnostic product shall be ex empt from the requirements of paraftraplis (a) and (b) of this section and from a standard promulgated pursuant to this part provided the following con ditions are met: (1) For a product in the laboratory re search phase of development, and not represented as an effective in vitro diag nostic product, all labeling bears the statement, prominently placed: "For Re search Use Only. Not for use in diagnoAie procedures." (2) For a product being shipped or delivered for product testing prior to full commercial marketing (eg., for u.,e on FEDERAL RCGBTiR, VOL. 38, MO. 50--THURSDAY, MARCH 15, 1973 ASI-PR 0001666 7IC0 i *pi fimens e'er:'. ed from human1, to cc:n- p.tin: U`v! u!:.,-.'S Of tno prov.u.-t with other prottit'-tor p-ccc, hires which ore ur ciuT'mt n.-o or recogni, rd nr, u...-;,TiU , oil V :rs the ; tutem'-n;, proml- l'i oily pise, q- "For Inii Uso CA.,. Thefi r:'" me no-.' Lb.uaer m.'-,t:cv, of th:, yn'mu I: - not be a." e.-tr '.<!' hud " (3) Tfi.;. pw 11 iii.'i',!]"- d'-l winy umAr >,,,. egra,,:: of tins serf!. u ;i: 'll is;: oof to (rw 1 DA a voti- li'. rimt .ruck : iirirorf; ure Im.ng II'r,i . of) YAffiin CO dm. s at tor the first cmn- n"ii. oil Mupmeut of at; m uro du1 gno:;[io [,; l . I: to L, the rev, on ra ' lung o',,,''' chip - meat a,J:-a11 MibT.ii. the miurme.t.nn ;c- quhed by fin? Drug I.i-tmg Act ns pro- vid. a in S 102 5 of tine ciuniter (d) The labeling of ;crjrr.! purpo.-e labm-Amy reagents (eg.. hydrochloric e.r,d' ;:ml < e 2 , rent Tubes and PUK-Ifes) v,ho.,e tiros are generally kr.r-'.-n by psr'oni, trained in their ure need ot beer t.h" directions for use required oy 5 167, '2 (a) mi cl (b), if their label ins meets the requirements of this para graph. (1) The lad 1 of a reagent shall bear the following informal ion: (i) The piopnetarv name and estab lished name (common or usual name', If any, of the reagent, (n) A declaration, of the established name (common or auial name', if any. and quantity, proportion or concentra tion ot the reagent ingredient (e.g., hy drochloric acid: Formula weignt 39 43, assay 3 i 9 percent, specific gravity 1 192 at 60" F.); and for a it '.pent, derived from biological material, the source and where applicable a measure of its activity. The quantity, proportion, concentration or activity shall be stated in the system gen erally used and recognized by the in tended user (eg., metric, international units, etc.'. (iii) A statement of the purdy and quality of the reagent, including a quan titative declaration of any impurities present. The requirement for this infor mation m-.y be met by a statement of conform: with a generally recognized and gencudly available standard which contains the same information (eg., those established by the A.merican Chcm-eul Society, U S Pharmacopeia, National Formulary. National Research Council). (iv) A statement of warnings or pre cautions for users as established in the regulations contained in Part 191 of this ch: liter and any other warnings appro priate to the hazard, presented by the product.; and a statement "For Labora tory Use" (v) Appropriate storage instructions adequate to protect the stability of the product. V/heil applicable, these instruc tions shall include such information, as conditions of tcmpeinlurt', light, humid ity. and other pertinent factors. The basis for such information shall be deter mined by reliable, meaningful. and spe cific test methods such as those described in Si 123,12 of this chapter. (v 11 A dc' lara.tion of the net quantity of content.;, e.xpi owed in terms of weight frtRSS AND r.3G'JLA7:ONS or volume, -"mnuicr.l count, or any cnmb.a; 1 tva of d'e.tj or other terms shuck ac'":1 ;.te!;. re,diet tile ccrd ents of the ptv.'.'u. ' The u.u? of me rib dee'y.;;1 ions is c;i(i .iny'd, wh'.-e'.er r.npron: in' a. (v.ri N. m a:'" place o; buime.-s cf man.hack;o r, r. ; w, or cm/.ributor. irrMio '"logi'-s and '.chi '-r."e v...: r:,f. =. the m2 I'c.i'g and : e urn nr b:si,. c; p re po, id st,uu;a:d ; and chirr r;..fi. d ;s...:- terx us cistern.:..oil by the Co.:'.-a.. p. rer. (c) 'firq'h'.f lor injur,naron i: 1 t meat. When ver a no-,; standard .s ;o do;"loped, the Comma.-'., nsr p:>- A lot o- (o.diA i.un.'eer, : "enti- hrii a noti-'e in the Fsssa.a rrs:.;:.,; ficc . - : c, -hum i1"ir it m pu .,.ch to lcguejt'.ng tiic sabsii-aor. of :di ;r,f.. r- dele:thm c^moiL'ie manufa.ctu.mg m ition, ciuto. :)',i 1ji.vs riA`, ms So g lit,ten. r.f the pre uet. sps-edie pioU'c cln.s for r-.i.-.,- or.i (lit) In the cm e of immediate con tainer.; too '-mall or o;Iu;; a; c unable to tice'Oiv.mo' fe a label e ith stibA'i-iu eoaae to m-sr ah such informafion. rued which arc pacbriyed within an outer contamer from which they are removed tor u:c, tile iniormiitior! required by para graphs (b)(2), (b)(3), (b)(4), (b)(5), and (b' (7) of tide ;ec( ton may appear in the outer container labeling only. (2) The i.d.,el of c: neial purpose I mb-- oratoiy feev^ant (c.g., a hca'-er or a pipetieh .snail bear a sdvt-'inent adaquafely deicribhiy the product, it; cmposition, and phy.-icU characteristics if necessary for its pre.'-r use. e.vduaJ.iou. Any int'-e-tsd p'-rs,.n r.my submit coirunMits and h.f'vss on any mat te - niavant to the ri.:,.o!.'j::v.r c: she stondaid. 1 xis-;ict.zi'g the factor.-, reysred by paragraph <a> of tins sca.st.'i, ha ae con'gdvred by the Comma.-dsiier Tfi.a format for such submit non cat,.' he r;te," :icd by the nature of the uhtzrmati.c'. co bs' ..ubuilrF'd. Ar.y t redsss p=rforma.uce ir.fo-rr.aticn submitted ahali relate to th" per/ermance c: that product as market'<1 or vatendcrl for mrvshet.ug. For information submiitexi bv n manu facturer of a product jrhic.h wdl be affc-ctea bv the stanslard, tfi.e specific jircduc: information requested and the format for su.b-mssior. shall be as de 167.3 FrO'-cihire for cM.iblidtin-, scribed 1 -low unless changed in the Fr.u- iimraibn^ or repealing ftiindurd*. eiial Rt cistEti notice. The tirr." a.dotted. (a.) Be;sis /or stundCTds r ad arnilcbie cpnrr 'his to dev'top-- s'r.mi-.rds. Win-' er in the judgment of the Commi-s t tai esto.blishraen: of a product class ; .andard is necessary to reduce or ehmr.ate unreasonable rKc of illness or injury a.-sociatod with exposure to or me of an in vitro diagnostic product and there are no other more practicable means to protect the public from such risk, lie may propose such a standard. In proposing a product class standard he shall consider, and publish in the Fude.".al RMCiSTEt findings on, the degree of risk or injury associated with the use of the product, the availability of informa tion relating to the sciences upon which the products or their uses are based, the approximate number of products subject to the standard, the medical need for the products, and the probable effect of the standard upon the utility, cost, or avail ability of the product, and available means of achieving the objective of the standard with a minimal disruption of supply and of reasonable manufacturing and other commercial practices. Three procedures are available for developing product class standards and may bs pro posed on the initiative of the Commis sioner or by petition of Interested per sons: (l) An exlstm; standard may bo utilized, <2) lntctexted persons outside of the Food and Drug Administration may develop a proposed standard or (3) the Food and Drug Administration may develop the standard. If a petition Is filed by an interested person, it shall be in `he foim prescribed in 5 2 65 of this chanter with the number of copies speci fied therein. for submission will ordinarily be VO days. Four comes of the information and data on any iroduct within the seritmated class si, -U be submitted, indexed, and bound. (1) Name of product class and date of Pros rax. Register statement. (2) Pron-ietary name of product. (3) Nan,,; of person responsible for submission. (4) Intended use or uses of the prod uct. (5) A statement categorizing the pro cedure (e.g., qualitative or quantitative*. (6) Copies of label and ail other labe'mg under which product is currently marketed or, for xi proposed pre-duct, the label and all other labeling under which marketing is intended, (7) Description of the product, as appropriate: For example, if the prcductis or includes a reagent, state the pro prietary name and established name (common or usual name,, if any, and quantity, propoi.ion, or concentration of each reaAive, catalytic, or inactive mgreuient. Tf the product is a biological material, list the source .and a me-.sure of its activity. Include a statement o: any purification or treatment required for U'-e. If the product is or includes an in strument or equipment, descr.be as ap propriate its use or functions, installa tion procedures and any spet-ial require ments, principle of operating instruc tions, calibration' procedures inciuam? materials and/or equipment tc* be used, operation precautions and limitations, hfitiu'dx, and service and maintenance in.-i,ructions. <) Stability information: A descrip tion of, ami data derived from, studies of <b) Advisor'/ committee. An advisory the stability of the product. For any coinnuUve oi qualified experts shall he product that requires manip'i'a'.'.cn Cv g.. appointed to advise the Food and Drug icconstitution or rnixir.g), sfr.bfitv data Admin;, tration on the priorities for es- shall be described for the reconstituted tabh-Umg product class standards, the or mixed product. Describe the m'.'.rr.j by scientific bnvs for hi vitro (iia'grostlc which the information was developed- pioduits, tiie selection of reference The data shah be for the product in tire FIDEa/A REGISTER, VOL 3 0, MO SO--TfiimoAr, MARCH 15, 1973 ASI-PR 0001667 RVi-ES AND hZCULA7;CN3 7101 r')utaii' jr in v 1 !, m *: '"ctiei to rr>- (111) I.i'c.'.t1 `on *)f lb* pre-.d i .-* 7:i- c.e v v; ,r. 1 7 `''hh long cind'd .053 A 0* h-.T Li i r In A 1? 1 A `1- tUldo a : `a* :'U 1*. o: be' h: ' : of -1 T1- - Lo stn .n tii; (h, .3 ir. - in I: 1 -,. ct:. , a i ii -e.11 cu` e.b- the - eduie er 1 p; . , '..n.u.on ef e.ie ,fe 's' 1 r.d r, d. s c;1:! f '; ; 1' 1 , - t .1 r o" ! * . d. e' n *, f'n- : h'oA- t: b-'- I 'Vt'cv, . :**, a t -G a* * i or nr hr ' : ' i T:: -* sinmlsi a . hi l`o I-j.Mi h' r>:'c.e TnciO'ic a :: Y > ft -, - Ir 'nm i . ;p , r. - mi : , ::: or !ii ; i-'- 1'" ..IV'O )[\ ]> >'L"0'a c! 'h: inch r.,,p ,o: r, r v i >* nr: ' ami .. s . 1 mg ip 1 iv a*,. >, ..'t'- rv to a :.r.-` IlC- t Cl.' t! * '.'ii:..:il none.' all * l. V ii "d. , ,, in ; . *h- imi r* ..rhh. " of r- - ul p 1 ' \ ( ` * L [ * j Ou'icl D ' ellb-'t:-10 , 1 7- Stam * ii.:- ( 1 ; m; e 1w -v A'r lilt* p.'op o' u e 1 C'- 11 5- ' '!1j l ry `"ns tin- p: live or ,s .* y tip, ;, il: -- 4; ir l h:e c:'.:s. o- ' h " ; f h`i'' , 1: .lie hum.id y twee: .eg u i : .. irbe.-j.-pi; 1,.T hi; t tl.e [,*;- i'lC. 1 to 05 - (D) jr 1 my:'; to t.-i 4 * A ,l tr :t n t of by fun ru ydy ewxrux; . A oh.,; o;; h : n so at tin hi:e V " :ji r\ . , i , , v, A Iv !;: j b ; .v pph Tf a ;uoImw jiroU ; - L .1 Lr*., y h 'i \\\r Ml l,J : .OA- c.o il'.'c ho or i nrv te.,t i., ;r. i.'hi-l ,n {['.*. ` All- 1.a.id u:..y me! Lhio, ry t o a. oICC t; -j a ecu l 'V < &. . to to h: .in 1 " iie eye' " j - C'f c"'y ui ii- ' ;u tv, the ;rl;*v'.e:i .or :he o: i(__*hA..1. mn.,.d'..n[ :.A h ; i. " a or c 111 i ), . ih*. ad huo'ul 1 .ot snail he stem.; nub o : .. tC., hi :A Live a ii; *-;r:.n of Lhe 11 - -'i to h!' i* ! : i th' 'j i ul A .. i: v subun.y. i to 1 p" J-t U J > chic. ; A J.Sjm: , Lr.Aioh, :n L '*1 i i :r, i; ; i'll OI T1I.J ch.e.g'r (Li) i`r' .-oiy fh ni ' .in.lobjgy: .\ hi 1l hi., ir;v` t ' J, LiiO iYiL`; 'n: i ,io ip, v, ii ii [ o r> rtj'.l r ,'hj' t [Kfi^ . All u- icrcnics to '"15 or' :*rl . i r h o r un: iv oriole c `'xChvf'o wiih r.hi' tY o. I. Y.:t or the proccil;.ir-.1 on whi-h u .i; ho: ch i-h: J1 ini iru-i'e.led. If tivi \r: oduct pros 'du' e i S ! 1 ' V 1 1 ` m i; [i-S one vli'.ch Iffi j publi !:;vd, cits' t'.s re f'.r- cuvc. If tkiti P'X1 duct i; b . ngi on a ri: ndl- f.calio'i of a publish?'! proceed; e, cue the reference, state the re'.sou for and the nature of lb; moduiratiou and th.e Gleet Mich inadiucalion rr/iy hne'e on the re sults of the procedure as compart'd to the oria.ual. Inc'.ud'* data iiii'.,ua ting the comp l:i.,on of til? UnGiued ptoey- dure to to; original proeeuuie. (11) Print ip'a of test. An explanation of the test procedure includin'; tut* chem ical, physical, p esc * ujloss's 1, or biological principle of the procedure v.itu chemical icjctloisi and techniques involved, if applicable. (12) Specimen collection and prepa (Iii Ifr-;;' eev; oi c'ydm-,: In "hub-' sli avaliable ama, yfliejui or unoxbk. 'wl, which siiiiuor' ; or x; cup ; of tiu; pic.1uct or it: p; need mm. imelixst d,L;.i tor bob: normal and abnormal aubj-cts and a dejcri'juon of the population or popula tion.. sii.si.su. Stale, lor (veil claim: u) Laboiui;; churri. (ii) Dacb-jround documentation: Pro vide a bibliography and rcpnr.ts of all PC;:'rmr.t reieronoeu. (in) Procedure usc-d for collecting evidence for claim, (iv) Description of stedis1 ical protocol. (v) Description of jam riling p: ocedure. (vi) Summary of raw results in tabular form. (vn> Analysis of results, (uu) statement of iuterp:elation of result:;. (T7) Summary of scientific basis of procedure: A summary of the* data and v icys setting forth the scientific latunale and purpose of toe product, and the sci entific basis for the corvliisiun rhat the* product has or as not been proven ac .. .an.' ' jiihcAy rcqii-ivsi of C..'? (--:c.v:>z r: ::h. the Com::.h.- - hoo", .Y.y ; nn.is'.dar : .-.hi- uc: (pt. inch a r.cmi-*: n.vnt, upon a sro.v mg tirii II.; .ranufacturer :m: t.em- on.-'rai.-i sum com-.jiency in t".-e pco- (iU'1'1 a of tii.Li pro-due--, in iomuinance vvitn tiic regml,cns, as u, adeq'iaje to iiisu.c the accuracy and reliability of r>--Lilto, and ` h; Commus-uoner i.i'ddl rs- vo :e the ivnuircmeut of iiiur vnnril lot testing under the .standard when it : -:<j lo*i eg nccc-sary to trie cxcuracy and rc- Lmbdlry of the results of the procure; ciisj covered by the staudaid. Any in- tfcstcd ix-tson may. within GO days after publication of the proposed stand ard in the F DuarsTca. file written comments c me propos.-d, in quintunli- cate, with ti'o Hearing Clerk. Depart ment of Health, Education, and Welfare, Room G-83. 5500 Fishers Lane. P.ockville. AID 20358. Comments may be accom panied by a memorandum or brief m support thereof. All comments may be reviewed at the Office of th.e Hearing ration: A description of the specim.1"' `m he subjected to analysis: (0 Hprcii'd w coutions regarding specimen collection.-,, including special preparation of th.e pa tient as it bears on the validity of the test. curate and rep-m.e f. r its intended tut*;. If them is an absence of controlled stud ies in the material submitted, an expl.mation as to any such studies are not considered necessary shall be included. (13) If the submission is by a manu Cleik dui-ng regular working hours, Monday through Friday. (f) Referral to an independent ad visory committaa. The Conmsv.ocer may, in his discretion, refer a proposal under paragraph (e) of tins section to (::) Additives, pre'ervativep tic., nec facturer, a statement sigr.ed by the per an independent advisory committee of essary to maintain the integrity of the son responsible for sue"' submission, that experts qualified in the subject matter specimen. (iii) Known interfering substances and their effect on the procedure and results. (iv) Appropriate storage, handling or sliioning instructions. (13) Procedure: A detailed, step-by- step descrip::ion of the Test procedure tiom reception of th.e specimen to obt?.a::p of re-nits, including any points that may be useful in improving r :ci- sion and .iccnracy. Clive the exact de.ails of cahb; ation. Identify reference mate riel. D',civic preparation of reference cam >!a u ' of blanhs, etc. Include a fleseuipi im h mo I nod , JO be used m deter mining U o standard curve. (11' Results: Explain tiic proci dure for calculati..; the v.buc* oi the unknown Give an >'yil.v. a*ion of each component of the lorrr.ula u ,_d pr the calcul *.t:on of the ur.know n Incliaic a siuno':; calcu lation. .vep-bv--.p-p, explaining (he an swer. Value.. ..hou;d bo ed to the appropriate number of ..igrufp ant II mrcs. Provide `-he ha. 1 m tv dualion of non- c,uauti'ah e te-h s> -ups. to the best of his km ledge it includes unfavorable information as well as any favorable information, known to him per tinent to an evaluation of the perform ance of the product. Thus, if any type of scientific data is submitted, a balanced submission of favorable and unfavorable data must be submitted. The came would be true of any other pertinent data o: information submitted, such .vs consumer surveys or marketing results, (d> Reuijio and evaluation. Any exist ing standard or petition for a product cli.vs standard, to letner with any infor mation and comments submitted .Pur suant to a published r.okce, v.ill be re viewed and evaluated by in; I-ood and Ding AJirunistrahon in consultation with its advisory committee and t.ie center for Disease Coihiol. (e) FviyjO.ied pro'luat clans standard. When the Con;ini.-..ion;r has concluded that the criteria in paragraph hi) of this .-action arc* met and ine uinarmajion mailable h *-s be'ii rev levied mid found to justify the e-dn-blisiunoi-.t of a product class sran.dard, lie shall publish in the Finer,in ltim.Tsii a proposed piodnot at issue, for a report and rccommv'dations with respect to any matter involved in such proposal which involves the cxerci:S of scientific judgment. Th.e Comnv.sioner shall designate the chair man of each panel. The independent ad visory committee may consult any per son irv connection with the matter re ferred to it. Any interested persen may request, in writing, an opportunity to PiCom.t oral views to the committee. Amy interested perron may present written data ami views which shall be consid ered by the committee. The full rtport(s) of the committee and summary minutes of its meetings shall be made avahable upon request after submhsion of the report(s) to the Commissioner. (g) Final product class standard. After reviewing ail comments received hi response to the proposal and consid ering Al available relevant information, the I end and Drug Administration, m con uiitution vvitli its advisory comiuittee and the Center for Disease Control, and after consideration of any repoih of an independent advisory committee ii the tkDigAi xzgi:tec, voi, 33, no. so-- thuisoav, match 15, 1973 fc*g. nhwytm ASI-PR 0001668 'i-iviHArr 1CJ RU.SS AND iat:o; ' ninvoivil ha; bam. ro refsr-cd, u ..i pul ' Ji 1 11 l tin; Fi!.'." :, U, a ia re a fir/J C-'ll'.T h- dnwj a pro- PK:t d\: sirv:. :..rd. r; : ord'r sh.di s`c in ibe Tt tV' ai r i 5; r ; > L'1,.a -,-ydrg the pp act Cl. i f t Ulffi' 1 d .'i<i tire date the 11 'nd- UJ 1 ii;,v. * e 1. cv live. (h 1 p, to a Inriid or rcpcVl ; tr.'ni cue 'lu'i ffi.r. a v.,.- r may pis, ce e to ' ,d or ic i 1 a-y sir uwaul ,. tab .1 pa > this procedure or any 11r i : Pi! j`.r i.:;y po'ikon th-e LSsa'i- Vil '> awr tire ;.h r.ciio'i. A. ] 'ji.tun ct furl ; l r-' action r.'tiles; cd anti :i tiv!r.dcd st; ' ::>. lu i up; urt of the cr l'.' a.I'm r i \u , of tiu- i a.t. ",n, the G, r.-r ir.r y deny pet ition if Iv; ii:;wl; a la : i >f vero or.uble sun b'ort or }*>t` :r, !-bI.Ga a props, id am-.-: '.dm cut (*i Ov r ap-ul of the erta bluhod start!.1 a. m lire Fans'su. Urcczorpc if lire- qua- sup; art has '.yen P--- anted Tbs peution . hail is; in the form cpoeified m 5 2 t;;> of ih.-- chapter with the number of c'-5 a.rd ether information as tpsci- fnrti vh'-mn. A new dru ; appLc.-fion. sub- mu. ed for an :n vitro d.-airnosac product which does nos comply whin r.n appli cable effective product citm; ruanaarri will be considered as a petition to amend the it,, dark. TV ikons for repeal or amend ment for which reaaone.bie support has been furnished \u!i bo handled punuar.t to the procedures established in para graphs (e)-<g) of this section. 107.1 <l'Tifulr .lijlity of submitted infomi.uUm. (a) Data and information submitted pursuant to the provisions of 5 167.3 or 5 107.2(c) and fillin': wdhin the con fidentiality pren .oils of 13 U.3 C. 1505 or 21 U.S C. 331 (j) .shall be treated as confidential by the rood and Drug Ad ministration and any consultant to whom. It is referred. Confidentiality of informa tion will be determined m accordance with the provision.! of Part 4 of this chapter. (b) Data and information submitted pursuant to 3 167 3 in connection with the establishment, amendment or repeal of a product class standard will be made publicly available at the Office of the If: ' i " ' i: of the Fso,'.! mi! Drug ir .ji: ':. *. 50 da- i a: tor ; ubi's;,, s.n of r. pro;s ! J a : 'icz cia; ; : tii'Kisi d, cau..,: to r ( ? uu.. oi L:. U'U; err . , I,f s p.!iy d 'i c>n:::;. or ctlur .'cl buhl or i"f:rr ,ai ion, <r oil :r c,.; *1,1. l! ii\! il :o ''i. >n to the r,-.- tail tl: ,t the " > ,r "a ; it Ii Or. ,i.rs 1 : r../'/ .* .:;*/ ; fail . v. i'ja '< - C11 y pa..-.' : - u r'i Tb C. 1595 Ci -1 'm J MKji. 5 If'7.7 (l i< i* ' d. Tl - ' a r.l'ir' :ri, a! pictwi'- <1 '. ihue ti';.iI o. im'ia ,, ,s i.osl r.<" V-V l;;1 ,.n.n fjOin wii s'., as .',! is's to i!'.C cc Tt' 0 i < 'll and D-u : Au- rnii"'*: \,.i: rcj: ' S' (.oniro'.oat-on of :G: ur.jv-,''. j in ;* 0 1J01irt. b'poii u; rt appeal, tric C cm mi:, iono]r, at h's ci: xce- t;on, ir.s.v auiy c. roctrve c:ior pain or n;! of I ra st.uua.rd pclH hr,7 aspfc.ai end fu'.ai court r.u.udicr.t.ion, ;rr.d may c .tab- lirh. a uen c- Lit-'' ;liter ur.al com t ac.j S i r,7.r, ru `'on. Amy in vitro dicumortic product is sub ject to regulatory sekuu if It fails to conform to an applicable product class standard or the general labeling require ments of 3 1S7.2. If the product 2; a de vice, it is adulterated in '.iolation of 1 ac tion 59! and it is misbranded m vio" on of section 392 ot the act. If the prow is a drug, it Li in violation ot section ..ho a,i well ns sections 301 and 392 of the act. If the product is a biological. It is in vio lation of sections 501, 502, and 505 of the Federal Food. Drug, and Cosmetic Act and section 231 of the Public Health Service Act. Deviations from an. estcuiji.:ked standard rtiav be justified only by an amendment to the standard. Compli ance with this part shall be deemed to con.-tmite compliance witn the labeling and new drug requirements of the act and with the labeling and licensing re quirements of seci ion 351 of the Public Health Service Act, unless the Commis sioner otherwise Informs the manufac turer or distributor of an in vitro diag nostic product of additional requirements imposed pursuant to either statute In order to protect the public health. 31 I <77.7 G-vrral mp:ir,wj,,-rN f, r insn. v (.!. lv.r*w- -.sis,i (Ji irt \ii-u lii-ipiu'-W:.- praffi, 1-. <a' n.`~'-"tirri:c. -1 r.n-l p.-v's-Z Aliy per on win, own; or r -r.-.cs civ eshfoTJ-nr,. at, c i.c ini.l m tl r 'uiuc- ti.re. pronoration, ccrn.mrtinmror i .-;.c- es. of an in v.uro < a:, t:c-!.;c prewri she ;ld register sail v-ras.u-rnam!; arc list taih pioducfoi m r.cror;,..r.r? v.rh the pro -dures c tab!irked unvsr irt 13" of th'i ch:,p>.r. Any cu-h ertabu. ti re ,t net currcnrly ihouia r1 cuter vv.th.n 30 da;.s of me e!:ecftve date ot ilia, r^Tilat.ou Any . m:h ettah- 1:-limitat rurrenriy ion. isrca r; a crus: csic.bli.v.incnt shall at Tim r.:s period for rucyi' Won use me c a :connate r^gk-trat.on form indicating that it is a producer of in v;r,,-0 ci.a--niij;.ie predicts. P.cgistrcnoii forms mav be co'amed from tie D`pertinent of Hearth, If'ideation, c.r.u Y/ert'nre, Food a: . Drill .ttmims- trr.tlon, 5350 Fishers Lone, P.cciViiie. 2.1D 25S52, or at any Food and Drug Admin istration district office. Uegiatratlon. arid ffi.tin:: do not constitute an ?.h mission. or larreement or cieterm nation that a prod uct is a "drug-" witnm the meaning of section 231(g) of tile act. (b) Compliance with good mamifac-- iman.? practices. In v itro diagnostic proa- - nets chart be manufactured m accordance with current gcod manufacturing prac tices. Tiie principles m* -blishcd m Part- 133 of this chapter, Drugs; Current Good Manufacturing ictice in Manu facturing Processing, ichir.y, or Hold- - lug", shuuld be follow d an a. guideline. Effective date. This ordm shall be ef fective on March 15, 1973, except that 5 167.2 (a), tbk and (d> shall be effective on March 15, 1974, and f 157.2(0 shall be effective on September 17,1073. (Swcs. 201, SOI, 502, 5C5, 508, 510, 701; 50 ShUt 1040-10 id, as nmetidod, I043-IQ51, os amene ed, I05J, Ha i-uceiided. lOSS, m amended. 10*X, as .amended; 21 US.C. 321, 331, 332, 353. 338,. 3S0, 371) Dated: March 12, 1973. Charles C. Edwarss, Commissioner of Food and Drugs. IFR Dcc.73-5C57 Filed 3-14-73;8:43 am] fEDcRAl RECI7TER, VOL. 33, NO. SO--THURSDAY, MARCH 15, 1973 asI-PR 0001669