1!1!12
`
`CHAPTER 84
`
`ylene oxide or rndi11l,ion ~l:(•l'iliiuti<.111 m1\)' bQ employQd !'or
`l,he empty <:<mtuiJH!f wil.h imbBequenl, fu10J)ti(; J'illinr,i. How(cid:173)
`evel', carnful (Wahuil.i(m of the re11idm1a !'rom othylene oxide
`(illd t heir p1Jt-1mh11l l.oxk t•ffoct 1mu~l- b<• 11nd(!l't1,kon.
`Bc1:1rn6t• of l-h1• rclut;ively new u$1'l of pl11aik mnhil'ial~ for
`pucka1~i ng ~t<!rihl J>rl!f)urntions, conllid<~robl(l i.1wl\11l:i1it1ti(1ll iA
`1:11-ill n•quired concerni11g potlmti11I int.er1H\tion11 and other
`problemB Uml; m1w be enco\mt,Or(ld,
`l•'(lr f\11•Uwr det.11il8 ao<,
`Chnpter 1:10.
`
`Glass
`Gl11B8 i!I cmploy<id 1)6 tho contllinor material of choice for
`I~ io compoAcd µl'incipally of 11ilicou dio)((cid:173)
`moHt injtict:ionH.
`ide with voryin~ u1111)\ml.!/ of (,thor oxiclcis l!uch al! sodium,
`1>otuHsium, calcium, m11gnl.!aium, 14luminum, boron and iron.
`'l'h<? ho!iic strnct.urul network ( if l{l!IM ik formed by the Kilicon
`oxide tetrnhcdron. Boric ox.id<~ will 1m(.(1r intc, thii1 11t1·uc ..
`ture, bu1; m"11t of the ot;hcr oxidm, do llOI:.
`'l'he luU.<Jr 11ro only
`lo()1rnly bound, arc pregcnt in the mit,work int<m~ticca 111\d l.ll'O
`rol~\tivcly free to migrnte. Thcac migl'l\tm'y oxides m t(\' be
`IMchod into o solution in contact with the i;l11~~. purticularl.y
`during the increased reactivity of t,hcrmnl ::iterilizt1tfon. The
`(»dde~ lhu$ di1111(1lvocl may hydrolyze to raise the pH of the
`1,oh1tio11, 1:ut:1\ly:,.e nio.ctionl.l (II' ontcr into t·co.etions. In l\
`manner oe y<lt 1111<:erlnin, a<mrn gl1.1ri11 c()mpound11 will ho at ..
`tu1:ked by t>olution6 1md, in time, dislodge iclu1111 fl11l<oH into
`t,he $Olo1,ion. Di$1,urbing fflll<:l:i()nlJ i,u()h m; Urnao, howovr.r,
`can be n:iinirnii.cd by ~hti 1>ro1>et a<1lMlion oft.ho glllali cc,mpr)•
`liitiOl\,Hl
`Typo11 ... ~ Th~ USP ha::i 11ictcd il1 1,hi~ 11elllct.ivo by 1>1·ovidi1111
`a clasaificatioi1 of glues; 11c1mely,
`'l'_ypc I, u lloro:,Hic11u, 1(lin\S,
`'f'y110 II, 11 R<Kl11-limo tmnied tl11HR,
`Type JIJ, 1) $111.li.1,llm" "'''"'·
`Nl', • •odn-limn KIUHA not ~11itnblo l'or t·.ontni ,11.,rn for pnrcnlorul11.
`'rype I i:lm\9 iB composed 1>1·incipully of silicon dioxide and
`l)orir. oxide, with low levels of the 11onnetwork-for111ing ox(cid:173)
`idos. It iH n chcmic111ly resistont i:la!ls (low ltmchnbility) also
`h1wing o low thermCLI coefficient of cxponaion.
`'l'ypa11 II llnd III glaRs compounds aro compo~ed of rela(cid:173)
`(.ivdy hi!{h -proportioni; of aodium oxide ond calcium oxide.
`'l'hi11 mnlrns tho glnAR chomiclllly le!l$ rcsiAto11l. Both types
`melt ttt II l1,w11r tem1H11·uu1r(1, m·e Maior t (> mold into w1rious
`shar>eB 1md hiwe tt higher thcrnlnl <:o~l'ficic.nt c,f (1x1>11n,;ion
`tlum 'l'ype l. While th\lfc iti m) ooe !il,unda1•d formulation for
`glil!!s among 111anufi1cl.urc1'1i of thotse USP t,y1><1 <:>.1t~gMios,
`Type II 1~lnH11 m1uully h111:1 a low~r 11oncentn\t.ion of t.l,e mir,l'O·
`tory ()X)dCll than Type m..
`Ill t1dditi<m, 'l'ype ll httl! b(!l)ll
`treated under controlled tempcrnture £Ind humidity coudi(cid:173)
`tions with sulfur dioxide to doullrnliie tJie int:tirnul surfac1~ (lf
`the container. While it remuin!I intru:t., this 9Urfoce will
`inc1·euse substanti11lly the chemical resist-once of Uie ~lna11,
`However, rcpcolcd oxpoNures to storilizlltion nnd ollmlinu
`do1,<,1·rient11 will brcnk down this donlkoli2ed imrfocc ond ex•
`p,w, the sodn,lilmi compound. Thoi·oforo, 'f:ypo II gin~~
`cont1tin«rn may he conr;idered t:o bl! <►frefoiivoly 1Nod chcmi•
`en! r<'liji11tonr!ll for only 01w 0110.
`The glua1J lyJ>CA nrc dllt.<mnined from t:hc r\lijultH (J( tW(>
`USP t;eHtis:
`t:h() Powdorod Glu11s Test.and t.ha Wnt<,r Mtnck
`Test. The latter is used only fo.r 'l'ype Il gl11t1ij 11nd ill per(cid:173)
`forrned Oil (,he wholo cont.oinor, bcca\1se of tho dealkalized
`~urface; thti former fa performed <ln powdered gluHs, which
`exposes inlernnl Hurfa<:Ofl of tho i;lmu; conwound. The re·
`suits arc hosed UJ>on the am(l\Ult of 11ll11,li titrntr:d by 0.02 N
`sulfuric ncid after an auto<:lnving cyclo with !:hr. alu!IB allmple
`in contRct wit,h 11 high-purit.y distilled wuter.
`Care must, be utiCld ill sele<:ti1,g 1:ho gln:11s typo to h1.1 (t~<1d for
`n pnrticuhn· injectuble pro<hH~I;, In genoml, 'l'ypo I gl,111\1 will
`
`be suitBblc for 1111 1>roduct,1:1, nlthou1:1h Bllll\ir dioxide trMt(cid:173)
`menl is iiomcl.ime~ utt1•d for u fortht!l' im:rt!t1i.e iu re1Ji1:1\:umic.
`Been use cost mw~t be c<m11i<fored, o,w of t;ht! other lei,~ 11)(pt111-
`~ivc typo~ mny be ncctipt11hle. 'l'yJlc 11 r,ht1,~ m11y bti Huit.ublc,
`for exomple, for ll :mlutfon which i!J buffered, lws n r>H below
`7 or is not rollCt:ivc with the glo118. Typt! Ill 1:h1ijt< mrnully will
`be nuitublo pl'incipully for tmhydrnus Jiq\cid1:1 or dry 1:1ub(cid:173)
`HI.JJ.nccs.
`Physical Ch11rnctcristics--•"Exnm1>les of t.hc physictd
`uhnpo of gJa,;~ nmpuh1 o.nd vinls nre illustrnted in f<'iK 84-:~.
`Commercially nvnilnblfl c,,ntllinm·1; vory in ~izo from 0.5 to
`l.000 mL. Sizea up to JOO mL •MY bo oht~incd 11s llmpuls
`and vinls, nnd lilq{l/f i:ii~.as !l!l O()~tlC➔1:1,
`'l'hl'! ln(Jfll' MC u,:;cd
`ntostly for intr11vcmc1os 1ll1d irrigt1!:.ing $l)h1t.i1)11>1. Smiillm·
`i;i:1.ea m·c-. ollso ovailahlc a11 curtridi;1;t<. Ampul1111i1d (:M\,ridt;w,
`m·o dt·.nwn from gh111B tubing. The 11Jm1ller vi1:1h11nny h<~ m1,de
`by molding or from t,ubing. Lnr/ICf viulK um! hol:llc~ nm
`mn<ll.l only by tn1)ldinl{, Conl11i11crs mudc by drnwing tubing
`oru HlH1ernlly opti11nlly clci11rm· 11nd httvc n lhin11er wall thnn
`n,vld<1d contnin(lri, (f!<lO l•'ig 1:14.:~). Molded containern o.re
`uniform in oxwrn11l dimcms:iiona, k tron{(t1r rmcl honvier.
`l•:n~y-opening 11mpula th,it pem1it 1;hc.1 \IAOr l<1 breok off the
`ti1> nt. the neck constriction without the u~e ol' n file 11re
`inarketecl under tho n11mor. Col<ll'•Brr.nk (l(imb/11) nnd
`8(:(1r<1-Urct1lc ( Wheaton). An oxomplc of o modification of
`container doi,ign to mMt 11 t>llrtic11l111· 1100d i!l thll double-(cid:173)
`chambered vh1I, under Lh0 Mmo Univi11l ( Uniufr,l), ck,;ignod
`to contnin 1.1 1'1'(1(111.c,-driC!d produi;t in tlw lowor nnd nolvcmt in
`the upper chamber, Othor l!Ju.onpl(!i, aro.i wid11-mn11Lh am(cid:173)
`puls with ifot or round0d bot.tom!! to foc:ilil.o1.r: filling with
`dry mntorinla or SuHJ)OnBiooi;, and v,iriorn'I modificnti<ma of
`the co1tridrco fo1· \Ille wit.h di1:11Jo11obhJ d08JlJ1<• \tnii~.
`Gl11s:-1 contnimm, muij t be 1:1t.w11g 1inou1,h \.o wit:l>lii<Uld t.he
`physical shocl111 of hundlin8 11nd 11hippin1( 1111d l;h<i vre&il\11'(!
`differentials Lhnt dev~.Jop, pnrt:iculurly durin11 the Aut:oduvc
`~tm·ilir.ntion cycle. They 1JH1ijl, be t,ble to withl!tnnd 1,hc
`thormnl shock rc!!ultinn from lnrgo temperature ch1111gcij
`during proccsl!ing, for exnmplc, when the hot bottle and
`contont!I RrD axpoao<l to room o.ir at t hll end of the 8terilizn•
`tion cyclo. Thol'efore, a glnas hnvinr: a low coeffici~nt of
`thormnl expnnaic.m i11 noceMs111·y.
`'l'ho contninor nlso must be
`lrnnap1mml to permit in~poction of tho contents.
`Proparati<Hlk which 11ro li1tht-,am11itivo must ho prntocl:cd
`by plucin~ them in omh11r gl111>s c<>ntninoriJ (>1· by encloi;ing
`fJi11 t glan6 cont.11inem in vp1\qw: c11rt;o)1~ lubol,id 14 rcm1\in on
`the coutaincr clurill[! t.he period of 111:1c. Sili1:0M (:01.1tings 111·11
`ijOllWt.ilne1:1 t\f)[llfod !;<) 1:onttlin\l!r1:1 to pJ:oducrJ u hydrophohi,i
`ijllfftlcc O.ij 1.1 metlflij 1>f 1·cthaii111i Mlhtit'l:!m,1➔ of' 1-1 lwtwy, t:11~1h
`
`1110 04<l. V11rlouu typos o/ 11mpul~ itn<l multlple-dosn vial~ for
`paronternlr. (COllrl08Y, Kl111bla).
`
`FRESENIUS EXHIBIT 1013
`Page 361 of 408
`
`

`

`l!llilJ)on11ion or the: frictfon of 11 rubhcr-tip of 11 ,;yrin/(Cl r1h1111.1 •
`er.
`'l'ho tJhm oftJintM-do11c contui11er11 ill limii!Jd to 1000 mL by
`the USP ~111d 11111ltiplt1-1lrnl(\ co11(J1it1cr11
`(A> :{() ml., unlc,;,;
`i.iut.c1d <1therwi11CJ in n l}1u·ticul11r nwnogrnph, Mult;it)lt,-doi,c
`vinls ur<i limil<'rd in size to rcdu<,c the number of punctlll'OiJ
`for wi1.hdrmvin1{ doscm 1111d t,he 11ccc1mw1nyin" rillk of c:011-
`t11111in11t.io11 of tho c:ontcml!!. A1:1 the mt11H:1 implicm, aingl<i(cid:173)
`do~c cont,11i11({l's tire <>pcncd with nscpt;i<: rn11·c and 1:hc ,,011-
`tenl-S o~<id 111.onr. time. Th<!!l\! >mty 1·t111gc1 in siz(', from 1000·
`ml, bou.1(,1; (.o 1-mL 01· lcc1ll ampub, vi11l1:1 or llyri1111cm.
`'l'hu
`int<il!)'ity of tho container i11 dc:it.roycd whcm opened i,o t,hut
`the contt1i11er c11nnot he closed 11g11in.
`A nmH.iple•do1<0 contuimir is dciiif'ned l)O thnt more 1·,hn11
`one dostl c11.11 be withdrnwn al difforont tim.oi;, the cont11in<ll'
`m11intt1i11ing 11 a(iul botwocn u9011.
`lt!!hcmld he evident that
`with full 11septk pror.nution;;, including 11t,orilo syringo und
`nocdle for withdrawing tlrn do!l0 1)nd disinfoction of t:hc ex·
`posod surface of the doil\1n:, t.hcrn ill ,;till n 11ubatt.mtinl riHk of
`introdud1111 co11t41mi1111ti111~ 111k1·oori:in11ii,:mH imd virui;ci; into
`tho co11t.cmt11 of t,)Hi vinl. H11111111,,c of thill l'i~lt, the USP
`rcquil'cs thrit 1111 n111l f,jphH.l•i1,u: vinls must c,1111.l\in 1.111 1mt.i ..
`hr1d.crinl 11~<lllt. Hom~1•<1r, Ui<itri iN 110 cffo<;1.iv1, ,rnt.ivirnl
`ogcnt nvuilnble for ~\lch l•tii:.
`'l'hcrofoni, 111 Jlpit<-1 of t he
`nclvnnt~1r;c• of flexibility ul' doa1\g<, provi<fod thu phyAicir-m hy
`o rnultip(e .. do:1c vi1.1l, the t((Nltm smfcl,y nf l!i111;ll)-d11A1\, ,fo;.
`1w;inbl1: nclminintrnt.iou m1it,!;l l111<, c1111scd thtlir \U}~l lO inm·1u1~11
`l'll))idly clurinl{ l'ccent, y,mn;.
`
`Rubber Closures
`
`In order t() perniit intr<idudion <>f n needle from 11 hy1>0•
`dcrmic ~yl'i111~1, int.o n mulliplo-close villl aud 1m)Vi<lc1 fOl'
`re11011lh1K M 110011 111;1 th(l 11c0dlc ii; withdrawn, t1ad, vi11l is
`i.onlcd wiUi n n.1bbo1· d111111ro h11lcl in pince hy 11n alv111i1111m
`bond. l~igure 84-1 illuetrlltl.l8 how this is done. ')'hi~ princi•
`pie 11lso i!! folle>wed ror $ingle-clo11<: containers of the Clit'(.ridg11
`type, except t.h!1t, Uu'll'I/. i11 only o ~illf!IC int1·och1<:ti•.111 of tlrn
`nocdlc lo make p<,>'!l'<iblC'. the withdrnw11I Vl' C)l'.l)\1l$ion of the
`conlenl.:1.
`H.ubh1:.r c)oijtJ 1'0" or<1 cnmpormcl of 11twor11I iil(<i·odicmt.,;, tho
`tlt'i11111ry OIi(\~ bcin!J nolmlll rnbbtlr (llltl\X), n i;ynl.lwt.ic poly(cid:173)
`mer 01· n comhinolion of Urnsc. 01.111~r illi;l'<idi@tfi include n
`vuk11ni1.i111; ngonl,, u,mully sulfur; 1111 11cc,~lorni.1w, onc-1 of ~t!V •
`ernl 11ct.iv..,, ll>'l(lmic compc11m<h1 1:1ud1 UH 2-m111·t11pt.ol.1cn1.o-(cid:173)
`thim:olc; till 11ctiv1lt•il', uutwlly ~.inc (1i.:id1i; fill(mi, rmch 11~
`cnrbon blul:lt or lim"sf.on<! 1111d vnl'iorn; o!,h11t ii)t(N!di(mt~ ~nch
`n~ nn timddun tri nncl luhric11nt11.
`'J.'Jw1.1e 11rc c<m1r1mmdod (.().
`gethcr und \,hon vulcuni7.cd int.he desired ~hl\p<!, moldn!' use
`or molds \llldcr hi1th 1m::i:mrc ,md t,cmpe.r1it;oro.
`Rubber do~urc~ musl, have sufficient clllijtidt.y to provide
`n Hnug fit hctwefilll them ond the li1> nnd nc,ck of the vi,,l 1111d
`must i;priug buck to close tilll hole mnde by Urn ne<1dlil imm11-
`
`PAl~f.:NTF.H/\k PRF.l' ARA TIONS
`
`1553
`
`l I
`
`l1xto11d(l(l view ol $et(l1in9 cornpoM1lts for II moltlpl<M.10~1,1
`Flo 64-4.
`vh1I (COuftli~Y. WMI).
`.
`
`dintely on withch:awnl. Thty mm1t, not, bC! no html that !,hey
`m·c highly rcsi:itunl, to thr, i1w,rtio11 of the ncecllc, 1md t.lwy
`must 1101; fru11m.<m1, at1 th<, hollow nu<idlo IHIM~1:~ thrmlt(h
`th<m1. Idctllly, Urny 1i'ho11ld h(i <iom1>let,ely nonrcnt;Uvo wii.h
`th<: ,:iolutioll t1nd it.~ in1:rcdiem,; :llld ~hould provide 1;1 colll·
`plet,i bnrricr to vupor tr11118fol'.
`'J'ho:rn q11aliti,,~ ore not per(cid:173)
`JI, i~,
`foclly mcL by any rubber compound l)ow 1.1V1\ilobki.
`f.hcm:forc, ci:mmtiul to det,crmine the ,:ompatibility n11d p,ir(cid:173)
`fomrnnce diaructeJ'ii,tt,,i<;i; of em:h 1·ubh(ir com1lmmd to b,!
`11sod, 11
`In adclit.iol\ t.o ~he phwicnl t:{11,ts of C1l11~1.idty, hnrdne1Jij,
`frllf:mcntu.t ion tmd vnpvr tri1n~for, do~urc,; ,;houlcl be cx(cid:173)
`posod t~l tlw prochwt fo)' J)l'(il:\Cr iht!d JH)tiodK of' l.imo at <le::1ig-
`11nted temperat,un: and hmnidit.y cl)t1diti@1;.
`'l'hc effect; on
`tho product of extrt\ct:ivei; frnm ~he l'llbhm· compound or loll~
`elf i11/!l'C~lieutr:< from t.hc, prmhwt Lo tlrn clo~urc 8ho11ld he
`d<it.ennim,d tlnul.vtkolly. Phy~i,io<;homk11l and toxic:olo1>i•
`cnl test~ for ev11Juutin11 n1hbo1· closuro~ nrc described i11 the
`USP.
`The physical nhnpo of Hc)lll(t t:ypicol clo~urcij nrny bl! ,;e(m in
`Fir.: 84-4. Moat or f,ht,lll hnv<l O lip nnd I\ p1·ot.n1din11 fltUll,lO
`thnt ox tends into 1:IHi ll(lCk of t:he vi11l m· bot.tl~i. M1mv dii,k
`clmmre~ are bc,i111;: \1,;wl now, 1111rliculnl'ly in t.hc hil(h:,:;pr11.1d
`p11clm1tin1~ of urHibiotici;. Slotted do~ur(ii; Ul'!! used 011
`frnezc -dricd J.m\du<:l,11 f.11 m11lrn iL po::1:;ibh, I,«> irnH,irl. the do(cid:173)
`~lll'C ptu'I. wuy 1111,() tl1r. oMlc of. the vi«I clm'ing tho drying
`ph1uie of th<i cycle, Purti11I ln~urlion provid,,;s *'IIIIC prntcc(cid:173)
`t.ion from cont11mii>ot.lon while pcrmit.t.ing wntcr vaJ>ot' to
`c~1cnpe from t:hc dryin1: product. Tim pl,mgcr f.y1>c i~ used t,o
`ueul one end t\f II Ctll'~i·idgc. At the timo of use, I.he 1>lunr,cr
`expel~ th<• p,•odo<:t by o noodlo hrnert:ed l,h1·ot1~h U1e closmc
`at the di11t.nl end of the c11rtrid1;<.\.
`l11\rn11m1<lus 1:1ol11tion
`clo11m'eij ofl,e11 hovo pcrmnncnt holct1 for 11daptt•.1·i; of 11dmin ..
`lst1·ut;io11 i;etij; irri1~ot.inn Aolution clo8111'Cll usui,lly nre de•
`:iiV,11('.d for pouring.
`
`i I
`I : 1 ii
`I
`
`i
`i
`
`Production Facilities
`I.ho 11scpti<: nron, the qunrn ntine 111·M nnd 1.hc !'ini~hinr, or
`A prod\lct. hnvin(< componl.!l\t8 of the best qualil,)' quickly
`mny become totally un11<,ceptahle if t.ho environment in
`1}11clrn1:in1t ,u·cn. All of these ijJ\011lcl be dciii1;n~id nod con(cid:173)
`structod for dc11ni111~ euse, 11ppropri(lf.c enviroum(u1t11I con(cid:173)
`which it, jij pr~ic:e~11(1CI ii; contumiouted or if U11i ruunut'MLllr•
`trol, efficient opcrntion t111d plH·ijo11110J C()Jllft11•1.. Th~ cxtrn
`ing prv<:cdtlTl\ is 11.ot. cnn·it,d out. l)l'opcrly.
`'J'h(H'C!foro, thr,
`1·oquil·emtmts for the aseptic ureu ore dciiig1wd \(l tirovide au
`pro<ll1Ctiim Ci\ciliti0a nud tlui p1·oc:tidure uaed io 1m.it:01is;ing
`the product mut<t moct a~mdnrd,; ndt{(tllt1I~ fo1· Uici l.n;,;k.
`environment wlwrc, fol' exampl(!, nn injoctk)n ,nny be ex(cid:173)
`posed t.o the envil'Onmti11L for~ br.i1if period duJ'ing ijubdivi•-
`The n1l!ll'or t.h(18(➔ ijl11nd11rdt1 app1·01tch perfection, l,h<1 bcLter
`11ion from II bulk co1ltuh1cr to tiHl indivi1hiul-d~1~c tontuinors
`and r.mt(lr 11ho\1ld be the prndt1<:t
`wit.hm1f: becuming cont~unim1t.(id. Contomh11mt~ such ns
`du~t. lint nnd microor,i1utiHIUH normally t1rC/ round flonting in
`th<! nir, lying orl co1>>Hor11 t\ltd othc1: i;1,rf111:11~, oil clothinti 1111d
`body ~urf,1cc1~ (>f pc1rn1m11el, i,1 1,ho exhal(,jd bi·coth of 1>or1;o11-
`'l'h(', d(1ai1(n and coiiLrol of w1
`nol ,md dcprmitocl on t;hc f10~1r.
`
`Arrangemont of Areo
`'rhc production m•c11 .,,m be (:«)llHiclerod in f.orn18 of filltl
`fun(ltiou11I 11rnns: Uw r.lennup uron, tho compmmding uron,
`
`FRESENIUS EXHIBIT 1013
`Page 362 of 408
`
`

`

`1654
`
`Cl-tAi:>TEI~ 8~
`
`<.lt>Ylt"lll .. fl Rt>Oll\
`(Al l l'9tP<>'"· 12 n 101 on<I Loovo I' llllno
`Ato11 Thtou11h Thie Room)
`
`'-.--
`
`r
`
`- - -L . - - - -1A l r1,.<>ck
`
`"-1
`
`Ounllty
`ConHul
`Arou
`
`Stodlo Flllln11 Room
`
`flUl110
`t:lc,iim"(1,\011t
`Ofllcu
`
`.,,_
`0
`C) _,
`
`Oh:posuhlu
`Cflrtl'ldgll Flllillfl
`Hoom (Slurl l6 At'Olll
`
`Artlpul Fillitl(J
`Room {~u,rllo A ron)
`
`$')rvira) Aroo
`
`Storll<l f'lll ln u Ao,,m
`
`s,oti1a Sui,,,u,u: ~nl<ir Har o - - - (cid:173)
`FIil 114 .. !i. Floor 1>IM 01 an asoptlc 11111110 area with Its servico nroo (coortosy, Wyeth).
`
`Air Lu~k
`
`ui1(•ptfo ,~r(,I) i11 dirncu:cl townrd 1,0 reduciug th(I prcAc11cc of
`t.hc11e c11nt:nmin1)nls thnt: they t1re no lo,,ger 11 hoznrd to fl8CP•
`tic fi!li))g. AlU1c,ul(h the n:ieptic cmm mu11~ b,i 1idj11ccnt to
`su1,port. 11to1\8 80 thnt nn efficient flow of compon(mt11 mny be
`achieved, barriN·~ muAt bo provided t.o minimi;1.(, ingrosij of
`contnminant.11 to \.h,, llGet)Uc nrcn. Such a barrier 1118y he n
`scaled partition, oft.on glni;s,pancled for 11reator viiJibiliW
`1md light. An<>tlwr typo of b11nier ia ml <mtrancewny
`tlm.>ugh security doora Lhnt rnquiros passni;e thro\•Hh 1111
`nirlock so desil!ned l.hnt b,)th d<,ors cannot be <>P<>Md at tho
`l"igore 8·1-6 i:how11 nn nrrnnllcrncnt of llijOJ)tk
`i!QlllO time.
`filling rooms with t1dj1we11t, ~upport tiroats.
`Flow Plnn•···ln geno1•nl, th1:1 r.ompononts for a prminternl
`prncluct. flow from th!! 1.1t11dcroom, oithor lo Urn c<1mpo111iding
`11rc11, 118 for illgrcdi<H\Lij ofUu, l'ormuln, or to the clounup 11rett,
`11R for conlniners 11ml equipm,.ml.. Sc(l Fig f14 .. (i for 11 proce~(cid:173)
`flow di11gram. Aft:er proj,ur pn,<:Mf\inf{ in t.he~e nrM~. t:he
`1:omponcnts flow int~, t.he 1:1ocurity of the oncptic t\rc11 for
`l'illing of the pmdm~t. in 11ppmpri11l(1 (:onf:nincrs. From there
`Urn 1>rocl11ct pnssc.s into l.he (jtu1r1rntine urcn where it is held
`until nil neemmary tcsb hRv(l been p(,rformcd. If the prod(cid:173)
`uc:t ia to he sterilh:cd in its fiMl (:ontoiner, the pnss11,ce
`norm1.1lly is interrupted nfter it }eQ'II(,~ U1e nn11ptic nroa for
`i;ub,ioction to the ~tcrilization ptocell!!. Aftor the re:iult:s
`f)'(lm nil tests ore known m1cl the product, h1111 bc!!n found
`ef1'<1ctivo and snfo, it pnK8CS to t.lie fini~hio" lil'll(I for fimd
`lnbelin(l' nnd pncknging. There rue ijOl\let:imM variations
`from thiH flow plan to meet tho specific: needt1 of 1\11 individ(cid:173)
`ual product or to conform to 1.1v11ilable facilities, Automntod
`oporntionr; convey the components from one 11rou to unothl)r
`with little 0 1· no lm11dli11g by operutors.
`...
`
`C:OMf'OUNI)-
`ING ARt;A
`
`ASEPTIC
`~' IL~ING
`Alli.(,\
`
`9TOCMOOOM
`
`CLElll'-l•UI'
`1\11~1\
`
`Sf~llll,11.Al'u,)i'j
`
`-·····1., .. ,. ...... --t---i--
`...
`
`OU/11!/INYll'-li:
`
`-l--- mmAGf.
`
`~~c
`PACKAGING su;1r1PIHO
`ANO
`FINISHING
`
`l"fo 04 .. 6. Proc:tll;ll•flow dl11grn11,.
`
`Clc11nu11 A,..eu- 'l'ho dennup area is construcwd Lo with(cid:173)
`Htnnd moisture, iit.eiun nnd dctcri:ents. The cciHn(1, wnllM,
`nnd 1'11)01· should l,e conijtructcd of impcrvioun mntllriala i,o
`tlrnt moisture wi.11 run of( o.nd not he held, One ol' tho
`"~pr11y-on-tilc" finiJ1IWI! with (I. vinyl m epoxy t1c11ling t\Ollt
`1>rovirlas fl cont.inum,~ ,mrfacc free from 11II hofos or crevi<;(iij.
`All ~\1ch surfnce8 cnn bo w118hed 1lt regular intc1·val8 to koep
`them thorouKhly clean.
`'l'h(i~o aroas 11lwuld he exhao11t.~d
`ade(}\lfl1:oly so that the 00ttt. nnd humidity will he removcid
`for thf) comfort of pcrsomll1l. Pr1:1tisutionA nnuit be taken to
`pl'(lve111: the nccumulation of dirt. and the grnwth of microor(cid:173)
`ti•mi11mH1 OKpoci11lly in the pr1111t•0\!1t \If hi1th humidity 1rnd
`t11~11t. In thh111rca r>repurnt.ion for(.)\() filling operation, 1md1
`tll:I lltl9C1mhli11g oquipmenl;, i8 uridtlrt,ak<nl. Ad(t(l\11.11-0 l!il\k
`rmd ,:oun~r kpncn mu11\. be f)tovid<1d . While thi~ 11re11 clcmtt
`nol, n!lecl l.o ho fl/!opti<:, it mu11t 1,e cl.c111111hlc and kept clMn
`nnd (.he microbial load must bc1 rn()11itor<1d 11nd controlled.
`J>r(1c1mtion~ nlRo must he tnkcn to [)t\\v(!lit deposit of pnrt.i·
`ck\ll or othvr contllminn11t11 on det111 Nlltoiuc,i·u und equip·
`]))(!tit ..
`CQmpounding Arca .. ,,.,In this arM tho f'ormuln i~ com•
`pouuded. Although it iH not es8entiul 1:h111, this orea be
`nseptic, 1:011\.rol over it ~hould be more 11t,ringent th1111 in the
`clemmp t\reu. For exMn1>lo, menn11 may need l;o b~ provided
`to control du11t: genernt.cd from weighing and c<impmmding
`operntions. Cabinet~ tmd c:ountors llhould, 1>t<1£oruhly, be
`'Phey should fi1. Hm1gly to
`constructed of atuinl</ij(; ~t.ooL
`wnllll und othc1· fumituro Ill> th~t thero aro no catch urOCiti for
`'('b~ 1ioilin14, wallA and floor 11hould bo
`dirl to ncc11m1.1\11te.
`com1tructcd similar to tlH>ijl/! ror t,h<, clonnup urea, l~il{\tr<1 84-
`7 illu11trotc:1 1mch tm ruM loc~11tod ndjllceJ)t. to an 111:1epti1;
`fillin111mm.
`
`A,;«ptic A1•<1a
`'l'hi11 arcn requir<Jij i:onstruction foat.ure1' do>1i1.<11od for
`'J.'h() coiling, wall11 nml fl1}0r must he
`mnximum ~ccmit,y,
`sonlod !IC> l,hnt- t.lwy muy bo wnahed and 8fl)li(;i:u,cl with 11
`disinfoctMI,, aa l)(+<odod. All counters :-iht>\dd b<~ c:mistructcd
`of 11tainleijH 8te<1l ,11nd lHmi: from the wnll 111.1 th11I. Uu,re nm no
`logs LO 11ccumulotc<lirt whel'o they rest on t.l\e Oo<,r. All light.
`fixture$, utility ijCl'Vice line$ nud ventilnU(lll fixtures should
`
`FRESENIUS EXHIBIT 1013
`Page 363 of 408
`
`

`

`_T _____________ .. _ .......... -. ....... ,..---·----....... --.. ····-·-.. ---.. --·-········ .. ·• ............. .
`
`. .. ' " " """ " " " '"""" ...... _ ... , ..... , ...
`
`'
`
`f'ARl:NTF.f~/\L Pl~l; PARA TIONS
`
`1665
`
`Air Cl~anlng
`
`'rhe 1.1h· i11 l.h,111e are11H ctm bo ooe of Urn ~re11test; tiourceB of
`cont;1unin11t.ion. It 1,tied not be, however, lwr.1111Me !\(WC!ml
`mulhuuiJ ut(i {lvailahlll for p1·(wir,li1115 d<lnn 1ii1· Urnt iH e~"'<Jll(cid:173)
`til\lly l're<i l'rom dirt. pnrticle1:1 und ,ni1iroorguni11ms.
`'l'o provide $lll;h 11ir, it must b11 ck11111cd Uwrvughly of nil
`'l'hiA m1.1y be clone l)y 11 ~cl'icn of t.rcotmt'!nl~~.
`coll1,iunin1u1ui.
`Air fr1m1 Lho oub1id11 fir11I, iH pm,1~cd through n 1mifilter1 tumol(cid:173)
`~Y of l{IOllli wool, doth or ahr11dded 1>l11~lic, to rem<1110 lnrgc
`purl,idllij, '!'hen it i1;1 lniowd by pi1~~ngC1 f.hrnul(h nn electro•
`,itutfo pr(➔(:ipitof,(1r (S11ppliorH: Am Air, El<wt.ro -Air, St.u.rtc•
`1mn./.). 8uch u \11\it.. il\d\1~1(,.jl ,ui Q.[{!1:l;dc11l chnrg,~ on particle"
`iu tJ1e nir und r(!)'l'l(1V(!l1 them by al;\.r1.1d i,m to oppo8it.dy
`charged plat,e1:1. 'l'h1;1 uir tlwn llllll$1i~ thrmlf{h tho most effi(cid:173)
`cient clenninti device, 11 JmPA (high efficiency p!u-ticult1t.e
`air) filter lmving un ufficie,wy of llt. 111111,1.-90.0'1% in 1·1:mnving
`po1ticles of 0.3 1cm tmd h.11:ger, b111.<ed on the DOP (J)ioclyl
`phtho.lnto) test (Supplier11: Am. Air, Ccuubridi;e, Rnl)il'co,
`Flanders).
`It'or porsonnol comfort, ni1· condit.io11i11g 1md humidity
`conlrol $hould be inool'pornted int.o the 1;1y1:1\;<rn,, A110Urnr
`1:1y£1tom1 t.ho K11thnhar system (Su.r/m:e Cumbw,ti,111), clcmrn
`t;l,11 1tfr of dirt ond micl'Oorgo.nilltnll by ww1hin1; it. in an 1uif;j ..
`11ep1.ic 11otut.io11 nnd, at the 8Umo time, wntrollj Uw h11midif,y.
`Thtl denn, 1111cptic nir iR introduced into t,he 11~ept.ic 1Jrctl Md
`m11in1.11i1u11l un<l<ir po8itivc pre~tl11rn1 whi1:h J)t1ivontij oot~id(i
`uir fr()t11 r\lllhing int.1'> I.he ll!!Cpt.ic nrtln l:11r1)UP,;h 1:r11dc11, !.(ilnJ)<J·
`rnrily upon dooru or other opcninr,s.
`JAUllhuo•-Ji'low 1<:11vironmcntll--· .. ,Thc required (s11viro11-
`lllOJlt:11l control of 11Bllpti1: nrcns h11s been m11de po8llibfo by
`the U6<1 of hunhim•-flow onclosm·e,;.
`l,1unit11.1r t1il'l'l◊w prc.>(cid:173)
`vidc11 ti tot:1ll 11W(!C!J) or o confined nrca becimsc 1:he entire btidy
`of uir moYOij wid1 011if<)rm velocity 11long pnrallol lines, ori1{i(cid:173)
`uating t.hr◊llffh II lllWA filu,1· or,e;11pying 0110 ont.ir<l side of
`the confimid nn111.
`'J' hercfore, it. ho~hcs the lot.nl 11rc11 wil,h
`very cl(!tlll 1:1ir, $WCoping aw11y co11t.111niuants.
`'l'hti 1ur1mg<fmen\. fi>r ~he dil'cction of L1idlow c1111 he hol'i(cid:173)
`:t.0ntt1l (~ec l<'it~ 81 -0) or vorticol (kc~ Fig 84-1.0), and nrny
`involVl! 1dimited 1:1,·oo 11uch 11s II wol'khcnch or an cntirn room.
`The effoctiw air viilo<:i\.y ill cnnsidored t.o he 90 ± 20 ft/min.
`ft. lnll8L be bOnl(I in mind th,·,t cauy co11imni11at.ion intro(cid:173)
`duced opatreiun by 1~quiprnc,n1;, orn•1f! of I.ho op1·!rotor or k•uki;
`iu thCI fihlw will be hl<>w11 clown1<tro11m. Jn lhc in,;Lnnco of
`IH>J·i:r.ont;11l now thill lltllY bo to I.he cri ticnl workinll ~itc, the
`fuce of t.lrn of)et11tor \Ir 1,1cr<)s~ f:h o room. Should the rnntnm(cid:173)
`immt bet, for c,xnmplo, penicillin powdor or viohlo mkroor-
`
`l'lg U4-7. Vlow from lh<! :lcl1vlco arm} wllh piptithig ll)IJChlni:1 /IO(l
`1;toc1<-ti ollif.l rolr,loocl o,1lslll<• <ii mo fj:;optl<: fllllnu ,m.a (courtrti;y,
`Wy1,11h).
`
`be r (it~l:ij~\!d in t.lw woll!\ m· @ili111i t.u tdimill(ltc lccl)!e~, jointB
`11ncl ot.l1()r lvc11t.ion$ f(ir the ncct1111ulnt.io11 ol' duut 11n<l dirt ..
`AB much M p<>Mihlo, 1-nnlrn contuining tho com1>oundod
`prodm:t, 11h1H1ld rem1lill ot1t.:1id~ l,hc 1.111<)pti<: filling nron 111ul
`I.lie 1>ro<h1c1. fod inl.<l the 111·011 t hrout:h holio lincB. 1-'igme !l4•
`8 ff.hows ~•.1d1 1111 nmmgcment;, Mecht1nic;11l l·ltlllipmont thnt:
`mui;t. be Joc11tNl i11 the; ll~C\J>tk ut1111 11h()11ld be housed 11~
`r.omplot.e.ly o~ poi;~ihlc within 11 alah1kw,-1JL0Hl cnhinet in
`ordo1· t <.> 11<~11.l ~h,: 1,,pc,rnti11g part~ nnd t;h(!ir dirt-producing
`1111d H<:cum ul11Lini: t,.mdoncioll from th\! 111:<er,tic 01wironmont.
`Mecl.11mic11I p,,i·I-.>< thot will cont-11c1·. t.l1c pt1r!l11u,rol product
`iihould be do,noontohk ~o \,hat. \,hey cu11 b<i 1;1t.11rililwd.
`Porttomwl 1;1nLori11g tlrn m,;eptic 11rM ijhmild ont.cl' only
`;l'h<-:y 11ll()uld be o ttir(!d it\ f.ltol'ilo cover•
`through 1111 ~1irlo(:k,
`oils witJi i;tcrilt: hal.$!, mMks mid fo<>t cov1m1. Movomont
`within \.lw n >o111 ,ilwuld he minin111I tllld in-::md•out move•
`mcnl; ri1tidly rni:i(;J'i(:tod clurin11 n filli nri 1ma:<iduro. 'rhc 1•c,
`quinmumll< for mnm prcp11ml.io11 jjl)(I ~he l)(lrijo1mol mny be
`rcli1xcd ijomewh::it ii' tho pl'Ocluct ill to b ti tt(,\!riliiod in o i:1c1.1lod
`110nt11ilwr. ~ome nm convi11cm.l, h,,wcv(1r, tlial. it. i,:; bettor t.o
`h1Wt\ one i;t nndiml (lroCC,\dUrt! nrntltill8 Uu~ moi:;t. rigid rcq11i1·e•·
`mcnt.:,.
`
`11£1>A FILTER
`
`·
`
`, ... l•llO!f.CllVE SCRIEN
`
`·--.l .............. ,. ..... / ........ , ........ .
`'00'?.,:.?,!
`.. -.. ···-··--···-"
`f' .....
`l; . ··~
`I
`' AIR FlOW
`
`I
`I
`
`Flo 04, ll. Pro~ucl lillr11tlon lrMI tho 11soptlc t:lt1glno room throuoh n
`Into tt,a 1~HOptic 1111100 roo,n (c;o11rlew. Tho Unlvarslty of
`f)Or1
`'fo1111osso0 ('.ollHgo or Phur11111oy).
`
`Fig 84-9. Horlzolll;;1l l,1111innr-Uow worltbtl1lch (corn·tosy, u<l,)pt1-di1111.
`Sondlo).
`
`lllOWER.
`
`..
`
`FRESENIUS EXHIBIT 1013
`Page 364 of 408
`
`

`

`.
`
`·.
`
`()LOWER
`
`PLMHC Cull'rAIN
`
`► ~ ~), 6nr~T r . -I . ·~ ..
`· _:: .. : .. _ ! i i ! l l l i
`I I 1 1 I 1'
`I I
`I I
`hi i i c\\ I I
`;:::1.-~~~ -· •. 'i i
`(
`I I
`J Jli
`I I 1
`I l
`I I
`I I
`~--
`_\._.}
`
`1556
`
`CHAPTl;R 84
`
`PkbfltHK ~
`
`HfPA FILTERS
`
`- ___ ,NN- • - - - A
`
`r,,.,,;, /&~ Q • .
`
`'
`
`w,
`
`,,..
`
`f
`
`AIR HOW
`
`\
`/
`
`4 4•····
`
`ftOOI(
`l~lg 04- 10. Vertical I11mlllt1f•lfow portable room with Oquipm~ntanct
`op1m1tor$ (courtesy, 1;1d11pl1-.1tion, Sandia).
`
`i:uni~ms, the dmn(or iR ap))nront. For opl.'.m~ion11 involvinl!
`Kuch co11tnmi1111nkl u vcrUCl)l sy11tcm. ill much lll(U'(l dm;irnhlo,
`with the 11ir fl owing thrn111{h porfol'Utiom in Ui~ 1)0\lllttmop
`or through rr.lurn louvers at floor level, whl:\rl! it con be
`directed for decoi,tllminiition. Vertical flow hufl btwn rec(cid:173)
`ommended for ~torility-tc>.Sting p1·ocodurcij.
`Lominnr•flow ctwironmont& provide well-controlled worl!
`n1·01.m only if proper 1>rec11utiorni arc observed. Ally ~ir cur•
`rents or movemen~~ llXCOBCJi1114 the vclocit.y of the HRPA(cid:173)
`filterncl nirflow muy in~r(ld\1co contamination, m1 mny c(11111h(cid:173)
`i11g, 1·euchi11g or <>(,her mnnipulnt.ions of oper11tur1:1.
`Therefore, hunil\llr-lfow WOl'k nreos should b~ prot()ctod
`by b<•ing l<m1t,ed within r.ontrollcd envirommint,i. J>er1um-
`111l1 prefurubly 1:1ho11ld b,; ottir(:d for nsepti<: pi·o,ie1111i11g llfl
`described bt,low. All movomr.ntK and proce11~1~$ Hh0\1ld be
`plnmrnd curufully l.u ovoid the introduct;ion of C()ll(Jllllinn(cid:173)
`tion up,;t:reum of \.he criticul work Ul'en. Chocktt of t.he ,1ir(cid:173)
`etreum t1lumld l,.,.. perf',1r111ed initially nnd at reg\llur i11i,1,v11l1<
`to be sure no h.,ol<~ havo devtllopod through or arm111d Urn
`HgPA filt,erH.
`'l'hiK ciln be done most effectively wi\;h eloc:(cid:173)
`t.ronic purti<:lo counter~ {SllJ>plierll: Air ?'ccl111iq1ws, Cli(cid:173)
`m.et, Mel One, P<1rl,icl!! M1nw1,1.r,'.ng, Royco).
`In the m11m1l'nd.ur1i of puronl.ornls, conventional cle11n(cid:173)
`room focilitiea fr<•(Jttc11tly 11re anJ>plcmcnted by w rt,icnl l11m(cid:173)
`inar-nirflow mo<h1l1:1i11111~p~1,(led 1,1.bovc critic11l !lites, Buch l\i,
`'l'hca!l cril,ical OJ>on:,,tions thereby are bathed
`fillin(,( lines.
`witb HEPA•filterod 11ir to provide, ox:tro pl'otc1ction for the
`l)l'Odu,:t.
`L11mir111r flow of HBPA-l'ilt.ored (Iii' should meet, !;he st1m·
`di1rd for 11 Class 100 de1m room f1a dofincd by Fedel'III Sttin•
`d,1rd 209C,>~ which 1.11.,11.011 thntauch 1111 CJwh-omncnlconu.1in~
`no more than 1()0 purUclcs per cu ft of 0.5 ,um 1\1\d litrger ~i1-:c.
`Convcntio1111l dea11 ,oomi1 would be of a lcHacr degree of
`donnlincH11, Klu:h 11~ Cl,tAA 10,000, ddined on 1,h(• lllllltll bn11k
`'!'his 11tuudurd hl\lJ btought order int.o dol'inillt,; dl.!111\ rooms
`nnd provid.,..d a ,_,ommon bn~ii, fol' !;heir dM~l'ipLio11.
`Wo1•kh,,nd1011 tmd other t.ypci!.I of lnmi111ir-f!ow enclosures
`1mi 11vnil11hlc from 11evcrul (1(>1)'111um:i,1l 1101n·co,c (Supplier1.1:
`
`Air C1mtrol, Atm.<)11· 'l'<Ich, Dahi!r, Controlled /!;IWil'<11rnumt,
`Enu,:rco, Flcw.<fon, O,mn.{rce, Lamina.ire, l,,:l),i,·ty, Vetio,
`Wcbc:r).
`
`Ultraviolet Radiation
`
`Ult.raviohH, (UV) light r11ya h11ve nu 1\111.ibi\<:tl'lri11I act.ion,
`thereby producing o diRinfcctant 1tction ol\ dinir.tly inndi•
`11tcd :mrfocca. Since thcnc rny:i t!llmwt 1>~Mtrnto most mu•
`tcl'ials, only a 1c1urfnr.e i,ffoct is produced, wit,h t.ho principal
`1txcoptio11 bcillfl limit(!d ponetration thrnugb llir Mid pu1·0
`wntor. UV light ray"' t.rnvol in .11trnighl linm.1 only; tlwrcforc,
`objor.t:a i11 tho pnth of the lii,ht. boom will cl.\Bl ~lrndowa with n
`re1c1ult11111. )fl.ck of irrocliat.io11 in tho uhndow area.
`UV rnyk nrc il'ril:utinK l~l tJic fikin ,md, pnrt.it:ulud.v, lho
`ey<!IJ of hltmon bein1:1tt, Thcl'Ofor<!, l)vl'KOauml in tlw n•·litl t>f
`inndi11t.ion mrn1t be pr<1tect(1d from dirnct oxpo11urc1.
`UV lmnpi:: lllllY be i1111t,nlled 60 att t.o provide oit lrnr dire(it 01
`indirt•ct. rc1dintion. Direct irmdi11Liou of 11 mom wht•n ptir(cid:173)
`:ion.ncl «r~ not. prcacmi jg a v1.1l11ubll:! mwrn~ of 1·edm:i11,; th()
`buct.erial ctnml. on working llutf111:H~ 11nd Ooorii. LampN in(cid:173)
`stull.ecl nbov~ )l(lod lovl1I, HO t:h11t: J)\11'1Jo1m11I pt'Ollont: 111·c not.
`in11dil1f..ed, tifl tl irrndinw dl'culutiul{ 11ir l,o l'\!d11<:1: t.lw micrn·
`binl lcvel con1.i11uou!!ly d11l'ing proce~1:1ing.
`Locul irmdit1tion n111y be usi:ful iu hood-t,ypc fixtur@, over
`filling imd ol,hor p1·occ~tJ operations, within l11r1ic·1 ~i Ol'llltC
`tnnks or in !\ti)' J.)lnco where nddilional pr()t.f:(.'1.io11 from ctin·
`taminntion iH l11H1dcd, provided any prod\ict J>l'llhent i!. 1.101,
`nffccted advcmily by UV rays. UV lmnp~ u~uolly nre nol
`employed in conj,mction with lmninnr-ffow l'ncilit:icfl be,
`cou11e the Hlsl:'A-l'iltorcd 11fr sweep~ cxpo~ed ~urf'ncca dcun
`and the 11ir it,8elf 11ow,; \.M foi;L fol' oclcqm\te Jel,h1.tl irrncliotion
`(1f microorgnnismM being coniod in the nir stream.
`'l'ho bcHI; pmcf,icul ~ourec of UV li1!hl r.ay1:1 ii; 1.h,~ cold-
`1:nthode mercury vapor l11mp. 'l'his lomp emit~ t\ hi11h pro(cid:173)
`portion of rndin1:ion oi t.hc 2fi:l.7 nm wnvelcngt.h. A ~pcwinl
`gl11m1 is 11:1•1<1 for l,h e tuhc~ tin thnt. tho myH will JHl~H L,, lhc
`out;,;id<i. Thi:i glm:1H gmduillly will change in oryst4d 1:11.1·m:.
`LU re with m;e HO t.lHII, J.>Hi;fli•f!((1 ,-,f U!Cl ruys i111trmhmlly ri.,du1!,>.cl.
`Such lumps, t.hcnifol'li, rornly hum out. r.1~ do vi11ibl<1-li1<hl
`lamp~ hutgmdt11dly 1·011<:h nn mniR11ion levl'.I whit:h ii:1 inoffr.(! ..
`t.ivo. These l11mpa nlHO mu1:11. be lttpt. clc11n, for d\11:1l 1111d
`It. ge11or(cid:173)
`J¥rco,130 will lower !,hr. efl'l.i<:l.iw1 mn isMion ct rostlc111ly.
`l)Jly iK i.totcd that trn inndiHtivn intensity of 20 1,w/1;in:l h1
`rnquirnd for effect.iv~ mJt.ib11ctnri11l octivil.y.
`
`Mainlenanco of the Aseptic Aroa
`bnport,\nl, o~poct.~ in tlm 1,mil,wl ot 1,11virn11111cnt.al <.:OIi·
`t11n1inuti(ln in the 11gcptic m·Nt nrc hou1Jl1kti1ipi11g nnd muint,t,(cid:173)
`nance. 'l'hcll(l Hhould not be done in II h11ph11Mi-d tnmlll(H' by
`tho genert1l ,n(lintcnonce crcw,:1, but. rnihol' hy crew!! giviin
`special inst.ruction rmd ,mdcl' the 1mpervii;ion of pn1"1:101mcl
`trained in tho 1:111·0 of tmch 1ucaij. In t{encrnl, clc1rnin1( 1md
`mai11t.en11nc(, ahonld be done 1ifter thl>' Mlll))IC\tio)l of thc
`day's worli with t1n i11torvnl of quiet..\ide b()fol'o the begi.1111i1111
`of anol,her t\ll()ptic oporntion. Wit,h t.he nclvcnt of lmniniu·
`flow of HEPA-filtQ1·ccl 11h- the rigora of <:lonnin1: h11vc beeu
`roducect