21 CFR Part 606 - Current Good Manufacturing Practice For Blood and Blood Components

Current as of April 1, 2005 Subpart A - General Provisions

Sec. 606.3 Definitions.

Subpart

- !r"ani#ation an$ Personnel

606.20 Personnel.

Subpart C - Plant an$ %acilities

606.&0 %acilities.

Subpart D - '(uip)ent
606.60 '(uip)ent. 606.65 Supplies an$ rea"ents.

Subpart ' - *+eserve$, Subpart % - Pro$uction an$ Process Controls

606.100 Stan$ar$ operatin" proce$ures. 606.110 Plateletp-eresis, leu.ap-eresis, an$ plas)ap-eresis.

Subpart G - %inis-e$ Pro$uct Control

606.120 /abelin", "eneral re(uire)ents. 606.121 Container label. 606.122 0nstruction circular.

Subpart 1 - /aborator2 Controls

606.1&0 /aborator2 controls. 606.151 Co)patibilit2 testin".

Subpart 0 - +ecor$s an$ +eports

606.160 +ecor$s. 606.165 Distribution an$ receipt3 proce$ures an$ recor$s. 606.140 A$verse reaction file. 606.141 +eportin" of pro$uct $eviations b2 license$ )anufacturers, unlicense$ re"istere$ bloo$ establis-)ents, an$ transfusion services. A561!+0678 21 5.S.C. 321, 331, 351, 352, 355, 360, 3609, 341, 34&3 &2 5.S.C. 216, 262, 263a, 26&. S!5+C'8 &0 %+ 53532, :ov. 1;, 1<45, unless ot-er=ise note$.

Subpart

- General Pro!isions

"606#$ %efinitions#
As use$ in t-is part8 >a? Blood )eans =-ole bloo$ collecte$ fro) a sin"le $onor an$ processe$ eit-er for transfusion or furt-er )anufacturin". >b? Unit )eans t-e volu)e of bloo$ or one of its co)ponents in a suitable volu)e of anticoa"ulant obtaine$ fro) a sin"le collection of bloo$ fro) one $onor. >c? Component )eans t-at part of a sin"le-$onor@s bloo$ separate$ b2 p-2sical or )ec-anical )eans. >$? Plasma for further manufacturing )eans t-at li(ui$ portion of bloo$ separate$ an$ use$ as )aterial to prepare anot-er pro$uct. >e? Plasmapheresis )eans t-e proce$ure in =-ic- bloo$ is re)ove$ fro) t-e $onor, t-e plas)a is separate$ fro) t-e for)e$ ele)ents an$ at least t-e re$ bloo$ cells are returne$ to t-e $onor. >f? Plateletpheresis )eans t-e proce$ure in =-ic- bloo$ is re)ove$ fro) a $onor, a platelet concentrate is separate$, an$ t-e re)ainin" for)e$ ele)ents are returne$ to t-e $onor alon" =it- a portion of t-e resi$ual plas)a. >"? Leukapheresis )eans t-e proce$ure in =-ic- bloo$ is re)ove$ fro) t-e $onor, a leu.oc2te concentrate is separate$, an$ t-e re)ainin" for)e$ ele)ents an$ resi$ual plas)a are returne$ to t-e $onor. >-? Facilities )eans an2 area use$ for t-e collection, processin", co)patibilit2 testin", stora"e or $istribution of bloo$ an$ bloo$ co)ponents. >i? Processing )eans an2 proce$ure e)plo2e$ after collection an$ before co)patibilit2 testin" of bloo$ an$ inclu$es t-e i$entification of a unit of $onor bloo$, t-e preparation of co)ponents fro) suc- unit of $onor bloo$, serolo"ical testin", labelin" an$ associate$ recor$.eepin". >9? Compatibility testing )eans t-e proce$ures perfor)e$ to establis- t-e )atc-in" of a $onorAs bloo$ or bloo$ co)ponents =it- t-at of a potential recipient. >.? Distributed )eans8

>1? 6-e bloo$ or bloo$ co)ponents -ave left t-e control of t-e license$ )anufacturer, unlicense$ re"istere$ bloo$ establis-)ent, or transfusion service3 or >2? 6-e license$ )anufacturer -as provi$e$ Source Plas)a or an2 ot-er bloo$ co)ponent for use in t-e )anufacture of a license$ biolo"ical pro$uct. >l? Control )eans -avin" responsibilit2 for )aintainin" t-e continue$ safet2, purit2, an$ potenc2 of t-e pro$uct an$ for co)pliance =it- applicable pro$uct an$ establis-)ent stan$ar$s, an$ for co)pliance =it- current "oo$ )anufacturin" practices. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at 6& %+ &5340, Au". 1<, 1<<<3 65 %+ 66635, :ov. 4, 20003 66 %+ 1;35, Ban. 10, 20013 66 %+ &0;;<, Au". 6, 2001,

Subpart B - &rgani'ation and Personnel

"606#20 Personnel#
>a? *+eserve$, >b? 6-e personnel responsible for t-e collection, processin", co)patibilit2 testin", stora"e or $istribution of bloo$ or bloo$ co)ponents s-all be a$e(uate in nu)ber, e$ucational bac."roun$, trainin", an$ eCperience, inclu$in" professional trainin" as necessar2, or co)bination t-ereof, to assure co)petent perfor)ance of t-eir assi"ne$ functions, an$ to ensure t-at t-e final pro$uct -as t-e safet2, purit2, potenc2, i$entit2 an$ effectiveness it purports or is represente$ to possess. All personnel s-all -ave capabilities co))ensurate =it- t-eir assi"ne$ functions, a t-orou"un$erstan$in" of t-e proce$ures or control operations t-e2 perfor), t-e necessar2 trainin" or eCperience, an$ a$e(uate infor)ation concernin" t-e application of pertinent provisions of t-is part to t-eir respective functions. >c? Persons =-ose presence can a$versel2 affect t-e safet2 an$ purit2 of t-e pro$ucts s-all be eCclu$e$ fro) areas =-ere t-e collection, processin", co)patibilit2 testin", stora"e or $istribution of bloo$ or bloo$ co)ponents is con$ucte$. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at &< %+ 23;33, Bune ;, 1<;&3 55 %+ 1101&, Dar. 26, 1<<03 62 %+ 5353;, !ct. 15, 1<<4,

Subpart C - Plant and Facilities

"606#(0 Facilities#
%acilities s-all be )aintaine$ in a clean an$ or$erl2 )anner, an$ s-all be of suitable si#e, construction an$ location to facilitate a$e(uate cleanin", )aintenance an$ proper operations. 6-e facilities s-all8 >a? Provi$e a$e(uate space for t-e follo=in" =-en applicable8 >1? Private an$ accurate eCa)inations of in$ivi$uals to $eter)ine t-eir suitabilit2 as bloo$ $onors. >2? 6-e =it-$ra=al of bloo$ fro) $onors =it- )ini)al ris. of conta)ination, or eCposure to activities an$ e(uip)ent unrelate$ to bloo$ collection.

>3? 6-e stora"e of bloo$ or bloo$ co)ponents pen$in" co)pletion of tests. >&? 6-e (uarantine stora"e of bloo$ or bloo$ co)ponents in a $esi"nate$ location pen$in" repetition of t-ose tests t-at initiall2 "ave (uestionable serolo"ical results. >5? 6-e stora"e of finis-e$ pro$ucts prior to $istribution. >6? 6-e (uarantine stora"e, -an$lin" an$ $isposition of pro$ucts an$ rea"ents not suitable for use. >4? 6-e or$erl2 collection, processin", co)patibilit2 testin", stora"e an$ $istribution of bloo$ an$ bloo$ co)ponents to prevent conta)ination. >;? 6-e a$e(uate an$ proper perfor)ance of all steps in plas)ap-eresis, plateletp-eresis an$ leu.ap-eresis proce$ures. ><? 6-e or$erl2 con$uction of all pac.a"in", labelin", an$ ot-er finis-in" operations. >b? Provi$e a$e(uate li"-tin", ventilation, an$ screenin" of open =in$o=s an$ $oors. >c? Provi$e a$e(uate, clean, an$ convenient -an$=as-in" facilities for personnel, an$ a$e(uate, clean, an$ convenient toilet facilities for $onors an$ personnel. Drains s-all be of a$e(uate si#e an$, =-ere connecte$ $irectl2 to a se=er, s-all be e(uippe$ =it- traps to prevent bac.sip-ona"e. >$? Provi$e for safe an$ sanitar2 $isposal for t-e follo=in"8 >1? 6ras- an$ ite)s use$ $urin" t-e collection, processin", an$ co)patibilit2 testin" of bloo$ an$ bloo$ co)ponents. >2? loo$ an$ bloo$ co)ponents not suitable for use or $istribution.

Subpart % - )*uipment#
"606#60 )*uipment#
>a? '(uip)ent use$ in t-e collection, processin", co)patibilit2 testin", stora"e an$ $istribution of bloo$ an$ bloo$ co)ponents s-all be )aintaine$ in a clean an$ or$erl2 )anner an$ locate$ so as to facilitate cleanin" an$ )aintenance. 6-e e(uip)ent s-all be observe$, stan$ar$i#e$ an$ calibrate$ on a re"ularl2 sc-e$ule$ basis as prescribe$ in t-e Stan$ar$ !peratin" Proce$ures Danual an$ s-all perfor) in t-e )anner for =-ic- it =as $esi"ne$ so as to assure co)pliance =it- t-e official re(uire)ents prescribe$ in t-is c-apter for bloo$ an$ bloo$ pro$ucts. >b? '(uip)ent t-at s-all be observe$, stan$ar$i#e$, an$ calibrate$ =it- at least t-e follo=in" fre(uenc2, inclu$e but are not li)ite$ to8

>c? '(uip)ent e)plo2e$ in t-e sterili#ation of )aterials use$ in bloo$ collection or for $isposition of conta)inate$ pro$ucts s-all be $esi"ne$, )aintaine$ an$ utili#e$ to ensure t-e $estruction of conta)inatin" )icroor"anis)s. 6-e effectiveness of t-e sterili#ation proce$ure s-all be no less t-an t-at ac-ieve$ b2 an attaine$ te)perature of 121.5 C >251 %? )aintaine$ for 20 )inutes b2 saturate$ stea) or b2 an attaine$ te)perature of 140 C >33; %? )aintaine$ for 2 -ours =it- $r2 -eat. *&0 %+ 53532, :ov. 1;, 1<453 &0 %+ 55;&<, Dec. 2, 1<45, as a)en$e$ at &5 %+ <261, %eb. 12, 1<;03 54 %+ 11263, Apr. 2, 1<<23 54 %+ 12;62, Apr. 13, 1<<2,

"606#6+ Supplies and reagents#

All supplies an$ rea"ents use$ in t-e collection, processin", co)patibilit2 testin", stora"e an$ $istribution of bloo$ an$ bloo$ co)ponents s-all be store$ in a safe, sanitar2 an$ or$erl2 )anner. >a? All surfaces co)in" in contact =it- bloo$ an$ bloo$ co)ponents inten$e$ for transfusion s-all be sterile, p2ro"en-free, an$ s-all not interact =it- t-e pro$uct in suc- a )anner as to -ave an a$verse effect upon t-e safet2, purit2, potenc2 or effectiveness of t-e pro$uct. All final containers an$ closures for bloo$ an$ bloo$ co)ponents not inten$e$ for transfusion s-all be clean an$ free of surface soli$s an$ ot-er conta)inants. >b? 'ac- bloo$ collectin" container an$ its satellite container>s?, if an2, s-all be eCa)ine$ visuall2 for $a)a"e or evi$ence of conta)ination prior to its use an$ i))e$iatel2 after fillin". SuceCa)inations s-all inclu$e inspection for brea.a"e of seals =-en in$icate$, an$ abnor)al $iscoloration. E-ere an2 $efect is observe$, t-e container s-all not be use$, or, if $etecte$ after fillin", s-all be properl2 $iscar$e$.

>c? +epresentative sa)ples of eac- lot of t-e follo=in" rea"ents or solutions s-all be teste$ on a re"ularl2 sc-e$ule$ basis b2 )et-o$s $escribe$ in t-e Stan$ar$ !peratin" Proce$ures Danual to $eter)ine t-eir capacit2 to perfor) as re(uire$8 Reagent or Solution Anti--u)an "lobulin loo$ "roupin" rea"ent /ec-tins Antibo$2 screenin" an$ reverse "roupin" cells 1epatitis test rea"ents S2p-ilis serolo"2 rea"ents 'n#2)es Do. Do. Do. 'ac- run. Do. 'ac- $a2 of use. Fre*uenc, of -esting 'ac- $a2 of use.

>$? Supplies an$ rea"ents t-at $o not bear an eCpiration $ate s-all be store$ in suc- a )anner t-at t-e ol$est is use$ first. >e? Supplies an$ rea"ents s-all be use$ in a )anner consistent =it- instructions provi$e$ b2 t-e )anufacturer. >f? 0te)s t-at are re(uire$ to be sterile an$ co)e into contact =it- bloo$ s-oul$ be $isposable =-enever possible. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at 5< %+ 23636, Da2 6, 1<<&,

Subpart ) .Reser!ed/ Subpart F - Production and Process Controls

"606#100 Standard operating procedures#
>a? 0n all instances, eCcept clinical investi"ations, stan$ar$ operatin" proce$ures s-all co)pl2 =it- publis-e$ a$$itional stan$ar$s in part 6&0 of t-is c-apter for t-e pro$ucts bein" processe$3 eCcept t-at, references in part 6&0 relatin" to licenses, license$ establis-)ents an$ sub)ission of )aterial or $ata to or approval b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-, are not applicable to establis-)ents not sub9ect to licensure un$er section 351 of t-e Public 1ealt- Service Act. >b? Eritten stan$ar$ operatin" proce$ures s-all be )aintaine$ an$ s-all inclu$e all steps to be follo=e$ in t-e collection, processin", co)patibilit2 testin", stora"e an$ $istribution of bloo$ an$ bloo$ co)ponents for transfusion an$ furt-er )anufacturin" purposes. Suc- proce$ures s-all be available to t-e personnel for use in t-e areas =-ere t-e proce$ures are perfor)e$. 6-e =ritten stan$ar$ operatin" proce$ures s-all inclu$e, but are not li)ite$ to, $escriptions of t-e follo=in", =-en applicable8 >1? Criteria use$ to $eter)ine $onor suitabilit2, inclu$in" acceptable )e$ical -istor2 criteria. >2? Det-o$s of perfor)in" $onor (ualif2in" tests an$ )easure)ents, inclu$in" )ini)u) an$ )aCi)u) values for a test or proce$ure =-en a factor in $eter)inin" acceptabilit2.

>3? Solutions an$ )et-o$s use$ to prepare t-e site of p-leboto)2 to "ive )aCi)u) assurance of a sterile container of bloo$. >&? Det-o$ of accuratel2 relatin" t-e pro$uct>s? to t-e $onor. >5? loo$ collection proce$ure, inclu$in" in-process precautions ta.en to )easure accuratel2 t-e (uantit2 of bloo$ re)ove$ fro) t-e $onor. >6? Det-o$s of co)ponent preparation, inclu$in" an2 ti)e restrictions for specific steps in processin". >4? All tests an$ repeat tests perfor)e$ on bloo$ an$ bloo$ co)ponents $urin" )anufacturin". >;? Pretransfusion testin", =-ere applicable, inclu$in" precautions to be ta.en to i$entif2 accuratel2 t-e recipient bloo$ sa)ples an$ cross)atc-e$ $onor units. ><? Proce$ures for investi"atin" a$verse $onor an$ recipient reactions. >10? Stora"e te)peratures an$ )et-o$s of controllin" stora"e te)peratures for all bloo$ pro$ucts an$ rea"ents as prescribe$ in FF600.15 an$ 610.53 of t-is c-apter. >11? /en"t- of eCpiration $ates, if an2, assi"ne$ for all final pro$ucts as prescribe$ in F610.53 of t-is c-apter. >12? Criteria for $eter)inin" =-et-er returne$ bloo$ is suitable for reissue. >13? Proce$ures use$ for relatin" a unit of bloo$ or bloo$ co)ponent fro) t-e $onor to its final $isposition. >1&? Gualit2 control proce$ures for supplies an$ rea"ents e)plo2e$ in bloo$ collection, processin" an$ pretransfusion testin". >15? Sc-e$ules an$ proce$ures for e(uip)ent )aintenance an$ calibration. >16? /abelin" proce$ures, inclu$in" safe"uar$s to avoi$ labelin" )iC-ups. >14? Proce$ures of plas)ap-eresis, plateletp-eresis, an$ leu.ap-eresis, if perfor)e$, inclu$in" precautions to be ta.en to ensure reinfusion of a $onorAs o=n cells. >1;? Proce$ure for preparin" recovere$ plas)a, if perfor)e$, inclu$in" $etails of separation, poolin", labelin", stora"e, an$ $istribution. >1<? Proce$ures in accor$ance =it- F610.&6 of t-is c-apter to loo. at prior $onations of E-ole loo$, bloo$ co)ponents, Source Plas)a an$ Source /eu.oc2tes fro) a $onor =-o -as $onate$ bloo$ an$ subse(uentl2 tests repeate$l2 reactive for antibo$2 to -u)an i))uno$eficienc2 virus >10H? or ot-er=ise is $eter)ine$ to be unsuitable =-en teste$ in accor$ance =it- F610.&5 of t-is c-apter. Proce$ures to (uarantine in--ouse E-ole loo$, bloo$ co)ponents, Source Plas)a an$ Source /eu.oc2tes inten$e$ for furt-er )anufacture into in9ectable pro$ucts t-at =ere obtaine$ fro) suc- $onors3 proce$ures to notif2 consi"nees re"ar$in" t-e nee$ to (uarantine sucpro$ucts3 proce$ures to $eter)ine t-e suitabilit2 for release of suc- pro$ucts fro) (uarantine3 proce$ures to notif2 consi"nees of E-ole loo$, bloo$ co)ponents, Sources Plas)a an$ Source /eu.oc2tes fro) suc- $onors of t-e results of t-e antibo$2 testin" of suc- $onors3 an$

proce$ures in accor$ance =it- F610.&4 of t-is c-apter to notif2 atten$in" p-2sicians so t-at transfusion recipients are infor)e$ t-at t-e2 )a2 -ave receive$ E-ole loo$ an$, bloo$ co)ponents at increase$ ris. for trans)ittin" -u)an i))uno$eficienc2 virus. >20? Proce$ures for $onor $eferral as prescribe$ in F610.&1 of t-is c-apter3 an$ proce$ures for $onor notification an$ autolo"ous $onor referrin" p-2sician notification, inclu$in" proce$ures for t-e appropriate follo=up if t-e initial atte)pt at notification fails, as prescribe$ in F630.6 of t-is c-apter. >c? All recor$s pertinent to t-e lot or unit )aintaine$ pursuant to t-ese re"ulations s-all be revie=e$ before t-e release or $istribution of a lot or unit of final pro$uct. 6-e revie= or portions of t-e revie= )a2 be perfor)e$ at appropriate perio$s $urin" or after bloo$ collectin", processin", co)patibilit2 testin" an$ storin". A t-orou"- investi"ation, inclu$in" t-e conclusions an$ follo=-up, of an2 uneCplaine$ $iscrepanc2 or t-e failure of a lot or unit to )eet an2 of its specifications s-all be )a$e an$ recor$e$. >$? 0n a$$ition to t-e re(uire)ents of t-is subpart an$ in confor)it2 =it- t-is section, an2 facilit2 )a2 utili#e current stan$ar$ operatin" proce$ures suc- as t-e )anuals of t-e or"ani#ations, as lon" as suc- specific proce$ures are consistent =it-, an$ at least as strin"ent as, t-e re(uire)ents containe$ in t-is part. >1? A)erican Association of loo$ an.s. >2? A)erican :ational +e$ Cross. >3? !t-er or"ani#ations or in$ivi$ual bloo$ ban.s, sub9ect to approval b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at &< %+ 23;33, Bune ;, 1<;&3 55 %+ 11013, Dar. 26, 1<<03 61 %+ &4&22, Sept. <, 1<<63 6& %+ &5340, Au". 1<, 1<<<3 66 %+ 31146, Bune 11, 2001,

"606#110 Plateletp0eresis1 leu2ap0eresis1 and plasmap0eresis#

>a? 6-e use of plateletp-eresis an$ leu.ap-eresis proce$ures to obtain a pro$uct for a specific recipient )a2 be at variance =it- t-e a$$itional stan$ar$s for specific pro$ucts prescribe$ in t-is part provi$e$ t-at8 >1? A p-2sician -as $eter)ine$ t-at t-e recipient )ust be transfuse$ =it- t-e leu.oc2tes or platelets fro) a specific $onor, an$ >2? t-e proce$ure is perfor)e$ un$er t-e supervision of a (ualifie$ license$ p-2sician =-o is a=are of t-e -ealt- status of t-e $onor, an$ t-e p-2sician -as certifie$ in =ritin" t-at t-e $onorAs -ealt- per)its plateletp-eresis or leu.ap-eresis. >b? Plas)ap-eresis of $onors =-o $o not )eet t-e $onor re(uire)ents of FF6&0.63, 6&0.6& an$ 6&0.65 of t-is c-apter for t-e collection of plas)a containin" rare antibo$ies s-all be per)itte$ onl2 =it- t-e prior approval of t-e Director, Center for iolo"ics 'valuation an$ +esearc-. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at &< %+ 23;33, Bune ;, 1<;&3 55 %+ 11013, Dar. 26, 1<<0,

Subpart G - Finis0ed Product Control

"606#120 3abeling1 general re*uirements#

>a? /abelin" operations s-all be separate$ p-2sicall2 or spatiall2 fro) ot-er operations in a )anner a$e(uate to prevent )iC-ups. >b? 6-e labelin" operation s-all inclu$e t-e follo=in" labelin" controls8 >1? /abels s-all be -el$ upon receipt, pen$in" revie= an$ proofin" a"ainst an approve$ final cop2, to ensure accurac2 re"ar$in" i$entit2, content, an$ confor)it2 =it- t-e approve$ cop2. >2? 'ac- t2pe of label representin" $ifferent pro$ucts s-all be store$ an$ )aintaine$ in a )anner to prevent )iC-ups, an$ stoc.s of obsolete labels s-all be $estro2e$. >3? All necessar2 c-ec.s in labelin" proce$ures s-all be utili#e$ to prevent errors in translatin" test results to container labels. >c? All labelin" s-all be clear an$ le"ible. *50 %+ 35&6<, Au". 30, 1<;5,

"606#121 Container 3abel#

>a? 6-e container label re(uire)ents are $esi"ne$ to facilitate t-e use of a unifor) container label for bloo$ an$ bloo$ co)ponents >eCcept Source Plas)a? b2 all bloo$ establis-)ents. >b? 6-e label provi$e$ b2 t-e collectin" facilit2 an$ t-e initial processin" facilit2 s-all not be re)ove$, altere$, or obscure$, eCcept t-at t-e label )a2 be altere$ to in$icate t-e proper na)e an$ ot-er infor)ation re(uire$ to i$entif2 accuratel2 t-e contents of a container after bloo$ co)ponents -ave been prepare$. >c? 6-e container label s-all inclu$e t-e follo=in" infor)ation, as =ell as ot-er speciali#e$ infor)ation as re(uire$ in t-is section for specific pro$ucts8 >1? 6-e proper na)e of t-e pro$uct in a pro)inent position, an$ )o$ifier>s?, if appropriate. >2? 6-e na)e, a$$ress, re"istration nu)ber, an$, if a license$ pro$uct, t-e license nu)ber of eac- )anufacturer. >3? 6-e $onor, pool, or lot nu)ber relatin" t-e unit to t-e $onor. >&? 6-e eCpiration $ate, inclu$in" t-e $a2, )ont-, an$ 2ear, an$, if t-e $atin" perio$ for t-e pro$uct is 42 -ours or less, t-e -our of eCpiration. >5? 0f t-e pro$uct is inten$e$ for transfusion, t-e appropriate $onor classification state)ent, i.e., Ipai$ $onorI or Ivolunteer $onorI, in no less pro)inence t-an t-e proper na)e of t-e pro$uct. >i? A pai$ $onor is a person =-o receives )onetar2 pa2)ent for a bloo$ $onation. >ii? A volunteer $onor is a person =-o $oes not receive )onetar2 pa2)ent for a bloo$ $onation.

>iii? enefits, suc- as ti)e off fro) =or., )e)bers-ip in bloo$ assurance pro"ra)s, an$ cancellation of nonreplace)ent fees t-at are not rea$il2 convertible to cas-, $o not constitute )onetar2 pa2)ent =it-in t-e )eanin" of t-is para"rap-. >6? %or E-ole loo$, Plas)a, Platelets, an$ partial units of +e$ loo$ Cells, t-e volu)e of t-e pro$uct, accurate to =it-in 10 percent3 or optionall2 for Platelets, t-e volu)e ran"e =it-in reasonable li)its. >4? 6-e reco))en$e$ stora"e te)perature >in $e"rees Celsius?. >;? 0f t-e pro$uct is inten$e$ for transfusion, t-e state)ents8 >i? I+C onl2.I >ii? ISee circular of infor)ation for in$ications, contrain$ications, cautions, an$ )et-o$s of infusion.I >iii? IProperl2 i$entif2 inten$e$ recipient.I ><? 6-e state)ent8 I6-is pro$uct )a2 trans)it infectious a"ents.I >10? E-ere applicable, t-e na)e an$ volu)e of source )aterial. >11? 6-e state)ent8 ICaution8 %or Danufacturin" 5se !nl2I, =-en applicable. >12? 0f t-e pro$uct is inten$e$ for transfusion, t-e A ! an$ +- "roups of t-e $onor s-all be $esi"nate$ conspicuousl2. %or Cr2oprecipitate$ A1%, t-e +- "roup )a2 be o)itte$. 6-e +"roup s-all be $esi"nate$ as follo=s8 >i? 0f t-e test usin" Anti-D loo$ Groupin" +ea"ent is positive, t-e pro$uct s-all be labele$8 I+positive.I >ii? 0f t-e test usin" Anti-D loo$ Groupin" +ea"ent is ne"ative but t-e test for D u is positive, t-e pro$uct s-all be labele$8 I+- positive.I >iii? 0f t-e test usin" Anti-D loo$ Groupin" +ea"ent is ne"ative an$ t-e test for D u is ne"ative, t-e pro$uct s-all be labele$8 I+- ne"ative.I >13? 6-e container label )ust bear enco$e$ infor)ation in a for)at t-at is )ac-ine-rea$able an$ approve$ for use b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-. >i? Who is subject to this machine-readable re uirement! All bloo$ establis-)ents t-at )anufacture, process, repac., or relabel bloo$ or bloo$ co)ponents inten$e$ for transfusion an$ re"ulate$ un$er t-e %e$eral %oo$, Dru", an$ Cos)etic Act or t-e Public 1ealt- Service Act. >ii? What blood products are subject to this machine-readable re uirement! All bloo$ an$ bloo$ co)ponents inten$e$ for transfusion are sub9ect to t-e )ac-ine-rea$able infor)ation label re(uire)ent in t-is section. >iii? What information must be machine-readable! 'ac- label )ust -ave )ac-ine-rea$able infor)ation t-at contains, at a )ini)u)8

>A? A uni(ue facilit2 i$entifier3 > ? /ot nu)ber relatin" to t-e $onor3 >C? Pro$uct co$e3 an$ >D? A ! an$ +- of t-e $onor. >iv? "o# must the machine-readable information appear! 6-e )ac-ine- rea$able infor)ation )ust8 >A? e uni(ue to t-e bloo$ or bloo$ co)ponent3 > ? e surroun$e$ b2 sufficient blan. space so t-at t-e )ac-ine- rea$able infor)ation can be scanne$ correctl23 an$ >C? +e)ain intact un$er nor)al con$itions of use. v? Where does the machine-readable information go! 6-e )ac-ine- rea$able infor)ation )ust appear on t-e label of an2 bloo$ or bloo$ co)ponent =-ic- is or can be transfuse$ to a patient or fro) =-ic- t-e bloo$ or bloo$ co)ponent can be ta.en an$ transfuse$ to a patient. >$? 'Ccept for recovere$ plas)a inten$e$ for )anufacturin" use or as ot-er=ise approve$ b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-, t-e paper of t-e container label s-all be =-ite an$ print s-all be soli$ blac., =it- t-e follo=in" a$$itional eCceptions8 >1? 6-e +- bloo$ "roup s-all be printe$ as follo=s8 >i? +- positive8 5se blac. print on =-ite bac."roun$. >ii? +- ne"ative8 5se =-ite print on blac. bac."roun$. >2? 6-e proper na)e of t-e pro$uct, an2 appropriate )o$ifier>s?, t-e $onor classification state)ent, an$ t-e state)ent Iproperl2 i$entif2 inten$e$ recipientI s-all be printe$ in soli$ re$ or in soli$ blac.. >3? 6-e follo=in" color sc-e)e )a2 be use$ optionall2 for $ifferentiatin" A ! loo$ Groups8 Blood Group4 ! A A Color of 3abel Paper lue 7ello= Pin. E-ite

>&? 0n. colors use$ for t-e optional color co$in" s2ste) $escribe$ in para"rap- >$?>3? of t-is section s-all be a visual )atc- to specific color sa)ples $esi"nate$ b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-.

>5? Special labels, suc- as t-ose $escribe$ in para"rap-s >-? an$ >i? of t-is section, )a2 be color co$e$ usin" t-e colors reco))en$e$ in t-e "ui$eline >see para"rap- >a? of t-is section?, or colors ot-er=ise approve$ for use b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-. >e? Container label re(uire)ents for particular pro$ucts or "roups of pro$ucts. >1? E-ole loo$ labels s-all inclu$e8 >i? 6-e volu)e of anticoa"ulant. >ii? 6-e na)e of t-e applicable anticoa"ulant i))e$iatel2 prece$in" an$ of no less pro)inence t-an t-e proper na)e approve$ for use b2 t-e Director, Center for iolo"ics 'valuation an$ +esearc-. >iii? 0f tests for uneCpecte$ antibo$ies are positive, bloo$ inten$e$ for transfusion s-all be labele$8 IContains $name of antibody%.I >2? 'Ccept for fro#en, $e"l2ceroli#e$, or =as-e$ +e$ loo$ Cell pro$ucts, re$ bloo$ cell labels s-all inclu$e8 >i? 6-e volu)e an$ .in$ of E-ole loo$, inclu$in" t-e t2pe of anticoa"ulant, fro) =-ic- t-e pro$uct =as prepare$. >ii? 0f tests for uneCpecte$ antibo$ies are positive an$ t-e pro$uct is inten$e$ for transfusion, t-e state)ent8 IContains $name of antibody%.I >3? /abels for pro$ucts =it- a $atin" perio$ of 42 -ours or less, inclu$in" an2 pro$uct prepare$ in a s2ste) t-at )a2 co)pro)ise sterilit2, s-all bear t-e -our of eCpiration. >&? 0f tests for uneCpecte$ antibo$ies are positive, Plas)a inten$e$ for transfusion s-all be labele$8 IContains $name of antibody%.I >5? +ecovere$ plas)a labels s-all inclu$e8 >i? 0n lieu of an eCpiration $ate, t-e $ate of collection of t-e ol$est )aterial in t-e container. >ii? 6-e state)ent as applicable8 ICaution8 %or Danufacturin" 5se !nl2I3 or ICaution8 %or 5se in Danufacturin" :onin9ectable Pro$ucts !nl2.I 0f t-e recovere$ plas)a -as a reactive screenin" test for evi$ence of infection $ue to a co))unicable $isease a"ent>s? un$er F610.&0 of t-is c-apter, or is collecte$ fro) a $onor =it- a previous recor$ of a reactive screenin" test for evi$ence of infection $ue to a co))unicable $isease a"ent>s? un$er F610.&0 of t-is c-apter, t-e recovere$ plas)a )ust be labele$ as re(uire$ un$er F610.&0>-?>2?>ii?>'? of t-is c-apter. >iii? %or recovere$ plas)a not )eetin" t-e re(uire)ents for )anufacture into licensable pro$ucts, t-e state)ent8 I:ot for 5se in Pro$ucts Sub9ect to /icense 5n$er Section 351 of t-e Public 1ealt- Service Act.I >f? loo$ an$ bloo$ co)ponents $eter)ine$ to be unsuitable for transfusion s-all be pro)inentl2 labele$8 I:!6 %!+ 6+A:S%5S0!:I, an$ t-e label s-all state t-e reason t-e unit is consi$ere$ unsuitable. 6-e provision $oes not appl2 to recovere$ plas)a labele$ accor$in" to para"rap- >e? >5? of t-is section.

>"? *+eserve$, >-? 6-e follo=in" a$$itional infor)ation s-all appear on t-e label for bloo$ or bloo$ co)ponents s-ippe$ in an e)er"enc2, prior to co)pletion of re(uire$ tests, in accor$ance =it- F6&0.2>f? of t-is c-apter8 >1? 6-e state)ent8 I%!+ 'D'+G':C7 5S' !:/7 7JJJJJJJJJJJ .I >2? +esults of an2 tests prescribe$ un$er FF610.&0, an$ 6&0.5>a?, >b?, or >c? of t-is c-apter co)plete$ before s-ip)ent. >3? 0n$ication of an2 tests prescribe$ un$er FF610.&0, an$ 6&0.5 >a? >b?, or >c? of t-is c-apter an$ not co)plete$ before s-ip)ent. >i? 6-e follo=in" a$$itional infor)ation s-all appear on t-e label for E-ole loo$ or +e$ loo$ Cells inten$e$ for autolo"ous infusion8 >1? 0nfor)ation a$e(uatel2 i$entif2in" t-e patient, e."., na)e, bloo$ "roup, -ospital, an$ i$entification nu)ber. >2? Date of $onation. >3? 6-e state)ent8 I%!+ A56!/!G!5S 5S' !:/7.I >&? 0n place of t-e bloo$ "roup label, eac- container of bloo$ inten$e$ for autolo"ous use an$ obtaine$ fro) a $onor =-o fails to )eet an2 of t-e $onor suitabilit2 re(uire)ents un$er F6&0.3 of t-is c-apter or =-o is reactive in t-e -epatitis tests prescribe$ un$er F610.&0 of t-is c-apter s-all be pro)inentl2 an$ per)anentl2 labele$8 I%!+ A56!/!G!5S 5S' !:/7.I >5? 5nits of bloo$ ori"inall2 inten$e$ for autolo"ous use, eCcept t-ose labele$ as prescribe$ un$er para"rap- >i?>&? of t-is section, )a2 be issue$ for -o)olo"ous transfusion provi$e$ t-e container label co)plies =it- all applicable provisions of para"rap-s >b? t-rou"- >e? of t-is section. 0n suc- case, t-e special label re(uire$ un$er para"rap- >i?>1?, >2?, an$ >3? of t-is section s-all be re)ove$ or ot-er=ise obscure$. >9? A tie-ta" attac-e$ to t-e container )a2 be use$ for provi$in" t-e infor)ation re(uire$ b2 para"rap- >e?>1?>iii?, >2?>ii?, an$ >&?, >-?, or >i?>1?, >2?, an$ >3? of t-is section. *50 %+ 35&6<, Au". 30, 1<;5, as a)en$e$ at 53 %+ 116, Ban. 5, 1<;;3 55 %+ 1101&, Dar. 26, 1<<03 54 %+ 10;1&, Dar. 31, 1<<23 5< %+ 23636, Da2 6, 1<<&3 63 %+ 166;5, Apr. 6, 1<<;3 6& %+ &5341, Au". 1<, 1<<<3 66 %+ 31162, Bune 11, 20013 64 %+ &<04, %eb. 1, 20023 6< %+ <141 %eb. 26, 200&3 40 %+ 1&<;&, Dar. 2&, 2005,

"606#122 5nstruction circular#

An instruction circular s-all be available for $istribution if t-e pro$uct is inten$e$ for transfusion. 6-e instruction circular s-all provi$e a$e(uate $irections for use, inclu$in" t-e follo=in" infor)ation8 >a? 0nstructions to )iC t-e pro$uct before use. >b? 0nstructions to use a filter in t-e a$)inistration e(uip)ent.

>c? 6-e state)ent IDo :ot A$$ De$icationsI or an eCplanation concernin" allo=able a$$itives. >$? A $escription of t-e pro$uct, its source, an$ preparation, inclu$in" t-e na)e an$ proportion of t-e anticoa"ulant use$ in collectin" t-e E-ole loo$ fro) eac- pro$uct is prepare$. >e? State)ents t-at t-e pro$uct =as prepare$ fro) bloo$ t-at =as ne"ative =-en teste$ for antibo$2 to 1u)an 0))uno$eficienc2 Hirus >10H? an$ nonreactive for -epatitis surface anti"en b2 %DA re(uire$ tests an$ nonreactive =-en teste$ for s2p-ilis b2 a serolo"ic test for s2p-ilis >S6S?. >f? 6-e state)ents8 IEarnin". 6-e ris. of trans)ittin" infectious a"ents is present. Careful $onor selection an$ available laborator2 tests $o not eli)inate t-e -a#ar$.I >"? 6-e na)es of cr2oprotective a"ents an$ ot-er a$$itives t-at )a2 still be present in t-e pro$uct. >-? 6-e na)es an$ results of all tests perfor)e$ =-en necessar2 for safe an$ effective use. >i? 6-e use of t-e pro$uct, in$ications, contrain$ications, si$e effects an$ -a#ar$s, $osa"e an$ a$)inistration reco))en$ations. >9? *+eserve$, >.? %or +e$ loo$ Cells, t-e instruction circular s-all contain8 >1? 0nstructions to a$)inister a suitable plas)a volu)e eCpan$er if +e$ loo$ Cells are substitute$ =-en E-ole loo$ is t-e in$icate$ pro$uct. >2? A =arnin" not to a$$ /actate$ +in"erAs 0n9ection 5.S.P. solution to +e$ loo$ Cell pro$ucts. >l? %or Platelets, t-e instruction circular s-all contain8 >1? 6-e approCi)ate volu)e of plas)a fro) =-ic- a sa)ple unit of Platelets is prepare$. >2? 0nstructions to be"in a$)inistration as soon as possible, but not )ore t-an & -ours after enterin" t-e container. >)? %or Plas)a, t-e instruction circular s-all contain8 >1? A =arnin" a"ainst furt-er processin" of t-e fro#en pro$uct if t-ere is evi$ence of brea.a"e or t-a=in". >2? 0nstructions to t-a= t-e fro#en pro$uct at a te)perature bet=een 30 an$ 34 C. >3? E-en applicable, instructions to be"in a$)inistration of t-e pro$uct =it-in 6 -ours after t-a=in". >&? 0nstructions to a$)inister to A !-"roup-co)patible recipients. >5? A state)ent t-at t-is pro$uct -as t-e sa)e -epatitis ris. as E-ole loo$3 ot-er plas)a volu)e eCpan$ers =it-out t-is ris. are available for treatin" -2povole)ia.

>n? %or Cr2oprecipitate$ A1%, t-e instruction circular s-all contain8 >1? A state)ent t-at t-e avera"e potenc2 is ;0 or )ore 0nternational 5nits of anti-e)op-ilic factor. >2? 6-e state)ent8 I5suall2 contains at least 150 )illi"ra)s of fibrino"enI3 or alternativel2, t-e avera"e fibrino"en level $eter)ine$ b2 assa2 of representative units. >3? A =arnin" a"ainst furt-er processin" of t-e pro$uct if t-ere is evi$ence of brea.a"e or t-a=in". >&? 0nstructions to t-a= t-e pro$uct for no )ore t-an 15 )inutes at a te)perature of bet=een 30 an$ 34C. >5? 0nstructions to store at roo) te)perature after t-a=in" an$ to be"in a$)inistration as soon as possible but no )ore t-an & -ours after enterin" t-e container or after poolin" an$ =it-in 6 -ours after t-a=in". >6? A state)ent t-at 0.< percent So$iu) C-lori$e 0n9ection 5.S.P. is t-e preferre$ $iluent. >4? A$e(uate instructions for poolin" to ensure co)plete re)oval of all concentrate$ )aterial fro) eac- container. >;? 6-e state)ent8 IGoo$ patient )ana"e)ent re(uires )onitorin" treat)ent responses to Cr2oprecipitate$ A1% transfusions =it- perio$ic plas)a factor H000 or fibrino"en assa2s in -e)op-ilia A an$ -2pofibrino"ene)ic recipients, respectivel2.I *50 %+ 35&40, Au". 30, 1<;5, as a)en$e$ at 53 %+ 116, Ban. 5, 1<;;3 6& %+ &5341, Au". 1<, 1<<<,

Subpart 6 - 3aborator, Controls

"606#1(0 3aborator, controls#
/aborator2 control proce$ures s-all inclu$e8 >a? 6-e establis-)ent of scientificall2 soun$ an$ appropriate specifications, stan$ar$s an$ test proce$ures to assure t-at bloo$ an$ bloo$ co)ponents are safe, pure, potent, an$ effective. >b? A$e(uate provisions for )onitorin" t-e reliabilit2, accurac2, precision an$ perfor)ance of laborator2 test proce$ures an$ instru)ents. >c? A$e(uate i$entification an$ -an$lin" of all test sa)ples so t-at t-e2 are accuratel2 relate$ to t-e specific unit of pro$uct bein" teste$, or to its $onor, or to t-e specific recipient, =-ere applicable.

"606#1+1 Compatibilit, testing#

Stan$ar$ operatin" proce$ures for co)patibilit2 testin" s-all inclu$e t-e follo=in"8

>a? A )et-o$ of collectin" an$ i$entif2in" t-e bloo$ sa)ples of recipients to ensure positive i$entification. >b? 6-e use of fres- recipient seru) or plas)a sa)ples less t-an 3 $a2s ol$ for all pretransfusion testin" if t-e recipient -as been pre"nant or transfuse$ =it-in t-e previous 3 )ont-s. >c? Proce$ures to $e)onstrate inco)patibilit2 bet=een t-e $onor@s cell t2pe an$ t-e recipient@s seru) or plas)a t2pe. >$? A provision t-at, if t-e unit of $onorAs bloo$ -as not been screene$ b2 a )et-o$ t-at =ill $e)onstrate a""lutinatin", coatin" an$ -e)ol2tic antibo$ies, t-e recipientAs cell s-all be teste$ =it- t-e $onorAs seru) >)inor cross)atc-? b2 a )et-o$ t-at =ill so $e)onstrate. >e? Proce$ures to eCpe$ite transfusion in life-t-reatenin" e)er"encies. +ecor$s of all sucinci$ents s-all be )aintaine$, inclu$in" co)plete $ocu)entation 9ustif2in" t-e e)er"enc2 action, =-ic- s-all be si"ne$ b2 a p-2sician. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at 6& %+ &5341, Au". 1<, 1<<<, 66 %+ 1;35, Ban. 10, 20013 66 %+ &0;;<, Au". 6, 2001,

Subpart 5 - Records and Reports

"606#160 Records#
>a?>1? +ecor$s s-all be )aintaine$ concurrentl2 =it- t-e perfor)ance of eac- si"nificant step in t-e collection, processin", co)patibilit2 testin", stora"e an$ $istribution of eac- unit of bloo$ an$ bloo$ co)ponents so t-at all steps can be clearl2 trace$. All recor$s s-all be le"ible an$ in$elible, an$ s-all i$entif2 t-e person perfor)in" t-e =or., inclu$e $ates of t-e various entries, s-o= test results as =ell as t-e interpretation of t-e results, s-o= t-e eCpiration $ate assi"ne$ to specific pro$ucts, an$ be as $etaile$ as necessar2 to provi$e a co)plete -istor2 of t-e =or. perfor)e$. >2? Appropriate recor$s s-all be available fro) =-ic- to $eter)ine lot nu)bers of supplies an$ rea"ents use$ for specific lots or units of t-e final pro$uct. >b? +ecor$s s-all be )aintaine$ t-at inclu$e, but are not li)ite$ to, t-e follo=in" =-en applicable8 >1? Donor recor$s8 >i? Donor selection, inclu$in" )e$ical intervie= an$ eCa)ination an$ =-ere applicable, infor)e$ consent. >ii? Per)anent an$ te)porar2 $eferrals for -ealt- reasons inclu$in" reason>s? for $eferral. >iii? Donor a$verse reaction co)plaints an$ reports, inclu$in" results of all investi"ations an$ follo=-up. >iv? 6-erapeutic blee$in"s, inclu$in" si"ne$ re(uests fro) atten$in" p-2sicians, t-e $onorAs $isease an$ $isposition of units. >v? 0))uni#ation, inclu$in" infor)e$ consent, i$entification of t-e anti"en, $osa"e an$ route of a$)inistration.

>vi? loo$ collection, inclu$in" i$entification of t-e p-leboto)ist. >vii? +ecor$s to relate t-e $onor =it- t-e unit nu)ber of eac- previous $onation fro) t-at $onor. >viii? +ecor$s of (uarantine, notification, testin", an$ $isposition perfor)e$ pursuant to FF610.&6 an$ 610.&4 of t-is c-apter. >iC? +ecor$s of notification of $onor $eferre$ or $eter)ine$ not to be suitable for $onation, inclu$in" appropriate follo=up if t-e initial atte)pt at notification fails, perfor)e$ un$er F630.6 of t-is c-apter. >C? 6-e $onor@s a$$ress provi$e$ at t-e ti)e of $onation =-ere t-e $onor )a2 be contacte$ =it-in ; =ee.s after t-e $onation. >Ci? +ecor$s of notification of t-e referrin" p-2sician of a $eferre$ autolo"ous $onor, inclu$in" appropriate follo=up if t-e initial notification atte)pt fails, perfor)e$ un$er F630.6 of t-is c-apter. >2? Processin" recor$s8 >i? loo$ processin", inclu$in" results an$ interpretation of all tests an$ retests. >ii? Co)ponent preparation, inclu$in" all relevant $ates an$ ti)es. >iii? Separation an$ poolin" of recovere$ plas)a. >iv? Centrifu"ation an$ poolin" of source plas)a. >v? /abelin", inclu$in" initials of t-e person>s? perfor)in" t-e proce$ure. >3? Stora"e an$ Distribution +ecor$s8 >i? Distribution an$ $isposition, as appropriate, of bloo$ an$ bloo$ pro$ucts. >ii? Hisual inspection of =-ole bloo$ an$ re$ bloo$ cells $urin" stora"e an$ i))e$iatel2 before $istribution. >iii? Stora"e te)perature, inclu$in" initiale$ te)perature recor$er c-arts. >iv? +eissue, inclu$in" recor$s of proper te)perature )aintenance. >v? ')er"enc2 release of bloo$, inclu$in" si"nature of re(uestin" p-2sician obtaine$ before or after release. >&? Co)patibilit2 test recor$s8 >i? +esults of all co)patibilit2 tests, inclu$in" cross)atc-in", testin" of patient sa)ples, antibo$2 screenin" an$ i$entification. >ii? +esults of confir)ator2 testin". >5? Gualit2 control recor$s8

>i? Calibration an$ stan$ar$i#ation of e(uip)ent. >ii? Perfor)ance c-ec.s of e(uip)ent an$ rea"ents. >iii? Perio$ic c-ec. on sterile tec-ni(ue. >iv? Perio$ic tests of capacit2 of s-ippin" containers to )aintain proper te)perature in transit. >v? Proficienc2 test results. >6? 6ransfusion reaction reports an$ co)plaints, inclu$in" recor$s of investi"ations an$ follo=up. >4? General recor$s8 >i? Sterili#ation of supplies an$ rea"ents prepare$ =it-in t-e facilit2, inclu$in" $ate, ti)e interval, te)perature, an$ )o$e. >ii? +esponsible personnel. >iii? iolo"ical pro$uct $eviations. >iv? Daintenance recor$s for e(uip)ent an$ "eneral p-2sical plant. >v? Supplies an$ rea"ents, inclu$in" na)e of )anufacturer or supplier, lot nu)bers, eCpiration $ate an$ $ate of receipt. >vi? Disposition of re9ecte$ supplies an$ rea"ents use$ in t-e collection, processin" an$ co)patibilit2 testin" of bloo$ an$ bloo$ co)ponents. >c? A $onor nu)ber s-all be assi"ne$ to eac- accepte$ $onor, =-ic- relates t-e unit of bloo$ collecte$ to t-at $onor, to -is )e$ical recor$, to an2 co)ponent or bloo$ pro$uct fro) t-at $onorAs unit of bloo$, an$ to all recor$s $escribin" t-e -istor2 an$ ulti)ate $isposition of t-ese pro$ucts. >$? +ecor$s s-all be retaine$ for suc- interval be2on$ t-e eCpiration $ate for t-e bloo$ or bloo$ co)ponent as necessar2 to facilitate t-e reportin" of an2 unfavorable clinical reactions. 6-e retention perio$ s-all be no less t-an 5 2ears after t-e recor$s of processin" -ave been co)plete$ or 6 )ont-s after t-e latest eCpiration $ate for t-e in$ivi$ual pro$uct, =-ic-ever is a later $ate. E-en t-ere is no eCpiration $ate, recor$s s-all be retaine$ in$efinitel2. >e? A recor$ s-all be available fro) =-ic- unsuitable $onors )a2 be i$entifie$ so t-at pro$ucts fro) suc- in$ivi$uals =ill not be $istribute$. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at 61 %+ &4&22, Sept. <, 1<<63 6& %+ &5341, Au". 1<, 1<<<3 65 %+ 66635, :ov. 4, 20003 66 %+ 31146, Bune 11, 2001,

"606#16+ %istribution and receipt7 procedures and records#

>a? Distribution an$ receipt proce$ures s-all inclu$e a s2ste) b2 =-ic- t-e $istribution or receipt of eac- unit can be rea$il2 $eter)ine$ to facilitate its recall, if necessar2.

>b? Distribution recor$s s-all contain infor)ation to rea$il2 facilitate t-e i$entification of t-e na)e an$ a$$ress of t-e consi"nee, t-e $ate an$ (uantit2 $elivere$, t-e lot nu)ber of t-e unit>s?, t-e $ate of eCpiration or t-e $ate of collection, =-ic-ever is applicable, or for cross)atc-e$ bloo$ an$ bloo$ co)ponents, t-e na)e of t-e recipient. >c? +eceipt recor$s s-all contain t-e na)e an$ a$$ress of t-e collectin" facilit2, $ate receive$, $onor or lot nu)ber assi"ne$ b2 t-e collectin" facilit2 an$ t-e $ate of eCpiration or t-e $ate of collection, =-ic-ever is applicable.

"606#180

d!erse reaction file#

>a? +ecor$s s-all be )aintaine$ of an2 reports of co)plaints of a$verse reactions re"ar$in" eacunit of bloo$ or bloo$ pro$uct arisin" as a result of bloo$ collection or transfusion. A t-orou"investi"ation of eac- reporte$ a$verse reaction s-all be )a$e. A =ritten report of t-e investi"ation of a$verse reactions, inclu$in" conclusions an$ follo=-up, s-all be prepare$ an$ )aintaine$ as part of t-e recor$ for t-at lot or unit of final pro$uct b2 t-e collectin" or transfusin" facilit2. E-en it is $eter)ine$ t-at t-e pro$uct =as at fault in causin" a transfusion reaction, copies of all suc- =ritten reports s-all be for=ar$e$ to an$ )aintaine$ b2 t-e )anufacturer or collectin" facilit2. >b? E-en a co)plication of bloo$ collection or transfusion is confir)e$ to be fatal, t-e Director, !ffice of Co)pliance an$ iolo"ics Gualit2, Center for iolo"ics 'valuation an$ +esearc-, s-all be notifie$ b2 telep-one, facsi)ile, eCpress )ail, or electronicall2 trans)itte$ )ail as soon as possible3 a =ritten report of t-e investi"ation s-all be sub)itte$ to t-e Director, !ffice of Co)pliance an$ iolo"ics Gualit2, Center for iolo"ics 'valuation an$ +esearc-, =it-in 4 $a2s after t-e fatalit2 b2 t-e collectin" facilit2 in t-e event of a $onor reaction, or b2 t-e facilit2 t-at perfor)e$ t-e co)patibilit2 tests in t-e event of a transfusion reaction. *&0 %+ 53532, :ov. 1;, 1<45, as a)en$e$ at &< %+ 23;33, Bune ;, 1<;&, 50 %+ 35&41, Au". 30, 1<;53 55 %+ 1101&, Dar. 26, 1<<03 6& %+ &5341, Au". 1<, 1<<<3 64 %+ <5;6, Dar. &, 2002,

" 606#181 Reporting of product de!iations b, licensed manufacturers1 unlicensed registered blood establis0ments1 and transfusion ser!ices#
>a? Who must report under this section! 7ou, a license$ )anufacturer of bloo$ an$ bloo$ co)ponents, inclu$in" Source Plas)a3 an unlicense$ re"istere$ bloo$ establis-)ent3 or a transfusion service =-o -a$ control over t-e pro$uct =-en t-e $eviation occurre$, )ust report un$er t-is section. 0f 2ou arran"e for anot-er person to perfor) a )anufacturin", -ol$in", or $istribution step, =-ile t-e pro$uct is in 2our control, t-at step is perfor)e$ un$er 2our control. 7ou )ust establis-, )aintain, an$ follo= a proce$ure for receivin" infor)ation fro) t-at person on all $eviations, co)plaints, an$ a$verse events concernin" t-e affecte$ pro$uct. >b? What do & report under this section! 7ou )ust report an2 event, an$ infor)ation relevant to t-e event, associate$ =it- t-e )anufacturin", to inclu$e testin", processin", pac.in", labelin", or stora"e, or =it- t-e -ol$in" or $istribution, of bot- license$ an$ unlicense$ bloo$ or bloo$ co)ponents, inclu$in" Source Plas)a, if t-at event )eets all t-e follo=in" criteria8 >1? 'it-er8 >i? +epresents a $eviation fro) current "oo$ )anufacturin" practice, applicable re"ulations, applicable stan$ar$s, or establis-e$ specifications t-at )a2 affect t-e safet2, purit2, or potenc2 of t-at pro$uct3 or

>ii? +epresents an uneCpecte$ or unforeseeable event t-at )a2 affect t-e safet2, purit2, or potenc2 of t-at pro$uct3 an$ >2? !ccurs in 2our facilit2 or anot-er facilit2 un$er contract =it- 2ou3 an$ >3? 0nvolves $istribute$ bloo$ or bloo$ co)ponents. >c? When do & report under this section! 7ou s-oul$ report a biolo"ical pro$uct $eviation as soon as possible but 2ou )ust report at a $ate not to eCcee$ &5-calen$ar $a2s fro) t-e $ate 2ou, 2our a"ent, or anot-er person =-o perfor)s a )anufacturin", -ol$in", or $istribution step un$er 2our control, ac(uire infor)ation reasonabl2 su""estin" t-at a reportable event -as occurre$. >$? "o# do & report under this sectionK 7ou )ust report on %or) %DA-3&;6. >e? Where do & report under this section! 7ou )ust sen$ t-e co)plete$ %or) %DA-3&;6 to t-e Director, !ffice of Co)pliance an$ iolo"ics Gualit2 >1%D-600? >see )ailin" a$$resses in F600.2 of t-is c-apter? b2 eit-er a paper or electronic filin"8 >1? 0f 2ou )a.e a paper filin", 2ou s-oul$ i$entif2 on t-e envelope t-at a PD+ >biolo"ical pro$uct $eviation report? is enclose$3 or >2? 0f 2ou )a.e an electronic filin", 2ou )a2 sub)it t-e co)plete$ %or) %DA-3&;6 electronicall2 t-rou"- C '+@s =ebsite at ===.f$a."ovLcber. >f? "o# does this regulation affect other FD' regulations! 6-is part supple)ents an$ $oes not superse$e ot-er provisions of t-e re"ulations in t-is c-apter. All biolo"ical pro$uct $eviations, =-et-er or not t-e2 are re(uire$ to be reporte$ un$er t-is section, s-oul$ be investi"ate$ in accor$ance =it- t-e applicable provisions of parts 211, 606, an$ ;20 of t-is c-apter. *65 %+ 66635, :ov. 4, 20003 40 %+ 1&<;&, Dar. 2&, 2005,