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`JAZZ EXHIBIT 2016
`Amneal Pharms. LLC (Petitioner) v. Jazz Pharms. Ireland LTD. (Patent Owner)
`Case IPR2016-00546
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`

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`Good Clinical, Laboratory and
`Manufacturing Practices
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`Techniques for the QA Prnfcssinnal
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`Ediled by
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`FA -Ca r:-1-:m
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`Clmr.-.'m'nHr.r. LU”;
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`N Dent
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`['uH.~':n’HHr£.
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`IJfi.'
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`RSC Publishing
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`Page 2 of 4
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`15 H N: '-1'?-‘ii-I}-IRE:-ilifll-ii 34- 2
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`Page 3 of 4
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`{.iL.l"‘ in .l'.l'r'it.I_g ilrh-'.fr.I.lrriI.|'i.-.'rr:
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`.rmr.l' l"’.lmrn:rn;'r3.li.fire-n'r'-.'
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`3l_l_.'
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`{ivt Develripnient nfiselatitin. sen-aratergr tree. I-IPLC rir GE} and speetral leg. MS rir N1-IR]
`[ire-eedures.
`{VJ Phqirtitgieehirietie studies in aniinals fig-. wnrlt on the ltineties i:it'fitt1Ih-'1 t~'. processes i:iE' ]:!I;tt‘t-.3'|t|
`drug anrljnr niajer titetahnlitesl, iitelurling lhinavailahility studies.
`|{1rl_l Te-.=tit:ultinetit.' studies [t'.e. the deterrtiinatien utdrttg levels in the plastita e-liattimals tluritig
`teitieeleg;-' studies}.
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`22.4
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`rt.REi’t.S I.'£l't’[l‘~i-G E-PE-CII-‘IE PH'.{"JIEt-LEl'|i’lE§ FOR GLI-"'
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`ll'tr’.lPLE.l"rIl-Il"~lTi-tt.Tl~t‘.'.'I'I"'~|
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`22.-1.]
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`Specific Problems Eneeuntererl
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`fits has been stated, ELI‘ regulatiritts st.-‘ere drawn up te er.-ver texienlngy studies. Drug inetahnlism
`and pliarintieeltitietie sturlies ttitTer s-ignifieantlgr Frettt nertiial
`ltwtlttilttgiflttl studies in several
`aspeets. The;-e are eeneerriert witli ariimal stuttie.-t that are erien-eiielert. is-itlinut the etearly tletined
`time span ti|'a l'U'}t'l|.'t_tlIt'tIg}' study‘. which has a delinite start and linish date.
`Fladiettetire niaterials. wliieh are lt'IllI:1'{tt'Ill}' ttnstahle due te radie deeay. may be available in tee
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`small a quantity tri permit nermal eheinieal purity testing.
`The eemptes instruinentttti-uh used in ttie periernianee el'drtig inetahe-ltsm. er pharrnaeetttrietie
`studies and their asseeiated anal}.-tieal teeltttique. requires speeifie ealihratleh. mtiitttenanee and
`E[tIi.ill[jr' eenlrel preeetitires te be set tip.
`
`The drug sttbstanee itself niag.-' well be destreg-"ed in a study" and thus pest: the seeendar:..' preblem
`nf' net being able te retain samples.
`there is etFten little
`In the ariimal speeies used t'e-1' drug ntetahnlisin and pharniaeelrineties.
`dillerenee between that til" at tesieelegieal study and thus prises a preblem ler “_iu5lifit.'atien el the
`test species”.
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`22.4.2. Attempts to Reselse the Prehleins
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`In view er the prehteiris eutttned. a phileiseiphy ell‘ ULP in terms ei' ritmtity st.-imisrris sheulrt he
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`applied ten drug metabelism and pharmaeel-rineties. Certain areas el' werlr. ]1?Iti.}' require ‘a theught
`prrieess' Le ensure regulatnry eritnpliunee.
`'|'he t‘n|ln1.=.'ing es:-atn pies deinrinstr-ate tlte range aiirl 1.'arietj..' nFdil'fieii!ties that e-an he etterrnntered
`and give an indieatirin m“hnu-' grind in.-inageinent teeltniques, grind seienee a11rl t'iI.|’ ean eneitist iii
`harrneny.
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`21.5 P Rfl'I'flC'[l| L5
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`ADME are net rn-utine prneedures. unlike ntainstreani tnxieeltigy and, therefnre. prritnerils niag.-'
`'.'arg.'estet1six-'e|g,'f'reIn eirperiitieiit trr eitperintent. tr tn.-ag.' he that until the erinelusirrn nfnne piece nl'
`wet}.-., rune etiiinet draw up ti ere-tees] ter the nest. lteriee it is eiittieult te ICfiItl‘l.]:1lt_t' with the rurreiit
`II..tgttlttl.DI}'
`I"t.'.I'.|ttl1'It.!IIII'..‘.I1l. fer detailed prete-eels. Fer example. in nietabelite tselatiun a eetnpletien
`
`date is estreinelg.-' diffieult tn prediet. Lil-tewise the start date is entirely.-' dependent tit-l't the [ireduetien
`niraditilahelled ntaterial. The date the prtitneel is supplied and signed hy the spnnstir alsn prises a
`prrihlein. It'JI"ten erintraet researeh erinipanies esirryiitg eiut studies an I1-eltalt‘ rif sprinsrirs. submit a
`prete-eel rtuty signed l:'r_'g.-' their stslt‘. hut weuttt net I'|ECE$StII‘ll).' exeeet tr: get the seerIier's siguttture
`en the final definitive pretueel until seine time later. Utii=t|ttll}' verbal agreement is J_-1l'|.'t:l1.. a. letter eI'
`eenlirtnutien. sent arid. enee the ratliulabelled material is tt"r'iill;ilZ||lt.':., the pre-tueel gees l'urward Ier
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`final spenser"s signature and the stutly starts.
`fltnnther area rit“nrun-entnfiliunee‘ suttnuttds tlte justifieatirin I'm" seleetiein nfthe test systetn. In
`tnest eases drug tnetahe-listn sttidies identify the likely speeies l'ei' tesieelngieal were The AJJMF.
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