SECOND EDITIDN
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`Pharmaceulinal
`Prelnrmulalinn and
`Fnrmulalinn
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`I Primal Bide PM IIIHHIII [Ins Eulmill ll lillnmil Illllll Hr:
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`Mark Gibson
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`Page 1
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`Pharmaceutical
`Pref ormulation and
`Formulation
`Second Edition
`
`edited by
`Mark Gibson
`AstraltrJ«:a R&O Cltamwood
`~. Ltle<SttfSfWe, IA(
`
`informa
`healthcare
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`--l--
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`Page 2
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`Page 3
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`E'4' ""9 - -
`Simil.nty, ;l lisc oi A.'\lUi~mcnts C'an be produo:d (()It tht<- prim.1ry p.ld;. 11u<.h oltl tht'
`fallow1ng:
`
`11t
`
`Th(' p.lCk ,.,..ill be <11Cttplal>le to regul.alOt)' authorities in the rounuies 10 be m.irketed
`(Olht.'1" appro\·t<d m.irk\otM prodl)('t& •lready u:si.- lhi11 typt' ol pa<k).
`Onl)' p;u;b 1h.1t can be multiple :KM.1rced ff(lln n10tt th;,n one- tiupptiocr/o:iuntry will
`"".-.
`
`Thie p.lC'k must hil\'l" consistency of dimensions and ~rform.tnce.
`Th(' p.i<J; will 11\C\'t (unction/u~r tcsb •nd spt.'Cilic.ations.
`
`~ dimensl0t\S, J"'!l'formanre limlls. and funrtlon/uset ttst llm.lts shoukt be spedOed
`in the product design report.
`6.v-.on though lh~ produ('I h.11J nol )'<'I ~n dc\·~·loptd • .- high-qu.11ily pivd1>ct
`«pt'rif1Co1liQn can be prup<ll$<'tl with t~~ .,nd limit.« th.11 1he produC'I shwld mt..'Ct a.I lhc tin\C
`a( manufow:tu.re And al the <.-nd of shelf life. For tlu• intr.lv~oUJ produci eX11mpk'. te!ll!i might
`l.ndudc ap~rance (dtar, p.utide frtt), pH, 05n1olalit)'. particulate Jc,•ds. sterility. <lnd
`t.'ndotoxin levels. Appropri,..ie Mand,.rd.11 or limits ~;in ;ilso be prop<>&«t on lh~ N!is of tht'
`kn()wledge uf $imilar t~ of proc::hms Uwt h"'v.;o Ollr(';Kiy IX'\...,, dc\'l'lop._"CI 1tnd from s t1nd .. rd
`pharm.11ropoelal monographs.
`Fbwilly, in this section, it Is useful to agTI.'t' on whllt die 1nlnlmum a.cceptal>le shelf lif.e for
`the product !>hoold ht-. The product wiO n~-t to be s tabk> enough to aUC"v lime for qu.ality
`rontrol (QC) h."81ing and qu.1lit)' a'll)C,lr.anct (QA) n:~1~ .after m.lnuf.tttun'; di,ITibuti()n h>
`whok.."halcrs, ph.lnMtislS.. and dC)('to~ ..ind with :.ttepl:t1ble bin!!" fur ~l'ln'lse until pn.'SCl"lbtod
`and used by p.1tlents. NonnaUy, a 1ninl.mum lh~yt-.tr shelf Ufo at N01'n 1emper.11tu.re (1~30 0
`ls lilfgl'h.-d. I l o.,.,~\'l't", if the th.'illmertt is~ ntn•cl, it m.1y ht- po!.'Siblc to ;ustify a $hort('r shell
`lift' and/or <;!Urn~ at lower lt'mpc:ntu~ if srabilit)' '11 likcly lo be il. p:nJbll:n1
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`CommerciaJ •nd Marketing ConskltfaUons
`Any phatmOKrurica..I company's «anomk obj.xtiv.o musl bt to 1N1Xin1ilc its ROI •fter launch.
`Thc-n:fo~ U11?oontm1?rt"fal \ti.lbility of a ne\...- product to be dfVclopcd lll't"d.s to "'-"oomm('millly
`11~~4L-d .tt th(' prnJut"I d~ign :.t.1gl! le> s.itbf)' the c·omp.any th.d it w1ll .icltic\'c" a s..itbfodory
`ROL Some of the fMtors lhlll $hould tw.> rons.ld"1"1.'d In the E'\'Jluatiion are as foll°"'·s:
`
`De\<elopmC'.nt ~s
`'rindng to mnrk~
`~ia.rb-t site (disease P~'·alenC't'. dlllg:nosls "nd trea1men1 r.1h."S, market \'.ltue)
`Competition (curren1. de,•eloping, •nd lmp.11(1 on fuluA' marked
`Unnw·t mcdkal nt't'd (effocth·.._.,.'S.'i ot curttnl tl\'i1lt1M'nl, impnwt'ment!I teq\lir(.'(t)
`11ri<ing tlnd n>lmbur.!lt'"l'nl"nl (n1m"l\t and futu~)
`CoC (lati,'t't)
`
`11te dl"\"('kl~I costs .uc 01n ~tim.1tc ol the t<QI costs of d-."\"('k>pmcnl of the pnxlurt
`thr(lugh lhi." \'arious 11t.1g~~ ()( R&O, induding prtc:linic:J1I, clinic.11.. ph.1rlllllC(.'Utic:..il (drug
`.,ub,.t.u.re and produd). and m.ui.et:in8 C'CieU?t. Ali a rult•, lh~ dt:\'f'lopmt•nt OlSb \'llH lnc-n:a~
`exponcntinJJy with de,•elopme1\t lime ('Se'e Fig. Z.. chap. I), and tht>rost ot rondu('ting the pN~
`IJJ dinkal i;o1dics ;lfC usually tht m061 (')(pet\Sivt' elC-mt.'nl of the 'IL'vck>~nt progr.1m,
`Estinwl\-s f.1f th<l lot."'11 oost of all milt~·ria.I, gbor, and ~rh..-~d costs should ~ inclvd4.-d.
`A majot ron.~ider.ulon for the d~lop«IC!nt OO!iits is Wh('ther to rontr.'l~ oul som~or ;tll ol
`the WOl'k (Spurlin et al, 1996). Co1\lt,,C't n>Selltth otg11nl.z.ations (CROs) <'An offer a brood rilnge
`of services covering all parts or the drug deveklpmml ptO«"SS. In tern's or produC'I
`dt.'Vc.'lopmcnt, pn.-lormuLition 1'-tudi(~. induding dr\lg ~ubr:l.tance ch.irn<;~'rii.1ti()n, fonnula1ion
`dt.-wliOj)m('nl, ~t.ibility t1,.~1ng. dink.11 trl.il m;,inuf;l.(h1nng.. and :te.1le·up/ t1,.ot:hnology tr:lnS(C"r,
`are 1ypkaJJy outsourttd. In f;act, most phar1na«'ULiC'al companies hli\'t' to cootract oul son'e
`aspect of R&.O b.."Oluse of lhe di\'e-ri;e requfr..-mrots and n\ultidisdplinary natun- of lhc work.
`Tiikcn lo U•C' ('~~me, ii is JX!Mibat co Cn!iltc a "\il1u;:1I"' phann.;ict"ulia.1 wmp;any ron by a
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`Page 4