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Ukuchongwa kwe-Oxidizing Leachable evela kwi-Clinical Syringe Rubber Stopper

Iimathiriyeli zepolymeric ezisetyenziselwa into enye ziya zisetyenziswa kakhulu kumanyathelo ahlukeneyo okulungisa i-biopharmaceutical.Oku kunokunxulunyaniswa ikakhulu kuluhlu olubanzi lwezicelo kunye nokuguquguquka okuhambelanayo kunye nokuguquguquka, kunye neendleko zabo eziphantsi kwaye ngenxa yokuba ukuqinisekiswa kokucoca akufuneki.[1][2]

Ngokuqhelekileyo, phantsi kweemeko eziqhelekileyo zokusetyenziswa kweekhompawundi zeekhemikhali ezifudukayo zibizwa ngokuba "zinokuvuzeka," ngelixa iikhompawundi ezifuduka phantsi kweemeko ezibaxiweyo zelebhu zihlala zibizwa ngokuba "zinokucatshulwa."Ukwenzeka kwezinto ezivuzayo kunokuba yinkxalabo enkulu ngokusingisele kwishishini lezonyango, njengoko iiproteni zonyango zidla ngokuthanda uhlengahlengiso lwesakhiwo olunokubangwa bubukho bezingcolisi, ukuba ezo zithwala amaqela asebenzayo asebenzayo.[3][4]Ukuphuma kwizinto zolawulo kunokuqwalaselwa njengomngcipheko omkhulu, nangona ixesha loqhagamshelwano lisenokungabi lide kakhulu xa lithelekiswa nokugcinwa kwexesha elide lemveliso.[5]
Ngokuphathelele kwiimfuno zolawulo, i-US Code of Federal Regulations Title 21 ithi izixhobo zokuvelisa[6] kunye nokuvalwa kwee-container[7] akusayi kuluguqula ukhuseleko, umgangatho okanye ukucoceka kwechiza.Ngenxa yoko kwaye ukuze kuqinisekiswe umgangatho wemveliso kunye nokhuseleko lwezigulane, ukwenzeka kwezi zingcolisi, ezinokuvela kubuninzi bezinto zoqhagamshelwano zeDP, kufuneka zibekwe esweni kwaye zilawulwe kuwo onke amanyathelo okucubungula, ngexesha lokuvelisa, ukugcinwa kunye nolawulo lokugqibela.
Kuba imathiriyeli yolawulo ichazwa ngokubanzi njengezixhobo zonyango, ababoneleli kunye nabavelisi bahlala bemisela kwaye bavavanye ukwenzeka kwabafuduki beekhemikhali ngokwenjongo yokusetyenziswa kwemveliso ethile, umzekelo, kwiingxowa zokugalelwa, kuphela isisombululo esimanzi esiqulathwe, umz., 0.9% (w) /v) I-NaCl, iyavavanywa.Nangona kunjalo, ngaphambili kwaboniswa ukuba ubukho bezithako zokuqulunqa ezineempawu zokunyibilikisa, ezifana neprotheni yonyango ngokwayo okanye i-non-ionic surfactants inokutshintsha kwaye iphucule ukutyekela kokufuduka kweekhompawundi ezingekho kwi-polar xa kuthelekiswa nezisombululo ezilula zamanzi. [7] [8] ]
Ke ngoko ibiyinjongo yeprojekthi ekhoyo ukuchonga iikhompawundi ezinokuthi ziphume kwisirinji yekliniki esetyenziswa ngokuqhelekileyo.Yiyo loo nto, senze izifundo ezifanisiweyo ezivuzayo zisebenzisa i-0.1% yamanzi (w/v) PS20 njengesisombululo se-DP.Izisombululo ezifunyenweyo ezinokuvuza zihlalutywe ngokukhutshwa okusemgangathweni kunye neendlela zokuhlalutya ezinokuvuza.Amalungu esirinji adityaniswa ukuze kuchongwe owona mthombo ukhuphayo ovulelekayo.[9]
Ngexesha lophononongo lwezinto ezivuzekayo ezisetyenziswa ekliniki kunye nesiqinisekiso se-CE sesirinji yolawulo olulahlwayo enokubakho kwikhompawundi yeekhemikhali ezinokuba yi-carcinogenic41, eyile, 1,1,2,2-tetrachloroethane ichongiwe kuxinzelelo olungaphezulu kwe-ICH M7-derived threshold yovandlakanyo (AET) ).Uphando olucokisekileyo lwaqaliswa ukuchonga isithinteli serabha esiqulethwe njengowona mthombo we-TCE oyintloko.[10]
Ewe, sinokubonisa ngokungathandabuzekiyo ukuba i-TCE yayingeyonto enokuvuzeka kwisithinteli serabha.Ukongeza, ulingo luveze ukuba ukuza kuthi ga ngoku, ikhompawundi engaziwayo eneempawu ze-oxidizing yayiphuma kwisithinteli serabha, esikwaziyo ukukhupha i-DCM ukuya kwi-TCE.
Ukuze kuchongwe ikhompawundi evuzayo, isithinteli serabha kunye nesicatshulwa sayo siphawulwe ngeendlela ezahlukeneyo zokuhlalutya.Iiperoxides zeorganic ezahlukeneyo, ezinokusetyenziswa njengabaqalisi bepolymerization ngexesha lokwenziwa kweplastiki, izixhobo zaphandwa ngesakhono sazo sokuxilisa iDCM ukuya kwiTCE. Ukuqinisekisa ngokungathandabuzekiyo kolwakhiwo lweLuperox⑧ 101 njenge-oxidizing leacable compound, uhlalutyo lwe-NMR lwenziwa.Isicatshulwa serabha ye-methanolic kunye ne-methanolic Luperox 101 yomgangatho wereferensi ziye zakhutshwa zibe ngumphunga ukuze zome.Iintsalela zaphinda zamiselwa kwi-methanol-d4 kwaye zahlalutywa yi-NMR.Umqalisi we-polymerization i-Luperox⑧101 ngoko ke yaqinisekiswa ukuba yinto enokuvuzeka kwi-oxidizing kwisivalo serabha yesirinji esilahlwayo.[12]
Ngophononongo oluthiwe thaca apha, ababhali bajonge ukwazisa malunga nokuthambekela kweekhemikhali eziphuma kwizixhobo zolawulo ezisetyenziswa eklinikhi, ngakumbi ngokubhekiselele kubukho bekhemikhali “ezingabonakaliyo” kodwa ezisebenza kakhulu.Ukubekw'esweni kwe-TCE kusenokuba yindlela eguquguqukayo nefanelekileyo yokubeka iliso kubulunga be-DP kuwo onke amanyathelo okusetyenzwa kwaye ngokwenza njalo kube negalelo kukhuseleko lwezigulane.[13]

Iimbekiselo

[1] I-Shukla AA, i-Gottschalk U. Ukusetyenziswa kobuchwepheshe obunye obulahlayo kwimveliso ye-biopharmaceutical.Iimpawu zeBiotechnol.2013;31(3):147-154.

[2] Lopes AG.Ukusetyenziswa okukodwa kwishishini le-biopharmaceutical: uphononongo lwempembelelo yangoku yetekhnoloji, imingeni kunye nemida.Inkqubo yeBioprod yokutya.2015;93:98-114.

[3] I-Paskiet D, i-Jenke D, i-Ball D, i-Houston C, i-Norwood DL, i-Markovic I. I-Product QualityResearch Institute (PQRI) evuzayo kunye ne-extractables yamanyathelo asebenzayo eqela elisebenzayo kwimveliso yeyeza ye-parenteral kunye ne-ophthalmic (PODP).PDA ] Pharm Sci Technol.2013;67(5):430-447.

[4] Wang W, Ignatius AA, Thakkar SV.Impembelelo yokungcola okushiyekileyo kunye nokungcola kwiprotheyini yokuzinza.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] I-Paudel K, i-Hauk A, i-Maier TV, i-Menzel R. Iimpawu zobungakanani bezinto ezivuzayo zitshona kwi-biopharmaceutical downstream processing.I-Eur J Pharmaceut Sci.2020;143:1 05069.

[6] United States Food and Drug Administration FDA.21 CFR Sec.211.65, Ukwakhiwa kwezixhobo.Ihlaziywe ukususela nge-1 ka-Epreli 2019.

[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Izikhongozeli zemveliso yeziyobisi kunye nokuvalwa.Ihlaziywe ukususela nge-1 ka-Epreli 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Ukusetyenziswa kwe-ethanol ye-binary ethanol / imodeli yezisombululo zamanzi ukulinganisa ukusebenzisana phakathi kwezinto zeplastiki kunye nokuqulunqwa kwamayeza.[Appl Polvmer Sci.2003:89 (4): 1049- 1057.

[9] BioPhorum Operations Group BPOG.Isikhokelo esigqwesileyo sovavanyo lokutsalwa kwepolymeric usetyenziso olunye olusetyenziswa kwimveliso ye-biopharmaceutical.BioPhorum Operations Group Ltd (ushicilelo olukwi-intanethi);2020.

[10] Khan TA, Mahler HC, Kishore RS.Ukusebenzisana okuphambili kwama-surfactants ekuqulunqweni kweeprotheyini zonyango: uphononongo.FurJ Pharm Riopharm.2015;97(Pt A):60- -67.

[11] United States iSebe lezeMpilo kunye neeNkonzo zoLuntu, uLawulo lokuTya kunye neDrugs FDA, iZiko loVavanyo lweDrugs kunye noPhando lweCDER, iZiko loVavanyo lweBiologics kunye noPhando lweCBER.Isikhokelo kushishino - uvavanyo lwe-immunogenicity

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Iziphumo zemiphezulu kunye nezinto ezivuzayo kuzinzo lwebiopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Ukuthotywa kwe-polysorbates ye-20 kunye ne-80 kunye nefuthe elinokubakho ekuzinzeni kwe-biotherapeutics.Pharm Res.2011;28(5):1194-1210.