xov xwm

Kev txheeb xyuas ntawm Oxidizing Leachable los ntawm Clinical Syringe Rubber Stopper

Ib leeg-siv cov ntaub ntawv polymeric yog nce siv nyob rau hauv ntau yam biopharmaceutical ua cov kauj ruam.Qhov no tuaj yeem raug ntaus nqi rau lawv cov kev siv ntau yam thiab cov kev sib txuas yooj yooj yim thiab yoog raws, nrog rau lawv cov nqi qis thiab vim tsis tas yuav tsum muaj kev saib xyuas kev tu cev.[1][2]

Feem ntau, nyob rau hauv ib txwm siv tej yam kev mob migrating tshuaj compounds yog hu ua "leachables," thaum com-pounds migrate nyob rau hauv exaggerated laboratory tej yam kev mob feem ntau hu ua "extractables."Qhov tshwm sim ntawm leachables tej zaum espe-cially yuav muaj kev txhawj xeeb ntau dua nrog rau kev lag luam kho mob, raws li kev kho cov proteins feem ntau nws muaj feem cuam tshuam rau cov qauv kev hloov kho uas tshwm sim los ntawm qhov muaj cov kab mob sib kis, yog tias cov dais muaj cov pab pawg ua haujlwm zoo.[3][4]Leaching los ntawm kev tswj cov ntaub ntawv tuaj yeem suav hais tias yog qhov kev pheej hmoo siab, txawm hais tias lub sijhawm tiv tauj yuav tsis ntev heev piv rau cov khoom khaws cia mus ntev.[5]
Raws li txoj cai tswjfwm, US Code of Federal Regulations Title 21 hais tias cov khoom tsim khoom[6] nrog rau cov thawv kaw[7] yuav tsis hloov qhov kev nyab xeeb, zoo lossis purity ntawm cov tshuaj.Yog li ntawd thiab txhawm rau ua kom cov khoom lag luam zoo thiab kev nyab xeeb ntawm cov neeg mob, qhov tshwm sim ntawm cov kab mob no, uas tuaj yeem tshwm sim los ntawm ntau cov ntaub ntawv DP tiv tauj, yuav tsum tau saib xyuas thiab tswj xyuas thoob plaws txhua kauj ruam ua, thaum lub sijhawm tsim khoom, khaws cia thiab kev tswj xyuas zaum kawg.
Txij li thaum cov ntaub ntawv tswj hwm feem ntau muab faib ua cov khoom siv kho mob, cov chaw muag khoom thiab cov chaw tsim khoom feem ntau txiav txim siab thiab ntsuas qhov tshwm sim ntawm cov tshuaj migrants raws li kev npaj siv cov khoom tshwj xeeb, piv txwv li, rau cov hnab ntim dej, tsuas yog cov tshuaj aqueous muaj, piv txwv li, 0.9% (w /v) NaCl, raug tshuaj xyuas.Txawm li cas los xij, yav dhau los nws tau pom tias muaj cov khoom xyaw tsim nrog cov khoom siv solubilizing, xws li cov protein kho nws tus kheej lossis cov tsis-ionic surfactants tuaj yeem hloov pauv thiab txhim kho txoj kev tsiv teb tsaws ntawm cov tebchaw uas tsis yog-polar piv rau cov tshuaj aqueous yooj yim.[7][8 ]
Yog li ntawd, nws yog lub hom phiaj ntawm txoj haujlwm tam sim no txhawm rau txheeb xyuas qhov muaj peev xwm leaching compounds los ntawm kev siv tshuaj kho mob syringe.Li no, peb tau simulated nyob rau hauv-siv leachable kev tshawb fawb siv aqueous 0.1% (w/v) PS20 raws li ib tug DP surrogate tov.Cov kev daws tau leachables tau txheeb xyuas los ntawm cov txheej txheem extractables thiab leachables analytical le caag.Cov syringe Cheebtsam raug disassembled los txheeb xyuas cov thawj leachable tso tawm qhov chaw.[9]
Thaum lub sij hawm ib tug in-siv leachables kawm nyob rau hauv ib lub tsev kho mob siv thiab CE-certified pov tseg kev tswj koob txhaj tshuaj muaj peev xwm carcinogenic41 chemical compound, uas yog 1,1 ,2,2-tetrachloroethane tau kuaj pom nyob rau hauv cov concentrations saum toj no los ntawm ICH M7-derived analytical soj ntsuam pib (AET ).Kev tshawb xyuas meej tau pib txhawm rau txheeb xyuas cov roj hmab uas muaj roj hmab uas yog thawj qhov chaw TCE.[10]
Tseeb tiag, peb tuaj yeem qhia meej meej tias TCE tsis yog ib qho kev tshem tawm ntawm cov roj hmab stopper.Tsis tas li ntawd, qhov kev sim qhia tau hais tias tam sim no tsis paub qhov sib xyaw nrog oxidizing zog yog leaching los ntawm cov roj hmab stopper, uas muaj peev xwm oxidize DCM rau TCE.[11]
Txhawm rau txheeb xyuas cov leaching compound, cov roj hmab stopper thiab nws cov extract tau tus cwj pwm nrog ntau yam kev tshuaj ntsuam xyuas.Different organic peroxides, uas tuaj yeem siv los ua polymerization pib thaum lub sij hawm tsim cov yas, cov khoom raug tshawb xyuas rau lawv lub peev xwm los oxidize DCM rau TCE. Rau qhov kev lees paub tsis tseeb ntawm qhov tsis zoo Luperox⑧ 101 qauv raws li oxidizing leachable compound, NMR tsom xam tau ua.Ib qho methanolic roj hmab extract thiab ib tus qauv siv methanolic Luperox 101 tau evaporated rau dryness.Cov residues tau rov tsim dua hauv methanol-d4 thiab tshuaj xyuas los ntawm NMR.Lub polymerization pib Luperox⑧101 yog li paub tseeb tias yog oxidizing leachable ntawm cov syringe roj hmab stopper pov tseg.[12]
Nrog rau qhov kev nthuav qhia no, cov kws sau ntawv tsom mus rau kev paub txog cov tshuaj leaching propensity los ntawm kev siv cov ntaub ntawv kho mob, tshwj xeeb tshaj yog hais txog qhov muaj "tsis pom" tab sis cov tshuaj leaching muaj zog heev.Kev soj ntsuam ntawm TCE yog li no yuav yog ib txoj hauv kev yooj yim thiab yooj yim los saib xyuas DP zoo thoob plaws txhua kauj ruam ua thiab yog li pab txhawb rau cov neeg mob kev nyab xeeb.[13]

Cov ntaub ntawv

[1] Shukla AA, Gottschalk U. Tib-siv pov tseg technologies rau biopharmaceutical manufacturing.Trends Biotechnol.2013; 31(3):147-154.

[2] Lopes AG.Ib leeg-siv hauv kev lag luam biopharmaceutical: kev tshuaj xyuas txog tam sim no tech-nology cuam tshuam, cov nyom thiab kev txwv.Khoom noj khoom haus Bioprod txheej txheem.2015; 93:98-114.

[3] Paskiet D, Jenke D, Pob D, Houston C, Norwood DL, Markovic I. Lub Tsev Kawm Ntawv Qib Siab Cov Khoom Siv Tshawb Fawb (PQRI) leachables thiab extractables ua hauj lwm pab pawg thawj coj cov khoom siv tshuaj tiv thaiv kab mob thiab ophthalmic (PODP).PDA] Pharm Sci Technol.2013; 67(5):430-447.

[4] Wang W, Ignatius AA, Thakkar SV.Kev cuam tshuam ntawm residual impurities thiab cov kab mob ntawm cov protein stability.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] Paulel K, Hauk A, Maier TV, Menzel R. Quantitative characterization of leachables sinks in biopharmaceutical downstream processing.Eur J Pharmaceut Sci.Xyoo 2020; 143: 105069.

[6] United States Food and Drug Administration FDA.21 CFR Sec.211.65, Kev tsim khoom siv.Hloov kho thaum lub Plaub Hlis 1, 2019.

[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Cov khoom ntim tshuaj thiab kaw.Hloov kho thaum lub Plaub Hlis 1, 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Kev siv binary ethanol/dej qauv daws teeb meem los ua kom muaj kev cuam tshuam ntawm cov khoom siv yas thiab cov tshuaj formulations.[Appl Polvmer Sci.2003:89(4):1049-1057.

[9] BioPhorum Operations Group BPOG.Cov kev coj ua zoo tshaj plaws rau kev sim extractables ntawm polymeric ib leeg siv cov khoom siv hauv biopharmaceutical manufacturing.BioPhorum Operations Group Ltd (kev tshaj tawm online);2020.

[10] Khan TA, Mahler HC, Kishore RS.Kev sib cuam tshuam tseem ceeb ntawm surfactants hauv kev kho cov protein ntau: kev tshuaj xyuas.FurJ Pharm Riopharm.2015; 97(Pt A): 60- -67.

[11] Tebchaws Asmeskas Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv thiab Tib Neeg, Kev Tswj Xyuas Khoom Noj thiab Tshuaj FDA, Lub Chaw Rau Tshuaj Ntsuam Xyuas Tshuaj thiab Tshawb Fawb CDER, Lub Chaw Saib Xyuas Kev Ntsuam Xyuas Biologics thiab Tshawb Fawb CBER.Kev taw qhia rau kev lag luam - kev ntsuas immunogenicity

[12] Bee JS, Randolph TW, Carpenter JF, Npis Sov SM, Dimitrova MN.Cov teebmeem ntawm qhov chaw thiab leachables ntawm kev ruaj ntseg ntawm biopharmaceuticals.J Pharmaceut Sci.2011; 100 (10): 4158--4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Qhov degradation ntawm polysorbates 20 thiab 80 thiab nws cov peev xwm cuam tshuam rau kev ruaj ntseg ntawm biotherapeutics.Pharm Res.2011;28(5):1194-1210.