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Kuzivikanwa kweOxidizing Leachable kubva kuClinical Syringe Rubber Stopper

Kamwechete-kushandisa polymeric zvinhu zviri kuwedzera kushandiswa mune akasiyana biopharmaceutical kugadzirisa matanho.Izvi zvinogona kunyanya kuve zvakakonzerwa nemhando dzakasiyana-siyana dzemashandisirwo uye kuchinjika kwakabatana uye kuchinjika, pamwe nemitengo yakaderera uye nekuti kuchenesa kwekuchenesa hakudiwi.[1][2]

Kazhinji, pasi pemamiriro ekushandiswa akajairwa kutama makemikari makomisheni anonzi "anobvisika," nepo macom-pound anotama ari pasi pemamiriro emurabhoritari akawandisa anowanzo kunzi "zvinobviswa."Kuitika kwezvinobvisika kunogona kunyanya kuve kwekunetsekera kukuru maererano neindasitiri yezvokurapa, sezvo mapuroteni ekurapa achiwanzoita gadziriso yezvimiro zvinogona kukonzerwa nekuvapo kwezvinosvibisa, kana izvo zvikaita mapoka anoshanda anoshanda.[3][4]Leaching kubva kuzvinhu zvekutonga zvinogona kutorwa senjodzi huru, kunyangwe nguva yekuonana ingasava yakarebesa kana ichienzaniswa nechigadzirwa chenguva refu yekuchengetedza.[5]
Nezvekudiwa kwemitemo, US Code yeFederal Regulations Title 21 inotaura kuti midziyo yekugadzira[6] pamwe nekuvharwa kwemidziyo[7] hazvizoshandura kuchengetedzeka, kunaka kana kuchena kwemushonga.Nekuda kweizvozvo uye kuitira kuve nechokwadi chemhando yechigadzirwa uye kuchengetedzwa kwevarwere, kuitika kwezvinosvibisa izvi, izvo zvinogona kubva muhuwandu hwakawanda hweDP yekubata zvinhu, inoda kutariswa uye kudzorwa mumatanho ese ekugadzirisa, panguva yekugadzira, kuchengetedza uye kutonga kwekupedzisira.
Sezvo zvinhu zvekutonga zvichiwanzo kurongerwa semidziyo yekurapa, vatengesi nevagadziri vanowanzo tarisa uye kuongorora kuitika kwemakemikari anotama zvichienderana nekushandiswa kunenge kuri kushandiswa kwechimwe chigadzirwa, semuenzaniso, emabhegi ekupinza, chete mhinduro ine mvura irimo, semuenzaniso, 0.9% (w) /v) NaCl, inoongororwa.Zvisinei, zvakamboratidzwa kuti kuvapo kwekugadzirwa kwezvinhu zvine solubilizing properties, zvakadai seprotein yekurapa pachayo kana vasiri-ionic surfactants inogona kuchinja uye kuwedzera kutama kwemaitiro asiri epolar kana achienzaniswa nemhinduro dzakapfava dzemvura.[7][8] ]
Naizvozvo chaive chinangwa chepurojekiti iripo kuona zvingangove zvinoburitsa makomisheni kubva kune sirinji yekiriniki inowanzo shandiswa.Nekudaro, isu takaita akateedzera-mu-kushandisa zvidzidzo zvinogoneka tichishandisa aqueous 0.1% (w/v) PS20 senge DP surrogate mhinduro.Izvo zvakawanikwa zvinogadziriswa zvinogadziriswa zvakaongororwa neyakajairwa extractable uye leachables analytical maitiro.Sirinji zvikamu zvakapatsanurwa kuti zvionekwe kwaibvisike kubvisika kwacho.[9]
Munguva ye-mu-kushandisa inobuda yekudzidza pane yakashandiswa nekiriniki uye CE-yakasimbiswa yekuraswa manejimendi sirinji ingangoita carcinogenic41 kemikari yemakemikari, iyo 1,1,2,2-tetrachloroethane yakaonekwa muhuwandu huri pamusoro peiyo kubva kuICH M7-yakatorwa analytical evaluation threshold (AET). )Kuferefeta kwakadzama kwakatangwa kuti paonekwe chivhariso cherabha sechinhu chikuru cheTCE. [10]
Hongu, isu taigona kuratidza pachena kuti TCE yanga isingabvisike kubva pachivharo cherabha.Pamusoro pezvo, kuyedza kwakaratidza kuti kusvika parizvino komboni isingazivikanwe ine oxidizing zvimiro yaive ichidonha kubva pane chivharo cherabha, chaigona kuita oxidize DCM kuenda kuTCE.[11]
Kuti tizive mukomboni weLeaching, chivhariso cherabha uye chinobuda chayo chaive chakasiyana-siyana chekuongorora nzira.Makasiana eorganic peroxides, anogona kushandiswa semapolymerization ekutanga panguva yekugadzirwa kwepurasitiki, zvinhu zvakaongororwa nekuda kwekugona kwavo kuita oxidize DCM kuTCE. Nekusimbisa kusinganzwisisike kweiyo intact Luperox⑧ 101 chimiro seyo oxidizing inobvisika komboni, kuongororwa kweNMR kwakaitwa.Iyo methanolic rabha inobvisa uye methanolic Luperox 101 referensi chiyero chakapepetwa kusvika pakuoma.Izvo zvakasara zvakagadziriswa mu methanol-d4 uye zvakaongororwa neNMR.Iyo polymerization initiator Luperox⑧101 yakasimbiswa kuve iyo oxidizing inobvirika yeinoraswa sirinji rabha chivharo.[12]
Nechidzidzo chakapihwa pano, vanyori vanovavarira kusimudzira ruzivo nezve kemikari leaching propensity kubva kukiriniki inoshandiswa manejimendi zvinhu, kunyanya zvine chekuita nekuvapo kwe "asingaoneki" asi anonyanya kuita makemikari leaching.Kuongorora kweTCE kunogona kunge kuri nzira inochinja-chinja uye iri nyore yekutarisa DP mhando mumatanho ese ekugadzirisa uye nekudaro kubatsira kuchengetedzeka kwevarwere.[13]

References

[1] Shukla AA, Gottschalk U. Inoshandiswa kamwe chete matekinoroji anoraswa ekugadzira biopharmaceutical.Trends Biotechnol.2013;31(3):147-154.

[2] Lopes AG.Kushandisa kamwechete muindasitiri yebiopharmaceutical: ongororo yezvino tech-nology maitiro, matambudziko uye zvisingakwanisi.Food Bioprod Process.2015;93:98-114.

[3] Paskiet D, Jenke D, Bhora D, Houston C, Norwood DL, Markovic I. The Product QualityResearch Institute (PQRI) inobvisika uye inobvisirwa kushanda kweboka zvirongwa zveparenteral uye ophthalmic drug product (PODP).PDA ] Pharm Sci Technol.2013;67(5):430- 447.

[4] Wang W, Ignatius AA, Thakkar SV.Mhedzisiro yezvakasara zvakasvibiswa uye zvinosvibisa pane protein kugadzikana.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] Paudel K, Hauk A, Maier TV, Menzel R. Quantitative characterization of leachables sinks in biopharmaceutical downstream processing.Eur J Pharmaceut Sci.2020;143:1 05069.

[6] United States Food and Drug Administration FDA.21 CFR Sec.211.65, Zvigadzirwa zvekuvaka.Yakadzokororwa kubva muna Kubvumbi 1, 2019.

[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Mishonga yezvigadzirwa zvemishonga uye kuvhara.Yakadzokororwa kubva Kubvumbi 1, 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Kushandiswa kwebhinari ethanol / mvura yemuenzaniso mhinduro kutevedzera kupindirana pakati pezvinhu zvepurasitiki nekugadzirwa kwemishonga.[Appl Polvmer Sci.2003:89(4):1049- 1057.

[9] BioPhorum Operations Boka BPOG.Yakanakisa dhizaini dhairekitori yezvinotorwa kuyedzwa kwepolymeric imwechete-kushandisa zvikamu zvinoshandiswa mukugadzira biopharmaceutical.BioPhorum Operations Group Ltd (kudhindwa kwepamhepo);2020.

[10] Khan TA, Mahler HC, Kishore RS.Kudyidzana kwakakosha kweva surfactants mukurapa kweprotein formulations: wongororo.FurJ Pharm Riopharm.2015;97(Pt A):60- -67.

[11] United States Department of Health and Human Services, Food and Drug Administration FDA, Center for Drug Evaluation and Research CDER, Center for Biologics Evaluation uye Reseach CBER.Nhungamiro yeindasitiri - immunogenicity assessement

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Mhedzisiro yenzvimbo uye zvinobvisika pakugadzikana kwebiopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Kushatiswa kwepolysorbates 20 uye 80 uye inogona kukanganisa kugadzikana kwebiotherapeutics.Pharm Res.2011;28(5):1194-1210.