izindaba

Ukuhlonzwa Kwe-Oxidizing Leachable kusuka ku-Clinical Syringe Rubber Stopper

Izinto ze-polymeric ezisetshenziswa kanye ziya ngokuya zisetshenziswa ezinyathelweni zokucubungula ze-biopharmaceutical .Lokhu kungase kubangelwe ububanzi bezinhlelo zabo zokusebenza kanye nokuguquguquka okuhlobene nokuvumelana nezimo, kanye nezindleko zabo eziphansi futhi ngenxa yokuthi ukuqinisekiswa kokuhlanza akudingekile.[1][2]

Ngokuvamile, ngaphansi kwezimo ezijwayelekile zokusetshenziswa kwezinhlanganisela zamakhemikhali ezifudukayo zibizwa ngokuthi “okuvuzekayo,” kuyilapho inhlanganisela efudukayo ngaphansi kwezimo eziyihaba zaselabhorethri zivame ukubizwa ngokuthi “okukhiphekayo.”Ukwenzeka kwezinto ezivuzayo kungase kukhathaze kakhulu maqondana nemboni yezokwelapha, njengoba amaprotheni okwelapha evame ukuthambekela ekuguqulweni kwesakhiwo okungase kubangelwe ukuba khona kokungcola, uma lawo maqembu esebenza ngamandla.[3][4]Ukukhishwa ezintweni zokuphatha kungabhekwa njengengcuphe enkulu, nakuba isikhathi sokuxhumana singase singabi side kakhulu uma siqhathaniswa nokugcinwa komkhiqizo isikhathi eside.[5]
Ngokuphathelene nezidingo zokulawula, I-US Code of Federal Regulations Title 21 ithi okokusebenza kokukhiqiza[6] kanye nokuvalwa kwamabhokisi[7] ngeke kuguqule ukuphepha, ikhwalithi noma ubumsulwa bomuthi.Ngenxa yalokho futhi ukuze kuqinisekiswe ikhwalithi yomkhiqizo kanye nokuphepha kweziguli, ukwenzeka kwalokhu kungcola, okungase kusuke enanini elikhulu lezinto zokuxhumana ze-DP, kudinga ukugadwa nokulawulwa kuzo zonke izinyathelo zokucubungula, ngesikhathi sokukhiqiza, ukugcinwa nokuphathwa kokugcina.
Njengoba izinto zokuphatha ngokuvamile zihlukaniswa njengezisetshenziswa zezokwelapha, abahlinzeki kanye nabakhiqizi bavame ukunquma futhi bahlole ukwenzeka kwabafuduki bamakhemikhali ngokuya ngokusetshenziswa okuhlosiwe komkhiqizo othile, isb, izikhwama zokumnika, kuphela isixazululo esinamanzi esiqukethwe, isb, 0.9% (w /v) I-NaCl, iyahlolwa.Kodwa-ke, ngaphambili kwaboniswa ukuthi ukuba khona kwezithako zokwakheka ezinezakhiwo ezincibilikisayo, njengephrotheni yokwelapha ngokwayo noma ama-non-ionic surfactants angase ashintshe futhi athuthukise ukuthambekela kokufuduka kwezinhlanganisela ezingezona ze-polar uma kuqhathaniswa nezixazululo ezilula ezinamanzi.[7][8] ]
Ngakho-ke bekuyinhloso yephrojekthi yamanje ukuhlonza izinhlanganisela ezingase ziphume esinjeni esisetshenziswa kakhulu somtholampilo.Ngakho-ke, senze izifundo ezilingisayo ezivulelekayo sisebenzisa i-aqueous 0.1% (w/v) PS20 njengesixazululo se-DP.Izixazululo ezitholakalayo ezitholakalayo zahlaziywa ngokukhipha okujwayelekile kanye nezindlela zokuhlaziya ezivuzayo.Izingxenye zesirinji zahlakazwa ukuze kuhlonzwe umthombo oyinhloko okhiphekayo.[9]
Ngesikhathi socwaningo lwezinto ezivuzayo ezisetshenziswayo esirinjini esilahlwayo esisetshenziswe emtholampilo kanye ne-CE-certified CE, kwatholwa ikhemikhali engaba yi-carcinogenic41, okuyi-1,1,2,2-tetrachloroethane ekugxilisweni kwayo ngaphezu komkhawulo wokuhlaziya osuselwa ku-ICH M7 (AET). ).Kwaqalwa uphenyo olunzulu ukuze kuhlonzwe isivalo senjoloba esiqukethwe njengomthombo oyinhloko we-TCE.[10]
Ngempela, singakhombisa ngokungananazi ukuthi i-TCE ibingeyona into evulelekayo esivimbeni senjoloba.Ngaphezu kwalokho, ucwaningo lwembula ukuthi inhlanganisela engaziwa kuze kube manje enezakhiwo ezikhipha i-oxidizing yayiphuma esitobhini senjoloba, eyayikwazi ukukhipha i-DCM ibe yi-TCE.[11]
Ukuze kuhlonzwe isakhi esicwiliswayo, isivalo senjoloba kanye nokukhishwa kwayo kwaphawulwa ngezindlela ezihlukahlukene zokuhlaziya.Ama-peroxides ahlukahlukene e-organic, angasetshenziswa njengabaqalisi be-polymerization ngesikhathi sokwenziwa kwepulasitiki, izinto ezisetshenziswayo zaphenywa ngamakhono azo okukhipha i-DCM ku-TCE. Ukuze uthole ukuqinisekiswa okungaguquki kwesakhiwo se-Luperox⑧ 101 esingaguquki njengenhlanganisela evuzekayo ene-oxidizing, ukuhlaziya kwe-NMR kwenziwa.Ukukhishwa kwerabha ye-methanolic kanye nezinga lesithenjwa se-methanolic Luperox 101 kuhwamuke kwaba komile.Izinsalela zakhiwe kabusha ku-methanol-d4 futhi zahlaziywa yi-NMR.I-polymerization initiator i-Luperox⑧101 yaqinisekiswa kanjalo ukuthi ikwazi ukuvuzeka oksijini yesivalo senjoloba yesirinji esilahlwayo.[12]
Ngocwaningo olwethulwe lapha, ababhali bahlose ukuqwashisa mayelana nokuthambekela kwamakhemikhali aphuma ezintweni zokuphatha ezisetshenziswa emtholampilo, ikakhulukazi maqondana nokuba khona kwamakhemikhali “angabonakali” kodwa asebenza kakhulu.Ngakho-ke ukuqapha kwe-TCE kungase kube indlela eguquguqukayo nefanele yokuqapha ikhwalithi ye-DP kuzo zonke izinyathelo zokucubungula futhi ngaleyo ndlela kube negalelo ekuphepheni kweziguli.[13]

Izithenjwa

[1] I-Shukla AA, i-Gottschalk U. Ubuchwepheshe obusetshenziswa kanye kuphela bokukhiqiza i-biopharmaceutical.Amathrendi e-Biotechnol.2013;31(3):147-154.

[2] Lopes AG.Ukusetshenziswa kanye embonini ye-biopharmaceutical: ukubuyekezwa komthelela wamanje we-tech-nology, izinselele kanye nemikhawulo.Inqubo ye-Food Bioprod.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 kanye nezinhlelo zokusebenza zeqembu elisebenzayo ezikhishwayo zomkhiqizo wezidakamizwa we-parenteral kanye ne-ophthalmic (PODP).PDA ] Pharm Sci Technol.2013;67(5):430-447.

[4] Wang W, Ignatius AA, Thakkar SV.Umthelela wokungcola okusele kanye nokungcola ekuzinzeni kwamaprotheni.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] I-Paudel K, i-Hauk A, i-Maier TV, i-Menzel R. Ukuchazwa kokulinganisa kwezinto ezivuzayo kuzika ekucutshungulweni kwe-biopharmaceutical downstream.I-Eur J Pharmaceut Sci.2020;143:1 05069.

[6] I-United States Food and Drug Administration FDA.21 CFR Sec.211.65, Ukwakhiwa kwemishini.Kubuyekezwe kusukela ngo-Ephreli 1, 2019.

[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Iziqukathi zomkhiqizo wezidakamizwa nokuvalwa.Kubuyekezwe kusukela ngo-Ephreli 1, 2020.

[8] U-Jenke DR, u-Brennan J, u-Doty M, u-Poss M. Ukusetshenziswa kwezixazululo zemodeli ye-ethanol kanambambili/zamanzi ukulingisa ukusebenzisana phakathi kwempahla yepulasitiki nokwakheka kwemithi.[I-Appl Polvmer Sci.2003:89(4):1049- 1057.

[9] I-BioPhorum Operations Group BPOG.Umhlahlandlela wokuzijwayeza ongcono kakhulu wokuhlolwa kwezinto ezikhishwayo zezingxenye ezisetshenziswa kanye ze-polymeric ezisetshenziswa ekukhiqizeni i-biopharmaceutical.I-BioPhorum Operations Group Ltd (ukushicilelwa ku-inthanethi);2020.

[10] Khan TA, Mahler HC, Kishore RS.Ukusebenzisana okubalulekile kwama-surfactants ekwakhiweni kwamaprotheni okwelapha: ukubuyekezwa.I-FurJ Pharm Riopharm.2015;97(Pt A):60- -67.

[11] Umnyango Wezempilo Nezinsizakalo Zabantu wase-United States, Ukuphathwa Kwezokudla Nezidakamizwa i-FDA, Isikhungo Sokuhlola Izidakamizwa Nokucwaninga CDER, Isikhungo Sokuhlola I-BiologicsEvaluation kanye Nokucwaninga CBER.Isiqondiso semboni - ukuhlolwa kwe-immunogenicity

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Imithelela yezindawo kanye nezinto ezivuzayo ekuzinzeni kwe-biopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Ukucekelwa phansi kwe-polysorbates 20 kanye ne-80 kanye nomthelela wawo ongaba khona ekuzinzeni kwe-biotherapeutics.I-Pharm Res.2011;28(5):1194-1210.