litaba

Ho Khetholloa ha Oxidizing Leachable ho tsoa ho Clinical Syringe Rubber Stopper

Lisebelisoa tsa polymeric tsa tšebeliso e le 'ngoe li ntse li sebelisoa haholo mehatong e fapaneng ea ts'ebetso ea biopharmaceutical.Sena se ka amahanngoa haholo le mefuta e mengata ea lits'ebetso le ho fetoha ha maemo ho amanang le ho ikamahanya le maemo, hammoho le litšenyehelo tsa bona tse batlang li le tlase le hobane netefatso ea tlhoekiso ha e hlokehe.[1][2]

Ka kakaretso, tlas'a maemo a tloaelehileng a ts'ebeliso ea lik'hemik'hale tse fallang li bitsoa "tse ka bulehang," athe lik'hemik'hale tse falla tlas'a maemo a feteletseng a laboratori hangata li bitsoa "lintho tse ka ntšitsoeng."Ho ba teng ha lintho tse ka kolohang ho ka ameha haholo indastering ea bongaka, kaha liprotheine tsa kalafo li atisa ho ba le liphetoho tse ka bakoang ke boteng ba lintho tse silafatsang, haeba li na le lihlopha tse sebetsang hantle. [3] [4]Leaching thepa ea tsamaiso e ka nkoa e le kotsi e kholo, le hoja nako ea ho kopana e ka 'na ea se ke ea e-ba telele haholo ha e bapisoa le polokelo ea nako e telele ea sehlahisoa.[5]
Mabapi le litlhoko tsa taolo, US Code of Federal Regulations Title 21 e bolela hore thepa ea ho etsa thepa[6] hammoho le ho koaloa ha lijana[7] li ke ke tsa fetola polokeho, boleng kapa bohloeki ba moriana.Ka lebaka leo le ho netefatsa boleng ba sehlahisoa le polokeho ea bakuli, ho hlaha ha litšila tsena, tse ka hlahang ho bongata bo boholo ba lisebelisoa tsa ho ikopanya le DP, li hloka ho hlahlojoa le ho laoloa mehatong eohle ea ts'ebetso, nakong ea tlhahiso, polokelo le tsamaiso ea ho qetela.
Kaha lisebelisoa tsa tsamaiso hangata li hlalosoa e le lisebelisoa tsa bongaka, hangata barekisi le bahlahisi ba etsa qeto le ho lekola liketsahalo tsa bafalli ba lik'hemik'hale ho latela sepheo sa tšebeliso ea sehlahisoa se itseng, mohlala, bakeng sa mekotla ea infusion, ke tharollo e nang le metsi feela, mohlala, 0.9% (w) /v) NaCl, ea hlahlojoa.Leha ho le joalo, pele ho ile ha bontšoa hore ho ba teng ha metsoako e entsoeng ka metsoako e nang le metsoako ea solubilizing, e kang protheine ea phekolo ka boeona kapa li-surfactants tse seng tsa ionic li ka fetoha le ho ntlafatsa tšekamelo ea ho falla ha metsoako e seng ea polar ha e bapisoa le tharollo e bonolo ea metsi. [7] [8] ]
Ka hona e ne e le sepheo sa morero oa hona joale ho tsebahatsa metsoako e ka 'nang ea tsoa ho tsoa ho sering e sebelisoang hangata ea kliniki.Kahoo, re ile ra etsa lithuto tse kentsoeng ka har'a ts'ebeliso re sebelisa metsi a 0.1% (w/v) PS20 joalo ka tharollo ea DP surrogate.Litharollo tse fumanoeng tse fumanehang li ile tsa hlahlobjoa ka mekhoa e tloaelehileng ea li-extractables le mekhoa ea tlhahlobo ea leachables.Likaroloana tsa syringe li ile tsa qhaqhoa ho khetholla mohloli oa mantlha o ka tsubeloang.[9]
Nakong ea phuputso ea lintho tse ka sebelisoang ka har'a syringe ea tsamaiso e sebelisoang ke tleliniki le CE-certified CE, k'hemik'hale e ka bang teng ea carcinogenic41, e leng 1,1,2,2-tetrachloroethane e ile ea fumanoa ka likhakanyo tse kaholimo ho moeli oa tlhahlobo ea tlhahlobo e tsoang ho ICH M7 (AET). ).Patlisiso e phethahetseng e ile ea qalisoa ho hlwaya sethibelo sa rabara e le mohloli oa mantlha oa TCE.[10]
Ehlile, re ka bonts'a ka mokhoa o hlakileng hore TCE e ne e se ntho e ka thijoang ho tsoa ho sethibelo sa rabara.Ho phaella moo, teko e senotse hore motsoako o sa tsejoeng ho fihlela joale o nang le thepa ea oxidizing e ne e le leaching ho tloha ho thibela rabara, e neng e khona ho oxidize DCM ho TCE.[11]
E le hore ho khethoe motsoako oa leaching, setopo sa rabara le sekhechana sa eona se ne se khetholloa ka mekhoa e sa tšoaneng ea ho hlahloba. Li-peroxide tse fapaneng tsa organic, tse ka sebelisoang e le li-polymerization initiator nakong ea tlhahiso ea polasetiki, lisebelisoa li ile tsa batlisisoa ka bokhoni ba tsona ba ho oxidize DCM ho TCE. Bakeng sa netefatso e sa tsitsang ea sebopeho sa Luperox⑧ 101 se sa fetoheng e le motsoako oa oxidizing o ka khonang, ho ile ha etsoa tlhahlobo ea NMR.Sesebelisoa sa rabara sa methanolic le maemo a referense ea methanolic Luperox 101 li ile tsa fetoha mouoane hore li ome.Masala a ile a tsosolosoa ka methanol-d4 'me a hlahlojoa ke NMR.Sesebelisoa sa polymerization Luperox⑧101 se ile sa netefatsoa hore ke sethibelo sa rabara se ka lahlehang sa seringe. [12]
Ka boithuto bo hlahisitsoeng mona, bangoli ba ikemiselitse ho hlokomelisa ka tšekamelo ea ho tsoa ha lik'hemik'hale ho tsoa ho lisebelisoa tsa tsamaiso tse sebelisoang ke bongaka, haholo mabapi le boteng ba lik'hemik'hale tse "sa bonahaleng" empa tse sebetsang haholo.Ka hona, ho beha leihlo TCE e ka ba mokhoa o feto-fetohang le o bonolo oa ho beha leihlo boleng ba DP methating eohle ea ts'ebetso, ka hona, ho kenya letsoho polokehong ea bakuli.[13]

Litšupiso

[1] Shukla AA, Gottschalk U. Litheknoloji tse sebelisoang hanngoe bakeng sa tlhahiso ea meriana ea likokoana-hloko.Mekhoa ea Biotechnol.2013;31(3):147-154.

[2] Lopes AG.Tšebeliso e le 'ngoe indastering ea biopharmaceutical: tlhahlobo ea phello ea theknoloji ea morao-rao, mathata le meeli.Mokhoa oa Bioprod oa Lijo.2015;93:98-114.

[3] Paskiet D, Jenke D, Ball D, Houston C, Norwood DL, Markovic I. The Product QualityResearch Institute (PQRI) leachables and extractable working group initiatives forparenteral and ophthalmic drug product (PODP).PDA ] Pharm Sci Technol.2013;67(5):430-447.

[4] Wang W, Ignatius AA, Thakkar SV.Tšusumetso ea litšila tse setseng le litšila holim'a botsitso ba protheine.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] Paudel K, Hauk A, Maier TV, Menzel R. Litšobotsi tse ngata tsa li-leachables li teba ka biopharmaceutical downstream processing.Eur J Pharmaceut Sci.2020;143:1 05069.

[6] United States Food and Drug Administration FDA.21 CFR Sec.211.65, Kaho ea lisebelisoa.E ntlafalitsoe ho tloha ka la 1 Mmesa 2019.

[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Lijana tsa lihlahisoa tsa lithethefatsi le ho koaloa.E ntlafalitsoe ho tloha ka la 1 Mmesa 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Tšebeliso ea litharollo tsa mohlala oa binary ethanol / metsi ho etsisa ho sebelisana pakeng tsa thepa ea polasetiki le lihlahisoa tsa meriana.[Appl Polvmer Sci.2003:89(4):1049- 1057.

[9] BioPhorum Operations Group BPOG.Tataiso e ntle ka ho fetisisa ea tlhahlobo ea lisebelisoa tsa lisebelisoa tsa polymeric tse sebelisoang ha ho etsoa tlhahiso ea biopharmaceutical.BioPhorum Operations Group Ltd (phatlalatso ea inthaneteng);2020.

[10] Khan TA, Mahler HC, Kishore RS.Litšebelisano tsa bohlokoa tsa li-surfactants mefuteng ea liprotheine ea kalafo: tlhahlobo.FurJ Pharm Riopharm.2015;97(Pt A):60- -67.

[11] Lefapha la United States la Bophelo bo Botle le Litšebeletso tsa Botho, Tsamaiso ea Lijo le Lithethefatsi FDA, Setsi sa Tlhahlobo ea Lithethefatsi le Lipatlisiso CDER, Center for Biologics Evaluation and Reseach CBER.Tataiso bakeng sa indasteri - tlhahlobo ea immunogenicity

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Liphello tsa bokaholimo le lintho tse ka lutlang botsitsong ba biopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Ho senyeha ha li-polysorbates 20 le 80 le tšusumetso e ka bang teng ho botsitso ba biotherapeutics.Pharm Res.2011;28(5):1194-1210.