ozi

Nchọpụta nke Enwere ike ịgbanye Oxidizing site na Syringe Rubber Syringe Clinical

A na-eji ihe polymeric eme otu ihe na usoro nhazi biopharmaceutical dị iche iche.Enwere ike ịsị na nke a bụ n'ihi ngwa ngwa ha dịgasị iche iche yana mgbanwe na ngbanwe na ngbanwe emetụtara, yana ọnụ ahịa ha dị ntakịrị yana n'ihi na ọ dịghị achọrọ nkwado nhicha.[1][2]

N'ozuzu, n'ọnọdụ a na-ejikarị eme ihe, a na-akpọ ogige kemịkalụ na-akwaga dị ka "ihe a na-apụghị ịpụ apụ," ebe a na-akpọkarị com-pounds na-akwaga n'okpuru ọnọdụ ụlọ nyocha ekwubigara ókè.Ihe omume nke leachables nwere ike bụrụ nchegbu ka ukwuu n'ihe gbasara ụlọ ọrụ ahụike, ebe ọ bụ na protein ndị na-agwọ ọrịa na-adịkarị mfe na mgbanwe nhazi nke nwere ike ịkpata site na ọnụnọ nke mmetọ ahụ, ma ọ bụrụ na ndị ahụ na-arụ ọrụ na-arụ ọrụ.[3][4].Enwere ike iweta ịchafụ site na ihe nchịkwa dị ka nnukwu ihe egwu, ọ bụ ezie na oge kọntaktị nwere ike ọ gaghị adị ogologo ma e jiri ya tụnyere nchekwa ogologo oge.[5]
N'ihe gbasara usoro iwu chọrọ, US Code of Federal Regulations Title 21 na-ekwu na akụrụngwa nrụpụta[6] yana mmechi akpa[7] agaghị agbanwe nchekwa, ịdịmma ma ọ bụ ịdị ọcha nke ọgwụ.N'ihi ya na iji hụ na ịdị mma ngwaahịa na nchekwa ndị ọrịa, ihe omume nke mmetọ ndị a, nke nwere ike ịmalite site na ọnụ ọgụgụ buru ibu nke kọntaktị DP, kwesịrị ka a nyochaa ma na-achịkwa usoro nhazi niile, n'oge mmepụta, nchekwa na nchịkwa ikpeazụ.
Ebe ọ bụ na a na-ekewakarị ihe nchịkwa dị ka ngwaọrụ ahụike, ndị na-ebubata ya na ndị na-emepụta ihe na-ekpebi ma na-enyocha ọnọdụ nke ndị na-akwaga kemịkalụ dabere na ebumnuche nke otu ngwaahịa, dịka, maka akpa infusion, naanị ngwọta mmiri dị n'ime, dịka 0.9% (w) /v) NaCl, na-enyocha.Otú ọ dị, e gosipụtara na mbụ na ọnụnọ nke mmepụta ihe na-emepụta ihe na-emepụta ihe na-edozi ahụ, dị ka protein ọgwụgwọ n'onwe ya ma ọ bụ ndị na-abụghị ionic surfactants nwere ike gbanwee ma welie ọchịchọ ịkwaga nke ogige ndị na-abụghị polar ma e jiri ya tụnyere ngwọta mmiri dị mfe.[7] [8] ]
Ya mere, ọ bụ ebumnuche nke ọrụ a iji chọpụta ogige ndị nwere ike ịpụpụ site na sirinji a na-ejikarị eme ihe.N'ihi ya, anyị mere simulated in-eji leachable ọmụmụ na-eji aqueous 0.1% (w/v) PS20 dị ka DP surrogate ngwọta.A tụlere azịza leachables enwetara site na ụzọ nyocha ọkọlọtọ na usoro nyocha.A chịkọtara ihe ndị sirinji iji mata isi mmalite ewepụtara ya.[9]
N'oge a na-eji leachables ọmụmụ ihe na ụlọ ọgwụ na-eji ụlọ ọgwụ na CE-gbaara agbapụta nke mkpofu nchịkwa sirinji ihe nwere ike ime ihe nwere ike ime ihe na-akpata ọrịa carcinogenic41, ya bụ 1,1,2,2-tetrachloroethane, ahụrụ na mkpokọta n'elu nke ICH M7 sitere na ọnụ ụzọ nyocha nyocha (AET). ).A malitere nyocha nke ọma iji chọpụta ihe nkwụsị rọba dị n'ime ya dị ka isi mmalite TCE.[10]
N'ezie, anyị nwere ike igosi n'enweghị mgbagha na TCE abụghị ihe a na-esi na rọba kwụsị.Na mgbakwunye, nnwale ahụ gosiri na ihe a na-amaghị ama nke nwere akụrụngwa oxidizing na-agbapụta site na nkwụsị rọba, nke nwere ike oxidize DCM ruo TCE.[11]
Iji chọpụta ogige leaching ahụ, a na-eji ihe nyocha dị iche iche mara ihe nkwụsị roba na wepụ ya na usoro nyocha dị iche iche. Different organic peroxides, nke a pụrụ iji mee ihe dị ka polymerization initiators n'oge mmepụta nke plastik, a na-enyocha ihe onwunwe maka ikike ha iji oxidize DCM na TCE. Maka nkwenye na-enweghị mgbagha nke usoro Luperox ⑧ 101 adịghị emebi emebi dị ka ogige oxidizing leachable, e mere nyocha NMR.Mwepụta rọba methanolic na ụkpụrụ ntụaka methanol Luperox 101 ka ewepụrụ ka ọ bụrụ nkụ.Emegharịrị ihe fọdụrụ na methanol-d4 yana NMR nyochara ya.Ya mere, onye mmalite polymerization Luperox⑧101 ka akwadoro na ọ bụ oxidizing leachable nke ihe nkwụsị rọba sirinji a na-atụfu ya.[12]
Site n'ọmụmụ ihe e gosipụtara ebe a, ndị odee bu n'obi ime ka mmadụ mata banyere kemịkalụ leaching propensity sitere na ihe nchịkwa eji eme ụlọ ọgwụ, ọkachasị n'ihe gbasara ọnụnọ kemịkalụ "anaghị ahụ anya" mana ọ na-emeghachi omume nke ukwuu.Nleba anya nke TCE nwere ike bụrụ ụzọ dị mma ma dị mma iji nyochaa ogo DP n'oge usoro nhazi niile wee si otú a na-enye aka na nchekwa ndị ọrịa.[13]

Ntụaka

[1] Shukla AA, Gottschalk U. Teknụzụ ndị a na-atụfu n'otu ebe maka nrụpụta biopharmaceutical.Ọnọdụ Biotechnol.2013;31 (3): 147-154 .

[2] Lopes AG.Otu eji eme ihe na ụlọ ọrụ biopharmaceutical: nyocha nke mmetụta teknụzụ-nology dị ugbu a, ihe ịma aka na njedebe.Usoro Bioprod nri.2015;93:98-114 .

[3] Paskiet D, Jenke D, Bọọlụ D, Houston C, Norwood DL, Markovic I. The Product QualityResearch Institute (PQRI) leachables na extractables na-arụ ọrụ otu atumatu forparenteral na ophthalmic ọgwụ ngwaahịa (PODP).PDA] Pharm Sci Technol.2013;67 (5): 430- 447 .

[4] Wang W, Ignatius AA, Thakkar SV.Mmetụta nke ihe ndị fọdụrụ na adịghị ọcha na mmetọ na nkwụsi ike protein.J Pharmaceut Sci.2014; 103 (5): 1315-1330.

[5] Paudel K, Hauk A, Maier TV, Menzel R. Nkọwapụta ọnụọgụ nke leachables na-agbada na nhazi biopharmaceutical downstream.Ọnụ ego nke Eur J Pharmaceut Sci.2020;143: 1 05069.

[6] United States Food and Drug Administration FDA.21 CFR nkeji 211.65, Ihe eji arụ ọrụ.Emegharịrị ka Eprel 1, 2019.

[7] United States Food and Drug Administration FDA.21 CFR sec.211.94, Ngwa ngwaahịa ọgwụ na mmechi.Emegharịrị ka Eprel 1, 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Iji ọnụọgụ abụọ ethanol/mmiri ihe ngwọta na-eme ka mmekọrịta dị n'etiti ihe plastik na usoro ọgwụ.[Appl Polvmer Sci.2003:89 (4): 1049- 1057 .

[9] BioPhorum Operations Group BPOG.Ntuziaka omume kacha mma maka nnwale nke ihe eji eme otu polymeric ejiri na nrụpụta biopharmaceutical.BioPhorum Operations Group Ltd (mbipụta n'ịntanetị);2020.

[10] Khan TA, Mahler HC, Kishore RS.Mkpakọrịta dị mkpa nke ndị surfactants na nhazi protein ọgwụgwọ: nyocha.Ụlọ ọrụ FurJ Pharm Riopharm.2015;97 (Pt A): 60- -67 .

[11] Ngalaba Ahụike na Ọrụ Ndị Ọrụ United States, Nchịkwa nri na ọgwụ FDA, Center for Drug Evaluation and Research CDER, Center for BiologicsEvaluation and Reseach CBER.Ntuziaka maka ụlọ ọrụ - nyocha nke immunogenicity

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Mmetụta nke elu na leachables na nkwụsi ike nke biopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Mbelata nke polysorbates 20 na 80 na mmetụta ya nwere na nkwụsi ike nke biotherapeutics.Pharm Res.2011;28 (5): 1194-1210.