Fa'ailoaina o se mea e mafai ona fa'asa'o mai le fa'ama'i fa'ama'i
O mea faʻaoga polymeric e tasi e faʻaaogaina o loʻo faʻaaogaina i laʻasaga eseese o le gaosiga o biopharmaceutical.O lenei mea e mafai ona mafua ona o le tele o latou faʻaoga ma le fesoʻotaʻi fetuutuunai ma fetuutuunai, faʻapea foʻi ma a latou tau maualalo ma ona e le manaʻomia se faʻamaoniga faʻamamaina.[1][2]
E masani lava, i lalo o tulaga masani o le faʻaaogaina o vailaʻau faʻaonaponei e taʻua o "leachables," ae o paʻu e femalagaʻi i lalo o tulaga faʻateleina falesuesue e masani ona taʻua o "mea e mafai ona aveeseina."O le tulai mai o le leachable atonu e sili atu ona popole e tusa ai ma pisinisi faafomai, aua o polotini togafitiga e masani ona faigofie i suiga o le fausaga e ono mafua ona o le i ai o mea leaga, pe afai o loʻo i ai i na vaega o loʻo gaoioi.[3][4]O le fa'amama mai mea tau pulega e mafai ona fa'apea o se fa'alavelave maualuga, e ui o le umi o feso'ota'iga atonu e le umi tele pe a fa'atusatusa i oloa teuina mo se taimi umi.[5]
E tusa ai ma mana'oga fa'atonutonu, o le US Code of Federal Regulations Title 21 o lo'o ta'u mai ai e faapea o meafaigaluega gaosi [6] fa'apea fo'i pusa tapuni[7] e le tatau ona suia le saogalemu, lelei po'o le mama o se vaila'au.O le mea lea ma ina ia mautinoa le lelei o oloa ma le saogalemu o tagata mamaʻi, o le tupu mai o nei mea leaga, e ono mafua mai i le tele o mea faʻafesoʻotaʻi DP, e manaʻomia ona mataʻituina ma pulea i laasaga uma o gaioiga, i le taimi o gaosiga, teuina ma le pulega mulimuli.
Talu ai o mea tau pulega e masani lava ona faʻavasegaina o masini faʻafomaʻi, e masani ona fuafua ma iloilo e le au faʻatau oloa ma le gaosiga o mea e tutupu mai vailaʻau e faʻatatau i le faʻaogaina o se oloa faʻapitoa, faʻataʻitaʻiga, mo taga infusion, naʻo le vai vai o loʻo i ai, eg, 0.9% (w. /v) NaCl, ua su'esu'eina.Ae ui i lea, na faʻaalia muamua o le i ai o mea faʻapipiʻi faʻatasi ai ma mea faʻafefeteina, e pei o le polotini therapeutic lava ia poʻo non-ionic surfactants e mafai ona suia ma faʻaleleia ai le femalagaiga o mea e le o polar compound pe a faatusatusa i vaifofo faigofie.[7][8] ]
O lea la na fa'amoemoe ai le poloketi o lo'o iai nei e fa'ailoa ai mea e mafai ona liu mai se tui fa'aoga masani.O le mea lea, na matou faia fa'ata'ita'iga i-fa'aogaina su'esu'ega fa'aogaina e fa'aaoga ai le vai 0.1% (w/v) PS20 e fai ma vaifofo sui DP.O vaifofo vai na maua na su'esu'eina e ala fa'ata'ita'i fa'ata'ita'i ma fa'ata'ita'iga e mafai ona maua.O vaega o le tui na talepeina ina ia iloa ai le puna muamua e mafai ona faamatuu atu.[9]
I le taimi o se su'esu'ega fa'aoga e mafai ona fa'aaogaina i luga o se tui fa'aoga tu'u'esea ma fa'amaonia e le CE, o se vaila'au fa'ama'i e ono mafai ona fa'ama'i pipisi, e ta'ua o le 1,1,2,2-tetrachloroethane na maua i fa'aputuga i luga a'e o le ICH M7 na maua mai i le fa'avae su'esu'ega au'ili'ili (AET). ).Na amata se su'esu'ega mae'ae'a e fa'ailoa ai le fa'aputu pa'u o lo'o iai o le puna muamua o le TCE.[10]
O le mea moni, e mafai ona matou fa'ailoa manino atu o le TCE e le'o se mea e fa'afefete mai le pa'u taofi.E le gata i lea, o le fa'ata'ita'iga na fa'aalia ai o se fa'alapotopotoga e le o iloa mamao ma mea fa'ama'i o lo'o tafe mai le pa'u pa'u, lea na mafai ona fa'ama'iina le DCM i le TCE.[11]
Ina ia mafai ona iloa le vaega leaching, o le paʻu taofi ma lona siʻosiʻomaga sa faʻavasegaina i metotia suʻesuʻe eseese. Eseese organic peroxides, e mafai ona faʻaaogaina e avea ma initiators polymerization i le taimi o le gaosiga o palasitika，mea na suʻesuʻeina mo o latou tomai e faʻamaʻi ai le DCM i le TCE. Mo se fa'amaoniga manino o le fausaga o le Luperox⑧ 101 o lo'o fa'ama'i fa'ama'i, na faia ai le su'esu'ega o le NMR.O se vaega o le pa'u methanolic ma le methanolic Luperox 101 fa'asino tulaga na fa'amamago.O toega na toe faʻaleleia i le methanol-d4 ma suʻesuʻeina e le NMR.O le polymerization initiator Luperox⑧101 na fa'amaonia mai o le fa'ama'i fa'ama'i fa'ama'i o le tui pa'u tu'u lafoa'i.[12]
Faatasi ai ma le suʻesuʻega o loʻo tuʻuina atu i inei, o loʻo faʻamoemoe le au tusitala e faʻalauteleina le faʻalauiloa e uiga i le faʻaogaina o vailaʻau mai mea faʻaoga faʻapitoa faʻapitoa, aemaise lava i le faʻatatau i le iai o vailaʻau faʻamaʻi "e le vaaia" ae sili ona malosi.O le mata'ituina o le TCE e ono avea ma auala fa'apitoa ma faigofie e mata'ituina ai le tulaga lelei o le DP i laasaga uma o gaioiga ma fa'apea ona saofagā i le saogalemu o gasegase.[13]
Fa'asinomaga
[1] Shukla AA, Gottschalk U. Fa'aoga tasi fa'aogaina tekinolosi fa'aaogaina mo le gaosiga o meaola fa'aola.Trends Biotechnol.2013;31(3):147-154.
[2] Lopes AG.Fa'aoga tasi i le alamanuia biopharmaceutical: o se toe iloiloga o a'afiaga fa'atekonolosi i le taimi nei, lu'itau ma tapula'a.Mea'ai Bioprod Process.2015;93:98-114.
[3] Paskiet D, Jenke D, Ball D, Houston C, Norwood DL, Markovic I. O le Product QualityResearch Institute (PQRI) leaachables and extractables 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.A'afiaga o mea leaga o totoe ma mea fa'aleagaina ile mautu o polotini.J Pharmaceut Sci.2014;103(5):1315-1330.
[5] Paudel K, Hauk A, Maier TV, Menzel R. Fa'avasegaga fa'afuainumera o le leachable goto i le biopharmaceutical fa'agaioia lalo.Eur J Pharmaceut Sci.2020;143: 1 05069.
[6] United States Food and Drug Administration FDA.21 CFR Sec.211.65, Fausia meafaigaluega.Toe fa'afouina ia Aperila 1, 2019.
[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Koneteina ma tapuni o oloa o fualaau.Toe fa'afouina ia Aperila 1, 2020.
[8] Jenke DR, Brennan J, Doty M, Poss M. Fa'aaogāina o vaifofo fa'ata'ita'i ethanol/vai e fa'ata'ita'i ai le fegalegaleaiga i le va o se mea palasitika ma fa'ama'i vaila'au.[Appl Polvmer Sci.2003:89(4):1049-1057.
[9] BioPhorum Operations Group BPOG.Fa'ata'ita'iga fa'ata'ita'iga sili mo su'ega e mafai ona maua mai o vaega fa'aoga tasi polymeric o lo'o fa'aogaina ile gaosiga ole biopharmaceutical.BioPhorum Operations Group Ltd (faasalalauga i luga ole laiga);2020.
[10] Khan TA, Mahler HC, Kishore RS.Fegalegaleaiga autu o surfactants i faʻasologa o polotini togafitiga: o se iloiloga.FurJ Pharm Riopharm.2015;97(Pt A):60- -67.
[11] Matagaluega o le Soifua Maloloina a le Iunaite Setete ma Auaunaga a Tagata, Pulea o Meaai ma Vailaau FDA, Nofoaga Autu mo Iloiloga Fualaau ma Suesuega CDER, Nofoaga Autu mo BiologicsEvaluation and Reseach CBER.Ta'iala mo alamanuia - su'esu'ega o le immunogenicity
[12] Bee JS, Randolph TW, Kamuta JF, Epikopo SM, Dimitrova MN.A'afiaga o luga ma mea e mafai ona fa'amama i le mautu o vaila'au fa'aola.J Pharmaceut Sci.2011;100 (10):4158- -4170.
[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Le faʻaleagaina o polysorbates 20 ma le 80 ma lona aʻafiaga i le mautu o biotherapeutics.Pharm Res.2011;28(5):1194-1210.
Taimi meli: Sep-23-2022