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Aqoonsiga Xakamaynta Oxidizing Leachable ee ka timaadda Joojiyaha Siringe Clinical

Qalabka polymeric-ka-la-isticmaalka ah ayaa si isa soo taraysa loogu isticmaalaa tillaabooyinka habaynta biopharmaceutical ee kala duwan.Tan waxaa inta badan loo nisbeyn karaa codsiyadooda kala duwan iyo dabacsanaanta la xiriirta iyo la qabsiga, iyo sidoo kale kharashkooda yar iyo sababtoo ah ansaxinta nadiifinta looma baahna.[1][2]

Guud ahaan, xaaladaha isticmaalka caadiga ah guuritaanka xeryahooda kiimikada waxaa loo tixraacaa sida "leachables," halka isku-dhafan ee ku haajiray xaaladaha shaybaarka la buunbuuniyay ayaa inta badan loo yaqaan "wax la saari karo."Dhacdooyinka leachable-gaar ahaan waxay noqon kartaa walaac weyn oo ku saabsan warshadaha caafimaadka, maadaama borotiinnada daweyntu ay inta badan u nugul yihiin wax ka beddelka qaabdhismeedka oo ay sababi karto joogitaanka wasakhooyinka, haddii kuwani ay wataan kooxo firfircoon oo firfircoon.[3][4]Ka-soo-baxa agabka maamulka waxa loo tixgelin karaa khatar sare, in kasta oo muddada xidhiidhka aanu aad u dheerayn marka loo eego kaydinta muddada-dheer ee alaabta.[5]
Marka la eego shuruudaha sharciyeynta, Xeerka Maraykanka ee Shuruucda Federaalka Ciwaanka 21 wuxuu dhigayaa in qalabka wax soo saarka[6] iyo sidoo kale xidhitaanka weelka[7] aysan beddeli doonin badbaadada, tayada ama nadiifnimada daroogada.Sidaa darteed iyo si loo hubiyo tayada badeecada iyo badbaadada bukaanka, dhacdada wasakhaysan, kuwaas oo laga yaabo inay ka soo jeedaan tirada badan ee qalabka xidhiidhka DP, waxay u baahan yihiin in la kormeero oo la xakameeyo dhammaan tallaabooyinka habaynta, inta lagu jiro wax soo saarka, kaydinta iyo maamulka kama dambaysta ah.
Maadaama agabka maamulka guud ahaan loo kala saaray qalab caafimaad, alaab-qeybiyeyaasha iyo soosaarayaashu waxay inta badan go'aamiyaan oo qiimeeyaan dhacdada soogalootiga kiimikada iyadoo loo eegayo isticmaalka loogu talagalay badeecad gaar ah, tusaale ahaan, bacaha faleebada, kaliya dareeraha aqueous ka kooban, tusaale, 0.9% (w) /v) NaCl, waa la baaraa.Si kastaba ha ahaatee, waxaa hore loo muujiyay in joogitaanka maaddooyinka qaabeynta leh guryaha milmiyeyaasha, sida borotiinka daweynta laftiisa ama kuwa aan-ionic surfactants ayaa laga yaabaa inay isbeddelaan oo ay kor u qaadaan u haajiridda xeryahooda non-polar marka la barbar dhigo xalalka aqueous fudud.[7][8]. ]
Sidaa darteed waxay ahayd ujeeddada mashruucan hadda socda si loo aqoonsado xeryahooda laga yaabo inay ka dareeraan saliingaha caadiga ah ee bukaan-socodka.Sidaa awgeed, waxaanu samaynay daraasado la adeegsan karo oo la adeegsan karo iyadoo la isticmaalayo aqueous 0.1% (w/v) PS20 sidii xal DP ah.Xalka la helay ee leachables waxaa lagu falanqeeyay hababka lafa-gur ee caadiga ah iyo kuwa leachables.Qaybaha saliingaha waa la kala saaray si loo aqoonsado isha siidaynta aasaasiga ah ee la nadiifin karo.[9]
Inta lagu guda jiro daraasadda leachables-ka-isticmaalka ee ku saabsan saliingaha maamulka la tuuri karo ee la-caadaystay ee CE-isku-dhafka kiimikaad ee suurtogalka ah ee kansarogenic41, kuwaas oo ah 1,1,2,2-tetrachloroethane ayaa lagu ogaadey xaddi ka sarreeya heerka qiimaynta falanqaynta ee ICH M7 (AET). ).Baadhitaan qotodheer ayaa la bilaabay si loo aqoonsado caag-joojinta ku jira isha TCE aasaasiga ah.[10]
Runtii, waxaan si aan gabasho lahayn u muujin karnaa in TCE aysan ahayn mid laga nadiifin karo caag-joojiyaha.Intaa waxaa dheer, tijaabadu waxay daaha ka qaaday in xarun aan ilaa hadda la garanayn oo leh sifooyin oksaydheyn ah ay ka soo baxayso caagga joojiyaha, taas oo awood u leh in ay ku oksijiso DCM ilaa TCE.[11]
Si loo aqoonsado xarunta leaching, caag joojiyaha iyo soosaarkooda waxaa lagu gartaa habab kala duwan oo falanqayn. Si loo xaqiijiyo xaqiijinta saxda ah ee Luperox⑧ 101 qaab dhismeedka oksidaynta leachable, falanqaynta NMR ayaa la sameeyay.Soosaaray caag methanol ah iyo halbeegga tixraaca ee Luperox 101 methanol ayaa lagu soo saaray qallayl.Hadhaaga waxa dib loogu dhisay methanol-d4 waxaana falanqeeyay NMR.Bilowgii polymerization Luperox⑧101 ayaa sidaas lagu xaqiijiyay inuu yahay oksaydhiyaha dheecaanka leh ee caagga saliingaha ee la tuuri karo.[12]
Daraasada halkan lagu soo bandhigay, qorayaashu waxay ujeedadoodu tahay in ay kor u qaadaan wacyiga ku saabsan u janjeersiga dheecaanka kiimikaad ee agabka maamulka ee kiliinikada loo isticmaalo, gaar ahaan marka la eego joogitaanka kiimikooyinka "aan la arki karin" laakiin aad u firfircoon.La socodka TCE waxa laga yaabaa inay sidaas noqoto hab habboon oo habboon si loola socdo tayada DP dhammaan tallaabooyinka habaynta oo markaas gacan ka geysta badbaadada bukaanka.[13]

Tixraacyo

[1] Shukla AA, Gottschalk U. Tignoolajiyada la tuuri karo ee hal-isticmaalka loogu talagalay soosaarka biopharmaceutical.Trends Biotechnol.2013;31 (3): 147-154.

[2] Lopes AG.Hal-isticmaalka warshadaha biopharmaceutical: dib u eegista saamaynta tignoolajiyada hadda jirta, caqabadaha iyo xaddidaadaha.Habka Bioprod Cuntada.2015;93:98-114.

[3] Paskiet D, Jenke D, Ball D, Houston C, Norwood DL, Markovic I. Machadka Cilmi-baarista Tayada Alaabada (PQRI) waa wax lagu nadiifin karo oo laga soo saari karo kooxda shaqada ee wax soo saarka daroogada indhaha (PODP).PDA ] Pharm Sci Technol.2013;67(5):430-447.

[4] Wang W, Ignatius AA, Thakkar SV.Saamaynta wasakhda haraaga ah iyo wasakhda ee xasiloonida borotiinka.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] Paudel K, Hauk A, Maier TV, Menzel R. Tilmaamaha tirada ee waxyaalaha leachable-ka ah waxay ku quustaan ​​habaynta biopharmaceutical-ka hoose.Eur J Pharmaceut Sci.2020;143: 1 05069.

[6] Maamulka Cuntada iyo Dawooyinka ee Maraykanka FDA.21 CFR Sec.211.65, Qalabka dhismaha.Dib loo eegay laga bilaabo Abriil 1, 2019.

[7] Maamulka Cuntada iyo Dawooyinka ee Maraykanka FDA.21 CFR Sec.211.94, Weelasha alaabta dawooyinka iyo xidhitaankaDib loo eegay laga bilaabo Abriil 1, 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Isticmaalka ikhtiyaariga ah ee ethanol / qaabka biyaha si loo qiyaaso isdhexgalka ka dhexeeya walxaha caaga ah iyo qaababka daawooyinka.[Appl Polvmer Sci.2003:89 (4):1049-1057.

[9] Kooxda Hawlgallada BioPhorum BPOG.Hagaha ugu fiican ee tijaabada wax-soo-saarka ee qaybaha polymeric-ka-hal-isticmaalka ee loo isticmaalo soosaarka biopharmaceuticalBioPhorum Operations Group Ltd (daabacaadda internetka);2020.

[10] Khan TA, Mahler HC, Kishore RS.Isdhexgalka muhiimka ah ee surfactants ee qaababka borotiinka daaweynta: dib u eegis.FurJ Pharm Riopharm.2015;97 (Pt A): 60- -67.

[11] Waaxda Caafimaadka iyo Adeegyada Aadanaha ee Maraykanka, Maamulka Cuntada iyo Dawooyinka ee FDA, Xarunta Qiimaynta Dawooyinka iyo Cilmi-baarista CDER, Xarunta Qiimaynta Bayolojiga iyo Cilmi-baarista CBER.Hagida warshadaha - qiimaynta difaaca jirka

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Saamaynta sagxadaha iyo waxyaalaha leachables ee xasiloonida biopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Burburinta polysorbates 20 iyo 80 iyo saamaynta ay ku yeelan karto xasilloonida biotherapeutics.Pharm Res.2011;28(5):1194-1210.