nkhani

Chizindikiritso cha Oxidizing Leachable kuchokera ku Clinical Syringe Rubber Stopper

Zida za polymeric zogwiritsidwa ntchito kamodzi zimagwiritsidwa ntchito mochulukira munjira zosiyanasiyana zopangira ma biopharmaceutical.Izi makamaka zimatheka chifukwa cha kuchuluka kwa ntchito zawo komanso kusinthasintha kogwirizana ndi kusinthasintha, komanso kutsika mtengo komanso chifukwa kutsimikizira koyeretsa sikofunikira.[1][2]

Nthawi zambiri, m'malo ogwiritsidwa ntchito bwino, mankhwala omwe amasamuka amatchedwa "otulutsa," pomwe ma pounds omwe amasamuka pansi pamikhalidwe ya labotale mokokomeza nthawi zambiri amatchedwa "zotulutsa."Kupezeka kwa zinthu zotayikira kungakhale kodetsa nkhawa kwambiri pankhani yazachipatala, chifukwa mapuloteni achire nthawi zambiri amakhala okonzeka kusinthika chifukwa cha zonyansazo, ngati ali ndi magulu ogwira ntchito. [3] [4]Kutuluka kuchokera kuzinthu zowongolera kumatha kuonedwa ngati pachiwopsezo chachikulu, ngakhale nthawi yolumikizana singakhale yayitali poyerekeza ndi kusungidwa kwanthawi yayitali. [5]
Pankhani ya zofunikira zamalamulo, US Code of Federal Regulations Title 21 ikunena kuti zida zopangira[6] komanso zotsekera zotsekera [7] sizingasinthe chitetezo, mtundu kapena kuyera kwa mankhwala.Chifukwa chake komanso pofuna kuwonetsetsa kuti zinthu zili bwino komanso chitetezo cha odwala, kupezeka kwa zonyansa izi, zomwe zitha kuchokera kuzinthu zambiri zolumikizirana ndi DP, ziyenera kuyang'aniridwa ndikuwongoleredwa pamachitidwe onse opangira, panthawi yopanga, kusungirako komanso kuwongolera komaliza.
Popeza zida zoyendetsera nthawi zambiri zimagawidwa ngati zida zamankhwala, ogulitsa ndi opanga nthawi zambiri amawona ndikuwunika zomwe zimachitika kwa anthu osamukira kumayiko ena molingana ndi zomwe akufuna kugwiritsa ntchito chinthu china, mwachitsanzo, m'matumba olowetsedwa, yankho lamadzi lokhalo, mwachitsanzo, 0.9% (w) /v) NaCl, imawunikidwa.Komabe, kale anasonyeza kuti kukhalapo kwa mapangidwe zosakaniza ndi katundu solubilizing, monga achire mapuloteni palokha kapena sanali ionic surfactants akhoza kusintha ndi kumapangitsa kusamuka chizolowezi sanali polar poyerekeza ndi zosavuta amadzimadzi njira. [7] [8] ]
Chifukwa chake chinali cholinga cha pulojekitiyi kuti adziwe zinthu zomwe zitha kutulutsa kuchokera mu syringe yomwe imagwiritsidwa ntchito nthawi zambiri.Chifukwa chake, tidachita zoyeserera zomwe zingagwiritsidwe ntchito pogwiritsa ntchito amadzimadzi 0.1% (w/v) PS20 ngati yankho la DP surrogate.Mayankho omwe adapezeka omwe amawunikidwa adawunikidwa ndi njira zodziwikiratu komanso njira zowunikiridwa.Zigawo za syringe zidasokonekera kuti zizindikire gwero loyamba lomwe limatha kutulutsa.[9]
Pakufufuza kosagwiritsidwa ntchito kosagwiritsidwa ntchito pa syringe yogwiritsidwa ntchito ndi CE-certified disposable management pawiri yomwe ingakhale ya carcinogenic41, yomwe ndi 1,1,2,2-tetrachloroethane idapezeka m'malo opitilira ICH M7-derived analytical evaluation threshold (AET). ).Kufufuza mozama kunayambika kuti azindikire choyimitsa mphira chomwe chili ngati gwero lalikulu la TCE.[10]
Zowonadi, titha kuwonetsa mosapita m'mbali kuti TCE sinatuluke pachoyimitsa mphira.Komanso, kuyesera anasonyeza kuti mpaka pano osadziwika pawiri ndi oxidizing katundu anali leaching kwa mphira choyimitsa, kuti anali wokhoza oxidize DCM kuti TCE.[11]
Pofuna kudziwa leaching pawiri, choyimitsa mphira ndi Tingafinye anali yodziwika ndi njira zosiyanasiyana kusanthula.Different peroxides organic, kuti angagwiritsidwe ntchito monga polima oyambitsa popanga pulasitiki, zipangizo anali anafufuza luso lawo oxidize DCM kuti TCE. Kuti mutsimikizire mosakayikira kuti Luperox ⑧ 101 imapangidwa ngati gawo lotulutsa oxidizing, kusanthula kwa NMR kunachitika.Dongosolo la rabara la methanolic ndi methanolic Luperox 101 yofananira zidasinthidwa kukhala zouma.Zotsalirazo zidapangidwanso mu methanol-d4 ndikuwunikidwa ndi NMR.The polymerization initiator Luperox⑧101 adatsimikiziridwa kuti ndi oxidizing chotchinga cha syringe choyimitsa mphira.[12]
Ndi phunziro lomwe laperekedwa apa, olembawo akufuna kudziwitsa anthu za chibadwa cha mankhwala omwe amachokera ku zipangizo zogwiritsira ntchito mankhwala, makamaka ponena za kukhalapo kwa mankhwala "osaoneka" koma omwe amawotchera kwambiri.Kuwunika kwa TCE kutha kukhala njira yosunthika komanso yosavuta yowunika momwe DP imagwirira ntchito munthawi yonseyi ndikuthandizira chitetezo cha odwala.[13]

Maumboni

[1] Shukla AA, Gottschalk U. Tekinoloje zotayidwa zogwiritsidwa ntchito kamodzi popanga biopharmaceutical.Trends Biotechnol.2013;31(3):147-154.

[2] Lopes AG.Kugwiritsa ntchito kamodzi pamakampani a biopharmaceutical: kuwunikanso zomwe zikuchitika paukadaulo waukadaulo, zovuta komanso zolephera.Food Bioprod Process.2015; 93:98-114.

[3] Paskiet D, Jenke D, Ball D, Houston C, Norwood DL, Markovic I. The Product QualityResearch Institute (PQRI) zolephereka ndi zotulukapo zogwirira ntchito zamagulu azamankhwala ndi ophthalmic mankhwala (PODP).PDA ] Pharm Sci Technol.2013;67(5):430-447.

[4] Wang W, Ignatius AA, Thakkar SV.Zotsatira za zotsalira zotsalira ndi zowonongeka pa kukhazikika kwa mapuloteni.J Pharmaceut Sci.2014;103(5):1315-1330.

[5] Paudel K, Hauk A, Maier TV, Menzel R. Mawonekedwe ochuluka a zinthu zotayira zimamira mu biopharmaceutical downstream processing.Malingaliro a kampani Eur J Pharmaceut Sci.2020; 143: 1 05069.

[6] United States Food and Drug Administration FDA.21 CFR Sec.211.65, Kupanga zida.Idasinthidwa kuyambira pa Epulo 1, 2019.

[7] United States Food and Drug Administration FDA.21 CFR Sec.211.94, Zotengera za mankhwala osokoneza bongo ndi zotsekera.Idasinthidwa kuyambira pa Epulo 1, 2020.

[8] Jenke DR, Brennan J, Doty M, Poss M. Kugwiritsa ntchito njira za binary ethanol / madzi zotsatsira kutsanzira kuyanjana pakati pa pulasitiki ndi mankhwala opangira mankhwala.[Appl Polvmer Sci.2003:89(4):1049- 1057.

[9] BioPhorum Operations Gulu BPOG.Chitsogozo chabwino kwambiri choyesera zotulutsa za polymeric zogwiritsidwa ntchito kamodzi zomwe zimagwiritsidwa ntchito popanga biopharmaceutical.BioPhorum Operations Group Ltd (kufalitsa pa intaneti);2020.

[10] Khan TA, Mahler HC, Kishore RS.Kuyanjana kwakukulu kwa ma surfactants pakupanga mapuloteni othandizira: kuwunika.FurJ Pharm Riopharm.2015; 97(Pt A): 60- -67.

[11] United States Department of Health and Human Services, Food and Drug Administration FDA, Center for Drug Evaluation and Research CDER, Center for BiologicsEvaluation and Reseach CBER.Upangiri wamakampani - kuwunika kwa immunogenicity

[12] Bee JS, Randolph TW, Carpenter JF, Bishop SM, Dimitrova MN.Zotsatira za malo ndi zotuluka pa kukhazikika kwa biopharmaceuticals.J Pharmaceut Sci.2011;100 (10):4158- -4170.

[13] Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC.Kuwonongeka kwa ma polysorbates 20 ndi 80 komanso zomwe zingakhudze kukhazikika kwa biotherapeutics.Pharm Res.2011;28(5):1194-1210.