[Zida zogwiritsira ntchito]
Peptide Engineering Center ya Shenzhen JYMed Technology Co., Ltd. ili ndi luso lamphamvu pakukula kwazinthu zopangira. Motsogozedwa ndi gulu lofufuza la asayansi 130, kuphatikiza ma PhD 12, likululi lili ndi ukadaulo wochulukirapo pakupanga ma peptide komanso kukhathamiritsa kwazinthu. Pogwiritsa ntchito matekinoloje apamwamba a solid-phase peptide synthesis (SPPS) ndi matekinoloje amadzimadzi a peptide synthesis (LPPS), kuphatikiza ndi zida zopangira zokha, timaonetsetsa kuti zinthu za peptide zimakhala zoyera kwambiri komanso zogwira ntchito kwambiri. Gulu lathu la R&D limapereka chithandizo chokwanira kuyambira pakupanga mamolekyu kupita ku chitukuko, kupereka mayankho ogwirizana kuti akwaniritse zosowa zosiyanasiyana zamakasitomala.
Zochita zonse zimachitika motsatira miyezo yolimba ya cGMP, mothandizidwa ndi zida zamakono zowunikira monga HPLC ndi mass spectrometry (MS), kuwonetsetsa kuti mtundu wazinthu ukugwirizana ndi zofunikira za pharmacopeial padziko lonse lapansi. Ku JYMed, tadzipereka kupatsa mphamvu makasitomala pakukula bwino komanso kutsatsa kwamankhwala opangidwa mwaluso kudzera muukadaulo ndi ntchito.
Kupititsa patsogolo Njira
Gulu lachitukuko la JYMed limakhazikika pakukhathamiritsa ndi kukulitsa kwa peptide API kupanga, kupereka mayankho ogwira mtima komanso odalirika omwe amayendetsedwa ndi luso laukadaulo. Ndi ukatswiri wakuya mu SPPS, LPPS, komanso kaphatikizidwe kosalekeza kotuluka, timapereka chithandizo chakumapeto mpaka kumapeto kuchokera pakuwunika kwa milligram mpaka kupanga ma kilogalamu zana.
Kupyolera mu nsanja yathu yobiriwira ya chemistry ya peptides, tapambana zovuta pakuphatikiza zovuta, kuwongolera kwambiri chiyero ndi zokolola. Izi zimatithandiza kukwaniritsa zofunika kwambiri za ma peptides apamwamba kwambiri omwe amagwiritsidwa ntchito pa oncology, matenda a metabolic, ndi njira zina zochiritsira zapamwamba.
Dongosolo lathu lopanga zinthu limatsatira mosamalitsa malangizo a cGMP ndipo lili ndi zida zodzipangira zokha komanso zida zowunikira zapamwamba monga UPLC ndi MS yapamwamba kwambiri. Kuphatikizidwa ndi machitidwe okhathamiritsa opangidwa mkati, timatsimikizira kulimba kwa ndondomeko komanso kusasinthika kwa batch-to-batch. JYMed yamaliza bwino ntchito zambiri zachitukuko za peptide API kudutsa masitepe oyambira mpaka pazamalonda, ndikupereka mayankho ofulumira, oyendetsedwa ndi data kuti apititse patsogolo luso lamankhwala padziko lonse lapansi.
Kupanga
Malo athu opangira amakhala 300 mu (pafupifupi 200,000 masikweya mita) okhala ndi malo okwana pafupifupi 54,000 masikweya mita. Malowa ali ndi malo opangira ma peptide, nyumba za QC ndi R&D, malo osungiramo katundu a Gulu A ndi B, malo osungiramo zosungunulira, malo ogwiritsira ntchito, malo osonkhanitsira zinyalala zolimba, ndi malo opangira madzi oyipa.
Hubei Jianxiang Biopharmaceutical Co., Ltd. imagwiritsa ntchito mizere 10 yopanga ma peptide API (kuphatikiza mizere yoyendetsa ndege) motsatira miyezo ya cGMP ya US, EU, ndi China. Izi zili ndi zida zambiri zolimba-gawo komanso madzi-gawo a peptide synthesis reactors, okwana malita 30,000 mu riyakitala.
Ndi dongosolo lokhazikitsidwa bwino la kasamalidwe ka mankhwala ndi dongosolo lotsatiridwa ndi EHS, Hubei Jianxiang wadutsa zoyendera za NMPA GMP, zowunikira zingapo za gulu lachitatu, ndi zowunikira za EHS zochokera kwa makasitomala otsogola padziko lonse lapansi. Mphamvu yake yopanga peptide pachaka yafika pamlingo wa matani angapo. Makamaka, kupanga ma analogi a GLP-1 kumakhala pakati pa zazikulu kwambiri ku China ndi voliyumu imodzi, ndipo ma peptides ena odzikongoletsera amaposa 100 kg pa batch, ndikuyika kampaniyo ngati wopanga mpikisano wa peptide API pamsika wapakhomo ndi wakunja.
High-Potency Peptide APIs
Mizere yopangira ma peptide API ya Jianxiang yamphamvu kwambiri imayimira mwayi wampikisano, wopereka mayankho otetezeka komanso ogwira mtima kwa makasitomala apadziko lonse lapansi. Malowa ali ndi magawo awiri a OEB4-level ndi awiri a OEB5-level apamwamba omwe amapangidwa kuti akwaniritse zofunikira zopangira mankhwala amphamvu kwambiri monga anti-tumor ndi cytotoxic peptides, kuonetsetsa chitetezo kwa ogwira ntchito ndi chilengedwe.
Mizere yopanga imagwiritsa ntchito matekinoloje otsogola a SPPS ndi LPPS okhala ndi makina owongolera okha, zomwe zimapangitsa kuti pakhale ma peptide apamwamba kwambiri komanso amphamvu kwambiri kuchokera pa gramu mpaka kilogalamu. Kusasinthika kwa batch ndi mtundu wazinthu zimagwirizana kwathunthu ndi miyezo yapadziko lonse ya pharmacopeial.
Kumangidwa pa dongosolo la kasamalidwe ka khalidwe logwirizana ndi cGMP, njira yonse yopangira-kuchokera ku zopangira zopangira, kaphatikizidwe, kuyeretsedwa mpaka kuyesedwa komaliza-imatha kutsatiridwa. Zida zowunikira zapamwamba monga HPLC ndi MS zimatsimikizira chiyero chazinthu ≥99% chokhala ndi mbiri zonyansa zoyendetsedwa. Kuthana ndi zofunikira zapadera zachitetezo cha ma API amphamvu kwambiri, magawo a OEB5-level amatenga njira zodzipatula, malo odziyimira pawokha, komanso njira zanzeru zowunikira kutayikira, komanso ma protocol olimba a PPE kuti atsimikizire chitetezo chokwanira.
Gulu lathu la R&D limaperekanso ntchito zachitukuko ndi kukhathamiritsa kwazinthu zomwe zimakhudza kuchuluka kwazinthu zonse kuyambira pakupanga mamolekyu ndikukula mpaka kumaphunziro apamwamba, kuthandizira kupita patsogolo mwachangu kwamankhwala opangidwa ndi peptide.
[Kupanga]
Gulu lathu lalikulu laukadaulo limapangidwa ndi ofufuza odziwa zambiri odziwa kupanga ndi kusanthula sayansi. Ndi ukatswiri wochuluka pazambiri zonse zachitukuko, timapereka ntchito zomaliza mpaka kumapeto kuyambira kafukufuku wamankhwala mpaka kupanga zamalonda. Takhazikitsa mphamvu zapadera zaukadaulo m'magawo akumalire monga mankhwala a GLP-1, ma peptides ndi ma peptide formulations, ma peptide osasunthika, komanso chitukuko cha radiopharmaceutical (RDC).
Pogwiritsa ntchito R&D yathu yogawidwa padziko lonse lapansi komanso malo opangira zinthu, tapanga njira yokwanira yopangira mapangidwe. M'munda wopangira ma peptide, timapereka njira zosiyanasiyana kuphatikiza ma jakisoni amitundu yambiri / mlingo umodzi wa cartridge, ufa wa lyophilized wa jakisoni, ndi mankhwala opumira. Pachitukuko cha RDC, gulu lathu ladziwa bwino njira zolumikizirana ndi ma radionuclides ndikulozera ma vectors, kupereka matekinoloje apamwamba othandizira kuwunika kwa oncology ndi chithandizo. Pofika kumapeto kwa 2024, gulu lathu lathandizira mapulojekiti atsopano opitilira 100 opangira mankhwala (okhudza magawo a Phase III), makamaka ma analogi a GLP-1, mankhwala ena a peptide, ndi ma RDC. Tatsirizanso bwinobwino mapulojekiti 5 oyesa kusasinthasintha kwa mankhwala omwe amaphatikizana ndi jakisoni ndi mankhwala ena.
Monga gulu loyendetsedwa ndiukadaulo, timakhala odzipereka pakupanga zatsopano komanso kumasulira mosalekeza kafukufuku munjira zenizeni padziko lapansi. Kuyesetsa kwathu sikungopereka mayankho otetezeka komanso ogwira mtima pamsika wapadziko lonse wamankhwala, kulimbikitsa kagwiritsidwe ntchito ka mankhwala a peptide ndi mafakitale amtundu wa RDC, komanso kukhazikitsa mpikisano wamphamvu pakuwunika kusasinthika kwamankhwala amtundu uliwonse.
Research Pre-formulation
Monga gawo lofunikira poyambira pakupanga mankhwala, kafukufuku wopangidwa asanapangidwe amakhala ngati ulalo wofunikira pakati pa kupezeka kwa mankhwala ndi kapangidwe kake. Upangiri wake wamaukadaulo umakhudza mwachindunji kukula kwa mawonekedwe a mlingo ndi kuthekera kwake.
Pachitukuko chatsopano chamankhwala, timachita maphunziro mwadongosolo pazinthu zazikulu za APIs - kuphatikiza kuyezetsa kusungunuka, kuwunika kwa polymorph, kuwunika kowonongeka kokakamizika, ndikuwunika koyambirira kwa kukhazikika - kuti tizindikire molondola mawonekedwe a physicochemical ndi njira zomwe zingawonongeke. Zidziwitso izi zimakhala ngati maziko opangira mapangidwe, kukhathamiritsa kwa njira, ndi chitukuko chokhazikika, ndikuchepetsa kuopsa kwa R&D ndikuwongolera kutha kwa mankhwala kuyambira pachiyambi.
Pachitukuko chamankhwala amtundu uliwonse, kusanthula mozama kwamankhwala omwe atchulidwa (RLD) ndikofunikira kwambiri pakufufuza koyambirira. Kupyolera mu uinjiniya wosinthira, timazindikira kapangidwe kake, njira yopangira, ndi mawonekedwe ofunikira (CQAs) a mankhwala omwe adayambitsa. Izi zimathandizira chitsogozo chowunikira pakufananiza ndi kuberekana, ndipo, mogwirizana ndi njira ya Quality by Design (QbD), zimatsimikizira kuti mankhwala opangidwa ndi generic amakwaniritsa zofanana pachitetezo, mphamvu, komanso kuwongolera kwamtundu - kuyika maziko olimba aukadaulo kuti ayese bwino kusasinthika.
Kukonzekera Kwadongosolo
Monga mlatho wofunikira pakati pa chitukuko cha mankhwala ndi mafakitale, chitukuko cha mankhwala chimagwira ntchito yofunika kwambiri pomasulira zotsatira za labu kukhala ntchito zachipatala. Gulu lathu limayang'ana kwambiri zaukadaulo wamapangidwe aukadaulo ndi zofunikira zamafakitale, kupanga dongosolo lachitukuko chokwanira lomwe limakhudza kamangidwe kakapangidwe, kukhathamiritsa kwa njira, kafukufuku wabwino, ndi kupanga koyendetsa ndege. Timapereka mayankho makonda ogwirizana ndi mitundu yosiyanasiyana yamankhwala (mamolekyu ang'onoang'ono, ma peptides, ma radiopharmaceuticals) ndi mawonekedwe a mlingo (majakisoni, zinthu zopumira, zotulutsa zotulutsidwa).
Pakukonza kwatsopano kwa mankhwala, timayika ntchito yathu pa zomwe zidapangidwa kale ndikuganizira zomwe tikufuna komanso njira yoyendetsera mawonekedwe a mlingo ndi kapangidwe kake. Pazovuta za kukhazikika kwa mankhwala a peptide, tapanga majekeseni amitundu yambiri / mlingo umodzi wa cartridge ndi jakisoni wa ufa wa lyophilized. Mwa kukhathamiritsa kachitidwe ka buffer ndi njira za lyophilization, timakulitsa kukhazikika kwazinthu. Kwa RDCs, takhazikitsa njira zolumikizirana zolondola pakati pa ma vectors ndi ma radionuclides limodzi ndi machitidwe owongolera kuti tiwonetsetse kuti ma radiolabeling akugwira ntchito komanso otetezeka. Pogwiritsa ntchito makonzedwe opangidwa ndi makompyuta (CADD) ndi mfundo za QbD, timakonzekeretsa bwino kapangidwe kake ndikusintha magawo kuti tiwongolere bwino zizindikiro zazikulu za kagwiridwe ka ntchito monga kutha, kutulutsa mbiri, ndi mikhalidwe yolunjika.
Pakupanga mankhwala amtundu uliwonse, timaphatikiza uinjiniya wosinthika wa ma RLD ndi kukhathamiritsa kwapatsogolo kuti tikwaniritse kupanga ndi kufanana. Kwa mafomu ovuta a mlingo monga ma jakisoni ndi njira zopumira, timafananiza molondola ma CQA monga kugawa kwa tinthu, chiyero, ndi mbiri zonyansa. Kupyolera m'machulukidwe owonjezereka ndi kutsimikiziranso koyesa, timawonetsetsa kuti ma generic akugwirizana ndi mankhwala omwe akugwiritsidwa ntchito pachitetezo, mphamvu zake, komanso kutha kwa kupanga - ndikupangitsa kuvomereza koyenera.
Mpaka pano, tathandizira bwino mapulojekiti opitilira 30 opangira mankhwala atsopano komanso anthawi zonse, kuphatikiza mankhwala a GLP-1, ma peptide otulutsidwa mosalekeza, ndi ma RDC. Tagonjetsa zopinga zaukadaulo monga kuwonongeka kwa peptide, kuchepa kwa ma radiolabeling, komanso zovuta zokulirapo m'mitundu yovuta. Kuchokera ku mayesero a labu mpaka kupanga oyendetsa ogwirizana ndi GMP, timayendetsedwa ndi injini ziwiri za "teknoloji yatsopano + kumasulira kwa mafakitale," kupereka chithandizo chokwanira pa chitukuko cha mankhwala atsopano kuchokera ku lingaliro kupita ku chipatala, ndikupangitsa kupanga kwapamwamba, kotsika mtengo kwa generics zomwe zimayendetsa kusintha koyenera kuchokera ku zotsatira za R & D kupita ku mtengo wachipatala.
Kupanga Kupanga
Monga gawo lomaliza pakumasulira mankhwala a R&D kuti agwiritsidwe ntchito pachipatala, kupanga mapangidwe ndiye ulalo wofunikira womwe umalumikiza luso la labotale ndi zinthu zamalonda. Kudalira malo athu Integrated kupanga ndi mizere wanzeru kupanga, takhazikitsa dongosolo la unyolo kupanga zonse kuphimba woyendetsa lonse-mmwamba, ndondomeko kutsimikizira, ndi malonda-ang'ono kupanga. Ndi mphamvu zamphamvu pamitundu ingapo ya mlingo, mankhwala, ndi katchulidwe kake, timakwaniritsa zofunikira zamankhwala opangidwa mwatsopano kuyambira pakukula kwachipatala mpaka kumalonda, kwinaku tikuthandizira kupanga mankhwala apamwamba kwambiri, akuluakulu.
1. Luso laukadaulo & Zopanga Zopanga
Kuthekera kwa mawonekedwe osiyanasiyana: Kwa mankhwala ovuta monga ma peptides ndi RDCs, takhazikitsa makina opanga makina ogwirizana ndi GMP amitundu yambiri / mlingo umodzi wa cartridge wobaya ndi jakisoni wa ufa wa lyophilized. Zokhala ndi matekinoloje odzaza okha, lyophilization, komanso ukadaulo wosabala, timawonetsetsa kuwongolera kokhazikika kuchokera kuzinthu zopangira mpaka kumapeto kwazinthu.
Pakupanga ma peptide, timathana ndi zovuta zokhazikika pogwiritsa ntchito kukhathamiritsa kwa buffer system, mbiri yofananira ya lyophilization, ndi njira zosungirako kuzizira. Pulatifomu yathu yokhazikika, yomangidwa pamakina a QbD, imathandizira kuti pakhale kusintha kosavuta kuchoka pamayesero a labotale kupita kukupanga makina oyendetsa (10L-100L), kuwonetsetsa kuti njira zimagwiranso ntchito komanso kusasinthika kwa batch-to-batch kudzera pakuwunika mwadongosolo komanso kutsimikizira magawo ofunikira (CPPs).
Thandizo lamakono lamankhwala: Kapangidwe kathu kakuphatikiza zachipatala za Gawo I-III zopanga zitsanzo ndi zolembetsa zamagulu, kufulumizitsa nthawi yopangira mankhwala.
Kupanga mankhwala amtundu uliwonse: Timapereka njira zosinthira mwachangu ndikuwongolera kuti tikwaniritse zofunikira zapadziko lonse lapansi zama generic otsika mtengo komanso apamwamba kwambiri.
2. Quality Control & Compliance
Takhazikitsa njira yoyendetsera kasamalidwe kabwino ka moyo wokhudza kuwunika kwazinthu zopangira, kuyang'anira zomwe zikuchitika, ndikutulutsa komaliza kwazinthu. Malo athu ali ndi zida zowunikira zapamwamba monga HPLC, LC-MS, ndi ma radio-TLC scanner, zomwe zimathandizira kuwunika kolondola kwa CQAs kuphatikiza mbiri zonyansa, kufanana kwazomwe zili, sterility, komanso kuyendetsa bwino ma radiolabeling.
Masamba athu opanga ndi ovomerezeka ndi China NMPA kuti atsatire GMP ndipo amatsatira mosamalitsa malangizo a ICH, kuwonetsetsa kutsatiridwa kwathunthu komanso kutsata malamulo apadziko lonse lapansi kwamakasitomala athu apadziko lonse lapansi.
3. Phindu la Industrial & Zopindula
Mpaka pano, takulitsa bwino ndikugulitsa zinthu zopitilira 100, kuphatikiza jakisoni wa GLP-1, ma peptide omwe amatulutsidwa mosalekeza, ndi mankhwala omwe akutsata a RDC. Kupanga kwathu kwapachaka kumafika mamiliyoni ambiri a Mlingo/Mbale. Timapereka ntchito zopanga "zokhazikika" zomwe zimathandizira mankhwala opangidwa kuchokera ku zitsanzo zachipatala mpaka kukhazikitsidwa kwa msika, zomwe zimafupikitsa nthawi yogulitsa. Kupyolera mu kukhathamiritsa kwa ndondomeko ndi kukonzanso makina, timathandizira makasitomala a mankhwala osokoneza bongo kuti athe kuwongolera mtengo ndi kukonza bwino, kupititsa patsogolo kupezeka kwa mankhwala ochizira okwera mtengo padziko lonse lapansi.
Kuyambira kumasulira kwaukadaulo kupita kukupanga zambiri, timatsatira mfundo za "ubwino woyamba, woyendetsedwa bwino," kuphatikiza mosadukiza R&D ndi kupanga kuti tikhale ogwirizana nawo odalirika pakusintha luso lazamankhwala kukhala mayankho azachipatala padziko lonse lapansi.
