[Raw Materials]
Peptide Engineering Center yeShenzhen JYMed Technology Co., Ltd. ine hunyanzvi hwakasimba mukuvandudza zvinhu. Inotungamirwa neboka rekutsvagisa revasayendisiti zana nemakumi matatu, kusanganisira gumi nevaviri PhDs, muzinda uyu une hunyanzvi hwekuita peptide synthesis uye process optimization. Tichishandisa advanced solid-phase peptide synthesis (SPPS) uye liquid-phase peptide synthesis (LPPS) matekinoroji, akasanganiswa neatomatiki ekugadzira michina, tinova nechokwadi chepamusoro-kuchena uye chepamusoro-chiitwa peptide zvigadzirwa. Chikwata chedu cheR&D chinopa masevhisi akakwana kubva pakugadzira mamorekuru kusvika pakusimukira, achipa mhinduro dzakagadzirirwa kusangana nezvinodiwa nevatengi zvakasiyana.
Zviitiko zvese zvinoitwa pasi pekuomesera cGMP zviyero, zvinotsigirwa neino-ye-iyo-inoongorora zviridzwa zvakaita seHPLC uye mass spectrometry (MS), kuve nechokwadi chekuti mhando yechigadzirwa inoenderana nepasi rose pharmacopeial zvinodiwa. PaJYMed, takazvipira kupa simba vatengi mubudiriro yakabudirira uye kushambadzira kwehunyanzvi hwekurapa kuburikidza nehunyanzvi muhunyanzvi uye sevhisi.
Process Development
JYMed's process development timu inyanzvi mukugadzirisa uye kuwedzera-kumusoro kwepeptide API yekugadzira, ichipa inoshanda uye yakavimbika yakagadziridzwa mhinduro inotungamirwa nehunyanzvi hwekuvandudza tekinoroji. Nehunyanzvi hwakadzama muSPPS, LPPS, uye inoenderera mberi kuyerera, isu tinopa ekupedzisira-kusvika-kumagumo masevhisi ekusimudzira kubva pamilligram-chiyero chekuongorora kusvika kuzana-kirogiramu-chikero kugadzirwa.
Kuburikidza nechero yedu yegirinhi chemistry papuratifomu yepeptides, isu takakunda zvinonetsa mukugadzira akaomesesa akateedzana, zvakanyanya kuvandudza kuchena uye goho. Izvi zvinotigonesa kuzadzisa zvinoomesesa zvinodikanwa zvepamusoro-potency peptides anoshandiswa mune oncology, metabolic zvirwere, uye kumwe kurapa kwepamusoro.
Yedu yekugadzira sisitimu inoomerera kune cGMP nhungamiro uye ine yakazara otomatiki synthesis mauniti uye epamberi ekuongorora maturusi akadai seUPLC uye yakakwirira-resolution MS. Yakabatana neyemukati yakagadziridzwa maitiro ekugadzirisa modhi, isu tinoona kusimba kwemaitiro uye batch-kune-batch kuenderana. JYMed yakabudirira kupedza akawanda peptide API mapurojekiti ekuvandudza kune preclinical kusvika kumatanho ekutengesa, ichiunza nekukurumidza, inofambiswa nedata mhinduro kukurumidza kugadzirwa kwemishonga yepasi rose.
Manufacturing
Nzvimbo yedu yekugadzira inosvika mazana matatu mu (inoda kusvika 200,000 square metres) ine yakazara yakavakirwa-nzvimbo inotenderedza 54,000 square metres. Nzvimbo iyi inosanganisira mashopu ekugadzira peptide, zvivakwa zveQC neR&D, matura eKirasi A neB, nzvimbo yekudzoreredza zvinonyungudutsa, nzvimbo dzekushandisa, nzvimbo yekuunganidza marara, uye chiteshi chekuchenesa mvura.
Hubei Jianxiang Biopharmaceutical Co., Ltd. inoshandisa gumi peptide API mitsetse yekugadzira (kusanganisira pilot-scale lines) inoenderana neCGMP zviyero zveUS, EU, neChina. Aya akashongedzerwa neakawanda ezvakasimba-chikamu uye mvura-chikamu peptide synthesis reactor, anokwana anopfuura 30,000 litres mune reactor vhoriyamu.
Iine yakanyatsosimbiswa yemishonga yemhando yekutonga system uye EHS yekuteedzera system, Hubei Jianxiang apasa pamutemo NMPA GMP ongororo, akawanda echitatu-bato maodhisheni, uye EHS ongororo kubva kune vanotungamira pasi rese vatengi. Yayo yegore peptide yekugadzira simba yasvika akawanda-toni chiyero. Zvikuru, kugadzirwa kweGLP-1 analogs kunomira pakati pehukuru muChina ne-single-batch vhoriyamu, uye mamwe mapeptide ezvekuzora anodarika 100 kg pabatch, achiisa kambani seanokwikwidza kemikari synthesis peptide API mugadziri mumisika yemumba neyekunze.
High-Potency Peptide APIs
Jianxiang's high-potency peptide API mitsara yekugadzira inomiririra musimboti wemakwikwi mukana, inopa yakachengeteka uye inoshanda mhinduro kune vatengi vepasirese. Nzvimbo iyi inosanganisira maviri OEB4-level uye maviri OEB5-level-yepamusoro-containment units akagadzirirwa kusangana nezvinodiwa zvekugadzira zvinodikanwa zvemakomponi ane simba senge anti-tumor uye cytotoxic peptides, kuve nechokwadi chekuchengetedzwa kwevashandi nenharaunda.
Mitsetse yekugadzira inoshandisa indasitiri inotungamira SPPS uye LPPS matekinoroji ane akazara otomatiki ekudzora masisitimu, achigonesa scalable kugadzirwa kwepamusoro-kuchena uye yakakwirira-potency peptides kubva pagiramu kusvika pakirogiramu. Batch kusawirirana uye mhando yechigadzirwa inoenderana zvizere nepasi rose pharmacopeial zviyero.
Yakavakirwa pane cGMP-inopindirana yemhando manejimendi sisitimu, iyo yese yekugadzira maitiro-kubva pakusarudzwa kwezvinhu zvakasvibirira, synthesis, kucheneswa kusvika pakuyedzwa kwekupedzisira-inoteedzera zvizere. Yepamberi yekuongorora zviridzwa seHPLC neMS inovimbisa kuchena kwechigadzirwa ≥99% ine inodzorwa kusachena profiles. Kugadzirisa izvo zvakasarudzika zvinodikanwa zveakakwira-potency APIs, iyo OEB5-level mauniti anotora yakavharwa-yega masisitimu, yakazvimirira isina-kudzvanywa nharaunda, uye nehungwaru yekuvuza yekutarisisa masisitimu, pamwe neakasimba PPE mapuroteni ekuzadzisa vimbiso yekuchengetedza.
Chikwata chedu cheR&D chinopawo akagadziridzwa maitiro ekuvandudza uye masevhisi ekugadzirisa anofukidza kukosha kwese cheni kubva pakugadzira mamorekuru uye kukwira kusvika kuzvidzidzo zvemhando yepamusoro, zvichitsigira kukurumidza kufambira mberi kwehunyanzvi hwepeptide-based therapeutics.
[Kugadzira]
Chikwata chedu chehunyanzvi chehunyanzvi chinoumbwa nevaongorori vane ruzivo vanonyanya kugadzira uye kuongorora sainzi. Nehunyanzvi hwakakura mukati mese kuumbwa kwekuvandudza kukosha kweketani, isu tinopa ekupedzisira-kusvika-kumagumo masevhisi kubva kupreclinical tsvakiridzo kusvika pakugadzira kutengeserana. Isu takagadzira yakasarudzika masimba etekinoroji mumiganhu yemiganhu senge GLP-1 mishonga, peptides uye peptide maumbirwo, yakaramba ichiburitswa peptide maumbirwo, uye radiopharmaceutical (RDC) kuvandudzwa.
Tichishandisa R&D yedu yakagovaniswa pasi rose uye zvivakwa zvekugadzira, isu takavaka yakazara dhizaini yekuvandudza sisitimu. Mundima yekugadzira peptide, tinopa zvigadziriso zvakasiyana zvinosanganisira multi-dose/imwe-dose cartridge injectable solution, lyophilized poda yejekiseni, uye inhalation solutions. Mukuvandudza kweRDC, timu yedu yakagonesa akakwenenzverwa nzira dzekubatanidza ma radionuclides uye kunanga mavheji, ichipa hunyanzvi hwekuvandudza tekinoroji yekutsigira chaiyo oncology diagnostics uye kurapa. Kubva mukupera kwa2024, timu yedu yakatsigira anopfuura zana mapurojekiti ekuvandudza zvinodhaka (anofukidza preclinical kusvika Phase III nhanho), akanyanya kunangana neGLP-1 analogs, mamwe mishonga yepeptide, uye RDCs. Isu takabudirirawo kupedzisa 5 generic drug consistency evaluation mapurojekiti anosanganisira zvinobaya jekiseni uye mamwe magadzirirwo.
Sechikwata chinofambiswa nehunyanzvi, tinoramba takazvipira kuita hunyanzvi uye kuenderera mberi nekushandura tsvakiridzo mumhinduro dzepasirese. Kuedza kwedu hakungope mhinduro dzakachengeteka uye dzinoshanda kumusika wepasi rose wemishonga, kusimudzira kiriniki neindasitiri yekushandiswa kwepeptide neRDC mishonga, asi zvakare kumisa muganho wakasimba wemakwikwi mumunda weiyo generic drug consistency ongororo.
Pre-formulation Research
Sedanho rakakosha rekutanga mukuvandudza zvinodhaka, pre-formulation research inoshanda sechinhu chakakosha pakati pekuwanikwa kwezvinodhaka uye dhizaini yekugadzira. Hunhu hwayo hwetekinoroji hunokanganisa zvakananga dosage fomu kuvandudza uye kugona kwemaitiro.
Pakuvandudzwa kwemishonga mitsva, tinoronga zvidzidzo pamusoro pezvinhu zvakakosha zve APIs - kusanganisira solubility test, polymorph screening, kumanikidzirwa kuderedzwa kuongororwa, uye kuongororwa kwekutanga kwekugadzikana - kunyatsoona maitiro e physicochemical uye nzira dzinogona kukanganisa. Aya manzwisisiro anoshanda sehwaro hwekugadzira dhizaini, mashandiro ekugadzirisa, uye mhando yekusimudzira, pakupedzisira inoderedza njodzi dzeR&D nekuvandudza kugona kwezvinodhaka kubva pakutanga.
Mukuvandudzwa kwezvinodhaka, kuongororwa kwakadzama kweiyo referensi yakanyorwa mushonga (RLD) ndiyo inonyanya kutariswa ye pre-formulation research. Kuburikidza nereverse engineering, isu tinosarudza kuumbwa kwekuumbwa, maitiro ekugadzira, uye akakosha emhando hunhu (CQAs) yemushonga wekutanga. Izvi zvinogonesa nhungamiro yakanangwa yekufananidza uye kubereka kwemaitiro, uye, zvinoenderana neHunhu neKugadzira (QbD) nzira, inova nechokwadi chekuti chigadzirwa chegeneric chinowana kuenzana mukuchengetedzeka, kushanda, uye kutonga kwemhando - kuisa hwaro hwakasimba hwehunyanzvi hwekubudirira kuenderana kuongorora.
Kugadzira Kuvandudza
Sezambuko rakakosha pakati pekuvandudzwa kwezvinodhaka nekusimudzirwa kwemaindasitiri, kuvandudza kwekugadzira kunobata basa rakakosha mukuturikira mhedzisiro yerabhu kuita makiriniki ekushandisa. Chikwata chedu chinotarisa pahunyanzvi hwekugadzira matekinoroji uye zvinokatyamadza zvinodikanwa zveindasitiri, kuvaka yakazara-maitiro ekusimudzira sisitimu inovhara dhizaini yekugadzira, kugadzirisa maitiro, kutsvagisa kwemhando, uye kugadzirwa kwechikero. Isu tinopa zvigadziriso zvakagadzirirwa zvinoenderana nemhando dzakasiyana dzemishonga (mamorekuru madiki, peptides, radiopharmaceuticals) uye mafomu emupimo (majekiseni, zvigadzirwa zvekufemesa, zvakagadziriswa-kuburitswa maumbirwo).
Mukugadzirwa kutsva kwemishonga, isu tinoisa basa redu pa pre-formulation data uye tinofunga zvakanangwa chiratidzo uye nzira yekutonga yedosage fomu uye dhizaini dhizaini. Nekuda kwekugadzikana kwemishonga yepeptide, takagadzira akawanda-dose/imwe-dose cartridge injectable solution uye lyophilized poda jekiseni. Nekukwenenzvera mabuffer masisitimu uye lyophilization maitiro, isu tinovandudza zvakanyanya kugadzikana kwechigadzirwa. Kune RDCs, isu takagadzira chaiwo conjugation maitiro pakati pekutarisa mavheji uye radionuclides pamwe nemhando yekudzora masisitimu kuti ive nechokwadi chinoshanda uye chakachengeteka radiolabeling. Tichishandisa dhizaini yekombuta-inobatsira dhizaini (CADD) uye QbD misimboti, isu tinogadziridza maumbirwo nemaitiro maparameter kuti tinyatso kudzora makiyi ekuita senge kuparara, kuburitsa maprofile, uye maitiro ekunanga.
Mukugadzirwa kwemishonga yegeneric, tinosanganisa reverse engineering yeRLDs nemberi process optimization kuti iwane kuumbwa uye kuenzana kwemaitiro. Kune yakaoma dosage mafomu senge majekiseni uye inhalation mhinduro, isu tinonyatso fananidza CQA senge particle size kugovera, kuchena, uye kusachena profiles. Kuburikidza nemaitiro ekukwira-kumusoro uye chikero-chekusimbisa, tinova nechokwadi chekuti mageneric anofanana nemushonga wekutarisa mukuchengetedzeka, kushanda zvakanaka, uye kugadzirisa kwekugadzira-kugonesa mvumo yekutonga inoshanda.
Kusvika pari zvino, takabudirira kutsigira mapurojekiti makumi matatu ekugadzirwa kwemishonga mitsva neyakajairwa, kusanganisira mishonga yeGLP-1, peptide inoburitswa inoburitswa, uye RDCs. Isu takakunda mabhodhoro ehunyanzvi senge peptide kudzikisira, yakaderera radiolabeling kunyatsoita, uye chiyero-kumusoro matambudziko muakaoma dosage mafomu. Kubva pamiyedzo yelab-scale kuenda kuGMP-inoenderana nekugadzirwa kwemutyairi, isu tinopihwa simba neinjini mbiri dze "tekinoroji yekuvandudza + shanduro yeindasitiri," ichipa rutsigiro rwakakwana rwekuvandudzwa kwezvinodhaka kubva pane pfungwa kuenda kukiriniki, uye kugonesa yemhando yepamusoro, inodhura-inoshanda kugadzirwa kwemajeneric anofambisa shanduko inobudirira kubva muR&D mibairo kuenda kune kukosha kwekiriniki.
Formulation Manufacturing
Sedanho rekupedzisira mukuturikira mushonga R&D mukushandiswa kwekiriniki, kugadzirwa kwekugadzira ndiyo yakakosha link inobatanidza hunyanzvi hwerabhoritari nezvigadzirwa zvekutengesa. Tichivimba nezvivakwa zvedu zvekugadzira zvepasi rose uye mitsara yekugadzira ine hungwaru, isu takagadzira yakazara-cheni yekugadzira sisitimu inovhara mutyairi wendege-up, kusimbiswa kwemaitiro, uye kushambadzira-chiyero kugadzirwa. Nekugona kwakasimba pamhando dzakasiyana-siyana dzedozi, zvigadzirwa, uye zvakatemwa, tinozadzisa zvidikanwi zvekukwanisa kwemishonga yeutsva kubva pakuvandudzwa kwekiriniki kusvika pakutengesa, tichitsigira kugadzirwa kwemhando yepamusoro, kwakakura kwemishonga yemazuva ese.
1. Unyanzvi Unyanzvi & Manufacturing Infrastructure
Diversified dosage form kugona: Pamishonga yakaoma senge peptides uye RDCs, takagadzira maGMP-anoenderana neakasarudzika masisitimu ekugadzira akawanda-dose/imwe-dose cartridge majekiseni emajekiseni uye lyophilized poda jekiseni. Yakashongedzerwa neotomatiki yekuzadza, lyophilization, uye sterile filtration tekinoroji, isu tinova nechokwadi chekupedzisira-kusvika-kumagumo otomatiki kudzora kubva pambishi yekuisa kusvika pakupedzwa kwechigadzirwa.
Nezve peptide magadzirirwo, isu tinogadzirisa kugadzikana kwezvinetso kuburikidza nebuffer system optimization, akagadzirirwa lyophilization profiles, uye inotonhora cheni yekuchengetedza mhinduro. Yedu yakazara-yekuita-yepamusoro-yepamusoro chikuva, yakavakirwa paQbD chimiro, inogonesa shanduko yakatsetseka kubva muyedzo-yemuyedzo kuenda kukutyaira-chikero kugadzira (10L-100L), kuve nechokwadi chekuberekana uye batch-ku-batch kuenderana kuburikidza nehurongwa hwekuongorora uye kusimbiswa kweiyo yakakosha maitiro paramita (CPPs).
Rutsigiro rwemishonga rutsva: Sisitimu yedu yekugadzira inovhara kiriniki Phase I-III sampuli yekugadzira uye kunyoresa batch kutumira, ichimhanyisa mitsva yekuvandudza zvinodhaka nguva.
Kugadzirwa kwezvinodhaka zveGeneric: Isu tinopa kukurumidza kufambisa uye chiyero-up mhinduro kuzadzisa kudiwa kwepasirese kwezvinodhura-zvinoshanda, zvemhando yepamusoro generic.
2. Quality Control & Compliance
Isu takagadzira yakazara lifecycle yemhando manejimendi system inovhara mbiru yekuongorora, mu-maitiro ekutarisa, uye yekupedzisira kuburitswa kwechigadzirwa. Zvivako zvedu zvakashongedzerwa nezviridzwa zvepamberi zvekuongorora zvakaita seHPLC, LC-MS, uye radio-TLC scanner, inogonesa kuongororwa kwakaringana kweCQAs kusanganisira kusachena profiles, kufanana kwemukati, sterility, uye radiolabeling kunyatsoita.
Nzvimbo dzedu dzekugadzira dzakasimbiswa neChina NMPA yekutevedzera GMP uye inoomerera kune ICH nhungamiro, kuve nechokwadi chekuteedzera kuzere uye kurongeka kwemitemo yepasirese kune vatengi vedu vepasirese.
3. Industrial Value & Achievements
Parizvino, takabudirira kukwidza nekutengesa pamusoro pezvigadzirwa zvekugadzira zvinodarika zana, zvinosanganisira majekiseni eGLP-1, peptide inoburitswa-yakagadziriswa, uye yakanangana nemishonga yeRDC. Yedu yegore yekugadzira kugona inosvika makumi emamiriyoni emadhora / mabhodhoro. Isu tinopa "one-stop" masevhisi ekugadzira anotsigira mishonga yekuvandudza kubva kukiriniki samples kusvika kumusika kutanga, kupfupisa zvakanyanya nguva-kumusika. Kuburikidza nekuita optimization uye otomatiki kukwidziridzwa, isu tinobatsira vatengi vezvinodhaka zvegeneric kuwana kudzora mutengo uye kuvandudzwa kwemhando, tichisimudzira kuwanikwa kwepasirese kwepamusoro-kukosha kwekurapa.
Kubva pakuturikira tekinoroji kusvika pakugadzirwa kwakawanda, tinosimudzira misimboti ye "mhando yekutanga, inofambiswa zvakanaka," kubatanidza zvisina musono R&D nekugadzira kuti uve shamwari yakavimbika mukushandura hunyanzvi hwemishonga kuita mhinduro dzekiriniki pasi rese.
