[Iimpahla ezingekasilwa]
Iziko lobuNjineli bePeptide laseShenzhen JYMed Technology Co., Ltd. linesakhono esomeleleyo kuphuhliso lwemathiriyeli ekrwada. Ikhokelwa liqela lophando leenzululwazi ze-130, kubandakanywa ii-PhD ze-12, iziko linobuchule obuninzi kwi-peptide synthesis kunye nokuphucula inkqubo. Ukusebenzisa i-peptide synthesis yesigaba esiqinileyo (SPPS) kunye ne-liquid-phase peptide synthesis (LPPS) technologies, idibaniswe nezixhobo zokuvelisa ezizenzekelayo, siqinisekisa ukucoceka okuphezulu kunye neemveliso ze-peptide eziphezulu. Iqela lethu le-R&D libonelela ngeenkonzo ezibanzi ukusuka kuyilo lwemolekyuli ukuya kuphuhliso lwenkqubo, lubonelela ngezisombululo ezilungiselelwe ukuhlangabezana neemfuno ezahlukeneyo zabaxumi.
Yonke imisebenzi iqhutyelwa phantsi kwemigangatho engqongqo ye-cGMP, exhaswa zizixhobo zohlalutyo zangoku ezifana ne-HPLC kunye ne-mass spectrometry (MS), ukuqinisekisa ukuba umgangatho wemveliso uhambelana neemfuno ze-pharmacopeial zehlabathi. E-JYMed, sizimisele ukuxhobisa abathengi kuphuhliso oluyimpumelelo kunye norhwebo lwezonyango ezitsha ngokugqwesa kubuchwephesha kunye nenkonzo.
Uphuhliso lweNkqubo
Iqela lophuhliso lwenkqubo ye-JYMed ligxile ekuphuculeni nasekunyuseni umgangatho wokwenziwa kwe-peptide API, ebonelela ngezisombululo ezisebenzayo nezithembekileyo ezilungiselelweyo eziqhutywa yiteknoloji entsha. Ngobuchule obunzulu kwi-SPPS, i-LPPS, kunye ne-flow synthesis eqhubekayo, sinikezela ngeenkonzo zophuhliso zokuphela ukuya ekupheleni ukusuka kwi-milligram-scale screening ukuya kwi-kilogram-scale-scale production.
Ngeqonga lethu lekhemistri eluhlaza ye-peptides, soyise imiceli mngeni ekwenzeni ulandelelwano oluntsonkothileyo, siphucula kakhulu ubunyulu kunye nesivuno. Oku kusenza sikwazi ukuhlangabezana neemfuno ezingqongqo zeepeptides eziphezulu ezisetyenziswa kwi-oncology, izifo ze-metabolic, kunye nolunye unyango oluphambili.
Inkqubo yethu yokwenziwa kwemveliso ithobela ngokungqongqo izikhokelo ze-cGMP kwaye ixhotyiswe ngokupheleleyo ngeeyunithi ezizisebenzelayo zokwenziwa kunye nezixhobo zokuhlalutya ezikumgangatho ophezulu ezifana ne-UPLC kunye ne-MS enesisombululo esiphezulu. Ngokudityaniswa neemodeli zokuphucula inkqubo ephuhliswe ngaphakathi, siqinisekisa ukomelela kwenkqubo kunye ne-batch-to-batch consistency. I-JYMed igqibe ngempumelelo iiprojekthi ezininzi zophuhliso lwe-peptide API kuzo zonke ii-preclinical ukuya kwizigaba zorhwebo, ukuhambisa izisombululo ezikhawulezayo, eziqhutywa yidatha ukukhawulezisa ukusungulwa kwamayeza ehlabathi.
Ukuvelisa
Indawo yethu yemveliso inama-300 emu (malunga nama-200,000 square metres) kunye nendawo eyakhiweyo ejikeleze i-54,000 square metres. Eli ziko liquka iindibano zocweyo zokwenziwa kweepeptide, izakhiwo ze-QC kunye ne-R&D, iindawo zokugcina iimpahla zoDidi A kunye no-B, iziko lokubuyisela izinto ezinyibilikayo, amaziko aluncedo, indawo yokuqokelelwa kwenkunkuma eqinileyo, kunye nesikhululo sokucocwa kwamanzi amdaka.
I-Hubei Jianxiang Biopharmaceutical Co., Ltd. isebenzisa imigca yemveliso ye-peptide ye-10 ye-peptide (kubandakanywa nemigca ye-pilot-scale) ehambelana nemigangatho ye-cGMP yase-US, EU, ne-China. Ezi zixhotyiswe ngamawaka ee-rectors zesigaba esiqinileyo kunye nesigaba solwelo se-peptide synthesis, iyonke iyonke ngaphezu kwe-30,000 yeelitha kumthamo wereactor.
Ngenkqubo yolawulo lomgangatho wamayeza esekwe kakuhle kunye nenkqubo yokuthotyelwa kwe-EHS, u-Hubei Jianxiang uphumelele uhlolo olusemthethweni lwe-NMPA GMP, uphicotho oluninzi lomntu wesithathu, kunye nophicotho lwe-EHS oluvela kubathengi abahamba phambili behlabathi. Umthamo wayo wonyaka wemveliso yepeptide ufikelele kwisikali seetoni ezininzi. Ngokucacileyo, imveliso ye-analog ye-GLP-1 iphakathi kwezona zinkulu eTshayina ngevolumu yebhetshi enye, kwaye ezinye iipeptide zokuthambisa zidlula i-100 kg ngebhetshi nganye, ibeka inkampani njengomvelisi we-API okhuphisanayo we-chemical synthesis peptide kwiimarike zasekhaya nezamazwe ngamazwe.
I-High-Potency Peptide APIs
Imigca yemveliso ye-Jianxiang ephezulu ye-peptide ye-API imele inzuzo engundoqo yokhuphiswano, enikezela ngezisombululo ezikhuselekileyo nezisebenzayo kubathengi behlabathi. Eli ziko libandakanya i-OEB4-level kunye neeyunithi ezimbini ze-OEB5-high-containment eziyilelwe ukuhlangabezana neemfuno ezifunekayo zokwenziwa kweekhompawundi ezinamandla kakhulu ezifana ne-anti-tumor kunye ne-cytotoxic peptides, ukuqinisekisa ukhuseleko kubasebenzi kunye nokusingqongileyo.
Imigca yemveliso isebenzisa i-SPPS ehamba phambili kwi-industry kunye ne-LPPS iteknoloji eneenkqubo zokulawula ezizenzekelayo ngokupheleleyo, ivumela ukuveliswa kwe-scalable ye-high-purity kunye ne-high-potency peptides ukusuka kwigram ukuya kwisikali sekhilogram. Ukungaguquguquki kwebhetshi kunye nomgangatho wemveliso ihambelana ngokupheleleyo nemigangatho ye-pharmacopeial yamazwe ngamazwe.
Eyakhelwe kwinkqubo yokulawula umgangatho ohambelana ne-cGMP, yonke inkqubo yokuvelisa-ukusuka ekukhethweni kwezinto eziluhlaza, ukuhlanganiswa, ukuhlanjululwa ukuya kuvavanyo lokugqibela-iyalandeleka ngokupheleleyo. Izixhobo zokuhlalutya eziphambili ezifana ne-HPLC kunye ne-MS ziqinisekisa ukucoceka kwemveliso ≥99% kunye neeprofayili zokungcola ezilawulwayo. Ukujongana neemfuno ezizodwa zokhuseleko ze-APIs ezinamandla aphezulu, iiyunithi ze-OEB5-level zisebenzisa iinkqubo zokuzihlukanisa ezivaliweyo, iimeko ezizimeleyo zoxinzelelo olubi, kunye neenkqubo ezihlakaniphile zokubeka iliso lokuvuza, kunye nemigaqo engqongqo yePPE yokuqinisekisa ukhuseleko olubanzi.
Iqela lethu le-R&D likwabonelela ngophuhliso lwenkqubo elungiselelweyo kunye neenkonzo zokuphucula ezigubungela lonke ikhonkco lexabiso ukusuka kuyilo lwemolekyuli kunye nokunyuka ukuya kwizifundo ezisemgangathweni, ukuxhasa ukuqhubela phambili okukhawulezayo konyango olusekwe kwipeptide.
[Uyilo]
Iqela lethu elingundoqo lobugcisa liqulunqwe ngabaphandi abanamava abachwephesha ekuqulunqeni nasekuhlalutyeni inzululwazi. Ngobuchule obubanzi kulo lonke uqulunqo lwexabiso lophuhliso lwekhonkco, sinikezela ngeenkonzo zokugqibela ukusuka kuphando lwezonyango ukuya kwimveliso yorhwebo. Siye saseka amandla awodwa obuchwepheshe kwimimandla yemida efana namachiza e-GLP-1, ii-peptides kunye ne-peptide formulations, ii-peptide formulations ezizinzileyo, kunye nophuhliso lwe-radiopharmaceutical (RDC).
Ukusebenzisa i-R&D yethu esasazwe kwihlabathi jikelele kunye nezixhobo zokuvelisa, sakhe inkqubo yoqulunqo olubanzi. Kwintsimi yokwenziwa kwepeptide, sibonelela ngezisombululo ezahlukeneyo ezibandakanya idosi eninzi/idosi enye yeekhatriji ezitofwa izisombululo, umgubo olilophilized wenaliti, kunye nezisombululo zokuphefumla. Kuphuhliso lwe-RDC, iqela lethu likwazi kakuhle iindlela zokudibanisa ii-radionuclides kunye nokujolisa kwii-vectors, ezibonelela ngetekhnoloji entsha yokuxhasa ukuxilongwa kwe-oncology kunye nonyango oluchanekileyo. Ukuya kuthi ga ekupheleni kuka-2024, iqela lethu liye laxhasa ngaphezulu kwe-100 yeeprojekthi zophuhliso lwamachiza amatsha (ezibandakanya amanqanaba angaphambi kweklinikhi ukuya kwiSigaba sesi-III), egxile ikakhulu kwi-analog ye-GLP-1, amanye amachiza e-peptide, kunye nee-RDCs. Siye sagqiba ngempumelelo iiprojekthi ezi-5 zokuvavanya ukungaguquguquki kwamachiza enziwe afana nalawo aveliswe ngumenzi abandakanya atofwayo kunye nolunye umxube.
Njengeqela eliqhutywa yitekhnoloji, sihlala sizibophelele ekuveliseni nasekuguquleni okuqhubekayo kophando kwizisombululo zehlabathi lokwenyani. Iinzame zethu aziboneleli kuphela ngezisombululo ezikhuselekileyo nezisebenzayo kurhwebo lwehlabathi loxubo-mayeza, ukukhuthaza ukusetyenziswa kwezonyango kunye nemizi-mveliso ye-peptide kunye ne-RDC yamachiza, kodwa kusekwa umda oqinileyo wokhuphiswano kwicandelo lovavanyo lokungaguquguquki kwamachiza enziwe afana nalawo aveliswe ngumenzi.
UPhando lokuqulunqwa kwangaphambili
Njengenyathelo lokuqala eliphambili kuphuhliso lwamachiza, uphando lokuqulunqwa kwangaphambili lusebenza njengekhonkco elibalulekileyo phakathi kokufunyanwa kwechiza kunye noyilo loyilo. Umgangatho wayo wobugcisa uchaphazela ngokuthe ngqo uphuhliso lwefomu yedosi kunye nokuba nokwenzeka kwenkqubo.
Ukuphuhliswa kwamachiza amatsha, siqhuba ngokucwangcisiweyo izifundo kwiipropati eziphambili ze-APIs - kubandakanywa ukuvavanywa kwe-solubility, ukuhlolwa kwe-polymorph, ukuhlalutya ukuthotywa okunyanzeliswayo, kunye nokuhlolwa kokuzinza kwangaphambili - ukuchonga ngokuchanekileyo iimpawu ze-physicochemical kunye neendlela ezinokuthi zenzeke. Olu lwazi lusebenza njengesiseko soyilo loyilo, ukuphuculwa kwenkqubo, kunye nophuhliso olusemgangathweni olusemgangathweni, ekugqibeleni lunciphisa umngcipheko weR&D kunye nokuphucula ukusebenziseka kweziyobisi kwasekuqaleni.
Kuphuhliso lwamachiza enziwe afana nalawo aveliswe ngumenzi, uhlalutyo olunzulu lwechiza elikuluhlu lwereferensi (RLD) lugqaliselo olusembindini wophando olwenziwe kwangaphambili. Ngokusebenzisa ubunjineli obubuyela umva, simisela ukuqulunqwa kokwenziwa, inkqubo yokwenziwa kwemveliso, kunye neempawu zomgangatho obalulekileyo (ii-CQAs) zeyeza lokuqala. Oku kuvumela isikhokelo esijoliswe ekuqulunqeni ukuhambelana kunye nokuveliswa kwenkqubo, kwaye, ngokuhambelana noMgangatho ngokuYila (QbD) indlela, iqinisekisa ukuba imveliso yegeneric ifezekisa ukulingana ngokukhuselekileyo, ukusebenza kakuhle, kunye nokulawula umgangatho-ukubeka isiseko esiluqilima sobuchwephesha ukuze kuhlolwe ngempumelelo ukuhambelana.
Uphuhliso Loqulunqo
Njengebhulorho ebalulekileyo phakathi kophuhliso lwamachiza kunye noshishino, uphuhliso loqulunqo ludlala indima ebalulekileyo ekuguquleleni iziphumo zelebhu kwizicelo zeklinikhi. Iqela lethu ligxile kubuchwephesha bokuyila obutsha kunye neemfuno zemizi-mveliso enokunyuka, ukwakha inkqubo yophuhliso yenkqubo epheleleyo equka uyilo loyilo, ukuphuculwa kwenkqubo, uphando olusemgangathweni, kunye nemveliso yokulinga. Sinikezela ngezisombululo ezenzelwe ukuba zilungele iintlobo ezahlukeneyo zamachiza (iimolekyuli ezincinci, i-peptides, i-radiopharmaceuticals) kunye neefom zedosi (izitofu, iimveliso zokuphefumla, ukukhutshwa okuzinzileyo).
Kuphuhliso olutsha lokwenziwa kwechiza, sisekela umsebenzi wethu kwidatha yokuqulunqwa kwangaphambili kwaye sithathela ingqalelo isalathiso ekujoliswe kuso kunye nendlela yolawulo yefomu yedosi kunye noyilo lwenkqubo. Kwimingeni yozinzo lwamachiza e-peptide, siye saqulunqa isisombululo sekhatriji enedosi eninzi/idosi enye kunye neenaliti zomgubo ezitofwayo. Ngokulungisa iinkqubo ze-buffer kunye neenkqubo ze-lyophilization, siphucula kakhulu uzinzo lwemveliso. Kwii-RDCs, siye saseka iinkqubo ezichanekileyo zokudibanisa phakathi kwee-vectors ezijoliswe kuyo kunye ne-radionuclides kunye neenkqubo zokulawula umgangatho ukuqinisekisa ukuba i-radiolabeling esebenzayo nekhuselekileyo. Sisebenzisa uyilo loyilo oluncediswa yikhompyutha (CADD) kunye nemigaqo ye-QbD, siphucula ngokulungeleleneyo iifomyulwa kunye nenkqubo yeeparamitha ukulawula ngokuchanekileyo izikhombisi zokusebenza ezingundoqo ezifana nokuchithwa, ukukhulula iiprofayili, kunye nokuziphatha okujoliswe kuyo.
Kuphuhliso lwamachiza enziwe afana nalawo enziwe afana nalawo aveliswe ngumenzi, sidibanisa ubunjineli obungasemva bee-RLDs kunye nokuphucula inkqubo yokuqhubela phambili ukuphumeza ukuqulunqwa kunye nokulingana kwenkqubo. Kwiifom zedosi eziyinkimbinkimbi ezifana nezitofu kunye nezisombululo ze-inhalation, sifanisa ngokuchanekileyo i-CQAs ezifana nokusabalalisa ubungakanani besuntswana, ubunyulu, kunye neeprofayili zokungcola. Ngokusebenzisa inkqubo yokunyusa kunye nokuqinisekisa ubungakanani bovavanyo, siqinisekisa ukuba iigenerics ziyahambelana nechiza lereferensi kukhuseleko, ukusebenza ngokufanelekileyo, kunye nokulawulwa kokwenziwa kwemveliso-ukuvumela ukuvunywa kokulawula okusebenzayo.
Ukuza kuthi ga ngoku, siye saxhasa ngempumelelo iiprojekthi zophuhliso ezingama-30 zawo omabini amachiza amatsha kunye namayeza enziwe afana nalawo aveliswe ngabenzi, kubandakanywa amachiza e-GLP-1, amayeza akhutshwa ngokuzinzileyo e-peptide, kunye nee-RDCs. Soyisile imiqobo yobuchwephesha efana nokuthotywa kwe-peptide, ukusebenza kakuhle kwe-radiolabeling, kunye nemiceli mngeni yokunyusa kwiifom zedosi enzima. Ukusuka kulingo lwelebhu ukuya kwimveliso yokulinga ethobela i-GMP, sinikwe amandla ziinjini ezimbini “zobuchule obutsha + ukuguqulelwa kwemizi-mveliso,” ebonelela ngenkxaso ebanzi yophuhliso lwamachiza amatsha ukusuka kwingcinga ukuya kwikliniki, nokwenza ukuba umgangatho ophezulu, ungabizizo kakhulu ukuveliswa kwemveliso yegenerics eqhuba inguqu esebenzayo ukusuka kwiziphumo zeR&D ukuya kwixabiso lezonyango.
Ukwenziwa kokwenziwa kwemveliso
Njengenyathelo lokugqibela lokuguqulela ichiza i-R&D kusetyenziso lwezonyango, ukwenziwa kokwenziwa likhonkco elibalulekileyo elidibanisa ukusungulwa kwelabhoratri kunye neemveliso zorhwebo. Ngokuthembela kumaziko ethu emveliso adityanisiweyo kwihlabathi jikelele kunye nemigca yokuvelisa ekrelekrele, siye saseka inkqubo yokuvelisa ikhonkco epheleleyo egubungela isikali sokulinga, ukuqinisekiswa kwenkqubo, kunye nemveliso yorhwebo. Ngesakhono esinamandla kuzo zonke iifom ezininzi zedosi, iimveliso, kunye neenkcukacha, siyahlangabezana neemfuno zamachiza aqalayo ukusuka kuphuhliso lwezonyango ukuya kurhwebo, ngelixa sixhasa umgangatho ophezulu, ukuveliswa kwamachiza enziwe afana nalawo aveliswe ngumenzi.
1. UbuKhono boBugcisa kunye neZiseko zoMveliso
Izakhono zefomu yedosi ehlukeneyo: Kumachiza anzima afana neepeptides kunye ne-RDCs, siye saseka iinkqubo ze-GMP ezithobelayo ezikhethekileyo zokuvelisa i-multi-dose / i-cartridge yedosi enye yezisombululo ezitofwayo kunye ne-lyophilized powder injections. Ukuxhotyiswa ngokuzaliswa ngokuzenzekelayo, i-lyophilization, kunye nobuchwepheshe bokuhluza inzalo, siqinisekisa ukuphela kokuphela kokulawula okuzenzekelayo ukusuka kwigalelo lezinto eziluhlaza ukuya kupakisho olugqityiweyo lwemveliso.
Ukwenziwa kweepeptide, sijongana nemingeni yozinzo ngokusebenzisa inkqubo ye-buffer optimization, iiprofayili ezilungiselelwe i-lyophilization, kunye nezisombululo zokugcina ikhonkco elibandayo. Iqonga lethu elipheleleyo lenkqubo yokunyusa izinga, elakhelwe kwisakhelo se-QbD, lenza utshintsho olugudileyo ukusuka kwizilingo zesikali selebhu ukuya kwimveliso yokulinga (10L-100L), iqinisekisa ukuveliswa kwenkqubo kunye nokuhambelana kwebhetshi ukuya kwibhetshi ngovavanyo olucwangcisiweyo kunye nokuqinisekiswa kweeparamitha zenkqubo ebalulekileyo (CPPs).
Inkxaso yamachiza entsha: Inkqubo yethu yokuvelisa ibandakanya iSigaba se-I–III sokwenziwa kweesampulu kunye nokubhaliswa kweebhetshi, ukukhawulezisa amaxesha amatsha ophuhliso lwamachiza.
Imveliso yamachiza enziwe afana nalawo aveliswe ngumenzi: Sinikezela ngenkqubo ekhawulezayo yodluliselo kunye nezisombululo ezongezelelekileyo ukuze kuhlangatyezwane nebango lehlabathi leegenerics ezinexabiso elisebenzayo, ezikumgangatho ophezulu.
2. Ulawulo loMgangatho kunye nokuthotyelwa
Siye saseka inkqubo yolawulo lomgangatho wobomi bomjikelo obanzi oquka uhlolo lwemathiriyeli ekrwada, ukubeka iliso kwinkqubo, kunye nokukhutshwa kwemveliso yokugqibela. Izixhobo zethu zixhotyiswe ngezixhobo zokuhlalutya eziphambili ezifana ne-HPLC, i-LC-MS, kunye ne-radio-TLC scanners, eyenza uvavanyo oluchanekileyo lwee-CQAs kubandakanya iiprofayili zokungcola, ukufana komxholo, ubunyumba, kunye nokusebenza kakuhle kwe-radiolabeling.
Iindawo zethu zokwenziwa kwemveliso ziqinisekiswa yi-NMPA yaseTshayina yokuthobela i-GMP kwaye ithobela ngokungqongqo izikhokelo ze-ICH, iqinisekisa ukulandeleka okugcweleyo kunye nolungelelwaniso lolawulo lwehlabathi kubathengi bethu behlabathi.
3. Ixabiso leShishini kunye neeMpumelelo
Ukuza kuthi ga ngoku, siye sanyusa ngempumelelo saza sarhweba ngaphezu kweemveliso ze-100, kubandakanywa ii-GLP-1 ezitofwayo, ii-peptide ezikhutshwa ngokuzinzileyo kwimixube, kunye namachiza ekujoliswe kuwo e-RDC. Umthamo wethu wonyaka wemveliso ufikelela kumashumi ezigidi zeedosi/iibhotile. Sinikezela ngeenkonzo zokuvelisa “ezinye” ezixhasa amachiza aqalayo ukusuka kwiisampulu zeklinikhi ukuya ekuqalisweni kwemarike, sinciphisa kakhulu ixesha lokuya kwintengiso. Ngokuphucula inkqubo kunye nophuculo oluzenzekelayo, sinceda abathengi bamachiza enziwe afana nalawo aveliswe ngumenzi ukuba bafezekise ulawulo lweendleko kunye nokuphucula umgangatho, siphucula ukufikeleleka kwehlabathi kunyango lwexabiso eliphezulu.
Ukusuka kuguqulelo lwetekhnoloji ukuya kwimveliso eninzi, sibambelela kwimithetho-siseko "yomgangatho wokuqala, oqhutywa ngokufanelekileyo," ngokudibana ngaphandle komthungo i-R&D kunye nemveliso ukuze ube liqabane elithembekileyo ekuguquleni ukuveliswa kwamayeza kwizisombululo zeklinikhi kwihlabathi liphela.
