[Lisebelisoa tse so fetoloe]
Setsi sa Boenjiniere sa Peptide sa Shenzhen JYMed Technology Co., Ltd. se na le bokhoni bo matla ho nts'etsopele ea thepa e tala. Setsi sena se etelletsoe pele ke sehlopha sa lipatlisiso sa bo-ramahlale ba 130, ho kenyeletsoa le li-PhD tse 12, setsi sena se na le boiphihlelo bo pharaletseng ba ho kopanya peptide le ho ntlafatsa ts'ebetso. Re sebelisa theknoloji e tsoetseng pele ea "solid-phase peptide synthesis" (SPPS) le "liquid-phase peptide synthesis" (LPPS), e kopantsoeng le lisebelisoa tse ikemetseng tsa tlhahiso, re netefatsa lihlahisoa tsa peptide tse hloekileng le tse sebetsang haholo. Sehlopha sa rona sa R&D se fana ka lits'ebeletso tse felletseng ho tloha ho moralo oa limolek'hule ho isa ntlafatsong ea ts'ebetso, ho fana ka litharollo tse etselitsoeng ho fihlela litlhoko tse fapaneng tsa bareki.
Mesebetsi eohle e etsoa tlas'a litekanyetso tse thata tsa cGMP, tse tšehetsoeng ke lisebelisoa tsa morao-rao tsa tlhahlobo tse kang HPLC le mass spectrometry (MS), ho netefatsa hore boleng ba sehlahisoa bo lumellana le litlhoko tsa lefats'e tsa pharmacopeial. Ho JYMed, re ikemiselitse ho matlafatsa bareki tsoelo-peleng e atlehileng le khoebong ea mekhoa e mecha ea kalafo ka bokhabane ba theknoloji le litšebeletso.
Nts'etsopele ea Ts'ebetso
Sehlopha sa nts'etsopele ea ts'ebetso sa JYMed se sebetsa ka ho khetheha ho ntlafatseng le ho holisa tlhahiso ea peptide API, se fana ka litharollo tse ikhethileng le tse tšepahalang tse tsamaisoang ke boqapi ba mahlale. Ka boitseanape bo tebileng ba SPPS, LPPS, le phallo e tsoelang pele ea phallo, re fana ka lits'ebeletso tsa nts'etsopele ea ho qetela ho tloha ho li-milligram-scale ho isa tlhahiso ea lik'hilograma tse lekholo.
Ka sethala sa rona sa k'hemistri e tala bakeng sa li-peptide, re hlotse liphephetso tsa ho kopanya tatellano e rarahaneng, ho ntlafatsa bohloeki le chai haholo. Sena se re nolofalletsa ho fihlela litlhoko tse thata tsa li-peptide tse matla tse sebelisoang ho oncology, mafu a metabolism, le liphekolo tse ling tse tsoetseng pele.
Sistimi ea rona ea tlhahiso e latela ka tieo litataiso tsa cGMP 'me e na le li-unit tsa maiketsetso tse ikemetseng le lisebelisoa tse tsoetseng pele tsa tlhahlobo tse kang UPLC le MS ea boleng bo holimo. Mmoho le mekhoa ea ntlafatso ea ts'ebetso e ntlafalitsoeng ka hare, re netefatsa ts'ebetso e matla le ho ts'oara batch-to-batch. JYMed e atlehile ho phethela merero e mengata ea nts'etsopele ea peptide API ho pholletsa le pele ho maemo a khoebo, e fana ka litharollo tse potlakileng, tse tsamaisoang ke data ho potlakisa ntlafatso ea meriana ea lefats'e.
Tlhahiso
Sebaka sa rona sa tlhahiso se boholo ba 300 mu (hoo e ka bang 200,000 square metres) se nang le sebaka se ahiloeng se ka bang 54,000 square metres. Setsi sena se na le lithupelo tsa tlhahiso ea lipeptide, meaho ea QC le R&D, libaka tsa polokelo tsa Sehlopha sa A le sa B, setsi sa ho hlabolla li-solvents, litsi tsa ts'ebeliso, sebaka sa pokello ea litšila le seteishene sa ho hloekisa metsi a litšila.
Hubei Jianxiang Biopharmaceutical Co., Ltd. e sebelisa mela ea tlhahiso ea 10 peptide API (ho kenyeletsoa le mehala ea sekala sa sefofane) e tsamaellanang le litekanyetso tsa cGMP tsa US, EU, le China. Tsena li na le lisebelisoa tse ngata tsa "solid-phase" le "liquid-phase-peptide synthesis reactors", tse etsang kakaretso ea lilithara tse fetang 30,000 ka bophahamo ba "reactor".
Ka sistimi e hlophisitsoeng hantle ea taolo ea boleng ba meriana le sistimi ea ho latela melao ea EHS, Hubei Jianxiang o fetile tlhahlobo ea semmuso ea NMPA GMP, lihlahlobo tse ngata tsa mokha oa boraro, le litlhahlobo tsa EHS tse tsoang ho bareki ba ka sehloohong lefatšeng ka bophara. Bokhoni ba eona ba selemo le selemo ba tlhahiso ea peptide bo fihlile sekala sa lithane tse ngata. Haholo-holo, tlhahiso ea li-analogues tsa GLP-1 e har'a tse kholo ka ho fetisisa Chaena ka bophahamo ba palo e le 'ngoe,' me li-peptide tse ling tsa cosmetic li feta 100 kg ka batch, li beha k'hamphani e le moetsi oa tlholisano oa lik'hemik'hale oa peptide API mebarakeng ea lapeng le ea machabeng.
High-Potency Peptide APIs
Mehala ea tlhahiso ea API ea Jianxiang ea matla a phahameng a peptide e emela monyetla oa tlholisano oa mantlha, e fanang ka tharollo e bolokehileng le e sebetsang ho bareki ba lefats'e. Setsi sena se kenyelletsa likarolo tse peli tsa boemo ba OEB4 le tse peli tsa boemo bo phahameng ba OEB5 tse etselitsoeng ho fihlela litlhoko tse boima tsa tlhahiso ea metsoako e matla haholo joalo ka anti-tumor le cytotoxic peptides, ho netefatsa polokeho ea basebetsi le tikoloho.
Mehala ea tlhahiso e sebelisa theknoloji e etellang pele indastering ea SPPS le LPPS e nang le litsamaiso tsa taolo tse ikemetseng ka botlalo, tse nolofalletsang tlhahiso e mpe ea li-peptide tse hloekileng le tse matla haholo ho tloha sekaleng sa gram ho ea ho kilogram. Ho tsitsa ha sehlopha le boleng ba sehlahisoa li lumellana ka botlalo le litekanyetso tsa machaba tsa pharmacopeial.
E hahiloe holim'a tsamaiso ea boleng bo lumellanang le cGMP, ts'ebetso eohle ea tlhahiso-ho tloha ho khetho ea thepa e tala, ho kopanya, ho hloekisa ho ea tekong ea ho qetela-e ka fumanoa ka ho feletseng. Lisebelisoa tse tsoetseng pele tsa tlhahlobo tse kang HPLC le MS li netefatsa bohloeki ba sehlahisoa ≥99% ka lintlha tse laoloang tsa litšila. Ho sebetsana le litlhoko tse ikhethang tsa polokeho ea li-API tsa matla a holimo, likarolo tsa boemo ba OEB5 li amohela litsamaiso tse koetsoeng, maemo a ikemetseng a khatello e mpe, le lits'ebetso tse bohlale tsa ho lekola ho lutla, hammoho le liprothokholo tse tiileng tsa PPE bakeng sa tiisetso e felletseng ea polokeho.
Sehlopha sa rona sa R&D se boetse se fana ka lits'ebeletso tse ikhethileng tsa nts'etsopele ea ts'ebetso le ts'ebetso ea ntlafatso e akaretsang ketane eohle ea boleng ho tloha ho moralo oa limolek'hule le ho nyoloha ho fihlela lithutong tsa boleng, ho ts'ehetsa tsoelo-pele e potlakileng ea mekhoa e mecha ea kalafo e thehiloeng ho peptide.
[Moetso]
Sehlopha sa rona sa mantlha sa tekheniki se entsoe ka bafuputsi ba nang le boiphihlelo ba sebetsanang le boqapi le mahlale a tlhahlobo. Ka boitseanape bo pharalletseng ho pholletsa le ketane ea boleng ba ntlafatso ea tlhahiso, re fana ka lits'ebeletso tsa ho qetela ho tloha ho lipatlisiso tsa pele ho ea ho tsa khoebo. Re thehile matla a ikhethang a theknoloji masimong a moeli a joalo ka lithethefatsi tsa GLP-1, li-peptides le li-peptide formulations, li-peptide tse sa khaotseng, le nts'etsopele ea radiopharmaceutical (RDC).
Ka ho sebelisa lisebelisoa tsa rona tsa R&D tse ajoang lefatšeng ka bophara, re thehile sistimi e felletseng ea ntlafatso ea tlhahiso. Lefapheng la ho etsa peptide, re fana ka litharollo tse fapaneng tse kenyelletsang litharollo tsa cartridge ea lethal dose e le 'ngoe, lyophilized powder bakeng sa ente, le tharollo ea ho hema. Nts'etsopele ea RDC, sehlopha sa rona se ithutile mekhoa e ntlafalitsoeng ea ho kopanya li-radionuclides le ho lebisa li-vector, e fanang ka mahlale a macha ho ts'ehetsa tlhahlobo le kalafo ea oncology. Ho tloha bofelong ba 2024, sehlopha sa rona se tšehelitse merero e mecha ea ntlafatso ea lithethefatsi e fetang 100 (e akaretsang mehato ea pele ho Phase III), e shebaneng haholo le li-analogue tsa GLP-1, lithethefatsi tse ling tsa peptide le li-RDC. Hape re atlehile ho phethela merero e 5 ea tlhahlobo ea ho tsitsa ha lithethefatsi tse tloaelehileng tse kenyelletsang liente le litlhare tse ling.
Joalo ka sehlopha se khannoang ke theknoloji, re lula re ikemiseditse ho ntlafatsa le ho fetolela diphuputso tse mabapi le ditharollo tsa lefatshe la sebele. Boiteko ba rona ha bo fane feela ka litharollo tse bolokehileng le tse sebetsang tsa 'maraka oa lefats'e oa meriana, ho khothaletsa ts'ebeliso ea bongaka le indasteri ea litlhare tsa peptide le RDC, empa hape ho theha tlholisano e matla lebaleng la tlhahlobo ea ho lumellana ha lithethefatsi tse tloaelehileng.
Patlisiso ea pele ho sebopeho
Joalo ka mohato oa mantlha oa nts'etsopele ea lithethefatsi, lipatlisiso tsa pele ho sebopeho li sebetsa e le sehokelo sa bohlokoa lipakeng tsa ho sibolloa ha lithethefatsi le moralo oa tlhahiso. Boleng ba eona ba tekheniki bo ama ka kotloloho ntlafatso ea foromo ea litekanyetso le bokhoni ba ts'ebetso.
Bakeng sa nts'etsopele ea lithethefatsi tse ncha, re etsa lithuto ka mokhoa o hlophisitsoeng mabapi le thepa ea bohlokoa ea li-API - ho kenyelletsa tlhahlobo ea solubility, tlhahlobo ea polymorph, tlhahlobo ea ho senyeha e qobelloang, le liteko tsa pele tsa botsitso - ho tseba hantle litšobotsi tsa physicochemical le litsela tse ka senyehang. Litlhahiso tsena li sebetsa e le motheo oa moralo oa moralo, ntlafatso ea ts'ebetso, le nts'etsopele ea maemo a boleng, qetellong e fokotsa likotsi tsa R&D le ho ntlafatsa ts'ebeliso ea lithethefatsi ho tloha qalong.
Ho nts'etsopele ea lithethefatsi tse tloaelehileng, tlhahlobo e tebileng ea lithethefatsi tse thathamisitsoeng (RLD) ke sepheo sa mantlha sa lipatlisiso tsa pele ho tlhahiso. Ka boenjiniere ba morao-rao, re khetholla sebopeho sa tlhahiso, ts'ebetso ea tlhahiso, le litšoaneleho tsa boleng ba bohlokoa (CQAs) tsa sethethefatsi se qalileng. Sena se nolofalletsa tataiso e lebisitsoeng bakeng sa ho bapisa sebopeho le tlhahiso ea ts'ebetso, 'me, tumellanong le mokhoa oa Quality by Design (QbD), o netefatsa hore sehlahisoa sa generic se finyella ho lekana ka polokeho, katleho, le taolo ea boleng-ho rala motheo o tiileng oa theknoloji bakeng sa tlhahlobo e atlehileng ea ho lumellana.
Ntlafatso ea Sebopeho
Joalo ka borokho ba bohlokoa lipakeng tsa nts'etsopele ea lithethefatsi le nts'etsopele ea indasteri, nts'etsopele ea tlhahiso e phetha karolo ea bohlokoa ho fetoleleng liphetho tsa laboratoring ho likopo tsa bongaka. Sehlopha sa rona se tsepamisitse maikutlo ho mahlale a macha a ho theha le litlhoko tse mpe tsa indasteri, ho aha sistimi e felletseng ea ntlafatso e akaretsang moralo oa moralo, ntlafatso ea ts'ebetso, lipatlisiso tsa boleng, le tlhahiso ea maemo a holimo. Re fana ka litharollo tse ikhethileng tse etselitsoeng mefuta e fapaneng ea lithethefatsi (limolek'hule tse nyane, li-peptide, radiopharmaceuticals) le mefuta ea litekanyetso (liente, lihlahisoa tse hemang, litlhare tsa tokollo e tsitsitseng).
Ho nts'etsopele e ncha ea tlhahiso ea lithethefatsi, re theha mosebetsi oa rona ho data e entsoeng esale pele 'me re nahana ka sesupo se reriloeng le tsela ea tsamaiso bakeng sa foromo ea litekanyetso le moralo oa ts'ebetso. Bakeng sa mathata a botsitso ba lithethefatsi tsa peptide, re thehile litharollo tse nang le liente tse nang le litekanyetso tse ngata / tsa tekanyo e le 'ngoe le liente tsa phofo tse lyophilized. Ka ho ntlafatsa lits'ebetso tsa buffer le lits'ebetso tsa lyophilization, re ntlafatsa haholo botsitso ba sehlahisoa. Bakeng sa li-RDC, re thehile mekhoa e nepahetseng ea ho kopanya pakeng tsa li-vector le li-radionuclide hammoho le mekhoa ea ho laola boleng ho netefatsa hore radiolabeling e sebetsa hantle ebile e bolokehile. Ka ho sebelisa moralo o thusoang ke komporo (CADD) le melaoana ea QbD, re ntlafatsa libopeho le mekhoa ea ts'ebetso ho laola ka nepo matšoao a bohlokoa a ts'ebetso joalo ka ho qhalana, ho lokolla liprofaele, le boitšoaro ba sepheo.
Ho nts'etsopele ea lithethefatsi tse tloaelehileng, re kopanya boenjineri ba morao-rao ba li-RLD le ntlafatso ea ts'ebetso ho fihlela tlhahiso le ts'ebetso e lekanang. Bakeng sa liforomo tse rarahaneng tsa litekanyetso tse kang liente le litharollo tsa ho inhalation, re bapisa ka nepo CQAs joalo ka kabo ea boholo ba likaroloana, bohloeki, le li-profile tsa litšila. Ka ho eketsa ts'ebetso le netefatso ea litekanyetso, re etsa bonnete ba hore li-generic li lumellana le setlhare sa ts'ireletso ka polokeho, katleho, le taolo ea tlhahiso-e lumellang tumello e sebetsang ea taolo.
Ho fihlela joale, re atlehile ho tšehetsa merero e fetang 30 ea ntlafatso ea litlhare tse ncha le tse tloaelehileng, ho kenyeletsoa litlhare tsa GLP-1, li-peptide tse lokolloang ka nako e telele, le li-RDC. Re hlōtse mathata a tekheniki a kang ho senyeha ha peptide, katleho e tlaase ea radiolabeling, le liphephetso tsa ho eketseha ka mefuta e rarahaneng ea litekanyetso. Ho tloha litekong tse leka-lekaneng ho ea ho tlhahiso ea lifofane e tsamaellanang le GMP, re matlafatsoa ke lienjineri tse peli tsa "boqapi ba theknoloji + phetolelo ea indasteri," e fanang ka tšehetso e felletseng bakeng sa nts'etsopele ea lithethefatsi tse ncha ho tloha mohopolong o mong ho ea ho tleliniking, le ho nolofalletsa tlhahiso ea bongata ba boleng bo holimo, e baballang chelete e ngata e tsamaisang phetoho e atlehileng ho tloha ho liphetho tsa R&D ho ea boleng ba bongaka.
Tlhahiso ea Tlhahiso
E le mohato oa ho qetela oa ho fetolela R&D ea lithethefatsi ts'ebelisong ea bongaka, tlhahiso ea litlhare ke sehokelo sa bohlokoa se hokahanyang boiqapelo ba laboratori le lihlahisoa tsa khoebo. Re ipapisitse le lisebelisoa tsa rona tsa tlhahiso tse kopaneng lefatšeng ka bophara le mehala e bohlale ea tlhahiso, re thehile sistimi ea tlhahiso e felletseng e akaretsang boemo ba sefofane, netefatso ea ts'ebetso le tlhahiso ea maemo a khoebo. Ka bokhoni bo matla ho mefuta e mengata ea litekanyetso, lihlahisoa, le litlhaloso, re kopana le litlhoko tsa bokhoni ba meriana e ncha ho tloha ntlafatsong ea bongaka ho ea ho ea khoebo, ha re ntse re tšehetsa tlhahiso ea boleng bo phahameng, e kholo ea meriana e tloaelehileng.
1. Bokhoni ba Tekheniki & Mehaho ea Motheo ea Tlhahiso
Bokhoni ba mefuta e fapaneng ea litekanyetso: Bakeng sa litlhare tse rarahaneng tse kang li-peptide le li-RDC, re thehile litsamaiso tse ikhethileng tse lumellanang le GMP bakeng sa litharollo tse kentsoeng tsa cartridge ea lethal dose e le 'ngoe le liente tsa phofo tse lyophilized. Re na le theknoloji ea ho tlatsa, ea lyophilization le ea sterile filtration, re etsa bonnete ba hore taolo ea boits'oaro e tlohang ho isa qetellong ho tloha ho lisebelisoa tse tala ho ea ho sephutheloana se felileng sa sehlahisoa.
Bakeng sa meralo ea peptide, re sebetsana le mathata a botsitso ka ho ntlafatsa sistimi ea buffer, liprofaele tse lokiselitsoeng tsa lyophilization, le litharollo tsa polokelo ea serame. Sethala sa rona sa ts'ebetso e felletseng, se hahelletsoeng holim'a moralo oa QbD, se thusa phetoho e bonolo ho tloha litekong tsa lab ho ea ho tlhahiso e leka-lekaneng (10L-100L), ho netefatsa ts'ebetso ea ho ikatisa le ho lumellana ha batch-to-batch ka tlhahlobo e hlophisitsoeng le netefatso ea li-parameter tsa bohlokoa tsa ts'ebetso (CPPs).
Tšehetso e ncha ea lithethefatsi: Sistimi ea rona ea tlhahiso e akaretsa tlhahiso ea sampole ea Mokhahlelo oa I-III le tlhahiso ea lihlopha tsa ngoliso, e potlakisang linako tse ncha tsa ntlafatso ea lithethefatsi.
Tlhahiso ea lithethefatsi tse tloaelehileng: Re fana ka tharollo e potlakileng ea phetisetso le litharollo tsa maemo a holimo ho fihlela tlhoko ea lefats'e ea lijeneriki tsa boleng bo holimo tse baballang chelete e ngata.
2. Taolo ea Boleng & Tumellano
Re thehile sistimi e felletseng ea taolo ea boleng ba bophelo e akaretsang tlhahlobo ea lisebelisoa tse tala, tlhahlobo e ntseng e tsoela pele, le tokollo ea ho qetela ea sehlahisoa. Mehaho ea rona e na le lisebelisoa tse tsoetseng pele tsa tlhahlobo tse kang HPLC, LC-MS, le li-scanner tsa radio-TLC, tse nolofalletsang tlhahlobo e nepahetseng ea li-CQA tse kenyelletsang lintlha tse sa hloekang, ho tšoana ha litaba, sterility, le katleho ea radiolabeling.
Liwebsaete tsa rona tsa tlhahiso li netefalitsoe ke China NMPA bakeng sa ho latela GMP mme li latela ka tieo litataiso tsa ICH, ho netefatsa ts'ebetso e felletseng le tumellano ea taolo ea machabeng bakeng sa bareki ba rona ba lefats'e.
3. Boleng ba Indasteri & Liphihlello
Ho fihlela joale, re atlehile ho nyolla le ho rekisa lihlahisoa tse fetang 100 tse entsoeng, ho kenyeletsoa le liente tsa GLP-1, li-peptide tse lokolotsoeng ka nako e telele, le litlhare tse lebisitsoeng tsa RDC. Bokhoni ba rona ba tlhahiso ea selemo le selemo bo fihla ho mashome a limilione a litekanyetso / linkho. Re fana ka lits'ebeletso tsa tlhahiso ea "one-stop" tse ts'ehetsang litlhare tse nchafalitsoeng ho tloha ho lisampole tsa bongaka ho fihlela li qala 'marakeng, tse khutsufatsang haholo nako ea ho ea 'marakeng. Ka ho ntlafatsa ts'ebetso le lintlafatso tsa li-automation, re thusa bareki ba lithethefatsi tse tloaelehileng ho fihlela taolo ea litšenyehelo le ntlafatso ea boleng, ho ntlafatsa phihlello ea lefats'e ea liphekolo tsa boleng bo holimo.
Ho tloha ho phetolelo ea thekenoloji ho isa tlhahisong ea batho ba bangata, re tšehetsa melao-motheo ea "boleng ba pele, bo tsamaisoang ka katleho," ho kopanya R&D ka mokhoa o sa reroang le tlhahiso ho ba molekane ea tšepahalang ho fetoleng mahlale a meriana hore e be tharollo ea bongaka lefatšeng ka bophara.
