Nyob rau hauv -Kev tsom xam qhov tob ntawm Chiba Koob Kev Lag Luam Cov Qauv Thiab Cov Ntawv Pov Thawj Zoo

Hauv kev lag luam ntawm cov khoom siv kho mob, cov qauv thiab cov ntawv pov thawj tsis yog tsuas yog cov kev txwv nkag rau hauv kev ua lag luam, tab sis kuj yog qhov lav rau cov khoom zoo thiab cov neeg mob kev nyab xeeb. Kiyama koob, raws li hom 2 lossis hom 3 cov cuab yeej kho mob uas nkag mus rau tib neeg lub cev ncaj qha, nws cov khoom tsim thiab kev tsim khoom yuav tsum ua raws li cov qauv thoob ntiaj teb nruj, cov kev cai hauv cheeb tsam, thiab cov qauv kev lag luam. Los ntawm ISO 13485 kev tswj hwm zoo rau FDA 510 (k) lossis PMA kev pom zoo, los ntawm CE cim mus rau Tuam Tshoj NMPA kev tso npe, txhua daim ntawv pov thawj sawv cev rau kev ntsuam xyuas ntawm cov chaw tsim khoom muaj peev xwm, cov txheej txheem zoo, thiab cov ntaub ntawv pov thawj.
TS EN ISO 13485 Kev Tswj Xyuas Zoo: Lub hauv paus ntawm Cov Kab lis kev cai zoo
ISO 13485: 2016 "Quality Management System for Medical Devices - Requirements for Regulatory Purposes" is a globally applic standard for the manufacturing of Kiyama needles. Txawm li cas los xij, cov tuam txhab saum toj kawg nkaus siv "ISO 13485+" uas dhau mus dhau tus qauv. Cov txheej txheem no tsis tsuas yog ua tau raws li qhov yuav tsum tau muaj ntawv pov thawj tab sis kuj tsim kom muaj kab lis kev cai zoo uas tseem ceeb rau kev tiv thaiv thiab kev txhim kho txuas ntxiv.
Kev tswj kev tsim qauv yog lub hauv paus ntawm qhov system zoo. Cov qauv tsim khoom siv rau lub koob Chiba yuav tsum muaj kev qhia dav: cov kev cai kho mob (raug quab yuam <2N, tus nqi ntws> 3mL / s), cov kev cai tswj hwm (biocompatibility, tsis muaj menyuam), cov neeg siv khoom xav tau (kev ua haujlwm yooj yim, qhia meej meej), cov kev txwv (cov khoom siv, kev tsim muaj peev xwm). Cov khoom tsim tawm suav nrog cov khoom tshwj xeeb (qhov ntev kam rau ua ± 0.02mm), cov ntaub ntawv txheej txheem (cov lus qhia ua haujlwm), thiab cov qauv ntsuas (AQL sampling plan). Kev ntsuam xyuas kev tsim qauv yog ua tiav los ntawm kev sim hauv chav kuaj (qhov kev ntsuas quab yuam, kev ntsuas tus nqi ntws), thiab kev pom zoo tsim tau tiav los ntawm kev soj ntsuam kuaj mob (tsawg kawg 30 qhov kev sim tshuaj ntsuam xyuas). Cov kev hloov pauv tsim tau tswj hwm nruj raws li cov txheej txheem tswj kev hloov pauv. Ib qho kev hloov kho yuav tsum tau rov siv dua, nrog rau qhov hloov pauv nruab nrab ntawm 45 hnub.
Kev tswj cov khoom kom ntseeg tau qhov zoo ntawm cov khoom siv. Cov neeg muab khoom siv raw yuav tsum tau mus rau ntawm - kev tshuaj xyuas qhov chaw, thiab cov qhab nia suav nrog: cov txheej txheem zoo (40%), kev muaj peev xwm (30%), kev xa khoom (20%), thiab nqe (10%). Rau cov ntaub ntawv tseem ceeb xws li kev kho mob stainless hlau kav, txhua batch yuav tsum muaj kev ntsuam xyuas: tshuaj muaj pes tsawg leeg (ICP- MS tsom xam), mechanical zog (tensile test), qhov tseeb qhov ntev (laser txoj kab uas hla ntsuas), thiab nto zoo (electromagnetic detection). Kev ua tau zoo ntawm tus neeg muag khoom raug ntsuas txhua hli, thiab yog tias nws poob qis dua 85 cov ntsiab lus rau peb lub hlis sib law liag, kev kho yuav pib.
Kev tswj cov txheej txheem ntau lawm ua rau muaj kev saib xyuas tiag tiag - sijhawm. Rau cov txheej txheem tseem ceeb xws li rab koob sib tsoo, cov kev tswj tsis muaj xws li: spindle ceev (25000 ± 500 rpm), pub ceev (0.5 ± 0.05 mm / s), thiab coolant flow rate (5 ± 0.5 L / min). Kev tswj cov txheej txheem kev txheeb cais (SPC) yog siv los saib xyuas lub sijhawm tiag tiag, thiab tus nqi CpK yuav tsum muaj ntau dua lossis sib npaug rau 1.33 (kev lag luam xav tau Ntau dua lossis sib npaug rau 1.0). Txhua 2 teev, 5 cov khoom raug xaiv xaiv rau qhov tseem ceeb ntawm qhov ntsuas. Cov ntaub ntawv nkag mus rau hauv daim ntawv tswj, thiab txhua qhov txawv txav tau raug kho tam sim ntawd.
Kev tswj cov cuab yeej kuaj xyuas kom ntsuas qhov tseeb. Lub tshuab ntsuas kev sib koom tes (CMM) yog ntsuas los ntawm lub tuam txhab tso cai txhua xyoo nrog qhov tseeb ntawm 0.8 + L / 300 μm. Ua ntej siv txhua hnub, nws raug txheeb xyuas nrog cov qauv thaiv, nrog qhov yuam kev tsawg dua 0.001 hli. Kev ntsuas qhov ntsuas (MSA) yog ua txhua xyoo, thiab qhov rov ua dua thiab rov ua dua ntawm cov cuab yeej ntsuas (GR&R) tsawg dua 10%. Cov ntaub ntawv txheeb xyuas cov khoom siv tau ua tiav, suav nrog cov khoom siv naj npawb, qauv, qhov tseeb, hnub calibration, calibration voj voog, thiab cov xwm txheej siv.
Kev ntsuam xyuas Biocompatibility: Kev ua tiav ntawm ISO 10993
ISO 10993 series ntawm cov qauv yog phau Vajlugkub rau kev soj ntsuam biocompatibility ntawm cov cuab yeej kho mob. Txawm li cas los xij, qhov kev ntsuam xyuas ntawm rab koob Chiba yuav tsum muaj kev qhia ntau dua thiab nyob rau hauv - txoj hauv kev tob, vim nws ncaj qha los rau hauv kev sib cuag nrog tib neeg cov ntaub so ntswg thiab txawm tias cov hlab ntsha.
Chemical characterization yog lub hauv paus rau kev ntsuam xyuas. Raws li ISO 10993-18, tag nrho cov tshuaj muaj peev xwm yuav tsum tau txheeb xyuas. Los ntawm cov roj chromatography-mass spectrometry (GC{5}}MS) tsom xam ntawm cov leaching tov (ib txwm saline, cottonseed roj, ethanol-dej tov), ​​qhov kuaj pom txwv yog 0.1 ppm. Cov extractables muaj xws li: hlau ions (nickel, chromium, molybdenum), kev pab (lubricants, ntxuav tus neeg sawv cev), degradation khoom (monomers, oligomers). Kev ntsuas kev pheej hmoo yog nyob ntawm qhov kev txhawj xeeb toxicological (TTC). Tus nqi raug txhua hnub ntawm cov extractable yuav tsum qis dua 1.5 ug / hnub (carcinogen) lossis 150 ug / hnub (tsis yog carcinogen).
Kev kuaj cytotoxicity yog ua los ntawm ntau txoj hauv kev. Txoj kev MTT yog siv los txheeb xyuas cov haujlwm metabolic ntawm cov hlwb. Cov tshuaj extract yog npaj ntawm qhov concentration ntawm 3 cm² / mL, thiab muab rho tawm ntawm 37℃rau 72 teev. Cov ciaj sia taus ntawm L929 hlwb yuav tsum muaj ntau dua lossis sib npaug li 80% (tus qauv yuav tsum muaj ntau dua lossis sib npaug li 70%). Txoj kev sib cuag ncaj qha yuav koom nrog- coj tus qauv nrog cov hlwb rau 24 teev los soj ntsuam cov cell morphology thiab kev loj hlob. Txoj kev agar diffusion yog siv los ntsuas qhov diffusion toxicity ntawm cov extract, thiab tsis muaj cell dissolution cheeb tsam yuav tsum tshwm nyob ib ncig ntawm tus qauv. Txoj kev nruj tshaj plaws yog MEM elution txoj kev, uas kuaj pom lub sijhawm ntev - cuam tshuam ntawm cov extract ntawm kev loj hlob ntawm tes.
Qhov kev ntsuam xyuas rhiab heev siv cov txheej txheem scientific kawg. Qhov kev sim tshuaj tiv thaiv kab mob siab tshaj plaws (GPMT) siv guinea npua, tab sis muaj teeb meem cuam tshuam txog kev noj qab haus huv tsiaj. Tam sim no, qhov kev kuaj mob qog nqaij hlav hauv zos (LLNA) feem ntau siv. Qhov rhiab heev yog ntsuas los ntawm kev ntsuas lub cell proliferation nyob rau hauv lub pob ntseg lymph nodes ntawm nas, thiab qhov stimulation index (SI) yuav tsum <3. nyob rau hauv vitro txoj kev xws li h-CLAT (tib neeg cell kab activation test) yog validated, thiab sensitization muaj peev xwm raug soj ntsuam los ntawm kev kuaj CD{5{5} thiab CD.
Cov txheej txheem ntawm kev tshuaj ntsuam genetic toxicity tau ua tiav. Cov kab mob revertant mutation test (Ames test) siv tsib hom kab mob (TA98, TA100, TA1535, TA1537, WP2 uvrA), nrog lossis tsis muaj metabolic activation, thiab cov txiaj ntsig yuav tsum tsis zoo. Hauv vitro mammalian cell chromosome aberration test siv CHL hlwb los kuaj cov qauv chromosomal thiab cov lej txawv txav. Kev kuaj hauv vivo micronucleus siv nas pob txha hlwb, thiab tus nqi micronucleus yuav tsum yog <3‰ (kev tswj tsis zoo <2‰).
Cov implantation simulate siv tiag tiag. Cov leeg nqaij implantation tau ua nyob rau hauv cov leeg ntawm ib sab ntawm luav 's spines, nrog rau cov qauv cog (10 × 1mm) tau sau 4 lub lis piam thiab 12 lub lis piam tom qab cog. Cov qhabnias ntawm cov ntaub so ntswg muaj xws li: tus naj npawb ntawm cov hlwb inflammatory (0-4 cov ntsiab lus), lub thickness ntawm cov tshuaj ntsiav (0-4 ntsiab lus), thiab cov ntaub so ntswg necrosis (0-3 ntsiab lus), nrog rau tag nrho cov qhab nia yuav tsum yog <8 cov ntsiab lus (tus qauv <13 cov ntsiab lus). Rau cov koob hauv kev sib cuag nrog cov ntshav, yuav tsum tau kuaj ntshav hemolysis, thiab tus nqi hemolysis yuav tsum yog <5%.
Kev Ntsuam Xyuas Kev Ua Haujlwm: Tus Choj los ntawm Chaw Kho Mob mus rau Chaw Kho Mob
Kev ntsuas kev ua tau zoo ntawm rab koob Chiba yuav tsum simulate qhov xav tau tshaj plaws hauv kev siv tshuaj kho mob kom ntseeg tau tias muaj kev nyab xeeb thiab ua haujlwm tau zoo.
Kev ntsuas kev ua haujlwm puncture simulates cov ntaub so ntswg tiag. Siv tus qauv gel qauv (10% gel concentration, 37℃kub), nrog rau qhov ceev ntawm 10mm / s, qhov siab tshaj plaws puncture quab yuam thiab qhov nruab nrab puncture quab yuam yog ntsuas. Qhov siab tshaj plaws puncture quab yuam ntawm 22G Chiba koob yuav tsum tsawg dua 1.5N, thiab qhov sib txawv ntawm qhov sib txawv yuav tsum tsawg dua 15%. Tom qab qhov puncture, xyuas cov koob taub; yuav tsum tsis muaj chipping los yog burrs, thiab saib nyob rau hauv ib lub tshuab nqus tsev ntawm 50x magnification. Kev ntsuas cyclic puncture simulates ntau yam siv. Tom qab 100 punctures, qhov nce hauv puncture force yuav tsum tsawg dua 20%.
Kev ntsuas dej ntws ntsuas ntsuas qhov nqus thiab txhaj tshuaj muaj peev xwm. Suction test: Nyob rau hauv lub siab tsis zoo ntawm 0.1 MPa, lub sij hawm yuav tsum tau nqus 5 mL ntawm ib txwm saline yuav tsum tsawg tshaj li 3 vib nas this. Kev txhaj tshuaj: Nyob rau hauv lub siab zoo ntawm 0.1 MPa, lub sij hawm yuav tsum tau txhaj 5 mL ntawm ib txwm saline yuav tsum tsawg tshaj li 2 vib nas this. Flow-kev ntsuas kev sib raug zoo: ntsuas qhov ntws ntawm qhov sib txawv, kos qhov ntws-siab nkhaus, thiab cov kab sib txuas sib txuas yuav tsum siab dua 0.99.
Kev kuaj xyuas lub zog ua kom muaj kev ntseeg siab ntawm cov qauv. Peb-point dabtsi yog khoov xeem: ncua 20mm, loading ceev 1mm/min, ntsuas dabtsi yog khoov nruj thiab siab tshaj plaws dabtsi yog khoov quab yuam. Kev khoov nruj ntawm 22G Kailian koob yuav tsum nyob nruab nrab ntawm 0.15 thiab 0.25N / mm, thiab qhov siab tshaj plaws dabtsi yog khoov quab yuam yuav tsum siab tshaj 10N. torque resistance test: kho lub koob tuav, siv lub zog kom txog thaum tsis ua hauj lwm, qhov tsawg kawg nkaus torque 0.05N·m. Kev sim qaug zog: simulate lub plawv dhia, zaus 1.2Hz, amplitude 1mm, tsis muaj kab nrib pleb yuav tsum tshwm sim tom qab 10⁷ cycles.
Kev sib koom ua haujlwm ntawm Ru'er ua tau raws li ISO 80369. Kev sib txuas quab yuam kev sim: Thaum txuas nrog tus qauv kev sib koom ua ke, lub zog sib cais yuav tsum nyob hauv thaj tsam ntawm 5-15N. Kev ntsuas kev sib khi: Ua kom siab ntawm 0.3MPa rau 30 vib nas this, tsis muaj qhov xau. Kev ntsuas siab: Siv 1.2 npaug ntawm qhov siab tshaj plaws kev khiav hauj lwm siab (feem ntau yog 0.4MPa), thiab tuav rau 1 feeb, tsis muaj kev puas tsuaj. Kev ntsuas kev sib txuas dua: Tom qab 50 kev sib txuas thiab kev sib cais, kev ua haujlwm tseem ua tau raws li qhov yuav tsum tau ua.
5 Sterility Assurance thiab ntim validation
Sterility yog qhov yuav tsum tau muaj rau cov koob Chiyoda. Txawm li cas los xij, kev ua kom tsis muaj menyuam yuav tsum muaj kev tshawb fawb txog kev ua kom tsis muaj menyuam thiab tswj kev ntim khoom nruj.
Kev xaiv txoj kev ua kom tsis muaj menyuam yog nyob ntawm cov yam ntxwv ntawm cov khoom. Ethylene oxide (EO) sterilization yog txoj kev siv ntau tshaj plaws, tab sis kev tswj qhov seem yog qhov tseem ceeb. Kev ua kom tsis muaj menyuam yog ua tiav siv VDmax25, thiab cov cim kev lom neeg siv Bacillus subtilis var. niger spores (kuj 1.5-3.0). Sterilization tsis: EO concentration 600 ± 30 mg / L, kub 55 ± 2 degree, av noo 60 ± 10% RH, lub sijhawm 120 feeb. Kev soj ntsuam tom qab ua kom tsis muaj menyuam: 50℃qhov cua tsom rau 7 hnub, tshawb pom qhov seem: EO <4 ppm, 2-chloroethanol < 9 ppm.
Radiation sterilization yog tsim rau cov khoom uas tsis yog -kub- resistant. Cov koob tshuaj yog 25 kGy, nrog rau cov koob tshuaj sib xws ntawm 0.8 - 1.2. Kev txheeb xyuas kom tsis muaj menyuam ua raws li VDmax25, thiab cov khoom siv tshuaj lom neeg siv Bacillus subtilis (kuj 1.5 - 3.0). Cov khoom siv sib xyaw ua ke: Kev hloov pauv ntawm cov khoom siv tom qab hluav taws xob yuav tsum tsawg dua 10%, tshwj xeeb tshaj yog cov khoom siv polymer yuav tsum tsis txhob daj lossis nkig.
Kev pov thawj ntawm kev ntim khoom kom ntseeg tau tias muaj kab mob aseptic. Cov ntaub ntawv ntim khoom yuav tsum xeem dhau ISO 11607 kev xeem: roj permeability (khoom siv), sealing zog (sealing), thiab microbial barrier (tag nrho). Accelerated aging test: hnub nyoog 14 hnub ntawm 70℃thiab 60% RH, sib npaug rau kev cia ntawm chav tsev kub rau 2 xyoos. Tiag -time aging test: tsis tu ncua kuaj raws li qhov tseeb cia, tsawg kawg yog 12 lub hlis. Kev simulation kev thauj mus los: ISTA 2A tus qauv, suav nrog kev poob qis, kev vibration, thiab kev ntsuas compression, lub ntim yuav tsum tsis muaj zog thiab cov kab mob aseptic yuav tsum tsis muaj kev puas tsuaj.
Kev kuaj aseptic ua raws li cov txheej txheem teev tseg hauv cov tshuaj pharmacopoeia. Kev kuaj tsis muaj menyuam yog ua raws li "Suav Pharmacopoeia" lossis USP<71>, siv ob qho tib si ncaj qha inoculation txoj kev los yog cov txheej txheem membrane filtration. Lub sijhawm kab lis kev cai yog 14 hnub, thiab tsis pub muaj kev loj hlob ntawm microbial. Qhov kev tshawb pom endotoxin ntiav cov txheej txheem dynamic turbidity siv limulus amebocyte lysate (LAL), nrog rau qhov txwv tsis pub dhau.<20 EU per unit (the actual measurement is <0.25 EU per unit). Particle contamination detection: particles larger than 10 μm are less than 5 per unit, and particles larger than 25 μm are zero per unit.
Kev soj ntsuam kev soj ntsuam thiab cov pov thawj tiag - ntiaj teb
Rau cov khoom lag luam uas paub tab zoo li Chiyoda koob, kev soj ntsuam kev soj ntsuam feem ntau yog ua raws li cov lus sib npaug, tab sis yuav tsum muaj pov thawj kev tshawb fawb dav dav.
Qhov sib npaug sib cav yuav tsum muaj kev sib piv kom ntxaws. Piv nrog rau cov khoom lag luam uas twb muaj lawm (cov cuab yeej ua ntej): cov khoom siv ( tib qib stainless hlau), tsim qauv ( tib yam qauv qhov ntev ), kev npaj siv ( tib lub chaw kho mob indications ), cov yam ntxwv ntawm kev ua haujlwm ( tib yam kev ntsuas kev ua haujlwm ). Kev tsom xam qhov sib txawv: Txhua qhov sib txawv yuav tsum muaj lub hauv paus kev tshawb fawb; Piv txwv li, txhua qhov sib txawv me me yuav tsum tau ua pov thawj los ntawm kev ntsuas tshuab kom tsis txhob cuam tshuam kev nyab xeeb.
Kev tshuaj xyuas cov ntaub ntawv kho mob yuav tsum ua kom tiav thiab ua haujlwm. Tshawb nrhiav PubMed, Embase, Cochrane thiab lwm yam databases, nrog rau cov ntsiab lus suav nrog "Chiba koob", "percutaneous biopsy", "interventional radiology". Cov txheej txheem suav nrog: randomized tswj kev sim, kev tshawb fawb sib koom ua ke, rooj plaub (n> 30). Cov txheej txheem cais tawm: cov ntaub ntawv ceeb toom, kev sim tsiaj, tsis yog- cov khoom siv ntsig txog. Kev soj ntsuam zoo siv QUADAS-2 lub cuab yeej. Cov ntaub ntawv rho tawm muaj xws li: tus qauv loj, tus nqi ua tiav, tus nqi tsis sib haum, rhiab heev, tshwj xeeb. Meta-analysis suav cov txiaj ntsig sib xyaw ua ke, xws li 95% kev ntseeg siab ntawm qhov tseeb ntawm kev kuaj mob.