Ilabhoratri — umoya wegumbi elihlanzekile nobuqotho bamasampula Imodeli ephilayo

Wena ungumphathi welabhoratri. Igumbi le-ISO 7 le-aseptic elingu-75 m³ lisetshenziswa yiyunithi yokuphatha umoya ngezihlungi ze-HEPA; abantu bakhipha izinhlayiya, izicabha zivumela umoya wekholidoli ungene, futhi i-fume hood idonsa ukukhipha okungashintshi okungathatha ingcindezi eyeqile yegumbi. Phansi ehholo ifriza yokushisa okuphansi kakhulu igcina amaraki amane amasampula ku-−80 °C. Njalo ngemizuzu emihlanu imodeli ilinganisa izinhlayiya egumbini, ukugeleza komoya ngezikhala zesicabha nokushisa okungena efrizeni. Ukulingisa kwemfundo kuphela — hhayi iseluleko se-GMP, sokulandela imithetho noma sokwelapha.

Okuzofunda

Isilingisi

Isikhathi 0 min
Ikilasi legumbi (ISO 14644-1, ≥0.5 µm) 6.86 · Izinhlayiya ≥0.5 µm 256 k/m³ · Umehluko wengcindezi nekholidoli (okumaphakathi esikhathini) 12.4 Pa · Ukushintsha komoya okuhlinzekiwe 20 · Abantu egumbini 3 · Izinga lokushisa lekhabhinethi yefriza -80.0 °C · Iraki yesampula efudumele kakhulu -80.0 °C · Isampula ngaphezu kuka-−60 °C (imizuzu-amaraki) 0 minIgumbi le-asepticISO 6.9Ukuhlinzeka 20/h · 0.45 kW○○○I-hood⇡→ 12.4 PaIkholidoli⇄ 0Ifriza engu-−80 °C❄-80.0 °C1✓ -80°2✓ -80°3✓ -80°4✓ -80°Ifriza yesipeleIbhokisi leqhwaelomile · 20.0 kgIzinhlayiya ≥0.5 µm 256 k/m³Umsebenzi owenziwe uma uqhathaniswa nohlelo 0%Iraki yesampula efudumele kakhulu -80.0 °CIsampula ngaphezu kuka-−60 °C (imizuzu-amaraki) 0 min
  • Iraki ku-−70 °C noma ngaphansi
  • Iraki phakathi kuka-−70 no-−60 °C
  • Iraki engaphezu kuka-−60 °C (ukweqa)
  • Umuntu ogqoke i-coverall yegumbi elihlanzekile
  • Umuntu ogqoke ijazi lelabhoratri
  • Izinhlayiya zasemoyeni (isikali selogarithimu)
  • I-compressor iyasebenza / i-hood iyasetshenziswa
  • I-compressor iyimile / i-hood ekulindeni

Izilawuli

Umoya ohlinzekwayo ngezihlungi ze-HEPA ophahleni. Umoya omningi uyayehlisa futhi ususe izinhlayiya ngokushesha, kodwa amandla efeni akhuphuka ngekhyubhu yokugeleza. Iyunithi eyonakele ayikwazi ukunikeza lokho ocela kona.

Wonke umuntu ukhipha izinhlayiya; wonke umuntu ongena noma ophuma uvula isicabha. Abantu abambalwa kusho nomsebenzi omncane owenziwayo.

Ama-coverall egumbi elihlanzekile anciphisa cishe uhhafu wezinhlayiya ezingu-≥0.5 µm umuntu azikhipha uma kuqhathaniswa nejazi lelabhoratri phezu kwezingubo zangaphakathi. Ukushintsha kuthatha cishe imizuzu engu-10.

Isicabha esisodwa se-airlock ngesikhathi nokuvulwa okufushane: cishe u-10 s no-0.5 m³ womoya wekholidoli ekuvulweni ngakunye esikhundleni sika-40 s no-2 m³. Ukulinda e-airlock kuthatha isikhathi esincane.

Ukukhipha kulandela ukuhlinzeka kuncishiswe lo mehluko, ovuza ngezikhala zesicabha futhi ugcina igumbi ngaphezu kwekholidoli. Ukukhipha akukaze kwehle ngaphansi kokukhipha kwe-hood nekhabhinethi yokuphepha uqobo.

Inciphisa ukukhipha okungashintshi kusuka ku-1100 kuye ku-500 m³/h, ikhulula umoya wengcindezi eyeqile yegumbi. Umsebenzi odinga i-hood uyalinda.

Imisa ukuvulwa okuvamile nokuvulwa ngenxa yokuxhwala. Ukuvulwa ngakunye kushintsha umoya wekhabhinethi ngomoya wegumbi.

Ihambisa amaraki ezikhaleni ezikhululekile zefriza yesipele ngemva kwesikhathi sokubiza abasebenzi (isikhathi eside ebusuku). Lezi zikhala ziyisigcinelo sesimo esiphuthumayo sesakhiwo, zikhululwa kuphela efrizeni enephutha noma ekhalisa i-alamu — isicelo ngenkathi isabambe u-−80 °C siyenqatshwa. Iraki ngalinye lichitha cishe imizuzu emibili emoyeni wegumbi endleleni.

Ipaka amaraki asele efrizeni emabhokisini avikelwe ukushisa ngeqhwa elomile (u-10 kg ngeraki ngalinye, ngokusho kwesitoko). Ibhokisi ligcina u-−78.5 °C inqobo nje uma leli qhwa lisekhona.

Izikhombisi

Ikilasi legumbi (ISO 14644-1, ≥0.5 µm)
6.86
isixwayiso
Umehluko wengcindezi nekholidoli (okumaphakathi esikhathini)
12.4Pa
kuvamile
Iraki yesampula efudumele kakhulu
-80.0°C
kuvamile
Isampula ngaphezu kuka-−60 °C (imizuzu-amaraki)
0min
kuvamile
Izinhlayiya ≥0.5 µm256 k/m³
Ukushintsha komoya okuhlinzekiwe20 1/h
Amandla efeni yokuhlinzeka0.45 kW
Abantu egumbini3
Umsebenzi owenziwe uma uqhathaniswa nohlelo0 % · kubucayi
Umehluko wengcindezi, izicabha zivaliwe12.4 Pa
Ukuvulwa kwezicabha kuleli phuzu0
Izinga lokushisa lekhabhinethi yefriza-80.0 °C
Iqhwa elomile elisele20.0 kg
Amaraki asefrizeni4

Isitayela

Ikilasi legumbi (ISO 14644-1, ≥0.5 µm): — 9.004.00

Izimo eziphuthumayo

Izinga 1 · Ukubuyela ekilasini ngaphambi kwesinyathelo se-aseptic

Ngu-08:00. Ebusuku igumbi lisebenze ku-setback yokonga amandla ngokushintsha komoya okungu-5 ngehora kanye ne-hood ekulindeni, futhi inkontileka egqoke izingubo zasemgwaqweni isanda kuqeda umsebenzi ngaphakathi: isibali sifunda cishe izinhlayiya ezingu-3 million nge-m³. Abantu abayisithupha begqoke amajazi elabhoratri bayalungisa. Ngo-08:30 iqembu labantu abathathu liqala isinyathelo se-aseptic esidinga igumbi ku-ISO 7 noma kangcono kuze kube ngu-10:00. Gcina iqembu egumbini futhi inkokhelo yefeni ibe nengqondo.

  • Igumbi ku-ISO 7 noma kangcono phakathi nesinyathelo sonke
  • Okungenani abantu abathathu egumbini phakathi nesinyathelo
  • Amandla efeni yokuhlinzeka amaphakathi ≤ 0.6 kW

Izinga 2 · Ukwehluleka kwefriza ebusuku

Ngu-21:00 futhi wena useshifini yokubizwa. Ifriza engu-−80 °C inamaraki amane amasampula angenakushintshwa. Cishe ngo-22:00 i-compressor yayo iyama; uchwepheshe wesevisi angafika kuphela ngo-07:30. Ifriza yesipele inendawo yamaraki amabili — isigcinelo sesimo esiphuthumayo sesakhiwo, esikhululwa kuphela efrizeni enephutha noma ekhalisa i-alamu — futhi kukhona u-20 kg weqhwa elomile endaweni, elanele amabhokisi amabili. Noma yini oyicelayo, kufanele kuqale kufike othile: cishe imizuzu engu-30 ebusuku. Unogada ozungezayo ubheka ifriza ngezikhathi ezithile. I-SOP yelabhoratri ithi akukho sampula okufanele idlule u-−60 °C, futhi iqembu licela isikhala sokuphepha: amaraki akufanele neze afudumale ngaphezu kuka-−68 °C.

  • Akukho raki engaphezu kuka-−60 °C ubusuku bonke
  • Akukho mizuzu yokweqa ekugcineni
  • Amaraki angalokothi afudumale ngaphezu kuka-−68 °C (isikhala sokuphepha)

Izinga 3 · Isiphatha-moya esiphuthumayo, igumbi eligcwele

Isifundo sokuqeqeshwa esiyihora elingu-4 esisebenzayo sinabantu abayisikhombisa begqoke amajazi elabhoratri egumbini kanye nomfudlana ongaguquki wezivakashi ngesicabha sekholidoli. Imizuzu eyishumi ngemva kokuqala, ifeni yokuhlinzeka iqala ukwehluleka: ingahlinzeka kuphela ama-40 % omthamo wayo (ukushintsha komoya okungu-16 ngehora) kuze kulungiswe kusasa. I-fume hood iyasetshenziswa futhi idonsa u-1100 m³/h wokukhipha okungashintshi. Gcina igumbi ku-ISO 7, ugcine okungenani u-10 Pa ngaphezu kwekholidoli, futhi uqedele umsebenzi ohleliwe.

  • Igumbi ku-ISO 7 noma kangcono
  • Umehluko wengcindezi omaphakathi ≥ 10 Pa
  • Umsebenzi ohleliwe uqediwe

Isisekelo — imodeli engemuva kwezinombolo

Wonke ubudlelwano isilingisi esibusebenzisayo, nomthombo wabo. Izinto ezihlala zingashintshi ezimakwe njengokuthathelwa yizilinganiso zesibonelo.

I-ISO 14644-1 imisa umkhawulo wekilasi ngosayizi ngamunye wezinhlayiya; isinyathelo esisodwa sekilasi siyisici seshumi. Ku-0.5 µm, i-ISO 7 ivumela izinhlayiya ezingu-352 000 ngemitha ekhubikhi.
Cn = 10^N·(0.1/D)^2.08 ⇒ N = log10(C) + 2.08·log10(D/0.1); ISO 7 at 0.5 µm = 352 000 /m³, ISO 5 = 3 520 /m³[1]
Egumbini elixutshwe kahle yonke inhlayiya engenayo noma ekhishwayo iyehliswa umoya ohlinzekwayo ithathwe iyiswe ngaphandle; izinga lizinza lapho ukuvela kulingana nokususwa, C = G/Q.
V·dC/dt = G + Q_s·(1−η)·(f·C_out + (1−f)·C) + (Q_in + Q_door)·C_corr − (Q_s + Q_in + Q_door)·C (exact solution per 5-min tick); steady C = G/Q[5][7]
Ngemva kokuphazamiseka okweqile kuyancipha ngokukhula okuphindaphindwayo ngesilinganiso sokushintsha komoya: ukwehla okuphindwe ka-100 kuthatha amahora angu-ln(100)/N, okuyilokho ukuhlolwa kokululama kwe-ISO 14644-3 okukulinganisayo.
C(t) − C∞ = (C₀ − C∞)·e^(−N·t); 100:1 recovery t = ln(100)/N (20 1/h → 13.8 min, 5 1/h → 55 min)[2][5][3]
Abantu bangumthombo oyinhloko. Izilinganiso ezilinganisiwe zezinhlayiya ezingu-≥0.5 µm: cishe izigidi ezingu-2.1 ngomzuzu ezingutsheni zangaphakathi, cishe isigidi esingu-1.0 ezingutsheni zegumbi elihlanzekile; umuntu ngamunye nesikhathi ngasinye kuyahluka.
G = Σ people e·exp(0.3·z − 0.045), z ~ N(0,1); e = 35 500 /s (lab coat over indoor clothing; measured for indoor clothing), 17 000 /s (cleanroom coverall), ≥ 0.5 µm[4]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Umoya wokuhlukanisa uvuza ngezikhala zesicabha; ingcindezi edingekayo ukuyiphusha ikhula ngesikwele sokugeleza. Uma ukukhipha okungashintshi kuthatha okwengeziwe kunalokho ukuhlinzeka okushiya kona, igumbi liba yingcindezi engeyinhle futhi lidonsela umoya wekholidoli ngaphakathi.
Q_off = Q_s − max(E_fixed, Q_s − offset); ΔP = ρ/2·(Q_off/(C_d·A))², C_d = 0.61, A = 0.02 m²; ΔP_avg = ΔP·(1 − time doors open)[6][3][5]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Isicabha esivulekile asinawo umehluko wengcindezi; ukuvulwa ngakunye kushintshisana nomoya omncane wekholidoli egumbini. Ukuvulwa okufushane nge-airlock kushintshisana kakhulu kancane.
openings ~ Poisson((1·people + traffic)·Δt) + people in/out; per opening 40 s and 2 m³ of corridor air exchanged (10 s, 0.5 m³ with airlock discipline)[3][5]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Amandla efeni akhula ngekhyubhu yokugeleza komoya: ukuphindaphinda kabili ukushintsha komoya kuthatha cishe amandla aphindwe kasishiyagalombili.
P = 0.45 kW·(Q_s / 1500 m³/h)³[8]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Ifriza engenayo i-compressor yayo iyafudumala njengomzimba ofanayo: ngokushesha kuqala, bese kancane lapho isondela ezingeni lokushisa legumbi. Isikhathi esingashintshi τ = C/UA sibeka iwashi.
C·dT/dt = UA·(T_amb − T) + Q_door − Q_comp; T(t) = T_amb + (T₀ − T_amb)·e^(−t/τ), τ = C/UA = 20 h; −80 → −60 °C in τ·ln(102/82) ≈ 4.4 h[9]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Ukuvulwa ngakunye kushintsha umoya obandayo wekhabhinethi ngomoya wegumbi ofudumele, onomswakama; ukushisa kwawo nesithwathwa esisishiya emuva kufudumeza okuphakathi.
Q_door = 2·ρ·V_cab·c_p·(T_amb − T) (cabinet air replaced, ×2 for moisture and frost); V_cab = 0.7 m³ → ≈ 1.2 K per opening at −80 °C[9]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Amasampula alandela indawo azungezwe yiyo ngokulibaza; ukuthwala iraki emoyeni wegumbi imizuzu embalwa kubiza amadigri amaningana.
T_rack ← lag(T_rack, T_surroundings, τ = 1 h); handling: 2 min in room air with τ = 0.5 h (≈ +6 K from −75 °C); excursion = Σ racks minutes above −60 °C[9][11]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Iqhwa elomile liyashintsha libe umhwamuko ku-−78.5 °C futhi lamunca cishe u-573 kJ ngekhilogremu: ibhokisi lihlala kuleli zinga lokushisa kuze kuphele iqhwa.
chest at −78.5 °C while ice remains; dm/dt = −(UA_chest·(T_amb + 78.5) + rack heat)/573 kJ/kg[10][11]Isimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.
Ezinye izinto ezingaguquki zokusebenza ezisetshenziswa yimodeli.
room 75 m³, AHU ≤ 40 air changes/h × health · HEPA 99.95 %, 20 % outdoor air at 35·10⁶ /m³ · corridor 2·10⁶ /m³ · fixed exhaust 1100 m³/h (hood in use) / 500 m³/h (standby) · gowning change 10 min · 1 door trip per person-hour · work × 0.8 with the hood in standby, × 0.95 with airlock discipline · freezer UA 2 W/K, compressor 600 W, alarm −70 °C, SOP limit −60 °C · 4 racks of 15 kJ/K · backup freezer −80 °C, its free slots released only for a freezer in fault or alarm (emergency reserve) · 10 kg dry ice per rack, chest UA 0.25 W/KIsimo esicatshangelwayo: usayizi wegumbi, umthamo we-AHU, ukukhipha okungashintshi, indawo yokuvuza, izikhathi zezicabha nemithamo eshintshwayo, amandla efeni, ukuvikelwa kokushisa kwefriza nosayizi we-compressor, ukushisa komthamo weraki, ukuchayeka ekuphatheni, ukukhululwa kwezikhala zefriza yesipele ezimeni eziphuthumayo kuphela nomkhawulo we-SOP ongu-−60 °C kuyizinombolo zesibonelo zelabhoratri ejwayelekile; imithetho yefiziksi namazinga okusabalala ashicilelwe njengoba kucashunwe.

Ukungahleliwe: i-generator ye-mulberry32 enembewu; ukusabalalisa okusetshenzisiwe — uniform, exponential (inverse CDF), normal (Box–Muller), Poisson (Knuth). Imbewu iyabonisa futhi ingabelwana.

Imithombo

  1. ISO 14644-1:2015 Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration (Cn = 10^N·(0.1/D)^2.08) — ISO, 2015
  2. ISO 14644-3:2019 Cleanrooms and associated controlled environments — Part 3: Test methods (recovery test, 100:1 recovery time) — ISO, 2019
  3. EudraLex Vol. 4, Annex 1: Manufacture of Sterile Medicinal Products (C(2022) 5938) — §4.13 airlock entry and exit doors not opened simultaneously (interlock for grade A/B, visual/audible warning for C/D), §4.14 adjacent rooms of different grades: air pressure difference of a minimum of 10 Pascals (guidance value), §4.29 iii and Table 5 Note 1: "clean up" period, guidance value of less than 20 minutes — European Commission, 2022
  4. W. Whyte, M. Hejab — Particle and microbial airborne dispersion from people, European Journal of Parenteral & Pharmaceutical Sciences 12(2):39–46 (≥0.5 µm: 2.13·10⁶/min indoor clothing, 1.02·10⁶/min cleanroom garments) — Pharmaceutical and Healthcare Sciences Society, 2007
  5. W. Whyte — Cleanroom Technology: Fundamentals of Design, Testing and Operation, 2nd ed. (well-mixed dilution C = G/Q, decay and recovery, pressure cascades, door openings) — Wiley, 2010
  6. ASHRAE Handbook — Fundamentals, ch. 16 Ventilation and Infiltration (flow through openings Q = C_d·A·√(2ΔP/ρ)) — ASHRAE, 2021
  7. EN 1822-1:2019 High efficiency air filters (EPA, HEPA and ULPA) — Part 1: Classification (H13 ≥ 99.95 % at MPPS) — CEN, 2019
  8. Fan affinity laws: flow ∝ speed, pressure ∝ speed², power ∝ speed³ — U.S. DOE — Improving Fan System Performance: A Sourcebook for Industry
  9. F. P. Incropera, D. P. DeWitt et al. — Fundamentals of Heat and Mass Transfer, 7th ed., §5.1–5.3 lumped capacitance (Newton cooling, τ = ρVc/hA) — Wiley, 2011
  10. NIST Chemistry WebBook — Carbon dioxide, phase change data (ΔsubH = 25.2 kJ/mol at 195 K, Giauque & Egan 1937 → ≈ 573 kJ/kg; sublimation at 194.7 K = −78.5 °C at 1 atm) — NIST
  11. ISBER Best Practices: Recommendations for Repositories, 5th ed. (storage equipment monitoring and alarms, backup storage capacity, emergency plans) — International Society for Biological and Environmental Repositories, 2023

Obani abenza lokhu ukuze baziphilise

Imodeli yemfundo — hhayi yezinqumo zokusebenza. Izindawo zangempela zilinganisa yonke into ehlala ingashintshi kumishini nedatha yazo.