natgillin/translations-raw huggingface dataset:
The Applicant determined the sampling schedule in the study undertaken taking into account the general information from the available published references which in general supported a gastric emptying time range of less than 1 hour to approximately 5 hours where varying intakes of food were involved. 
Predlagatelj je opredelil urnik vzorčenja v izvedeni študiji ob upoštevanju splošnih informacij iz razpoložljivih objavljenih referenc, ki v splošnem podpirajo časovni razpon praznjenja želodca od manj kot 1 ure do približno 5 ur, pri čemer se upoštevajo različni vnosi hrane.
Confirmatory Pharmacokinetic Study (study code: 2009-2106) 
Potrditvena farmakokinetična študija (koda študije: 2009-2106)
The CHMP considered that the Applicant has complied with the requested response and submitted the data, along with additional data regarding stability of pantoprazole under different conditions. 
CHMP je menil, da se je predlagatelj ustrezno odzval na zahtevek in predložil podatke, vključno z dodatnimi podatki o stabilnosti pantoprazola v različnih pogojih.
It was anticipated that outliers would occur with both study groups (test and originator groups) in the fed study. 
Pričakovano je bilo, da bodo osamelci prisotni v obeh študijskih skupinah (skupini s testnim in originatorskim zdravilom) v študiji po zaužitju hrane.
The CHMP noted that the results were coherent with the available published information on food interaction of pantoprazole formulations, which describe a potential delayed absorption and an increase in variability. 
Odbor CHMP je ugotovil, da se rezultati ujemajo z razpoložljivimi objavljenimi informacijami o medsebojnem delovanju formulacij pantoprazola s hrano, ki opisujejo morebitno odloženo absorpcijo in povečanje variabilnosti.
The Applicant presented the results of a further confirmatory fed study, with a final sampling point of 30 hours. 
Predlagatelj je predstavil rezultate nadaljnje potrditvene študije po zaužitju hrane s končno vzorčno točko 30 ur.
the CHMP has recommended the granting of the Marketing Authorisations subject to the conditions, as set out in Annex IV. 
CHMP je priporočil odobritev dovoljenja za promet z zdravilom v skladu s pogoji iz Dodatka IV.
The primary analysis was conducted on AUClast and Cmax, using the log-transformed ratios and 90 % Confidence Intervals (CIs). 
Primarna analiza je vključevala analizo AUClast in Cmaks z logaritemsko preoblikovanimi razmerji in 90 % intervali zaupanja.
Confirmatory Food Interaction Study -2009-2106 
Potrditvena študija medsebojnega delovanja s hrano - 2009-2106
The CHMP concluded, based on the study results, that a difference in PK mechanism for the test and the originator is extremely unlikely given the clear demonstration of bioequivalence in the main analysis and in the secondary (whole analysis with measurable values). 
CHMP je na podlagi rezultatov študije sklenil, da je razlika v mehanizmu farmakokinetike pri testnem in originatorskem zdravilu izjemno malo verjetna glede na jasen dokaz bioekvivalence v glavni in v sekundarni analizi (celotna analiza z merljivimi vrednostmi).
The CHMP concluded that the overall study design was acceptable. 
CHMP je sklenil, da je celotna zasnova študije sprejemljiva.
As such, the planned sampling schedule should provide an adequate estimation of the Cmax and should cover the plasma concentration time curve sufficiently to provide a reliable estimate of the extent of absorption. 
Načrtovani urnik vzorčenja mora podati ustrezno oceno Cmaks in zadostno opredeliti krivuljo plazemske koncentracije v odvisnosti od časa, da se zagotovi zanesljiva ocena obsega absorpcije.
This kinetic alteration appears frequently with pantoprazole and is the basis as to why the Summary of Product Characteristics for Pantoprazole products in the EU state: ‘Swallow whole with water before a meal'. 
Ta kinetična sprememba je pogosta pri pantoprazolu, zato je v povzetku glavnih značilnosti zdravil, ki vsebujejo pantoprazol, v EU navedeno: „Pogoltnite cele z vodo pred obrokom“
The CHMP considered that the overall analytical documentation was satisfactory, however retrieved the issue of long-term stability as a major objection and requested the Applicant to submit long-term stability data in the answer to the adopted LoOI. 
CHMP je menil, da je celotna analitična dokumentacija zadostna, vendar je izpostavil vprašanje dolgoročne stabilnosti kot glavni zadržek in predlagatelja pozval, naj odgovoru na sprejet seznam izrazitih zadržkov priloži podatke o dolgoročni stabilnosti.
The CHMP adopted also a LoOIs asking the Applicant to further clarify the pending issues. 
CHMP je sprejel tudi seznam izrazitih zadržkov, v katerem je predlagatelja pozval, naj podrobneje pojasni še nerešena vprašanja.
The Applicant provided the evaluation of lag-times and % extrapolated AUC. 
Predložil je oceno časovnih zamikov in odstotek ekstrapoliranega AUC.
• The rate of outlying cases from the test formulation must be no greater than the reference + 20 % 
• delež osamelcev za testno formulacijo ne sme biti večji od referenčnega +20 % (zaokroženo na najbližjo celo vrednost);
Pharmacokinetic Variables 
Farmakokinetične spremenljivke
The wider acceptance interval (75-133 %) for bioequivalence is considered justified, since pantoprazole is found to be highly variable under fed conditions. 
Širši sprejemljiv interval (75133 %) za bioekvivalenco je utemeljen, saj se je pantoprazol pri uporabi po zaužitju hrane izkazal za zelo variabilnega.
The Applicant justified the highly variable pharmacokinetics of pantoprazole, after food administration, referring to the biopharmaceutical classification system (BCS). 
Predlagatelj je visoko variabilne farmakokinetične lastnosti pantoprazola po zaužitju hrane utemeljil z biofarmacevtskim klasifikacijskim sistemom.
The CHMP considered this issue resolved. 
CHMP je sklenil, da je to vprašanje pojasnjeno.
Then the expert referred to two newer studies (De Campos DR et al: Drug Res 2007; Filipe A et al. Drug Res 2008; and Mendes Drug Res 2008) which revealed that administration of pantoprazole with food can provoke decreases in Cmax and AUC and markedly delay the absorption. 
Nadalje se je strokovnjak skliceval na dve novejši študiji (De Campos DR et al: Drug Res 2007; Filipe A et al. Drug Res 2008; in Mendes Drug Res 2008), v katerih je bilo ugotovljeno, da lahko dajanje pantoprazola s hrano povzroči zmanjšanje Cmaks in AUC ter bistveno odloži absorpcijo.
The Applicant showed that the ‘predefinition' of outliers was consistent with the current guidance on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 and in EMEA/CHMP/EWP/40326/2006). 
Predlagatelj je dokazal, da je „predhodna določitev“ osamelcev skladna z veljavnimi smernicami o proučevanju bioekvivalence (CPMP/EWP/QWP/1401/98 in EMEA/CHMP/EWP/40326/2006).
The aim of this study was to test the effect of food on the kinetics of the two pantoprazole formulations and their stability/degradation, the absence of dose dumping, and to exclude formulation differences. 
Namen te študije je bil preveriti učinek hrane na kinetiko dveh formulacij pantoprazola in njuno stabilnost/razpadanje, odsotnost sprostitve celotnega odmerka naenkrat, ter izključiti razlike med formulacijama.
In addition, data on the PK parameters from study 2009-2106 were provided. 
Poleg tega je predložil podatke o farmakokinetičnih parametrih iz študije 2009-2106.
Pantoprazole is a proton pump inhibitor (PPI), indicated for the treatment of gastrointestinal diseases associated with acid hypersecretion as gastric and duodenal ulcer, reflux oesophagitis (treatment and prevention of relapse) treatment of non-erosive gastroesophageal reflux disease (GERD), prevention non steroid anti-inflammatory drugs (NSAIDs) related ulcers, Zollinger-Ellison-Syndrome and eradication of H. pylori. 
Pantoprazol je zaviralec protonske črpalke (PPI), indiciran za zdravljenje bolezni prebavil, povezanih s čezmernim izločanjem kisline, kot so razjeda želodca in dvanajstnika, refluksni ezofagitis (zdravljenje in preprečevanje ponovitve), zdravljenje neerozivnega gostroezofagealnega refluksa (GERD), preprečevanje razjed zaradi nesteroidnih protivnetnih zdravil (NSAID), Zollinger-Ellisonov sindrom, izkoreninjenje H. pylori.
The study was conducted in fed conditions and a high fat, high calorie breakfast was served 30 minutes prior to drug administration. 
Študija je bila izvedena po zaužitju hrane, in sicer so osebe 30 minut pred dajanjem zdravila zaužile visokokalorični zajtrk z veliko maščobami.
The basis of Pantoprazole Bluefish application is the establishment of bioequivalence between the proposed generic formulation and the originator (Pantecta 40 mg by Altana Pharma AG, Spain). 
Podlaga vloge za zdravilo Pantoprazole Bluefish je vzpostavitev bioekvivalence med predlagano generično formulacijo in originatorskim zdravilom (Pantecta 40 mg družbe Altana Pharma AG, Španija).
Given the main analysis results, the probability for bioinequivalency was evaluated by the Applicant and it resulted to be less than 1 % for Cmax and 0.02 % for AUClast. 
Predlagatelj je s pomočjo rezultatov glavne analize ocenil verjetnost bioinekvivalence; izkazalo se je, da je verjetnost za Cmaks manjša od 1 %, za AUClast pa manjša od 0,02 %.
The CHMP noted that the difference in the Cmax between the test and the originator has no clinical significance. 
CHMP je menil, da razlika v Cmaks med testnim in originatorskim zdravilom ni klinično pomembna.
The following Potential Serious Risk to Public Health (PSRPH) concern was therefore referred to the CHMP: the Study PAN 2006/006 (fed bioequivalence) did not adequately evaluate the properties of the test formulation in relation to the intake of a meal and the possibility of a formulation difference between the test and the reference product has therefore not been sufficiently excluded. 
Naslednji zadržek glede morebitnega resnega tveganja za javno zdravje je bil zato predložen odboru CHMP: s študijo PAN 2006/006 (bioekvivalenca po zaužitju hrane) niso bile ustrezno ocenjene značilnosti testne formulacije glede na zaužitje obroka, zato možnost razlike med formulacijama v testnem in referenčnem zdravilu ni bila zadostno izključena.
For these two pH values similar dissolutions were proven. 
Za ti dve pHvrednosti sta bili dokazani podobni hitrosti raztapljanja.
To carry out the main analysis, the data of those volunteers that were identified as outliers was excluded from the set of data included in the analysis. 
Pred izvedbo glavne analize so bili podatki o tistih prostovoljcih, ki so bili opredeljeni za osamelce, izključeni iz nabora podatkov za analizo.
Major concern- LoOI - Q1: The Applicant was requested to submit the documentation of long-term stability of frozen plasma in order to fully document the accuracy of laboratory evaluations. 
Glavni zadržek - seznam izrazitih zadržkov - V1: Predlagatelj je bil pozvan, naj predloži dokumentacijo o dolgoročni stabilnosti zamrznjene plazme, da bi bilo mogoče v celoti dokumentirati točnost laboratorijskih ocen.
These studies were: cross-over, openlabel, randomised treatment sequence bioequivalence studies carried out in healthy volunteers; they took into account the current guidelines and the pharmacological characteristics of pantoprazole, the prolonged T-max, the increased variability (especially Cmax), and the unaltered half-life under fed conditions. 
Ti dve študiji sta bili navzkrižni, odprti, randomizirani bioekvivalenčni študiji zaporedja zdravljenja, izvedeni z zdravimi prostovoljci; upoštevali sta veljavne smernice in farmakološke značilnosti pantoprazola, podaljšan T-maks, povečano variabilnost (zlasti Cmaks) in nespremenjeno razpolovno dobo pri uporabi po zaužitju hrane.
In its first part the expert report displays the basic facts on pantoprazole PK and PD: the previously known properties of pantoprazole of a 77% bioavailability, an only modest delay of absorption, increased variability, but unaltered rate and extent of absorption when given with food. 
Prvi del strokovnega poročila navaja osnovna dejstva o farmakokinetičnih in farmakodinamičnih lastnostih pantoprazola: predhodno znane značilnosti pantoprazola glede 77 % biološke razpoložljivosti, le neznatna odložitev absorpcije, povečana variabilnost, vendar nespremenjena hitrost in obseg absorpcije pri dajanju s hrano.
The CHMP, considering the data reported, concluded that there was no formulation difference of any clinical significance. 
CHMP je po obravnavi predloženih podatkov sklenil, da med formulacijama ni klinično pomembne razlike.
The Applicant stated that the reference product in all bioequivalence studies conducted was Pantecta, marketed in Spain. 
Razložil je, da je referenčno zdravilo, ki je bilo uporabljeno v vseh izvedenih bioekvivalenčnih študijah, zdravilo Pantecta, ki je odobreno v Španiji.
Furthermore, an increase in T-max from 1-4 hours under fasting conditions to between 5 and 12 hours (attributed to delayed absorption with food) was published by the FDA in their Summary of Approval of the originator, Protonix 20 mg and Protonix 40 mg. [US FDA Summary of Approval Protonix 20 mg and Protonix 40 mg]. 
Poleg tega je ameriški urad FDA v svojem povzetku odobritve originatorskega zdravila, Protonix 20 mg in Protonix 40 mg, objavila povečanje T-maks z 1-4 ur na tešče na 5-12 ur (zaradi odložene absorpcije ob zaužitju hrane) [Povzetek odobritve zdravil Protonix 20 mg in Protonix 40 mg ameriškega urada FDA].
In individual patients it was demonstrated that AUC, but not Cmax, correlates with the degree of acid suppression, which is known to correlate with the cure of acid-related diseases, and that there is no temporal association between the peak plasma concentration and the maximum acid suppression caused by the proton pump inhibitors [Hatlebakk, 1996]. 
Pri posameznih bolnikih je bilo dokazano, da je AUC, ne pa tudi Cmaks, povezan s stopnjo zaviranja izločanja kisline, za katero je znano, da je povezana z zdravljenjem bolezni, ki jih povzroča kislina, ter da ni časovne povezave med najvišjo plazemsko koncentracijo in največjim zaviranjem izločanja kisline, ki ga povzročajo zaviralci protonske črpalke [Hatlebakk, 1996].
CONDITIONS OF THE MARKETING AUTHORISATION 
DODATEK IV POGOJI ZA DOVOLJENJE ZA PROMET Z ZDRAVILOM
The originator medicinal product used in the bioequivalence studies was Pantecta 40 mg developed by Altana Pharma AG, Spain. 
Originatorsko zdravilo, ki je bilo uporabljeno v bioekvivalenčnih študijah, je bilo zdravilo Pantecta 40 mg, ki ga je proizvedla družba Altana Pharma AG iz Španije.
The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure as mentioned in Annex III for Pantoprazole Bluefish and associated names (see Annex I). 
Veljaven povzetek glavnih značilnosti zdravila, označevanje in navodila za uporabo so enaki zadnjim različicam, pripravljenim v postopku usklajevalne skupine in navedenim v Dodatku III za zdravilo Pantoprazole Bluefish in z njim povezana imena (glejte Dodatek I).
The Applicant presented several literature references to justify the PK variability of pantoprazole. 
Predlagatelj je predložil več referenčnih gradiv za utemeljitev variabilnosti farmakokinetike pantoprazola.
The CHMP considers that bioequivalence between the test and the originator has been demonstrated also under fed conditions; 
CHMP meni, da je bila bioekvivalenca med testnim in originatorskim zdravilom dokazana tudi pri uporabi po zaužitju hrane;
The manufacturer was Altana for studies Pan 2006/006 and Pan 2006/007, and Nycomed for study 2009-2106. 
Zdravilo, uporabljeno v študijah Pan 2006/006 in Pan 2006/007, je proizvedla družba Altana, zdravilo iz študije 2009-2106 pa družba Nycomed.
The Applicant presented the results of two bioequivalence studies at a single oral dose of 40 mg, in healthy volunteers: PAN-2006/007 (fast study), PAN-2006/006 (fed study). 
Predlagatelj je predložil rezultate dveh bioekvivalenčnih študij z enojnim peroralnim odmerkom 40 mg z zdravimi prostovoljci: PAN-2006/007 (študija na tešče), PAN-2006/006 (študija po zaužitju hrane).
The CHMP, in the adopted List of Questions, requested the Applicant to discuss the design and results of the fed bioequivalence study, in the following key aspects: (i) The justification for the design of the study, particularly the 15 h sampling schedule and the rationale for pre-defining outliers based on the well-characterised and anticipated delayed absorption of pantoprazole with food in a small proportion of subjects - this should be discussed with reference to the current guidelines and in terms of the ability of the evaluable data to exclude a formulation difference under fed conditions. 
Odbor CHMP je v sprejetem seznamu vprašanj predlagatelja pozval, naj obrazloži zasnovo in rezultate bioekvivalenčne študije po zaužitju hrane z naslednjih ključnih vidikov: (i) Obrazložitev zasnove študije, zlasti 15-urnega urnika vzorčenja in razlage za vnaprejšnjo določitev osamelcev na podlagi dobro opisane in pričakovane odložene absorpcije pantoprazola s hrano pri majhnem deležu oseb - to je treba pojasniti ob upoštevanju veljavnih smernic in glede na to, ali je s pomočjo ocenljivih podatkov mogoče izključiti razliko med formulacijama pri uporabi po zaužitju hrane.
The Applicant considered that the design of both of these bioequivalence studies took into account the requirements of the current bioequivalence guidelines (CPMP/EWP/QWP/1401/98), the known pharmacokinetic characteristics of pantoprazole, and the stated administration instructions as detailed in the SmPC (“swallow whole with water before a meal”). 
Predlagatelj je menil, da zasnova obeh bioekvivalenčnih študij upošteva zahteve iz veljavnih smernic glede bioekvivalence (CPMP/EWP/QWP/1401/98), znane farmakokinetične značilnosti pantoprazola in navedena navodila za dajanje, ki so podrobno razložena v povzetku glavnih značilnosti zdravila („pogoltnite celo z vodo pred obrokom“).
It was demonstrated that the effect of such delays on the absorption of pantoprazole in terms of the drug efficacy, in individual patients is relevant for AUC, but not for the Cmax as AUC correlates with the degree of acid suppression [Hatlebakk, 1996; Thompson, 1997]. 
Dokazano je bilo, da učinek takšne odložene absorpcije pantoprazola na učinkovitost zdravila pri posameznih bolnikih vpliva na AUC, ne pa na Cmaks, saj je AUC povezan s stopnjo zaviranja izločanja kisline [Hatlebakk, 1996; Thompson, 1997].
The Reference Member State (RMS) for the decentralised procedure for Pantoprazole Bluefish application was Sweden and the Concerned Member States (CMS) were: Austria, Germany, Denmark, Spain, Finland, France, Hungary, Ireland, Italy, The Netherlands, Norway, Poland and Portugal. 
Referenčna država članica decentraliziranega postopka za uporabo zdravila Pantoprazole Bluefish je bila Združeno kraljestvo, zadevne države članice pa so bile Češka republika, Nemčija, Poljska in Slovaška.
The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure. 
Veljavni povzetek glavnih značilnosti zdravila, ovojnina in navodilo za uporabo so končne različice, dogovorjene v postopku Kordinacijske skupine.
The findings from the food interaction study together with the demonstration of bioequivalence in the fasting state (the recommended method of dosing), and with the extensive in vitro dissolution data (designed to mimic the gastric “milieu” after food) were considered to adequately exclude a formulation difference in terms of the integrity of the enteric coating and the risk of dose dumping. 
Izsledki študije medsebojnega delovanja s hrano, skupaj z dokazom bioekvivalence na tešče (priporočen način odmerjanja) in z obširnimi podatki o raztapljanju in vitro (namenjeni posnemanju želodčnega „okolja“ po zaužitju hrane) so ustrezno izključili razliko med formulacijama glede integritete črevesne obloge in tveganja sprostitve celotnega odmerka naenkrat.
Usual in- and exclusion criteria for studies in healthy volunteers were applied in order to exclude subjects with relevant illness. 
Da bi bilo mogoče izključiti osebe z določenimi boleznimi, so se za določitev zdravih prostovoljcev za študije uporabljala običajna merila za vključitev in izključitev.
The wash-out phase was sufficiently long considering the short half-life of the compound. 
Premor je bil dovolj dolg glede na kratko razpolovno dobo spojine.
Bluefish Pharmaceuticals AB submitted two bioequivalence studies which compared the proposed 40 mg formulation to the reference product, Pantecta 40 mg gastro-resistant tablets; one study was conducted under fasting conditions [PAN-2006/007] and the other study under the fed condition [PAN-2006/006]. 
Za zdravilo Pantoprazole Bluefish Pharmaceuticals AB sta bili predloženi dve bioekvivalenčni študiji, v katerih so primerjali predlagano formulacijo 40 mg z referenčnim zdravilom Pantecta 40 mg gastrorezistentnimi tabletami; ena študija je bila izvedena na tešče [PAN-2006/007], druga po zaužitju hrane [PAN-2006/006].
Standard criteria for bioequivalence were used i.e. the 90 % CI for the AUC and Cmax ratios must lie within the accepted range of 0.80-1.25. 
Uporabljena so bila standardna merila bioekvivalence, tj. 90 % intervalov zaupanja za razmerja AUC in Cmaks mora biti v sprejemljivem razponu 0,80-1,25.
The CHMP addressed a List of Questions and a further List of Outstanding Issues to the Applicant on issues related the bioequivalence with the originator under fed conditions. 
Odbor CHMP je na predlagatelja naslovil seznam vprašanj in nadaljnji seznam izrazitih zadržkov glede vprašanj, povezanih z bioekvivalenco pri uporabi originatorskega zdravila po zaužitju hrane.
Other concerns LoOI-Q1: The Applicant was requested to clarify the origin and name of the reference product used in the new bioequivalence study 
Drugi zadržki s seznama izrazitih zadržkov - V1: Predlagatelj je bil pozvan, naj pojasni izvor in ime referenčnega zdravila, uporabljenega v novi bioekvivalenčni študiji.
LoOI - Q3: The Applicant was requested to submit additional PK evaluations for test and reference product for the new bioequivalence study as the Lag-times and the % extrapolated AUC. 
Seznam izrazitih zadržkov - V3: Predlagatelj je bil pozvan, naj predloži dodatne ocene farmakokinetike za testno in referenčno zdravilo, ki sta bili uporabljeni v novi bioekvivalenčni študiji, kot so časovni zamiki in odstotek ekstrapoliranega AUC.
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET 
DODATEK III POVZETEK GLAVNIH ZNAČILNOSTI ZDRAVILA, OZNAČEVANJE IN NAVODILO ZA UPORABO
Introduction to the Study - PAN-2006-006, Food Interaction The Applicant presented the main analysis of the plasma samples excluding outliers in study PAN-2006/006 and also the analysis of the whole sample including all cases. 
Predlagatelj je predstavil glavno analizo vzorcev plazme, razen osamelcev, v študiji PAN-2006/006 in analizo celotnega vzorca, vključno z vsemi primeri.
According to this, pantoprazole is classified as a provisional BCS class III, i.e. a high solubility-low permeability drug. 
Po tem sistemu je pantoprazol na podlagi biofarmacevtskega klasifikacijskega sistema uvrščen v prehodni razred III kot visoko topno zdravilo z nizko prepustnostjo.
The Applicant reassured in its answer on the above. 
Predložil je odgovor in v njem pojasnil zahtevano.
Furthermore, the in vitro gastro-resistance and in vitro dissolution data presented and discussed in this response support bioequivalence conclusion. 
Poleg tega zaključek o bioekvivalenci podpirajo podatki o gastrorezistenci in vitro in raztapljanju in vitro, ki so predstavljeni in obravnavani v tem odgovoru.
Analytical methods -fasted and fed studies 
Analitične metode v študijah na tešče in po zaužitju hrane