natgillin/translations-raw huggingface dataset:
The provided data are not sufficient to assure that study conditions have negligible influence on the data to the level required for this type of regulatory submission. 
Na podlagi predloženih podatkov ni mogoče zaključiti, da imajo študijski pogoji zanemarljiv vpliv na podatke do ravni, zahtevane za to vrsto regulativne vloge.
Bioequivalence between the test product and the originator 
Bioekvivalenca med testnim in originatorskim zdravilom
All references to the target species pigs should be removed from the final versions of the summary of product characteristics, labelling and package leaflet agreed during the Coordination group procedure. 
Vse reference za ciljne vrste prašičev je treba odstraniti iz končne različice povzetka glavnih značilnosti zdravila, označevanja in navodila za uporabo, kot je bilo dogovorjeno v postopku koordinacijske skupine.
In order to do this, the applicant must establish a link between the test and reference products and as the product is systemically active, the assumptions behind the concept of bioequivalence would allow this. 
Predlagatelj mora v ta namen vzpostaviti povezavo med testnimi in referenčnimi zdravili in ker je zdravilo sistemsko aktivno, predpostavke koncepta bioekvivalence to omogočajo.
List of the name, pharmaceutical form, strength of the veterinary medicinal product, animal species, route of administration, applicant in the Member States 
Seznam imen, farmacevtskih oblik, jakosti zdravil za uporabo v veterinarski medicini, živalskih vrst, poti uporabe zdravila in predlagateljev v državah članicah
This is the standard that has been generally requested from applicants seeking to change the strength of an injectable formulation (other than for intravenous route). 
To je standard, ki se ga na splošno zahteva od vseh predlagateljev, ki želijo spremeniti jakost pripravka za injiciranje (ki ni intravensko).
• Even if the formulations were inequivalent, the lack of bioequivalence would not be clinically relevant due to a wide therapeutic window. 
• Tudi če formulaciji ne bi bili ekvivalentni, pomanjkanje bioekvivalence zaradi velike terapevtske širine ne bi bilo klinično relevantno.
The application was submitted as a generic hybrid application under Article 13(3), as there is currently no authorised product with the same concentration of meloxicam. 
V skladu s členom 13(3) je bila vloga predložena za generično hibridno vlogo, ker dovoljenje za zdravilo z enako koncentracijo meloksikama trenutno ne obstaja.
1 EMA CVMP Guideline on the conduct of bioequivalence studies for veterinary medicinal products (EMA/CVMP/016/00Rev.2) - http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/04/WC500105372.pdf 
1 Smernice CVMP EMA o izvajanju bioekvivalenčnih študij za zdravila za uporabo v veterinarski medicini (EMA/CVMP/016/00-Rev.2)http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/04/WC500105372.pdf
Considering the data submitted, the Committee concluded as follows on issues raised in the notification received from the Netherlands. 
Po preučitvi predloženih podatkov je Odbor glede vprašanj, ki jih je v sporočilu poslala Nizozemska, podal zaključke, ki so navedeni v nadaljevanju.
For horses and cattle the aqueous solution is administered via the intravenous route, therefore bioequivalence can be accepted as self-evident. 
Pri konjih in govedu se vodna raztopina injicira intravensko, zato je mogoče bioekvivalenco sprejeti kot samoumevno.
The applicant considered it is not necessary to prove bioequivalence for this hybrid application but that a justification of therapeutic equivalence is sufficient. 
Predlagatelj je izrazil mnenje, da bioekvivalence za to hibridno vlogo ni treba dokazati in da zadostuje obrazložitev terapevtske ekvivalence.
Reports from literature suggest that the rate of absorption of a substance may be increased with decreased injection volume and increased concentration. 
Poročila iz literature navajajo, da se lahko z zmanjšanjem vbrizgane količine in povečano koncentracijo stopnja absorpcije učinkovine poveča.
The applicant accepted the timing and number of sampling points required for bioequivalence and residues depletion studies are very different, according to the respective guidelines. 
Predlagatelj je sprejel časovno razporeditev in število vzorčenj, potrebnih za bioekvivalenco, študije izločanja ostankov pa so glede na zadevne smernice precej drugačne.
Czech republic CP-Pharma Handelsgesellschaft mbH Ostlandring 13 
Češka republika CP-Pharma Handelsgesellschaft mbH Ostlandring 13
The test and reference products are qualitatively identical aqueous solutions, which differ only in the concentration of meloxicam and one of the excipients. 
Testna in referenčna zdravila so kvalitativno identične vodne raztopine, ki se razlikujejo samo v koncentraciji meloksikama in ene od pomožnih snovi.
However, for regulatory approval of a generic/hybrid product where the purpose of the study is to show any formulation effects, it is expected that comparative pharmacokinetic data would be collected from a single study with controlled study conditions (e.g. sampling methods, analytical methods, homogenous animal group) to minimise the effect of other variables. 
Ne glede na to je treba za regulativno potrditev generičnega/hibridnega zdravila, pri katerem je namen študije pokazati vsakršne vplive pripravka, zbrati primerljive farmakokinetične podatke ene študije z nadziranimi študijskimi pogoji (npr. metodami vzorčenja, analitičnimi metodami, homogeno skupino živali), da se zmanjša vpliv drugih spremenljivk.
Effect that the number of animals sampled has on the reliability of the results (taking into account that for a standard bioequivalence study the test: reference ratio of the pivotal parameters must fall within predefined statistical limits.) 
Vpliv števila živali, na katerih je bilo izvedeno vzorčenje, na zanesljivost rezultatov (ob upoštevanju, da mora biti pri standardni bioekvivalenčni študiji razmerje med bistvenimi testnimi in referenčnimi parametri znotraj vnaprej določenih statističnih omejitev).
The Committee considered if the results from a residue depletion study may be used as a surrogate for data from a bioequivalence study. 
Odbor je preučil, ali se lahko ugotovitve študije izločanja ostankov uporabijo kot nadomestek za podatke bioekvivalenčne študije.
• as this is a generic ‘hybrid' application, in the absence of other data the principles of bioequivalence would need to be applied to determine the expected safety and efficacy of the product by extrapolation of the pre-clinical and clinical data from the reference product. 
• Ker gre za generično „hibridno“ vlogo, bi bilo treba zaradi pomanjkanja drugih podatkov s pomočjo načel bioekvivalence določiti pričakovano varnost in učinkovitost zdravila z ekstrapolacijo predkliničnih in kliničnih podatkov o referenčnem zdravilu.
In instances where it is not possible or scientifically relevant to conduct a blood-level bioequivalence/pharmacokinetic study, then alternative means (such as clinical end point studies) have to be used to demonstrate therapeutic equivalence. 
V primerih, ko ni bilo mogoče ali znanstveno relevantno izvesti bioekvivalenčne/farmakokinetične študije na krvni ravni, so za prikaz terapevtske ekvivalence uporabljali alternativna sredstva (kot so klinične študije z opazovanimi dogodki).
While there is a theoretical risk of increased inflammation at the site of injection due to increased tonicity of the 40 mg/ml formulation compared with the lower concentration of the reference product, injection site clinical observations and gross and microscopic pathology conducted during the residues study indicated that local inflammatory responses were minimal. 
Čeprav obstaja teoretično tveganje za povečanje vnetja na mestu injiciranja zaradi povečane toničnosti odmerka 40 mg/ml v primerjavi z manjšo koncentracijo referenčnega zdravila, klinična opazovanja mesta injiciranja ter skupne in mikroskopske patologije, izvedene med študijo ostankov, poročajo, da so bili lokalni vnetni odzivi minimalni.
The active substance is included in veterinary medicinal products currently authorised in the European Union via the centralised authorisation procedure, as well as nationally, for use in cattle, pigs, horses, dogs and cats. 
Zdravilna učinkovina se uporablja v zdravilih za uporabo v veterinarski medicini, ki so trenutno odobrena v Evropski uniji s centraliziranim in nacionalnim postopkom za injiciranje pri govedu, prašičih, konjih, psih in mačkah.
Relevance of the results from a residue depletion study as a demonstration of bioequivalence 
Relevantnost ugotovitev študije izločanja ostankov za prikaz bioekvivalence
In this instance, the principles of bioequivalence would need to be applied to enable extrapolation of the safety and efficacy data from the reference product. 
V tem primeru bi morali za ekstrapolacijo podatkov o varnosti in učinkovitosti referenčnega zdravila uporabiti načela bioekvivalence.
However, in a bioequivalence study, the principle is that blood concentrations are determined over a certain timeframe, critically including the absorption phase, to derive an estimate of Cmax and AUC with the knowledge that these correlate with therapeutic effect. 
Načelo bioekvivalenčne študije pa je, da se krvne koncentracije določijo v določenem časovnem okviru in kritično vključujejo fazo absorpcije, da se določi ocena vrednosti Cmax in AUC ob upoštevanju dejstva, da se ti dve vrednosti povezujeta s terapevtskih učinkom.
The tissue concentration levels were derived from samples taken at 4 hours and at 2, 4 and 8 days (20 mg/ml study) or 1, 3 and 5 days after the final administration (40 mg/ml study). 
Stopnje koncentracij v tkivih so bile izpeljane iz vzorcev, pridobljenih po 4 urah in po 2, 4 in 8 dneh (študija odmerka 20 mg/ml) ali 1, 3 in 5 dni po zadnje injiciranju (študija odmerka 40 mg/ml).
However, for pigs, where the product is administered intramuscularly, the applicant has not provided sufficient evidence of the relative rate and extent of absorption, to allow extrapolation of the data from the reference product. 
Vendar pri prašičih, pri katerih se zdravilo injicira intramuskularno, predlagatelj ni zagotovil zadostnih dokazov o relativni hitrosti in obsegu absorpcije, ki bi omogočali ekstrapolacijo podatkov o referenčnem zdravilu.
Timing and number of sampling points and how this relates to characterisation of the rate and extent of absorption and IV. Meloxicam concentrations in the tissues sampled (liver, kidney, muscle and injection site) and their relation to plasma pharmacokinetics. 
Časovna razporeditev in število vzorčenj ter kako se povezujejo z opisom značilnosti stopnje in obsega absorpcije in IV. Koncentracije meloksikama v vzorčnem tkivu (jetrih, ledvicah, mišicah in mestu injiciranja) in njihova povezava s plazemsko farmakokinetiko.
Grounds for the refusal of the granting of marketing authorisations for the target species pigs 
Podlaga za zavrnitev dovoljenja za promet z zdravilom za ciljne vrste prašičev
The main remaining risk arises from the uncertainty due to lack of data on the pharmacokinetic profile and exposure to meloxicam following intramuscular injection of the 40 mg/ml test product in pigs. 
Glavno preostalo tveganje je posledica negotovosti, ki izhaja iz pomanjkanja podatkov o farmakokinetičnem profilu in izpostavljenosti meloksikamu po intramuskularnem injiciranju 40 mg/ml testnega zdravila pri prašičih.
It also has anti-endotoxic properties which inhibit production of thromboxane B2 induced by E. coli endotoxin administration in calves, lactating cows and pigs. 
Deluje tudi antiendotoksično, saj zavira nastajanje tromboksana B2, izzvano z vnosom endotoksina E. coli pri govedu, kravah v obdobju laktacije in prašičih.
Overall summary of the scientific evaluation of Melosolute 40 mg/ml solution for injection 
Splošni povzetek znanstvenega vrednotenja zdravila Melosolute 40 mg/ml raztopina za injiciranje
In the CVMP list of questions, the applicant was requested to address (i) the effect of comparing results from separately conducted studies, (ii) the effect that the number of animals sampled has on the reliability of the results (taking into account that for a standard bioequivalence study the test/reference ratio of the pivotal parameters must fall within predefined statistical limits); (iii) the timing and number of sampling points and how this relates to characterisation of the rate and extent of absorption; and (iv) how meloxicam concentrations in the tissues sampled (liver, kidney, muscle and injection site) relate to plasma pharmacokinetics. 
Na seznamu vprašanj je CVMP od predlagatelja zahteval, da navede (i) vpliv primerjave rezultatov ločeno izvedenih študij, (ii) vpliv števila živali, na katerih je bilo izvedeno vzorčenje, na zanesljivost rezultatov (ob upoštevanju, da mora biti pri standardni bioekvivalenčni študiji razmerje med bistvenimi testnimi in referenčnimi parametri znotraj vnaprej določenih statističnih omejitev), (iii) časovno razporeditev in število vzorčenj ter kako se povezujejo z opisom značilnosti stopnje in obsega absorpcije in (iv) kako se koncentracije meloksikama v vzorčnem tkivu (jetrih, ledvicah, mišicah in mestu injiciranja) povezujejo s plazemsko farmakokinetiko.
However, the applicant claims there is a very fast distribution of meloxicam from the intramuscular injection site into the general circulation and subsequently a very fast elimination from tissues like liver, kidney and muscle taking into consideration the identical elimination half-life in pigs after intravenous or intramuscular administration, which justifies the claim for waiver of a bioequivalence study in pigs based on results of the residue depletion study in comparison to the Metacam 20 mg/ml product. 
Vendar predlagatelj trdi, da je porazdelitev meloksikama z mesta intramuskularnega injiciranja v splošni obtok zelo hitra, kar posledično pomeni zelo hitro izločanje iz tkiv, kot so jetra, ledvice in mišice, če upoštevamo identično razpolovno dobo izločanja pri prašičih po intravenskem ali intramuskularnem injiciranju, ki upravičuje zahtevek za oprostitev bioekvivalenčnih študij pri prašičih na osnovi rezultatov študije izločanja ostankov v primerjavi z zdravilom Metacam 20 mg/ml.
The CVMP does not accept that the comparison of residues from two different products at a single time point allows conclusions to be drawn about the blood concentration-time profile, or that the studies provide an accurate estimate of relative bioavailability. 
CVMP meni, da enkratna primerjava ostankov dveh različnih zdravil ne omogoča sklepanja o časovnem profilu krvne koncentracije in da študije ne omogočajo točne ocene relativne biološke uporabnosti.
Both studies showed that meloxicam is rapidly eliminated from the tissues of the pig, falling below MRL in most tissues within a day of administration. 
Študiji sta pokazali, da se meloksikam hitro izloča iz tkiva prašičev in v roku enega dneva injiciranja ostane pod mejnimi vrednostmi ostankov v večini tkiv.
This is supported by the evidence from the bioequivalence study between Metacam 5 mg/ml and Metacam 20 mg/ml which showed that Cmax and AUC were higher for the higher concentration formulation, and the findings in residues studies that suggest more rapid absorption from the 40 mg/ml product. 
To podpirajo ugotovitve bioekvivalenčne študije zdravila Metacam 5 mg/ml in zdravila Metacam 20 mg/ml, pri kateri sta bili vrednosti Cmax in AUC višji pri večjih koncentracijah zdravila, in ugotovitve študij ostankov, ki navajajo hitrejšo absorpcijo zdravila pri odmerku 40 mg/ml.
Based on the data presented and the responses to questions, the CVMP concluded that the data for Melosolute 40 mg/ml solution for injection for cattle, pigs and horses were not in accordance with the requirements of Directive 2001/82/EC, and that the benefit-risk balance is currently not favourable with respect to its proposed indications in the target species pigs. 
Na osnovi predloženih podatkov in odgovorov na vprašanja je CVMP zaključil, da podatki za zdravilo Melosolute 40 mg/ml raztopina za injiciranje za govedo, prašiče in konje niso v skladu z zahtevami Direktive 2001/82/ES in da razmerje med tveganji in koristmi trenutno ni ugodno.
• In horses, the proposed indications are for the alleviation of inflammation and relief of pain in both acute and chronic musculo-skeletal disorders and for the relief of pain associated with equine colic. 
• Pri konjih je predlagana indikacija za umirjanje vnetja in lajšanje bolečine pri akutnih ter kroničnih mišično-skeletnih obolenjih in za lajšanje s koliko povezane bolečine pri konjih.
Therefore the CVMP recommends the refusal of the granting of the marketing authorisation for Melosolute 40 mg/ml solution for injection for the target species pigs. 
CVMP zato priporoča zavrnitev izdaje dovoljenja za promet za zdravilo Melosolute 40 mg/ml raztopina za injiciranje za ciljne vrste prašičev.
Therefore the applicant has not provided satisfactory data in pigs to enable extrapolation of the safety and efficacy data from the Metacam 20 mg/ml product and to allow this species to be included in the product information. 
Predlagatelj torej ni predložil zadovoljivih podatkov za prašiče, ki bi omogočali ekstrapolacijo podatkov o varnosti in učinkovitosti zdravila Metacam 20 mg/ml in vključitev te vrste v podatke o zdravilu.
This is a ‘hybrid' application and the requirements differ from those of a generic product due to the fact that the test formulation contains an increase in concentration of the active substance compared to the reference formulation. 
Ker gre za „hibridno“ vlogo, se zahteve razlikujejo od tistih za generična zdravila, saj vsebujejo testni pripravki večjo koncentracijo zdravilne učinkovine kot referenčni pripravki.
These issues remained unsolved and therefore a referral under Article 33(1) of Directive 2001/82/EC to the CMD(v) was started. 
Ta vprašanja so ostala nerešena, zato je bil sprožen napotitveni postopek v skladu s členom 33(1) Direktive 2001/82/ES, ki je bil predložen Usklajevalni skupini za postopek medsebojnega priznavanja in decentralizirani postopekzdravila za uporabo v veterinarski medicini (CMD(v)).
• In pigs, the proposed indications are for use in non-infectious locomotor disorders to reduce the symptoms of lameness and inflammation, and for adjunctive therapy in the treatment of puerperal septicaemia and toxaemia (mastitis-metritis-agalactia syndrome) with appropriate antibiotic therapy. 
• Pri prašičih je predlagana indikacija za ublažitev ohromelosti in vnetja pri neinfekcijskih lokomotornih motnjah in za pomožno zdravljenje pri zdravljenju puerperalne septikemije ter toksemije (sindroma mastitisa, metritisa in agalaktije) ob ustreznem antibiotičnem zdravljenju.
It is also noted that the Bioequivalence GL does not give an exemption from in vivo studies for solutions intended for parenteral injection where there is a difference in the concentration of the active substance. 
Navedeno je tudi, da bioekvivalenčne smernice ne izvzemajo študij in vivo za raztopine za parenteralno injiciranje z razliko v koncentraciji zdravilne učinkovine.
• Residues studies would suffice as a substitute for bioequivalence, considering that as the meloxicam residues in liver and muscle were comparable at the 4 hour sampling point and as the withdrawal times for Melosolute 40 mg/ml and Metacam 20 mg/ml are the same, the pharmacokinetic parameters will be comparable. 
• Študije ostankov zadostujejo kot nadomestek za bioekvivalenco, saj bodo farmakokinetični parametri, glede na to, da so bili ostanki meloksikama v jetrih in mišicah primerljivi pri vzorčenju po 4 urah in da je karencaza zdravilo Melosolute 40 mg/ml in zdravilo Metacam 20 mg/ml enaka,
It is noticed that peak plasma concentration was reached 1 hour after the second administration in the residue depletion study using 14C-Meloxicam 20 mg/ml and declined rapidly from a Cmax of 1730 ng equivalent/ml at 1 hour after administration and over the next 95 hours (no sampling time points stated). 
V študiji izločanja ostankov so zabeležili, da se največja plazemska koncentracija pojavi 1 uro po drugem injiciranju zdravila 14C-Meloxicam 20 mg/ml in hitro upada s Cmax, ki znaša 1730 ng ekvivalenta/ml, 1 uro po injiciranju in naslednjih 95 ur (časi vzorčenj niso navedeni).
Potential serious risks were identified during the decentralised procedure by Ireland and the United Kingdom as they considered the bioequivalence of Melosolute 40 mg/ml solution for injection with the reference product, Metacam 20 mg/ml solution for injection had not been sufficiently demonstrated for the target species pigs, and no other satisfactory data had been provided to enable extrapolation of safety and efficacy data from the reference product for this species. 
Irska in Združeno kraljestvo sta med decentraliziranim postopkom opozorila na potencialno resna tveganja, saj za ciljne vrste prašičev bioekvivalenca zdravila Melosolute 40 mg/ml raztopina za injiciranje in referenčnega zdravila Metacam 20 mg/ml raztopina za injiciranje ni bila zadostno dokazana, predloženi pa niso bili nobeni drugi zadovoljivi podatki, ki bi omogočali ekstrapolacijo podatkov o varnosti in učinkovitosti referenčnega zdravila na te vrste.
For this generic ‘hybrid' application, the benefits are extrapolated from the safety and efficacy data for the reference product, Metacam 20 mg/ml. 
Za to generično „hibridno“ vlogo so koristi ekstrapolirane iz podatkov o varnosti in učinkovitosti referenčnega zdravila Metacam 20 mg/ml.
This is a generic ‘hybrid' application in which the applicant is extrapolating pre-clinical and clinical data from the reference product Metacam 20 mg/ml. 
Gre za generično „hibridno“ vlogo, pri kateri predlagatelj ekstrapolira predklinične in klinične podatke o referenčnem zdravilu Metacam 20 mg/ml.
This referral under Article 33(4) of Directive 2001/82/EC was made due to concerns that the applicant had not satisfactorily demonstrated the bioequivalence of Melosolute 40 mg/ml solution for injection with the reference product, Metacam 20 mg/ml solution for injection for the target species pigs, or provided other satisfactory justification to extrapolate the data of the reference product. 
Ta napotitveni postopek je bil v skladu s členom 33(4) Direktive 2001/82/ES sprožen zaradi pomislekov, da predlagatelj ni zadovoljivo dokazal bioekvivalence zdravila Melosolute 40 mg/ml raztopina za injiciranje z referenčnim zdravilom Metacam 20 mg/ml raztopina za injiciranje za ciljne vrste prašičev ali predložil drugih zadovoljivih obrazložitev za ekstrapolacijo podatkov o referenčnem zdravilu.
• In cattle, the proposed indications are for use in acute respiratory infection with appropriate antibiotic therapy to reduce clinical signs; for use in diarrhoea in combination with oral re hydration therapy to reduce clinical signs in calves of over one week of age and in young, non lactating cattle, and for adjunctive therapy in the treatment of acute mastitis, in combination with antibiotic therapy. 
• Pri govedu je predlagana indikacija za zmanjšanje kliničnih znakov pri akutnih okužbah dihal ob ustreznem antibiotičnem zdravljenju, za umirjanje driske v kombinaciji s peroralnim rehidracijskim zdravljenjem pri teletih, starejših od enega tedna, in mladih govedih, ki niso v obdobju laktacije,
In the absence of such a study, the residues depletion data provide no firm evidence that allows quantification of any difference in rate and extent of absorption of meloxicam between Melosolute 40 mg/ml and Metacam 20 mg/ml, and consequently the identification of its impact on clinical safety and efficacy is not possible. 
Če taka študija ni bila izvedena, podatki izločanja ostankov ne zagotavljajo trdnih dokazov za kvantifikacijo kakršnihkoli razlik v hitrosti in obsegu absorpcije meloksikama med zdravilom Melosolute 40 mg/ml in zdravilom Metacam 20 mg/ml, zato določanje njegovega vpliva na klinično varnost in učinkovitost ni mogoče.