natgillin/translations-raw huggingface dataset:
The study was stopped early due to safety reasons, but the available pharmacokinetics data of teicoplanin was still assessed to the extent the data would allow.
Študijo so prekinili zgodaj zaradi varnostnih razlogov, vendar so razpoložljive podatke o farmakokinetiki teikoplanina še vedno ocenjevali, dokler so podatki to dopuščali.
Apart from the difference in levels of the TA2 subcomponents, there are no concerns over the manufacturing process used, particularly in terms of impurities.
Razen razlik v ravneh podkomponent TA2 ni zadržkov glede uporabljenega proizvodnega postopka, zlasti z vidika nečistoč.
The CHMP noted the Applicant response, and the summary of advice received from national agencies.
CHMP je upošteval predlagateljev odgovor in povzetek nasvetov iz nacionalnih agencij.
However, although these monographs ensure acceptable quality, they do not establish therapeutic equivalence.
Vendar pa te monografije zagotavljajo sprejemljivo kakovost in ne terapevtske enakovrednosti.
The Applicant should provide an analysis based on whole (total) teicoplanin plasma concentrations.
Predlagatelj naj predloži analizo za celotne (skupne) plazemske koncentracije teikoplanina.
Overall the total numbers of adverse events observed were similar for both treatments.
Skupno število neželenih učinkov je bilo podobno pri obeh zdravljenjih.
From a GCP perspective and in terms of the data generated which support the CMC and non-clinical data, TEC062 cannot be considered a failed study.
Z vidika GCP in v smislu pridobljenih podatkov, ki podpirajo CMC in neklinične podatke, študije TEC062 ne moremo šteti za neuspešno.
200 mg/vial (66,7 mg/ml)
200 mg/vialo (66,7 mg/ml)
In addition, the evaluation of free drug AUC also failed to demonstrate equivalence.
Poleg tega vrednotenje AUC prostega zdravila ni dokazalo enakovrednosti.
On this basis, the Applicant concluded that small variations in the composition of the active fractions are unlikely to affect the safety and efficacy of the drug in vivo.
Predlagatelj je zaključil, da s tega stališča majhne razlike v sestavi aktivnih frakcij malo verjetno vplivajo na varnost in učinkovitost zdravila in vivo.
The CHMP adopted a list of questions to be addressed by the Applicant.
CHMP je pripravil seznam vprašanj, na katera naj bi predlagatelj odgovoril.
The Applicant claimed essential similarity to the innovator product Targocid, despite acknowledging differences in the profile of glycopeptides.
Predlagatelj je uveljavljal osnovno podobnost z inovatorskim zdravilom Targocid kljub priznavanju razlik v profilu glikopeptidov.
The CHMP acknowledged that safety and efficacy were established, as well as the general equivalence.
CHMP je potrdil dokaze o varnosti in učinkovitosti ter splošni enakovrednosti.
Question 4 - The Applicant states that in clinical practice, the dose of teicoplanin is adjusted to the clinical course and the trough serum concentrations especially in severe infections.
Vprašanje 4 - Predlagatelj navaja, da je v klinični praksi odmerek teikoplanina prilagojen kliničnemu poteku in najnižjim serumskim koncentracijam, zlasti pri hudih okužbah.
In conclusion, irrespective of the legal basis, the Applicant believes that the product is developed in accordance with all appropriate specifications for teicoplanin and that no additional nonclinical studies are necessary.
Torej, predlagatelj ne glede na pravno osnovo meni, da je zdravilo razvito skladno z vsemi zadevnimi specifikacijami za teikoplanin in da dodatne neklinične študije niso potrebne.
The Applicant stated that appropriate loading doses of teicoplanin must be considered mandatory for all patients regardless of their renal function in order to achieve therapeutically relevant concentrations early in the treatment period.
Predlagatelj je navedel, da morajo biti ustrezni začetni odmerki teikoplanina obvezni za vse bolnike, ne glede na njihovo ledvično funkcijo, da se dosežejo terapevtsko relevantne koncentracije zgodaj v poteku zdravljenja.
The Applicant considers it relevant to measure free drug AUC (as the sum of the major active drug components).
Predlagatelj meni, da je smiselno meriti AUC prostega zdravila (kot vsote poglavitnih komponent aktivnega zdravila).
The Applicant responded that the Phase I study (TEC062) provided in support of this application, should not be considered as a failed study, as it was conducted in accordance with the relevant guidelines and that an inspection identified no major findings specifically related to the conduct of the study.
Predlagatelj je odgovoril, da se študija faze I (TEC062), predložena v podporo vlogi za pridobitev dovoljenja, ne sme šteti za neuspešno, saj je bila izvedena skladno z ustreznimi smernicami, in da inšpekcija ni odkrila poglavitnih težav, specifično povezanih z izvedbo študije.
The CHMP agreed with the Applicant response and considered the issue to be resolved.
CHMP se je strinjal s predlagateljevim odgovorom in menil, da je vprašanje rešeno.
400 mg/vial (133,4 mg/ml)
400 mg/vialo (133,4 mg/ml)
In particular, the non-protein bound kinetics of the sub-components of teicoplanin that contribute to its activity (TA21-5) was examined.
Zlasti je pregledal kinetiko podkomponent teikoplanina, ki niso vezane na beljakovine in ki prispevajo k njegovi aktivnosti (TA21-5).
teicoplanin formulation, bioequivalence should be shown as the supporting clinical data is not sensitive enough to detect differences between formulations.
formulacijo teikoplanina, je treba dokazati biološko enakovrednost, saj podporni klinični podatki niso dovolj občutljivi za odkrivanje razlik med formulacijama.
The Applicant believes that the sum of the individual ratios determined for each subcomponent is essentially the same as for the total teicoplanin.
Predlagatelj meni, da vsota posameznih razmerij, ki je določeno za vsako podkomponento v osnovi enaka kot za skupni teikoplanin.
The Applicant further discussed the supporting pre-clinical data in detail, describing the studies submitted (two MIC studies using a number of organisms, a neutropenic mouse thigh infection model and a repeated dose toxicity study in rats).
Predlagatelj je dodatno podrobno razpravljal o podpornih predkliničnih podatkih in opisoval predložene študije (dve študiji MIK s številnimi organizmi, model okužbe stegna nevtropeničnih mišk ter študijo toksičnosti ponavljajočih se odmerkov na podganah).
The Applicant discussed the legal basis of their application, stating that it was accepted as such by the RMS and all other member states and considering that the requirements of this legal basis have been met.
Predlagatelj je razpravljal o pravni osnovi svoje vloge in navedel, da so jo sprejele referenčna država članica in vse druge države članice, ter štel zahteve omenjene pravne osnove za izpolnjene.
The Applicant therefore conducted a series of preclinical studies and reviewed the published literature on the biological activity of the individual subcomponents of teicoplanin.
Predlagatelj je zato izvedel niz predkliničnih študij ter opravil pregled objavljene literature o biološki aktivnosti posameznih podkomponent teikoplanina.
The variability seen in the subcomponent composition is inherent to a fermentation product, and both products show variability for all individual components, although remaining well within the JP and European specifications.
Variabilnost sestave podkomponent je inherentna fermentacijskemu produktu in obe zdravili kažeta variabilnost vseh posameznih komponent, ki pa ostaja precej znotraj japonske in evropske specifikacije.
These differences are indicative that Teicoplanin Hospira is not a generic of Targocid and the potential impact on the safety of the drug is still not clear.
Te razlike kažejo, da zdravilo Teicoplanin Hospira ni generično zdravilo zdravila Targocid in da potencialni vpliv na varnost zdravila še vedno ni jasen.
Regarding safety, the data from study TEC062 showed no differences between Teicoplanin Hospira and Targocid, however, the premature termination of the study does not allow solid conclusions to be drawn, although there were no suggestions of any differential safety profile between the two products.
Glede varnosti pa podatki iz študije TEC062 niso pokazali razlik med zdraviloma Teicoplanin Hospira in Targocid, vendar prezgodnja prekinitev študije ne omogoča trdnih zaključkov, čeprav ni znakov razlik v varnostnem profilu med zdraviloma.
Question 6 - The MIC values used in the calculations for each sub-component have not been approved by the EUCAST.
Vprašanje 6 - Vrednosti MIC, uporabljene v izračunih posameznih podkomponent, ni odobril Evropski odbor za testiranje občutljivosti za protibakterijske učinkovine (EUCAST).
The CHMP acknowledges that the specifications of the innovator are confidential however, analysing innovator product batches will provide insight into the variability of innovator subcomponent levels and achieving specifications within this variability range would ensure equivalence.
CHMP priznava, da so specifikacije inovatorja zaupne, vendar analiza serij inovatorskega zdravila omogoča vpogled v variabilnost ravni podkomponent v inovatorskem zdravilu in da doseganje specifikacije v tem razponu variabilnosti zagotovi enakovrednost.
Accidental overdosing showed no adverse events or abnormalities.
Nenamerno preveliko odmerjanje ni imelo neželenih učinkov ali nenormalnosti.
Question 1 - The differences in composition between the two products and the resulting differences between the AUC values do not clearly demonstrate that Teicoplanin Hospira and the reference product Targocid are essentially similar.
Vprašanje št. 1 - Različna sestava obeh zdravil in posledične razlike vrednosti AUC ne dokazujejo jasno, da sta zdravilo Teicoplanin Hospira in referenčno zdravilo Targocid v osnovi podobni.
The majority of the adverse events observed were mild in intensity and not considered related to drug administration.
Večina opaženih neželenih učinkov je bila blagih po intenzivnosti in se ni štela za posledico dajanja zdravila.
The Applicant concluded that all the studies support the efficacy and safety of Teicoplanin Hospira and that the results were similar to those obtained with the originator.
Predlagatelj je zaključil, da vse študije podpirajo učinkovitost in varnost zdravila Teicoplanin Hospira in da so bili rezultati podobni rezultatom originatorskega zdravila.
The Applicant stated that generic applicants do not have access to the specifications of the originator products and that it therefore attempted to develop an API containing subcomponents at levels similar to that seen in Targocid.
Predlagatelj je navedel, da predlagatelji generičnih zdravil nimajo dostopa do specifikacij originatorskih zdravil in da je zato poskušal razviti zdravilno učinkovino, ki vsebuje podkomponente v podobnih ravneh kot v zdravilu Targocid.
The CHMP noted the Applicant data and agreed that free drug is more important for biological activity and is thus the better parameter to demonstrate “pharmacodynamic”-equivalence.
CHMP je upošteval podatke predlagatelja in se strinjal, da je prosto zdravilo pomembnejše za biološko aktivnost in zaradi tega boljši parameter za dokaz „farmakodinamične“ enakovrednosti.
The Applicant is, therefore, requested to fully justify whether or not additional clinical data is required in the form of a comparative safety and efficacy study with the innovator product in advance of the product being granted a Marketing Authorisation.
Predlagatelja zato prosimo, da popolnoma utemelji, ali so pred odobritvijo dovoljenja za promet z zdravilom potrebni dodatni klinični podatki v obliki primerjalne študije varnosti in učinkovitosti z inovatorskim zdravilom.
Question 3 - The Applicant should discuss the scientific basis for the post hoc analysis on the free AUC instead of the total AUC.
Vprašanje 3 - Predlagatelj naj razpravlja o znanstveni osnovi za post hoc analizo AUC prostega zdravila namesto AUC skupnega zdravila.
According to the Applicant, this indicates essentially similar therapeutic outcome.
Predlagatelj to razlaga kot pokazatelja osnovne podobnosti terapevtskega izida.
The CHMP noted the data comparing the PK, PDD and safety of Teicoplanin Hospira and the originator.
CHMP je upošteval podatke primerjave farmakokinetike, PDD in varnosti zdravila Teicoplanin Hospira ter originatorskega zdravila.
While EUCAST approved subcomponent MICs are not available for any antibacterial, this should not constitute an argument against their use.
Čeprav EUCAST ni odobril vrednosti MIK za podkomponente pri nobenem protibakterijskem zdravilu, to še ne pomeni, da jih ne smemo uporabljati.
Due to the differences in systemic exposure between Teicoplanin Hospira and Targocid and because the effect of the subcomponent differences on tissue drug concentrations was not measured, the CHMP concluded that bioequivalence could not be demonstrated.
Zaradi razlik v sistemski izpostavljenosti med zdraviloma Teicoplanin Hospira in Targocid in ker učinek razlik v podkomponentah na koncentracije zdravila v tkivu ni bil izmerjen, CHMP meni, da biološke enakovrednosti ni mogoče dokazati.
Comparable free AUC/MIC activity cannot waive potential PK differences or the outcome of the bioequivalence study.
Primerljive aktivnosti AUC/MIK prostega zdravila ne morejo mimo možnih razlik v farmakokinetiki ali izidu študije biološke enakovrednosti.
The CHMP therefore adopted the following List of Outstanding Issues to be addressed by the Applicant: “Following discussion and considering the differences in the composition and the demonstrated PK differences, the CHMP was of the opinion that it was not sufficiently demonstrated that Teicoplanin Hospira is a generic of Targocid.
CHMP je zato pripravil naslednji seznam nerešenih vprašanj, na katera naj bi odgovoril predlagatelj: „CHMP je po razpravi in upoštevanju razlik v sestavi ter dokazanih razlik v farmakokinetiki menil, da ni dovolj dokazov, da je zdravilo Teicoplanin Hospira generično zdravilo zdravila Targocid.
The Applicant did not further discuss the outcomes of the partially completed bioequivalence studies evaluating AUC and Cmax, as the CHMP considered that due to the nature of this drug, the whole drug (total) AUC is not appropriate to demonstrate bioequivalence.
Predlagatelj ni dodatno razpravljal o izidih delno opravljenih študij biološke enakovrednosti, v katerih so vrednotili AUC in Cmax, saj je CHMP menil, da za dokazovanje biološke enakovrednosti AUC za celotno (skupno) zdravilo ni primerna zaradi narave zdravila.
The Applicant also provided a briefing document stating that other endpoints, including pharmacodynamics, protein binding and analysis of the PK and PD of the principal sub-components, were measured in the study as it is believed that only free drug (non-protein bound teicoplanin) contributes to pharmacodynamic activity.
Predlagatelj je predložil tudi navodila, ki kažejo, da so v študiji merili druge končne točke, vključno s farmakodinamiko, vezavo na beljakovine in analizo farmakokinetike in farmakodinamike glavnih podkomponent, saj so menili, da le prosto zdravilo (na beljakovine nevezani teikoplanin) prispeva k farmakodinamični aktivnosti.
Safety data obtained from clinical study and non-clinical toxicity study The Applicant stated that the dosing regimen of teicoplanin is predictable, therefore dose-dependent toxicity is not of concern under standard clinical use.
Podatki o varnosti, pridobljeni iz klinične študije in neklinične študije toksičnosti Predlagatelj je navedel, da je režim odmerjanja napovedljiv, zato od odmerka odvisna toksičnost ni zadržek pri standardni klinični rabi.
The CHMP considered that similarity with regards to the free drug is important and that with regards to free AUC, the sum of all free TA2 subcomponents is 13% higher for Teicoplanin Hospira.
CHMP je menil, da je podobnost v smislu prostega zdravila pomembna in da je pri AUC prostega zdravila vsota vseh prostih podkomponent TA2 13 % večja pri zdravilu Teicoplanin Hospira.
All subcomponents are well characterised and readily identifiable and there is no doubt that each individual subcomponent in Teicoplanin Hospira has the same characteristics as in Targocid.
Vse podkomponente so dobro opisane in enostavno določljive, zato ni dvoma, da ima vsaka posamezna podkomponenta zdravila Teicoplanin Hospira enake značilnosti kot v zdravilu Targocid.
As the CHMP considered that free AUC is the most important PK parameter and that the dominant pharmacodynamic driver of microbiological and clinical outcome is AUC/MIC, the Applicant concluded that the most important PK/PD parameter for assessing microbiological and clinical outcome is the free AUC/MIC.
Ker je CHMP štel AUC prostega zdravila kot najpomembnejši parameter farmakokinetike in AUC/MIK kot poglavitno farmadinamično gonilo mikrobiološkega in kliničnega izida, je predlagatelj menil, da je najpomembnejši parameter farmakokinetike in farmadinamike za oceno mikrobiološkega in kliničnega izida AUC/MIK.
The CHMP also noted that the PK parameters of the subcomponents are unknown in children and that composition differences may lead to more pronounced PK differences in children, as literature data indicates differences in PK properties in adults and children.
CHMP je upošteval tudi, da so parametri farmakokinetike podkomponent neznani pri otrocih in da lahko razlike v sestavi povzročijo bolj izrazite razlike farmakokinetike pri otrocih, saj podatki iz literature kažejo razlike v farmakokinetičnih značilnostih pri odraslih in otrocih.
The Applicant discussed the variation in subcomponent levels and stated that bioequivalence or essential similarity for Teicoplanin is best assessed by comparing the sum of free AUC/MIC for the subcomponents.
Predlagatelj je razpravljal o razlikah v ravneh podkomponent in navedel, da biološko enakovrednost ali osnovno podobnost teikoplanina najbolje vrednotimo s primerjavo vsote AUC/MIK prostih podkomponent.
The Applicant considered the AUC/MIC ratio individually for all 5 subcomponents, for the free drug, as teicoplanin is extensively protein bound, and the biological activity of the preparation mainly results from the free drug component.
Predlagatelj je upošteval posamezno razmerje AUC/MIK za vseh 5 podkomponent prostega zdravila, saj se teikoplanin močno veže na beljakovine, in biološko aktivnost pripravka predvsem iz rezultatov za prosto zdravilo.
Accordingly, the Applicant argued that the sum of free AUC/MIC of the subcomponents is substantiating comparable activity between the generic and the innovator.
Skladno s tem je predlagatelj argumentiral, da vsota AUC/MIK prostih podkomponent utemeljuje primerljivo aktivnost med generičnim zdravilom in inovatorskim zdravilom.
In addition, the use of MIC values from 1984 published data is not supported and correlating PK/PD with clinical outcome and the probability of achieving certain targets is not accepted for abridged products.
Poleg tega uporaba vrednosti MIK iz podatkov, objavljenih leta 1984, ni podprta, korelacija farmakokinetike in farmadinamike s kliničnim izidom ter verjetnostjo doseganja določenih ciljev pa ni sprejemljiva za zdravila s skrajšanim postopkom.
The Applicant examined both available active drug (free AUC) and whole drug and free AUC/MIC, concluding that Teicoplanin Hospira is at least as efficacious as Targocid.
Predlagatelj je pregledal razpoložljivo aktivno zdravilo (AUC prostega zdravila) in skupno zdravilo ter AUC/MIK prostega zdravila ter zaključil, da je zdravilo Teicoplanin Hospira vsaj tako učinkovito kot zdravilo Targocid.
The CHMP noted the neutropenic mouse study demonstrating efficacy in reducing bacterial count and demonstrating biological equivalence.
CHMP je upošteval, da študija na nevtropeničnih miškah dokazuje učinkovitost pri zmanjšanju bakterijskega števila in dokazuje biološko enakovrednost.
The CHMP accepted the Applicant response, as the provided guidance documents supporting teicoplanin monitoring were considered relevant.
CHMP je sprejel odgovor predlagatelja, saj je menil, da so predložene smernice, ki podpirajo spremljanje teikoplanina, pomembne.
The Applicant discussed the results of a post hoc analysis on the free AUC, rather than on total AUC.
Predlagatelj je razpravljal o rezultatih post hoc analize AUC prostega zdravila namesto AUC skupnega zdravila.
Therefore a bioequivalence study is not required, in line with the Note for Guidance on The Investigation of Bioavailability and Bioequivalence (CPMP/EWP/QWP/1401/98).
Zato v skladu z Obvestilom o smernici o raziskavah biološke razpoložljivosti in enakovrednosti (CPMP/EWP/QWP/1401/98) študija biološke enakovrednosti ni potrebna.
The issue was considered unresolved and needs further discussion.
CHMP je menil, da je zadržek nerešen in da zahteva dodatno razpravo.
The CHMP noted that for Teicoplanin Hospira to be considered as a generic product, the difference in the amounts of glycopeptides subcomponents must be acceptable and that this difference must not lead to a difference in safety and/or efficacy.
CHMP je opozoril, da se zdravilo Teicoplanin Hospira lahko šteje za generično zdravilo, če so razlike v količinah glikopeptidnih podkomponent sprejemljive in če ta razlika ne povzroči razlike v varnosti in/ali učinkovitosti.
The CHMP assessed the studies and concluded that the MIC results were similar between Teicoplanin Hospira and the originator and that no difference in antibacterial activity or in effectiveness was observed.
CHMP je ovrednotil študije in zaključil, da so rezultati MIK podobni pri zdravilu Teicoplanin Hospira in originatorskem zdravilu ter da ni opažene razlike v protibakterijski aktivnosti ali učinkovitosti.
As the ratios observed for Teicoplanin Hospira fall outside these ranges, equivalence cannot be assumed, based on the in vitro data alone.
Ker so razmerja v zdravilu Teicoplanin Hospira izven teh razponov, enakovrednosti ne moremo predpostavljati zgolj na in vitro podatkih.
It was considered that Teicoplanin Hospira and Targocid are comparable in terms of overall active drug content, but differ in the composition of the TA-2 subcomponents, resulting in major objections.
Štelo se je, da sta zdravili Teicoplanin Hospira in Targocid primerljivi v smislu skupne vsebnosti aktivnega zdravila, vendar se razlikujeta v sestavi podkomponent TA2, kar je povzročilo velike zadržke.
The effect of variability in PK on the expected outcome (AUC/MIC) was assessed and even with differences in distributions for the subcomponents, the overall AUC/MIC values are similar for the two products.
Ocenjevali so učinke variabilnosti farmakokinetike na pričakovani izid (AUC/MIK) in kljub razlikam v porazdelitvah podkomponent so skupne vrednosti AUC/MIK med zdraviloma podobne.
It is agreed that bound drug is not available to exert its therapeutic effect and that for antimicrobial agents, only free drug treats infections.
Dogovorjeno je, da vezano zdravilo ni zmožno izražati terapevtskega učinka ter da pri protimikrobnih snoveh okužbe zdravi le prosto zdravilo.
The Applicant submitted a request for a re-examination of the CHMP opinion, responding to the grounds supporting the decision that Teicoplanin Hospira cannot be considered to be a generic of the innovator Targocid and addressed one by one the three grounds for refusal of the granting of the Marketing Authorisations.
Predlagatelj je predložil zahtevek za ponovni pregled mnenja CHMP kot odziv na utemeljitev odločitve, da se zdravilo Teicoplanin Hospira ne more šteti za generično zdravilo inovatorskega zdravila Targocid, ter obravnaval vse tri podlage za zavrnitev odobritve dovoljenja za promet z zdravilom.
The Applicant discussed the compliance of Teicoplanin Hospira to the monographs, stating that the tighter controls over the individual components proposed signify that the active pharmaceutical ingredient used in Teicoplanin Hospira meets the requirements of both monographs and that the individual components are controlled to a far greater extent.
Predlagatelj je razpravljal o skladnosti zdravila Teicoplanin Hospira z monografijami, pri čemer navaja, da predlagani strožji nadzor nad posameznimi komponentami kaže, da zdravilna učinkovina v zdravilu Teicoplanin Hospira ustreza zahtevam obeh monografij ter da so posamezne komponente nadzorovane veliko bolje.