FrancophonIA/ELRC3.0 huggingface dataset:
English: As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the co-administration with these metabolic inducers (a separate formulation of dolutegravir is available for this dose adjustment, see section
Danish: Da Dovato er en fastdosistablet, skal der administreres yderligere en 50 mg dolutegravir-tablet ca. 12 timer efter Dovato i hele den periode, hvor disse metaboliske inducere samtidig gives (der findes en separat formulering af dolutegravir til denne dosisjustering, se pkt.
English: As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of carbamazepine is expected).
Danish: Da Dovato er en fastdosistablet, skal der administreres yderligere en 50 mg dolutegravir-tablet ca.
English: Do not take an antacid during the 6 hours before you take Dovato, or for at least 2 hours after you take it. You can take other acid-lowering medicines like ranitidine and omeprazole at the same time as Dovato.
Danish: Tag ikke et antacid i 6 timer, før du tager Dovato, eller i mindst 2 timer efter at du har taget Dovato.
English: As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the nevirapine co-administration (a separate formulation of dolutegravir is available for this dose adjustment, see section 4.2).
Danish: Da Dovato er en fastdosistablet, skal der administreres yderligere en 50 mg dolutegravir-tablet ca. 12 timer efter Dovato i hele den periode, hvor der samtidig gives nevirapin (der findes en separat formulering af dolutegravir til denne dosisjustering, se pkt.
English: Tablet coating
Danish: Tabletovertræk
English: A number of guidelines support monitoring.
Danish: Flere retningslinjer støtter monitoreringen.
English: The company presented no new data but reiterated the previous arguments.
Danish: Virksomheden fremlagde ingen nye data, men gentog de tidligere argumenter.
English: Re-examination procedure under Article 32(4) of Directive 2001/83/EC, as amended
Danish: Revurderingsprocedure i henhold til artikel 32, stk. 4, i direktiv 2001/83/EF, med senere ændringer
English: The originator product Targocid 400mg is registered in Germany since 10th March 1992.
Danish: Originallægemidlet Targocid 400 mg har været registreret i Tyskland siden 10. marts 1992.
English: However, the exact level of activity, which must be determined in order to propose the recommendations for use, has not been established.
Danish: Det nøjagtige aktivitetsniveau, som skal bestemmes for at kunne foreslå anbefalinger for brugen, er dog ikke blevet fastlagt.
English: Non-clinical study results
Danish: Resultater af den ikke-kliniske undersøgelse
English: The issue was considered unresolved and needs further discussion.
Danish: Spørgsmålet blev betragtet som uløst og skal behandles yderligere.
English: GROUNDS FOR REFUSAL
Danish: BEGRUNDELSER FOR AFSLAG
English: The procedure was therefore referred to the CHMP.
Danish: Proceduren blev derfor indbragt for CHMP.
English: ANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR REFUSAL
Danish: BILAG II FAGLIGE KONKLUSIONER OG BEGRUNDELSER FOR AFSLAG
English: The Applicant concluded that no additional clinical data are required.
Danish: Ansøgeren konkluderede, at det ikke var nødvendigt med yderligere kliniske data.
English: Taking into consideration the legal basis of the application, a clear negative trend was observed at the CHMP.
Danish: I betragtning af retsgrundlaget for ansøgningen var der en klar negativ tendens i CHMP.
English: OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF TEICOPLANIN HOSPIRA AND ASSOCIATED NAMES (SEE ANNEX I)
Danish: SAMLET RESUMÉ AF DEN FAGLIGE VURDERING AF TEICOPLANIN HOSPIRA OG TILKNYTTEDE NAVNE (SE BILAG I)
English: Most MIC values were identical for the two preparations, and the remaining 10.2% of the results were within one twofold dilution.
Danish: De fleste MIC-værdier var identiske for de to lægemidler, og de resterende 10,2 % af resultaterne lå inden for én dobbelt opløsning.
English: ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTES OF ADMINISTRATION, APPLICANTS IN THE MEMBER STATES
Danish: BILAG I LISTE OVER LÆGEMIDLERNES NAVNE, LÆGEMIDDELFORMER, STYRKER, INDGIVELSESVEJE OG ANSØGERE I MEDLEMSSTATERNE
English: Overall the total numbers of adverse events observed were similar for both treatments.
Danish: Overordnet set var det samlede antal observerede utilsigtede hændelser næsten det samme for begge behandlinger.
English: 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).
Danish: Derfor er en bioækvivalensundersøgelse ikke nødvendig i henhold til "Note for Guidance on The Investigation of Bioavailability and Bioequivalence" (CPMP/EWP/QWP/1401/98).
English: Question 6 - The MIC values used in the calculations for each sub-component have not been approved by the EUCAST.
Danish: Spørgsmål 6 - De MIC-værdier, der anvendes ved beregningerne for de enkelte underkomponenter, er ikke blevet godkendt af EUCAST.
English: Apart from the difference in levels of the TA2 subcomponents, there are no concerns over the manufacturing process used, particularly in terms of impurities.
Danish: Bortset fra forskellene i TA2-underkomponenternes niveauer er der ingen betænkeligheder med hensyn til den anvendte fremstillingsproces, navnlig når det gælder urenheder.
English: However, although these monographs ensure acceptable quality, they do not establish therapeutic equivalence.
Danish: Selv om disse monografier sikrer en acceptabel kvalitet, påviser de dog ikke terapeutisk ækvivalens.
English: In particular, the non-protein bound kinetics of the sub-components of teicoplanin that contribute to its activity (TA21-5) was examined.
Danish: Den ikke-proteinbundne kinetik i teicoplanins underkomponenter, som bidrager til dets aktivitet (TA21-5), blev navnlig undersøgt.
English: 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.
Danish: Undersøgelsen blev stoppet tidligt af sikkerhedsmæssige grunde, men de tilgængelige farmakokinetiske data for teicoplanin blev stadig vurderet i det omfang, dataene gjorde det muligt.
English: Question 5- The post hoc analysis conducted by the Applicant as a response to the concerned member state Day 145 comments was based on the individual Cmax/MIC or AUC/MIC ratios, determined for each subcomponent and then summed.
Danish: Spørgsmål 5 - Den post hoc-analyse, som ansøgeren foretog som svar på den berørte medlemsstats bemærkninger på dag 145, var baseret på de enkelte Cmax/MIC- eller AUC/MIC-forhold, som blev bestemt for hver underkomponent og herefter lagt sammen.
English: EUCAST reported values for the whole (total) teicoplanin should be used instead.
Danish: EUCAST's indberettede værdier for det samlede (totale) teicoplanin skulle have været anvendt i stedet for.
English: Question 2 - The Applicant is requested to fully justify why the Phase I study submitted should not be considered a failed study.
Danish: Spørgsmål 2 - Ansøgeren bedes give en fuldstændig redegørelse for, hvorfor den forelagte fase Iundersøgelse ikke skal betragtes som en mislykket undersøgelse.
English: Accidental overdosing showed no adverse events or abnormalities.
Danish: Uforsætlig overdosering viste ingen utilsigtede hændelser eller uregelmæssigheder.
English: 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.
Danish: Ansøgeren svarede, at fase I-undersøgelsen (TEC062), der blev forelagt til støtte for denne ansøgning, ikke skal betragtes som en mislykket undersøgelse, eftersom den blev foretaget i henhold til de relevante retningslinjer, og at man ved en kontrol ikke identificerede nogen vigtige resultater, der specifikt relaterer til undersøgelsens udførelse.
English: The Applicant believes that the sum of the individual ratios determined for each subcomponent is essentially the same as for the total teicoplanin.
Danish: Ansøgeren mener, at summen af de individuelle forhold, som blev bestemt for hver underkomponent, i det væsentlige er den samme som for det totale teicoplanin.
English: In 2005 Hospira UK submitted applications for Decentralised Procedure for Teicoplanin Hospira 200 mg & 400 mg powder and solvent for solution for injection in the framework of Article 28 of Directive 2001/83/EC, as amended.
Danish: I 2005 indgav Hospira UK ansøgninger via den decentrale procedure for Teicoplanin Hospira 200 mg og 400 mg pulver og solvens til injektionsvæske, opløsning, i henhold til artikel 28 i direktiv 2001/83/EF, med senere ændringer.
English: 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.
Danish: På dette grundlag konkluderede ansøgeren, at det er usandsynligt, at små variationer i sammensætningen af de aktive fraktioner kan påvirke lægemidlets virkning og sikkerhed in vivo.
English: The Applicant considers it relevant to measure free drug AUC (as the sum of the major active drug components).
Danish: Ansøgeren finder det relevant at måle AUC for det frie lægemiddel (som summen af de vigtigste aktive lægemiddelkomponenter).
English: 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.
Danish: Uanset retsgrundlaget mener ansøgeren således, at lægemidlet er udviklet i henhold til alle de relevante specifikationer for teicoplanin, og at det ikke er nødvendigt med yderligere ikke-kliniske studier.
English: Subsequently, therapeutic drug monitoring is important to ensure that dose regimens are optimized and that it is recommended that teicoplanin are monitored and dosage adjusted to ensure trough levels of at least 20mg/L.
Danish: Efterfølgende er terapeutisk monitorering af lægemidlet vigtigt for at sikre, at dosisregimenerne optimeres, og det anbefales, at teicoplanin monitoreres, og at dosis justeres for at sikre bundniveauer på mindst 20mg/l.
English: Ground 2: Bioequivalence was not demonstrated for each subcomponent.
Danish: Begrundelse 2: Der er ikke påvist bioækvivalens for hver underkomponent.
English: The CHMP acknowledged that safety and efficacy were established, as well as the general equivalence.
Danish: CHMP anerkendte, at sikkerhed og virkning var dokumenteret, hvilket også gælder for den generelle ækvivalens.
English: The CHMP adopted a list of questions to be addressed by the Applicant.
Danish: CHMP vedtog en liste med spørgsmål, som ansøgeren skulle besvare.
English: 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.
Danish: Disse forskelle indikerer, at Teicoplanin Hospira ikke er en generisk form af Targocid, og den potentielle indvirkning på lægemidlets sikkerhed er stadig ukendt.
English: The Applicant should provide an analysis based on whole (total) teicoplanin plasma concentrations.
Danish: Ansøgeren bedes fremlægge en analyse, der er baseret på plasmakoncentrationer for det samlede (totale) teicoplanin.
English: Ground 1: The Applicant has not sufficiently justified why the specifications of the innovator were not met.
Danish: Begrundelse 1: Ansøgeren har ikke givet en tilstrækkelig redegørelse for, hvorfor der ikke var overensstemmelse med originallægemidlets specifikationer.
English: The CHMP noted the Applicant response, and the summary of advice received from national agencies.
Danish: CHMP noterede sig ansøgerens svar og sammendraget af rådgivning fra de nationale agenturer.
English: The majority of the adverse events observed were mild in intensity and not considered related to drug administration.
Danish: Størstedelen af de utilsigtede hændelser, der blev observeret, havde ringe styrke og blev ikke anset for at hænge sammen med lægemidlets indgivelse.
English: Although the EMEA guideline for bioequivalence states that a bioequivalence study is not required for IV products, this study provided useful additional information.
Danish: Selv om der ifølge EMEA's retningslinjer for bioækvivalens ikke kræves en bioækvivalensundersøgelse for IVlægemidler, gav denne undersøgelse yderligere nyttig information.
English: Question 3 - The Applicant should discuss the scientific basis for the post hoc analysis on the free AUC instead of the total AUC.
Danish: Spørgsmål 3 - Ansøgeren bedes redegøre for det videnskabelige grundlag for post hoc-analysen af det frie AUC i stedet for det samlede AUC.
English: 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.
Danish: Ansøgeren anførte, at passende initialdoser teicoplanin må betragtes som obligatoriske for alle patienter uanset deres nyrefunktion, så man opnår terapeutisk relevante koncentrationer tidligt i behandlingsperioden.
English: Both products include the same subcomponents and despite differences in the subcomponent ratios, both comply with the European Pharmacopoeia (Ph.Eur.)
Danish: Begge lægemidler indeholder de samme underkomponenter, og på trods af forskellene i underkomponentforholdene er de begge i overensstemmelse med monografien i Den Europæiske Farmakopé (Ph.Eur.).
English: The CHMP accepted the Applicant response, as the provided guidance documents supporting teicoplanin monitoring were considered relevant.
Danish: CHMP godkendte ansøgerens svar, eftersom de fremsendte vejledninger til støtte for teicoplaninmonitorering blev betragtet som relevante.
English: The Applicant therefore conducted a series of preclinical studies and reviewed the published literature on the biological activity of the individual subcomponents of teicoplanin.
Danish: Derfor foretog ansøgeren en række prækliniske undersøgelser og gennemgik den offentliggjorte litteratur om den biologiske aktivitet i teicoplanins enkelte underkomponenter.
English: 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.
Danish: Ansøgeren bedes derfor give en fyldestgørende begrundelse for, hvorvidt det er nødvendigt med yderligere kliniske data i form af en undersøgelse, der sammenligner sikkerhed og virkning med originallægemidlet, inden der udstedes markedsføringstilladelse for lægemidlet.
English: 200 mg/vial (66,7 mg/ml)
Danish: 200 mg/hætteglas (66,7 mg/ml)
English: The related substances resulting from the fermentation process are well documented and the Applicant undertook a toxicity study program to demonstrate a similar safety profile to that of the originator.
Danish: De relaterede stoffer fra fermenteringsprocessen er veldokumenterede, og ansøgeren iværksatte et toksicitetsundersøgelsesprogram for at påvise, at lægemidlet har en sikkerhedsprofil, der svarer til originallægemidlets.
English: 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.
Danish: Ansøgeren undersøgte både det tilgængelige aktive lægemiddel (det frie AUC) samt hele lægemidlet og det frie AUC/MIC og konkluderede, at Teicoplanin Hospira er mindst lige så effektivt som Targocid.
English: The half- lives of the TA2 components correlates to their lipophilicity, and because Teicoplanin Hospira has a lower proportional content of subcomponents with a longer half-life and a higher proportion with a shorter half-life, the overall elimination of total teicoplanin is faster, and the resulting AUC is lower.
Danish: Halveringstiden for TA2-komponenterne hænger sammen med deres lipofilicitet, og eftersom Teicoplanin Hospira har et lavere proportionalt indhold af underkomponenter med længere halveringstid og en højere andel af underkomponenter med kortere halveringstid, er den samlede elimination af det totale teicoplanin hurtigere, og det heraf følgende AUC lavere.
English: 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.
Danish: Variabiliteten i underkomponenternes sammensætning skyldes et fermenteringsprodukt, og begge lægemidler viser variabilitet med hensyn til alle de enkelte komponenter, selv om de holder sig pænt inden for de japanske og europæiske specifikationer.
English: 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.
Danish: Alle underkomponenter er velbeskrevne og hurtigt identificerbare, og der er ingen tvivl om, at hver enkelt underkomponent i Teicoplanin Hospira har de samme egenskaber som i Targocid.
English: 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).
Danish: Ansøgeren redegjorde desuden detaljeret for de underbyggende prækliniske data og beskrev de fremlagte undersøgelser (to MICundersøgelser, hvor der blev brugt en række organismer, en lårinfektionsundersøgelse hos neutropeniske mus og en toksicitetsundersøgelse med gentagne doser hos rotter).
English: 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.
Danish: Spørgsmål 4 - Ansøgeren anfører, at ifølge klinisk praksis bliver teicoplanindosen justeret efter det kliniske forløb og de lave serumkoncentrationer, navnlig ved alvorlige infektioner.
English: The Applicant should provide data (e.g. guidance documents) demonstrating that adjustment of the dose to the clinical course is generally accepted and practised.
Danish: Ansøgeren bedes fremlægge data (f.eks.vejledninger), der viser, at en justering af dosis efter det kliniske forløb er en generelt anerkendt og udbredt praksis.
English: 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.
Danish: CHMP bemærkede, at hvis Teicoplanin Hospira skal betragtes som et generisk lægemiddel, skal forskellen i mængderne af glykopeptidunderkomponenter være acceptabel, og denne forskel må ikke medføre en forskel i sikkerhed og/eller virkning.
English: The results show that free drug for each teicoplanin subcomponent was similar.
Danish: Resultaterne viser, at det frie lægemiddel for hver teicoplaninunderkomponent næsten var det samme.
English: Comparable free AUC/MIC activity cannot waive potential PK differences or the outcome of the bioequivalence study.
Danish: Sammenlignelig aktivitet i det frie AUC/MIC kan ikke hindre potentielle farmakokinetiske forskelle eller udfaldet af bioækvivalensundersøgelsen.
English: 400 mg/vial (133,4 mg/ml)
Danish: 400 mg/hætteglas (133,4 mg/ml)
English: It was however noted that tissue concentrations of drug components were not measured and that regarding the toxicology, it cannot be concluded whether the products are comparable as the histopathology was investigated only for Teicoplanin Hospira.
Danish: Det blev dog bemærket, at lægemiddelbestanddelenes vævskoncentrationer ikke blev målt, og at det for toksikologiens vedkommende ikke kan fastslås, om lægemidlerne er sammenlignelige, eftersom histopatologien kun er undersøgt for Teicoplanin Hospira.
English: Phase 1 Clinical PK/PD
Danish: Fase 1 - klinisk farmakokinetik/farmakodynamik
English: The Applicant discussed the results of a post hoc analysis on the free AUC, rather than on total AUC.
Danish: Ansøgeren redegjorde for resultaterne af post hoc-analysen af det frie AUC i stedet for det samlede AUC.
English: It is agreed that bound drug is not available to exert its therapeutic effect and that for antimicrobial agents, only free drug treats infections.
Danish: Der er enighed om, at bundet lægemiddel ikke er tilgængeligt og kan udøve sin terapeutiske virkning, og at det med hensyn til antimikrobielle stoffer kun er frit lægemiddel, der kan behandle infektioner.
English: As the ratios observed for Teicoplanin Hospira fall outside these ranges, equivalence cannot be assumed, based on the in vitro data alone.
Danish: Eftersom de observerede forhold for Teicoplanin Hospira ligger uden for dette område, kan det ikke antages, at der er ækvivalens baseret på in vitro-dataene alene.
English: 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.
Danish: CHMP noterede sig ansøgerens data og var enigt i, at det frie lægemiddel er vigtigere for den biologiske aktivitet, og at det derfor er det bedste parameter til at påvise farmakodynamisk ækvivalens.
English: It must therefore be demonstrated that the subcomponent ratio differences do not result in efficacy and/or safety differences and the CHMP is of the opinion that the clinical and non-clinical data and the bioequivalence trials provided are insufficient to demonstrate this.
Danish: Det skal derfor påvises, at forskellene i underkomponentforholdene ikke resulterer i virknings- og/eller sikkerhedsforskelle, og efter CHMP's mening giver de fremlagte kliniske og ikke-kliniske data og bioækvivalensundersøgelser ikke en tilstrækkelig dokumentation for dette.
English: 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.
Danish: Virkningen af den farmakokinetiske variabilitet på det forventede resultat (AUC/MIC) blev vurderet, og selv med forskellene i fordelingen for underkomponenternes vedkommende var de overordnede AUC/MIC-værdier næsten de samme for begge lægemidler.
English: 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.
Danish: CHMP vedtog derfor følgende liste over uafklarede spørgsmål, som skulle sendes til ansøgeren: "Efter en drøftelse og i betragtning af forskellene i sammensætning og de påviste farmakokinetiske forskelle var CHMP af den opfattelse, at der ikke er tilstrækkelig dokumentation for, at Teicoplanin Hospira er en generisk form af Targocid.
English: 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.
Danish: Ansøgeren konkluderede, at alle undersøgelser underbygger Teicoplanin Hospiras virkning og sikkerhed, og at resultaterne lignede de resultater, der var opnået med originallægemidlet.
English: 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.
Danish: CHMP var af den opfattelse, at lighed med hensyn til det frie lægemiddel er vigtigt, og hvad angår det frie AUC, er summen af alle frie TA2-underkomponenter 13 % højere for Teicoplanin Hospira.