natgillin/translations-raw huggingface dataset:
De nationale kompetente myndigheder skal sikre, at de berørte indehavere af markedsføringstilladelse opfylder nedenstående betingelser, idet de skal:
The national competent authorities shall ensure that the following conditions are fulfilled by the concerned marketing authorisation holders:
Liste over veterinærlægemidlernes navne, lægemiddelformer, styrker, måldyrearter, administrationsveje og indehavere af markedsføringstilladelse i medlemsstaterne
List of the names, pharmaceutical form, strength of the veterinary medicinal products, animal species, route of administration, marketing authorisation holders in the Member States
Dosen og behandlingsvarigheden skal underbygges.
Justification of the dose and the duration of treatment are required.
Indehaveren af markedsføringstilladelse vurderede også, at veterinærlægemidlet kan anvendes til behandling af mastitis-metritis-agalakti (MMA)-syndrom forbundet med E. coli, men anerkendte, at det er nødvendigt med flere data for at vurdere det rigtige dosisregime hos voksne dyr.
The marketing authorisation holder also considered that the veterinary medicinal product could be used to treat Mastitis-Metritis-Agalactia (MMA) syndrome associated with E. coli, but acknowledged that further data are needed to assess the correct dose regimen in adult animals.
Samlet resumé af den videnskabelige vurdering af paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin (se bilag I)
Overall summary of the scientific evaluation of Veterinary medicinal products containing paromomycin to be administered parenterally to pigs (see Annex I)
De mest relevante væv, hvad angår restkoncentrationer af paromomycin, var muskelvævet ved injektionsstedet og nyrerne.
The most relevant tissues for the presence of paromomycin residue were muscle at the injection site and kidney.
Derudover er behandlingsvarigheden ikke blevet godtgjort, og indehaveren af markedsføringstilladelse har ikke fremlagt kliniske data, der begrunder den anbefalede dosis.
Furthermore, the duration of treatment has not been justified and no clinical data have been provided by the marketing authorisation holder to justify the recommended dose.
Tilbageholdelsestiden blev fastsat hos dyr med en gennemsnitlig vægt på 37,2 kg (interval 3242,8 kg), der blev behandlet med den anbefalede dosis i den maksimale behandlingsvarighed.
The withdrawal period was determined in animals with a mean weight of 37.2 kg (range of 32 to 42.8 kg) treated according to the recommended posology at the longest duration of treatment.
Muskelvæv ved injektionsstedet er ikke det mest velegnede væv til beregning af tilbageholdelsestiden, da dette væv ofte er kendetegnet ved stor variabilitet i restkoncentrationer, hvilket i dette tilfælde også bekræftes ved det begrænsede antal prøver med koncentrationer over kvantificeringsgrænsen (2/4 på dag 12).
Muscle of injection site is not the most reliable tissue for withdrawal time calculation, as it is often characterised by a high variability in residues levels, confirmed also in this case by the limited number of samples with concentrations above limit of quantification (2/4 on Day 12).
For at dokumentere produktets effekt blev der fremlagt følsomhedsdata for E. coli og A. pleuropneumoniae, og der blev udført en farmakokinetisk/farmakodynamisk analyse.
In order to justify efficacy of the product, susceptibility data were provided for E. coli and A. pleuropneumoniae and a pharmacokinetics/pharmacodynamics (PK/PD) analysis was performed.
Paromomycin har bredspektret aktivitet mod en lang række grampositive og gramnegative bakterier og har koncentrationsafhængig effekt.
Paromomycin has broad spectrum activity against numerous Gram-positive and Gram-negative bacteria and acts in a concentrationdependent manner.
De veterinærlægemidler, der er omfattet af denne indbringelsesprocedure, indeholder 250 mg/ml paromomycinsulfat som aktivt stof (svarende til 175 mg/ml paromomycinbase eller en paromomycinaktivitet på 175.000 IE/ml).
The veterinary medicinal products involved in this referral contain 250 mg/ml paromomycin sulfate as active substance (equivalent to 175 mg/ml paromomycin base or to a paromomycin activity of 175,000 IU/ml).
Paromomycins virkningsmekanisme er velbeskrevet, og det samme gælder mekanismen for antimikrobiel resistens over for paromomycin.
The mechanism of action of paromomycin has been well described as well as the mechanisms of antimicrobial resistance to paromomycin.
CVMP vurderer således, at effekten af disse veterinærlægemidler ikke er underbygget for nogen indikationer eller dosering.
In conclusion, the CVMP considered that the efficacy of these veterinary medicinal products was not supported for any indication and posology.
Styrke Lægemiddelform Dyrearter Administration svej
Strength Pharmaceutical form
• Foretage en vurdering af benefit/risk-forholdet til bekræftelse af, at de kliniske fordele ved disse veterinærlægemidler opvejer de potentielle risici, hvad angår dyresundhed og udvikling af resistens samt (hvis relevant) de potentielle miljø- og brugerrisici.
• To provide a benefit-risk assessment outlining that the clinical benefits of these veterinary medicinal products outweigh potential risks relating to animal health and the development of resistance, and (if applicable) environmental and user risks.
Der blev indsendt en ansøgning i henhold til artikel 13, stk. 1, i direktiv 2001/82/EF, dvs. en generisk ansøgning om markedsføringstilladelse efter den decentrale procedure med Belgien som referencemedlemsstat for veterinærlægemidlet Parofor 175 mg/ml injektionsvæske, opløsning (BE/V/0027/003/DC).
An application was submitted under Article 13(1) of Directive 2001/82/EC, i.e. a generic application for a marketing authorisation under the decentralised procedure for the veterinary medicinal product ‘Parofor 175 mg/ml solution for injection', with Belgium as Reference Member State (BE/V/0027/003/DC).
Kvantificeringen af paromomycin i vævene blev udført under anvendelse af validerede HPLC- og MS/MS-analysemetoder.
The quantification of paromomycin in tissues was carried out by validated HPLC-MS/MS analytical methods.
Der skal foreligge relevante kliniske data (der omfatter et randomiseret, blindet GCP-feltstudie) for hver påberåbt behandlingseffekt ved en specifik type Escherichia coli.
Relevant clinical data (including GCP, randomised, blinded field study) are required for each claim related to a specific type of Escherichia coli.
Da colibacillose er et sygdomskompleks (neonatal diarré, diarré efter afvænning, ødemsyge, sepsis, polyserositis, coliform mastitis og urinvejsinfektion), der forårsages af forskellige typer Escherichia coli (enteropatogen E. coli, shigatoksin-producerende E. coli, enterotoksigen E. coli osv.), bør indehaverne af markedsføringstilladelse definere den eller de kliniske indikationer så nøjagtigt som muligt ved også at inkludere måldyrenes underkategori (alder og produktionstype).
Considering that colibacillosis is a disease complex (including neonatal diarrhoea, post-weaning diarrhoea, oedema disease, septicemia, polyserositis, coliform mastitis, and urinary tract infection) and is caused by different types of Escherichia coli (enteropathogenic E. coli, Shiga-toxin producing E. coli, enterotoxigenic E. coli, etc.), the marketing authorisation holders should define the clinical indication(s) as precisely as possible by including also the sub-category (age and production type) of the target animals.
For antimikrobielle stoffer som paromomycin, hvis effekt er koncentrationsafhængig, er høje plasmaniveauer, hvad angår patogenets MIC (Cmax/MIC-ratio, også kaldet inhibitorisk kvotient (IQ)), en væsentlig determinant for klinisk effekt; en Cmax/MIC-ratio > 8-10 foreslås for at opnå optimal effekt.
For antimicrobials like paromomycin, whose efficacy is concentration-dependent, high plasma concentration levels relative to the MIC of the pathogen (Cmax/MIC ratio, also known as the inhibitory quotient or IQ) are a major determinant of clinical efficacy; a Cmax/MIC ratio > 8-10 is suggested to achieve optimal efficacy.
Derfor anbefaler udvalget, at de eksisterende markedsføringstilladelser til de pågældende paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin, suspenderes.
Consequently, the Committee recommends the suspension of the existing marketing authorisations for the concerned veterinary medicinal products containing paromomycin to be administered parenterally to pigs.
Indikationen behandling af colibacillose, der er baseret på et overvurderet positivt resultat fra en teoretisk model for behandling af E. coli i plasma alene, hvor behandlingsvarigheden ikke er godtgjort, og hvor der ikke foreligger underbyggende kliniske data, kan derfor ikke accepteres.
Therefore, the indication against colibacillosis based on an overestimated success from a theoretical modelling, against E. coli strictly located in plasma, for an unjustified duration of treatment and not confirmed by clinical data, is not acceptable.
Denne model er desuden kun relevant for målstammer i plasma eller vævsområder med ækvivalent paromomycin-fordeling, idet der ikke kan forventes nogen forudsigelighed over for patogenet i andre væv.
Moreover, this model holds true only for target strains in plasma or tissue sites with equivalent paromomycin distribution, no predictability can be expected against the pathogen located in other tissues.
Videnskabelige konklusioner og begrundelser for suspendering af markedsføringstilladelserne
Scientific conclusions and grounds for suspension of the marketing authorisations
Prøver fra målvævene blev analyseret under anvendelse af HPLC-metoden kombineret med MS/MSmetoden.
Samples of the target tissues were analysed by HPLC method coupled with MS/MS detection.
I ovennævnte decentrale procedure er det blevet bemærket, at der er forskellige godkendte indikationer, doseringer og tilbageholdelsestider i den Europæiske Union (EU) for paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin.
During the aforementioned decentralised procedure, it has been noted that there are different approved indications, posology and withdrawal periods for veterinary medicinal products containing paromomycin to be administered parenterally to pigs across the European Union (EU).
Hvad angår A. pleuropneumoniae, viser den farmakokinetiske/farmakodynamiske analyse baseret på den inhibitoriske kvotient (Cmax/MIC > 8-10), at kun 10 % af målbakteriepopulationen vil være følsom over for paromomycin administreret i den anbefalede dosis.
Regarding A. pleuropneumoniae, the PK/PD analysis based on the inhibitory quotient (Cmax/MIC >8 to 10) shows that only 10% of the target bacterial population would be sensitive to paromomycin administered at the recommended posology.
Ved E. coli var den farmakokinetiske/farmakodynamiske analyse kun favorabel for stammer med en MIC-værdi på 4,44 µg/ml eller derunder.
In the case of E. coli, the PK/PD analysis was only favourable for strains with MICs equal to or below 4.44 µg/ml.
Endelig kan den farmakokinetiske/farmakodynamiske model ikke godtgøre behandlingsvarigheden.
Finally the PK/PD model does not allow justifying the duration of treatment.
• Fremskaffe relevante kliniske data til understøttelse af indikationen behandling af colibacillose ved den anbefalede dosis og behandlingsvarighed.
• To provide adequate clinical data in support of an indication against colibacillosis at the recommended dose and duration of treatment.
CVMP blev anmodet om at gennemgå alle tilgængelige prækliniske/kliniske data og restkoncentrationsdata for paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin, og anbefale relevante indikationer, doseringer og tilbageholdelsestider.
The CVMP was requested to review all available pre-clinical, clinical and residue depletion data for veterinary medicinal products containing paromomycin to be administered parenterally to pigs and recommend appropriate indications, dosing recommendations and withdrawal periods.
Samme indehaver af markedsføringstilladelse fremlagde data for at understøtte anvendelse af "Gabbrovet solution injectable" hos svin i en dosis på 14 mg paromomycinbase/kg kropsvægt i 5 dage i træk.
The same marketing authorisation holder provided data in order to justify the use of ‘Gabbrovet solution injectable' in pigs at a dose of 14 mg paromomycin base/kg bodyweight for 5 consecutive days.
På baggrund af de forhold, der er beskrevet i indbringelsesanmeldelsen, blev CVMP også anmodet om at anbefale, hvorvidt markedsføringstilladelserne til de pågældende veterinærlægemidler bør opretholdes, ændres, suspenderes eller tilbagekaldes.
The CVMP was also asked to recommend whether in view of the elements described in the referral notification the marketing authorisations for the veterinary medicinal products concerned should be maintained, varied, suspended, or withdrawn.
De mangler, der er bemærket i studiet (fravær af data om opbevaringsstabilitet, det brede interval af restkoncentration fundet i muskelprøver og fravær af en ringprøve i forbindelse med prøvetagning fra injektionsstedet), kan imidlertid ikke omfattes af en sikkerhedsmargin.
However, the deficiencies noted in the study (absence of data on storage stability, the wide recovery rates in muscle samples and the absence of ring sample in the sampling of the injection site) cannot be covered by any safety span.
• Fremskaffe relevante kliniske data (der omfatter et randomiseret, blindet GCP-feltstudie) til understøttelse af behandling af pleuropneumoni forårsaget af Actinobacillus pleuropneumoniae ved den anbefalede dosis og behandlingsvarighed.
• To provide adequate clinical data (including GCP, randomised, blinded field study) in support of the treatment of pleuropneumonia caused by Actinobacillus pleuropneumoniae at the recommended dose and duration of treatment.
Denne indbringelsesprocedure omfatter ikke sikkerhed for måldyrearten, men der er ingen kendte bivirkninger hos svin.
While target animal safety was not in the scope of this referral, there are no known adverse events in pigs.
Der blev imidlertid bemærket en række mangler i studiet, hvad angår opbevaring af prøver, stabilitet af restkoncentrationer under opbevaring, det brede interval af restkoncentration fundet i muskelvævet og fravær af en ringformet kontrolprøve fra vævet omkring den eksciderede prøve fra injektionsstedets kerne.
However, a number of deficiencies in the study were noted related to the storage of the samples, the stability of the residues in storage conditions, the wide range of recovery in muscle and the absence of a ring-shaped control surrounding the excised injection site core sample.
Derudover er der ikke fremlagt studier til dosisbestemmelse eller dosisbekræftelse for at stadfæste resultaterne af den farmakokinetiske/farmakodynamiske analyse, ligesom der ikke foreligger noget feltstudie.
Furthermore, neither dose determination, nor dose confirmation studies have been made available to confirm the results of the PK/PD analysis and no field trial was made available.
• CVMP vurderer, at anvendelse af paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin, ikke er understøttet af prækliniske/kliniske data og restkoncentrationsdata, og at de aktuelt anbefalede indikationer, doseringsregimer og tilbageholdelsestider kan udgøre en potentiel risiko for dyrs og menneskers sundhed.
• the CVMP considered that the use of veterinary medicinal products containing paromomycin to be administered parenterally to pigs is not supported by pre-clinical, clinical and residue depletion data and the currently recommended indications, dosing regimens and withdrawal period could pose a potential risk to animal and human health;
Vurdering af benefit/risk-forholdet og konklusioner Da der ikke foreligger relevante prækliniske/kliniske data og restkoncentrationsdata, og da anvendelse af disse lægemidler kan medføre en potentiel risiko for dyrs og menneskers sundhed, vurderer udvalget følgelig, at benefit/risk-forholdet for de pågældende paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin, er ugunstigt.
Evaluation and conclusions on the benefit-risk balance Therefore, the Committee considers that in the absence of adequate pre-clinical, clinical and residue depletion data and because the use of these medicinal products could pose a potential risk to animal and human health, the benefit-risk balance for the concerned veterinary medicinal products containing paromomycin to be administered parenterally to pigs is not favourable.
Dette resultat kan imidlertid føre til en overvurdering af paromomycins effekt ved den anbefalede dosis, da paromomycins procentvise binding til plasmaproteiner ikke blev klarlagt, hvilket kan reducere mængden af paromomycin i plasma, der kan være virksom mod E. coli.
This result, however is likely to overestimate the efficacy of paromomycin at the recommended dose since the % binding of paromomycin to plasma proteins was not determined, which would reduce the portion of paromomycin in plasma able to work against E. coli.
Der blev gennemført et restkoncentrationsstudie hos svin med intramuskulær administration af den maksimale anbefalede dosis på 14 mg paromomycin/kg kropsvægt/dag i 5 dage i træk.
The residue depletion study was performed in pigs with the intramuscular administration of the maximum recommended dose of 14 mg paromomycin/kg bodyweight/day for 5 consecutive days.
Desuden vil dette allerede ringe resultat sandsynligvis føre til overvurdering af paromomycins effekt i den anbefalede dosis, da paromomycins procentvise binding til plasmaproteiner ikke blev klarlagt, hvilket vil reducere mængden af paromomycin i plasma, der kan være virksom mod A. pleuropneumoniae.
This already poor result is in addition likely to overestimate the efficacy of paromomycin at the recommended dose since the % binding of paromomycin to plasma proteins was not determined, which would reduce the portion of paromomycin in plasma able to work against A. pleuropneumoniae.
• Et nyt restkoncentrationsstudie er påkrævet, uanset om doseringsregimet er ændret eller ej. Tilbageholdelsestiden bør baseres på robuste og komplette data (dyreforsøgsfase og validering af analysemetode) i overensstemmelse med gældende retningslinjer.
The withdrawal period should be based on robust and complete data (animal phase and validation of the analytical method) in accordance with the guidelines in force.
I fravær af tilstrækkelige data til at understøtte indikationerne og doseringen er der en risiko for, at administration af produktet i den aktuelt anbefalede dosis og behandlingsvarighed vil føre til ineffektiv behandling og mulig unødig lidelse hos de behandlede dyr.
In the absence of adequate data to support indications and posology, there is a risk that product administration at the currently recommended dose and duration of treatment will lead to ineffective treatment and a potential unnecessary suffering in the treated animals.
Der blev gennemført et farmakokinetisk studie hos måldyrearter under anvendelse af den anbefalede dosis (14 mg paromomycin/kg kropsvægt).
A pharmacokinetic study was carried out in target animals at the recommended dose (14 mg/kg bodyweight of paromomycin).
I fravær af relevante data til at understøtte indikationerne og doseringen er der en risiko for, at administration af produktet i den aktuelt anbefalede dosis vil føre til ineffektiv behandling og mulig unødig lidelse hos de behandlede dyr.
In the absence of adequate data to support indications and posology, there is a risk that product administration at the currently recommended dose will lead to ineffective treatment and a potential unnecessary suffering in the treated animals.
De aktuelt godkendte indikationer er uspecifikke, idet der ikke nævnes nogen specifikke patogener, f.eks. hvad angår behandling af bakterieinfektioner forårsaget af patogener, der er følsomme over for paromomycin, eller bakterieinfektioner i luftveje, det urogenitale system, mastitis, enteritis, abscesser, sår, hunde-leishmaniasis og kirurgi.
The currently authorised indications are unspecific and no specific pathogens are mentioned, i.e. for the treatment of bacterial infections caused by pathogens which are susceptible to paromomycin or for bacterial infections of the respiratory tract, uro-genital tract, mastitis, enteritis, abscess, wounds, canine leishmaniosis and surgery.
o Vurdering af indvirkningen på miljøet o Potentiel indvirkning på brugersikkerheden o Potentiel indvirkning på tolerabiliteten hos måldyrearten.
o Potential effect(s) on the user safety;
• Behandling af E. coli ved svine-colibacillose (neonatal diarré, diarré efter fravænning,
• Treatment of E. coli involved in swine colibacillosis (neonatal diarrhoea, post-weaning diarrhoea, oedema disease) and against Actinobacillus pleuropneumoniae strains with a
Nederlandene Huvepharma NV Uitbreidingstraat 80
The Netherlands Huvepharma NV Uitbreidingstraat 80
Risikostyring og risikominimerende foranstaltninger Da der ikke foreligger tilstrækkelige data til understøttelse af indikationer, doseringer og tilbageholdelsestider, kan CVMP ikke anbefale nogen relevante indikationer, doseringer eller tilbageholdelsestider for de pågældende veterinærlægemidler.
As no adequate data are available to support indications, posology and withdrawal periods, the CVMP is not able to recommend any appropriate indications, dosage and withdrawal periods for the concerned veterinary medicinal products.
En af indehaverne af markedsføringstilladelse foreslog en tilbageholdelsestid på 16 dage ud fra en lineær regressionsmodel med nyrerne som begrænsende væv, og 16 dage for muskelvæv ved injektionsstedet under anvendelse af den "alternative" metode i overensstemmelse med CVMP's vejledning i metoder til harmonisering af tilbageholdelsestider (EMEA/CVMP/036/95).
One of the marketing authorisation holders proposed a withdrawal time of 16 days based on a linear regression with kidney as limiting tissue, and 16 days with muscle of injection site by using the ‘alternative' method, in line with CVMP note for guidance on the approach towards harmonisation of withdrawal periods (EMEA/CVMP/036/95).
Begrundelser for suspendering af markedsføringstilladelserne
Grounds for suspension of the marketing authorisations
Grækenland Huvepharma NV Uitbreidingstraat 80
Belgium Huvepharma NV Uitbreidingstraat 80
Den statistiske evaluering til fastsættelse af tilbageholdelsestiden blev gennemført i henhold til CVMP's vejledning i metoder til harmonisering af tilbageholdelsestider (EMEA/CVMP/036/95)1.
The statistical evaluation to establish withdrawal period was carried out following the CVMP note for guidance on the approach towards harmonisation of withdrawal periods (EMEA/CVMP/036/95)1.
Parofor 175 mg/ml Paromomycin 175 mg/ml
Parofor 175 mg/ml
• CVMP er af den opfattelse, at benefit/risk-forholdet for paromomycin-holdige veterinærlægemidler, der administreres parenteralt til svin, er negativt, fordi der ikke foreligger relevante data til understøttelse af disse veterinærlægemidlers effekt i de foreslåede indikationer i den anbefalede behandlingsdosis, og at denne mangel udgør en risiko for ineffektiv behandling og udvikling af antimikrobiel resistens.
• the CVMP concluded that the benefit-risk assessment for veterinary medicinal products containing paromomycin to be administered parenterally to pigs is negative because there were inadequate data to support efficacy of these veterinary medicinal products for the proposed indications at the recommended treatment dose and that this deficiency poses a risk of ineffective treatment and antimicrobial resistance development; the CVMP has recommended the suspension of the marketing authorisations for veterinary medicinal products containing paromomycin to be administered parenterally to pigs as referred in Annex I. The conditions to lift the suspension of the marketing authorisations are set out in Annex III.