natgillin/translations-raw huggingface dataset:
Drøftelse af specifikke spørgsmål i meddelelsen om indbringelsen af sagen
Discussion of specific issues raised in the referral notification
Baseret på de 11 indgivne restkoncentrationsundersøgelser af ivermectin af tilstrækkelig kvalitet beregnede CVMP tilbageholdelsestiderne for 12 produkter.
Based on the 11 ivermectin residue depletion studies of adequate quality provided, the CVMP calculated the withdrawal periods for 12 products.
Disse undersøgelser understøtter det synspunkt, at der i de undersøgelser, som var indgivet til CVMP, forekom kilder til variation, som var vigtigere end virkningerne af formuleringen.
These observations support the view that in the studies provided to the CVMP, sources of variation were present that were more important than formulation effects.
Italien Fatro Via Emilia, 285
Via Emilia, 285
Da MRL-muskelværdier for ivermectin ikke forefindes, blev den ADI-baserede metode anvendt til evaluering af den samlede daglige indtagelse af restkoncentrationer som følge af indtagelse af væv fra hvert dyr (EMEA/CVMP/542/03-Final)2.
Since there is no muscle MRL for ivermectin, the ADI-based approach was used for evaluating the total daily intake of residues that may arise from the consumption of tissues of each animal (EMEA/CVMP/542/03-Final)2.
Af de samlede data, som var indsendt af indehaverne af markedsføringstilladelserne og de nationale kompetente myndigheder i medlemsstaterne, blev kun 11 restkoncentrationsundersøgelser af ivermectin anset for at være af tilstrækkelig kvalitet til at understøtte en beregning af tilbageholdelsestider, da der kun i disse undersøgelser var blevet indsamlet og analyseret relevant væv, inklusive injektionssteder.
From the overall data submitted by the MAHs and the National Competent Authorities of the Member States only 11 ivermectin residue depletion studies were considered of adequate quality for the purpose of calculating withdrawal periods, as only in these studies the relevant tissues including the injection sites were sampled and analysed.
Slovenien VETERINA Plus d.o.o.,Dunajska 1000 Ljubljana
VETERINA Plus d.o.o.,Dunajska 1000 Ljubljana,
I disse undersøgelser udviste forskellige formuleringer forskellige absorptionsmønstre for avermectiner (herunder ivermectin), mens andre parametre var de samme (f.eks. art, race, vægt og injektionssted).
In these studies, different formulations showed different absorption patterns of avermectins (including ivermectin), while all other parameters were the same (such as species, breed, weight, and place of injection).
Der blev anvendt en sikkerhedsmargen på 30 % på baggrund af den store variation i indtagelsestallene, som primært skyldes variationen i restkoncentrationer på injektionsstederne.
A safety span of 30% was used in view of the large variation in the intake figures, which was primarily caused by the variation of residues found in injection sites.
SAMLET RESUMÉ AF DEN FAGLIGE VURDERING AF INJICERBARE VETERINÆRLÆGEMIDLER INDEHOLDENDE IVERMECTIN
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF INJECTABLE VETERINARY MEDICINAL PRODUCTS CONTAINING IVERMECTIN
Blandt de formuleringsgrupper, som produkterne blev inddelt i under denne procedure, indeholdt to kombinationsprodukter; en med produkter indeholdende de aktive stoffer ivermectin og clorsulon og en anden med produkter indeholdende de aktive stoffer ivermectin og closantel.
Of the formulation groups to which products were allocated in this procedure, two contained combination products; one with products containing the active substances ivermectin and clorsulon, and the second with products containing the active substances ivermectin and closantel.
Det blev forsøgt at finde en sammenhæng mellem koncentrationskurvernes hældninger eller skæringspunkter og hver af følgende parametre: formuleringsgruppe, kropsvægt, race, køn, alder og injektionsvolumen ved hjælp af ANOVA- eller Pearson-metoden.
An attempt was made to find a correlation between the slopes or intercepts of the depletion curves and any of the following parameters: formulation group, bodyweight, breed, sex, age, and injection volume, using ANOVA or Pearson's methodology.
Hvad angår produkter, som har vist sig at være bioækvivalente, skal det principielt bemærkes, at definitionen af bioækvivalens ikke garanterer ens niveauer af restkoncentrationer på injektionsstedet længe efter de tidspunkter, hvor plasmaprøverne blev taget.
As a matter of principle with regards to products that have been shown to be bioequivalent, it should be noted that the definition of bioequivalence does not guarantee equal levels of residues at the injection site far beyond the time points where plasma samples were taken.
Ud fra de tilgængelige data blev der ikke fundet nogen sammenhænge, der kunne forklare forskellen i koncentrationsprofiler eller beregnede tilbageholdelsestider, og ingen af de registrerede parametre kunne identificeres som en stor enkelt kilde til variation.
From the data available no correlations were found that could explain the difference in depletion profiles or estimated withdrawal periods, and none of the parameters recorded could be identified as a large single source of variation.
Af tabel 1 ovenfor fremgår det, at intervallet for beregnede tilbageholdelsestider for gruppe 1, hvor et antal undersøgelser var tilgængelige, varierede betydeligt (fra 21 til >49 dage).
From table 1 above, it is clear that for group 1, for which a number of studies was available, the range of calculated withdrawal periods varied considerably (from 21 to >49 days).
Ingen egnede data Ingen egnede data Ingen egnede data
No suitable data No suitable data No suitable data
01-048 Warsawa Poland
01-048 Warsaw Poland
Ser man på de samlede restkoncentrationsdata for clorsulon, kunne den statistiske metode ikke anvendes til beregning af tilbageholdelsestiden, da de relevante statistiske antagelser ikke var opfyldt.
Considering the totality of the data on clorsulon residue depletion, the statistical method could not be used for calculating the withdrawal periods as the relevant statistical assumptions were not met.
Derfor gælder der i alle tilfælde en tilbageholdelsestid på mindst 49 dage for kombinationsprodukter.
Therefore, a withdrawal period of at least 49 days will apply for the combination products in all cases.
Det højeste variationsniveau i restkoncentrationer og koncentrationsprofiler konstateret inden for og på tværs af formuleringsgrupperne, kan nemt have maskeret en virkning af formuleringen.
The high level of variation in residue concentrations and depletion profiles seen both within and between formulation groups could easily have masked a formulation effect.
Slovakiet CEVA Animal Health Slovakia, spol.
Slovak Republic CEVA Animal Health Slovakia, spol.
Finland Scanvet Eläinlääkkeet Oy PL 27
Scanvet Eläinlääkkeet Oy PL 27
De data, der blev undersøgt af CVMP, resulterede i beregning af forskellige tilbageholdelsestider for produkter, der er ens i det væsentlige, men denne variabilitet vurderes ikke at afspejle de produktspecifikke virkninger, men vurderes i stedet at være et resultat af den måde, hvorpå produkterne anvendes (dvs. at variationen opstår som følge af forskelle, som f.eks. dyrets kropsvægt, race, køn, injektionsvolumen og prøvetagningsprocedure).
While the data examined by the CVMP did lead to the calculation of different withdrawal periods for products that are essentially the same, this variability is not considered to reflect product specific effects but is rather a feature of the way the products were used (i.e. the variation results from differences such as animal bodyweight, breed, sex, age, injection volume and sampling procedure).
a Socio Unico Via Vittor Pisani, 16
Merial Italia S.p.A. a Socio Unico, Via Vittor Pisani, 16
Dzierzoniwska street 21
z.o.o., Dzierzoniwska street 21
Da ækvivalensen af lokale restkoncentrationer på injektionsstedet ikke kan forudsiges ud fra bioækvivalensen af plasma, og fordi offentliggjorte data viser, at formuleringen kan have en indvirkning på restkoncentrationsprofilerne for ivermectin, vurderede CVMP, at der generelt ikke er grundlag for automatisk at ekstrapolere en tilbageholdelsestid, som er fastlagt for én formulering, til en anden formulering, selv om bioækvivalens af plasma er blevet påvist.
Because the equivalence of local residue levels at the injection site cannot be predicted based on plasma bioequivalence, and because published data indicate that formulation can have an impact on residue depletion profiles for ivermectin, the CVMP considered that, in general, there is no basis for automatically extrapolating a withdrawal period established for one formulation to a second formulation, even if plasma bioequivalence has been shown.
Kosynierów Gdyńskich 13-14 66-400 Gorzów Wlkp.
Kosynierów Gdyńskich 13-14, 66-400 Gorzów Wlkp., Poland
Ungarn Veterina Polska Sp. Zo.o.
Veterina Polska Sp. Zo.o.
Ungarn Bayer Hungária Ltd. H-1123 Budapest Alkotás u. 50.
Bayer Hungária Ltd. H-1123 Budapest Alkotás u. 50.
Ved anvendelsen af den alternative metode i forbindelse med data fra de individuelle restkoncentrationsundersøgelser blev tilbageholdelsestiden beregnet fra det første tidspunkt, hvor alle beregnede indtagelser var under ADI-værdien, med tilføjelse af en sikkerhedsmargen.
When the alternative approach was used for individual residue study data the withdrawal period was derived from the first time point at which all calculated intakes were below the ADI, with the addition of a safety span.
På baggrund af de samlede data og på baggrund af den kendsgerning, at den beregnede indtagelse på og efter dag 49 kun ligger over ADI-værdien for to dyr, vurderede udvalget, at en tilbageholdelsestid på 49 dage ville sikre en sikkerhedsgrad svarende til den, der blev beregnet ved hjælp af den statistiske metode (og en tilbageholdelsestid baseret på tolerancetærsklen på 95 %).
The Committee considered that based on the totality of the data, and based on the fact that at and beyond day 49 the intake calculation remains above the ADI for only two animals, a withdrawal period of 49 days would provide a degree of safety comparable to that provided using the statistical approach (and a withdrawal period based on the 95% tolerance limit).
Variabiliteten i beregnede tilbageholdelsestider afspejler variabiliteten i koncentrationsprofilerne og navnlig variabiliteten i restkoncentrationerne fra injektionsstedet.
The variability in calculated withdrawal periods reflects the variability in the depletion profiles and particularly the variability in depletion of residues from the injection site.
Et centralt spørgsmål i denne procedure er, om der forekommer en virkning af formuleringen i restkoncentrationer fra væv og navnlig fra injektionsstedet.
A key question raised by this referral asks whether there is a formulation effect on residue depletion from tissues and particularly from the injection site.
I figuren nedenfor afbildes alle tilgængelige data vedrørende den samlede indtagelse af ivermectinreststoffer sammenlignet med ADI-værdien.
In the figure below, all available data for the total intake of ivermectin residues is plotted and compared to the ADI.
Det skal bemærkes, at spredningen af data for mange af undersøgelserne bevirkede, at den harmoniserede statistiske metode til beregning af tilbageholdelsestider ikke kunne anvendes, og den tilbageholdelsestid, der fås ved brug af den alternative metode, er stærkt afhængig af valget af tidspunkter.
It should be noted that for many of the studies the scatter of the data was such that the harmonised statistical method for the establishment of withdrawal periods could not be used, and the withdrawal period that results from use of the alternative method is always highly dependent on the choice of time points.
Andre kilder til variation i forbindelse med subkutan injektion af ivermectin blev derfor vurderet at være af større betydning end formuleringen, hvad angår restkoncentrationer og tilbageholdelsestider.
Other sources of variation connected to the subcutaneous use of ivermectin were therefore considered to be of more importance than formulation with regard to residue depletion and withdrawal periods.
• Udvalget vurderede de oprindelige data, der er indgivet i forbindelse med denne procedure, og konkluderede, at en virkning af formuleringen på restkoncentrationen på baggrund af disse data ikke kunne påvises, og at variabiliteten i dataene bevirkede, at en virkning af formuleringen på restkoncentrationen kunne have været maskeret.
• the CVMP assessed the original data provided during this referral and concluded that, based on these data, an impact of formulation on residue depletion could not be demonstrated and that the variability in the data was such that an effect of formulation on residue depletion could have been masked;
BILAG II FAGLIGE KONKLUSIONER OG BEGRUNDELSER FOR ÆNDRING AF PRODUKTRESUMÉET, ETIKETTERINGEN OG INDLÆGSSEDLEN
ANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
Belgien MERIAL Belgium S.A. Bld Sylvain Dupuis 243
Belgium MERIAL Belgium S.A. Bld Sylvain Dupuis 243
08028 Barcelona Spain
08028 Barcelona,
Ungarn Divasa Farmavic Hungaria Ltd. H-6070 Izsák, Kossuth L. u. 60.
Divasa Farmavic Hungaria Ltd. H-6070 Izsák, Kossuth L. u. 60.
Hos kvæg bruges injicerbare veterinærlægemidler indeholdende ivermectin enten som et enkelt aktivt stof eller i kombination med et andet aktivt stof mod angreb af endoparasitter og ectoparasitter ved subkutan indgivelse af 200 μg ivermectin/kg kropsvægt.
In cattle injectable veterinary medicinal products containing ivermectin, either as a single active ingredient or in combination with a second active substance, are used against infestations with endoparasites and ectoparasites by administering 200 μg ivermectin/kg bw subcutaneously.
Ungarn Bremer Pharma GmbH.
Bremer Pharma GmbH.
Bulgarien Bulgarien Wim de Korvrstraat 35 5831 AA, Boxmeer The Netherlands
Intervet International B.V. Wim de Korvrstraat 35, 5831 AA, Boxmeer, The Netherlands
Da tilbageholdelsestiden bestemt på grundlag af clorsulonkomponenten for disse produkter overstiger de 49 dage udledt for ivermectinkomponenten, anbefales 66 dage som tilbageholdelsestid for kombinationsprodukter indeholdende ivermectin og clorsulon.
Since the withdrawal period calculated based on the clorsulon component for these product exceeds the 49 days derived for the ivermectin component, 66 days is recommended as the withdrawal period for the combination products containing ivermectin and clorsulon.
Via Nettunense km 20, 300 04011 Aprilia
INTERVET PRODUCTIONS SRL Via Nettunense km 20, 300 04011 Aprilia
Slovakiet Pharmagal spol.s.r.o.
Slovak Republic Pharmagal spol.s.r.o.
Den samlede indtagelse af ivermectinreststoffer (µg) for en forbruger beregnet ud fra data for hvert dyr (datapunkter) sammenlignet med ADI-værdien (µg/person, vandret linje) på en logaritmisk skala.
On a log-scale, the total ivermectin residue intake (µg) for a consumer, calculated from data of each animal (data points), compared with the ADI (µg/person, horizontal line).
Hvis tilbageholdelsestiden bestemt på grundlag af restkoncentrationsdata for det andet aktive stof er mindre end 49 dage, anbefales tilbageholdelsestiden på 49 dage for produktet.
If the withdrawal period determined on the basis of residue depletion data for the second active substance is less than 49 days, then a withdrawal period of 49 days is recommended for the product.
En effekt af formuleringen kan samlet set hverken bekræftes eller afvises på baggrund af de undersøgte data.
Overall, from the data examined, the presence of a formulation effect can neither be confirmed nor refuted.
Den harmoniserede tilbageholdelsestid på 49 dage er kun relevant for ivermectinkomponenten af injicerbare produkter indeholdende ivermectin.
The harmonised withdrawal period of 49 days is relevant only to the ivermectin component of injectable products containing ivermectin.
Da variationen i restkoncentrationsprofiler som følge af kilder til variation i den subkutane injektion af ivermectin er meget større end virkningen af formuleringen, vurderede udvalget endvidere, at de samlede restkoncentrationsdata for ivermectin fra alle formuleringsgrupper skulle anvendes til at beregne én harmoniseret tilbageholdelsestid.
Moreover, because of the fact that the variation in the residue profile due to sources of variation connected to the subcutaneous use of ivermectin is much greater than the formulation effect, the Committee concluded that it would be appropriate to consider the totality of ivermectin residue data from all formulation groups to derive a single harmonised withdrawal period.
2.1 Beregning af harmoniseret tilbageholdelsestid for injicerbare produkter indeholdende ivermectin til kvæg
2.1 Calculation of a harmonised withdrawal period for ivermectin containing injectable products for use in cattle
Da dette er lavere end grænsen på 49 dage, der gælder for ivermectinkomponenten, anbefales en tilbageholdelsestid på 49 dage for kombinationsprodukter indeholdende ivermectin og closantel.
Since this is below the 49 days limit applied for the ivermectin component, a withdrawal period of 49 days is recommended for the combination products containing ivermectin and closantel.
Udvalget konkluderede derfor, at en harmoniseret tilbageholdelsestid på 49 dage kunne fastlægges for ivermectinkomponenten af alle injicerbare produkter indeholdende ivermectin til kvæg.
Therefore, the Committee concluded that a harmonised withdrawal period of 49 days could be established for the ivermectin component of all injectable products containing ivermectin, for use in cattle.
Hvis tilbageholdelsestiden bestemt på grundlag af restkoncentrationsdata for det andet aktive stof derimod er længere end 49 dage, bør den anbefalede tilbageholdelsestid for produktet baseres på restkoncentrationen af det andet aktive stof.
If, on the other hand, the withdrawal period determined on the basis of residue depletion data for the second active substance is greater than 49 days, then the recommended withdrawal period for the product should be based on depletion of residues of the second active substance.
Spanien DIVASA FARMAVIC, S.A. Ctra.
DIVASA FARMAVIC, S.A. Ctra.
Cypern Vetagrica Ltd 3 Othellou Street 2540 Dhali Industrial Estate Nicosia
3 Othellou Street, 2540 Dhali Industrial Estate Nicosia
2.2 Udledning af tilbageholdelsestiden for injicerbare veterinærlægemidler indeholdende ivermectin i kombination med et andet aktivt stof (kombinationsprodukter)
2.2 Derivation of the withdrawal period for injectable veterinary medicinal products contains ivermectin as well as a second active substance (combination products)
1000 Ljubljana Slovenia
Gerbičeva 50, 1000 Ljubljana Slovenia
Slovenien VET4VET d.o.o.
VET4VET d.o.o.
For injicerbare veterinærlægemidler indeholdende ivermectin i kombination med et andet aktivt stof skal restkoncentrationen af det andet aktive stof også tages i betragtning, ligesom der skal udledes en tilbageholdelsestid for det andet aktive stof.
For injectable veterinary medicinal products containing ivermectin in combination with another active substance residue depletion of the second active substance must also be considered, and a withdrawal period for the second active substance derived.
ÆNDRINGER I DE RELEVANTE DELE AF ETIKETTERINGEN
AMENDMENTS TO BE INCLUDED IN THE RELEVANT SECTIONS OF THE LABELLING
ROMVAC COMPANY S.A.
S.C. ROMVAC COMPANY S.A. Şos.
BILAG III ÆNDRING I PRODUKTRESUMÉ, ETIKETTERING OG INDLÆGSSEDDEL
ANNEX III AMENDMENT TO THE SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
B. For produkter anført i bilag I indeholdende ivermectin som det eneste aktive stof eller i kombination med closantel:
B. For products listed in Annex I containing ivermectin as sole active ingredient or in combination with closantel:
• Udvalget fandt, at der forekommer kilder til variation i forbindelse med subkutan injektion af ivermectin i som medfører forskellige koncentrationsprofiler i restkoncentrationsundersøgelser, og at denne er af meget større betydning end en variation, der kan være forårsaget af forskelle i formuleringerne.
• the CVMP considered that sources of variation linked to the subcutaneous use of ivermectin in cattle are present that lead to different depletion profiles in residue studies, and this variation is of much more importance than any variation that may be caused by formulation differences.
Så vidt muligt anvendte CVMP den statistiske metode til beregning af de individuelle tilbageholdelsestider baseret på enkelte undersøgelser, men i overensstemmelse med CVMP's "Note for Guidance: Approach towards harmonisation of withdrawal periods" (EMEA/CVMP/036/95)1.
Wherever possible the CVMP used the statistical method for calculating the individual withdrawal periods based on single studies, but in line with the CVMP Note for Guidance: approach towards harmonisation of withdrawal periods (EMEA/CVMP/036/95)1, where the necessary parameters were not shown to be valid for the statistical analysis, the alternative approach was used for calculating withdrawal periods.
Bulgarien Alfasan International B.V.
Alfasan International B.V., P.O.
Alstoe Ltd
Vetagrica Ltd
Litauen Invesa International S.A. Esmeralda 19
Invesa International S.A. Esmeralda 19
288 02 Nymburk Czech Republic
288 02 Nymburk,
AV Maria Lamas, Lote 19 - BLA Piso 2 Parque Industrial Comercial Serra das Minas 2635-432 Rio de Mouro Portugal
AV Maria Lamas, Lote 19 - BL - A Piso 2 Parque Industrial Comercial Serra das Minas
Alle pattedyrarter bestemt til levnedsmiddelproduktion
All mammalian food producing species
Cypern Panchris Feeds Ltd. P.O.Box 40261
Panchris Feeds Ltd. P.O.Box 40261, 6302 Larnaca Cyprus
Spanien Chemo Iberica Gran Vía Carlos III, 98 - 7ºth floor
Gran Vía Carlos III, 98 - 7ºth floor.
Estland Bremer Pharma GmbH Cherbourger Str. 25
Czech Republic Bremer Pharma GmbH Cherbourger Str. 25
3440 AB Woerden
3440 AB Woerden, The Netherlands
VIRBAC DE PORTUGAL Laboratorios LdaRua Dionísio Saraiva, Lote 1
United Kingdom VIRBAC DE PORTUGAL Laboratorios LdaRua Dionísio Saraiva, Lote 1,
Cypern Spyros Stavrinides Chemicals Ltd 28 Stasinou Avenue
Spyros Stavrinides Chemicals Ltd 28 Stasinou Avenue, 1060 Nicosia,
A. For produkter anført i bilag I indeholdende ivermectin og clorsulon som aktive stoffer: 4.11 Tilbageholdelsestid
A. For products listed in Annex I containing ivermectin and clorsulon as active ingredients: 4.11 Withdrawal period(s)
Bulgarien Centrovet Ltd. Av.Los Cerrilos 602 Santiago
Av.Los Cerrilos 602 Santiago,
• Udvalget fandt, at der bør fastlægges en fælles harmoniseret tilbageholdelsestid for alle de berørte produkter, der indeholder ivermectin som det eneste aktive stof, baseret på alle tilgængelige data for indtagelse af restkoncentrationer under hensyntagen til den observerede høje variation.
• the CVMP considered that, taking into account the high variation observed, a single harmonised withdrawal period based on all available residue intake data should be established for all products concerned that contain ivermectin as the only active substance;
P.O. Box 78
Box 78,
Mens de præcise kilder til variation er uidentificerede, er det ret sandsynligt, at prøvetagningsproceduren er en vigtig faktor.
While the precise sources of variation remain unidentified, it is quite likely that the sampling procedure is one important factor; it is difficult to be sure that the area with the highest residue concentration is accurately sampled, in particular for subcutaneous injections.
Letland Bimeda Chemical Export Ltd. (a division of Cross Vetpharm Group Limited)
Bimeda Chemical Export Ltd. (a division of Cross Vetpharm Group Limited),
A. For produkter anført i bilag I indeholdende ivermectin og clorsulon som aktive stoffer:
A. For products listed in Annex I containing ivermectin and clorsulon as active ingredients:
Rua Dionísio Saraiva, Lote 1
Rua Dionísio Saraiva, Lote 1, 1° Andar, Sala 2,
Closamectin Injection Ivermectin 5 mg/ml Closantel 125 mg/ml
Closiver Injection Ivermectin 5 mg/ml, Closantel 125 mg/ml
Vetoquinol Biowet Sp. z o.o.
Vetoquinol Biowet Sp. z o.o., ul.
1 CVMP Note for guidance: Approach towards harmonisation of withdrawal periods.
1 CVMP Note for guidance:
Kvæg: Kød og indvolde - 66 dage
Cattle: Meat and offal - 66 days.
Kvæg, får, geder, svin
Cattle, Sheep, Goats, Pigs