FrancophonIA/ELRC3.0 huggingface dataset:
English: Since formaldehyde is listed in Annex II of the MRL Council Regulation (EEC) No 2377/90 it has been accepted that it is not necessary for the protection of public health to establish a maximum residue limit.
Slovenian: Ker je formaldehid naveden v Dodatku II Uredbe Sveta o MRL (EGS) št. 2377/90, je bilo sprejeto, da za zaščito javnega zdravja ni potrebno določiti največje mejne vrednosti ostankov.
English: OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF APPM RESPIPHARM
Slovenian: SPLOŠNI POVZETEK ZNANSTVENEGA VREDNOTENJA ZDRAVILA APPM RESPIPHARM
English: The National Competent Authority of the Reference Member State, shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holder:
Slovenian: Pristojni nacionalni organ referenčne države članice zagotovi, da imetnik dovoljenja za promet z zdravilom izpolni naslednje pogoje:
English: There were no details of the statistical methods used, nor were there full reports of the field trials.
Slovenian: Predložene niso bile niti podrobnosti o uporabljenih statističnih metodah niti popolna poročila o terenskih preskušanjih.
English: In particular, it was requested to confirm that this vaccine covered the whole range of Apx toxins.
Slovenian: Še posebej je bila zahtevana potrditev, da to cepivo pokriva celoten razpon toksinov Apx.
English: It is considered that the principle requirements for the demonstration of efficacy are laid down by the Ph. Eur.
Slovenian: Šteje se, da so osnovne zahteve za dokaz učinkovitosti določene v Ph. Eur.
English: Quality issues:
Slovenian: Vprašanja glede kakovosti:
English: Slovak Republic1
Slovenian: Slovaška 1
English: This was considered important as pathological changes caused by P.multocida are not specific for infection with this organism.
Slovenian: To se je štelo za pomembno, saj patološke spremembe, ki jih povzroča P. multocida, niso specifične za okužbo s tem organizmom.
English: (*) Mean titre of agglutination antibodies after vaccination in rabbits
Slovenian: (*) Povprečni titer aglutinacijskih protiteles po cepljenju kuncev
English: The onset of immunity is stated as 14 days and the duration of immunity as 6 months.
Slovenian: Navedeno je, da imunost nastopi v 14 dneh in traja 6 mesecev.
English: In addition, it was considered that the field studies were not adequate and lacked direct confirmation of the presence of APP or appropriate monitoring of clinical signs or other efficacy parameters.
Slovenian: Poleg tega je bilo izraženo mnenje, da terenske študije niso bile zadostne in ni bilo neposredne potrditve prisotnosti APP ali ustreznega spremljanja kliničnih znakov ali drugih parametrov učinkovitosti.
English: The significance of toxigenic group is supported by the specific monograph (2008/1360) which states (Section 2.2.2 Immunogenicity) that “The challenge strain for the following test is chosen to ensure challenge with each Ap toxin produced by the serotypes to be stated on the label…”.
Slovenian: Pomen toksigenske skupine podpira specifična monografija (2008/1360), ki določa (razdelek 2.2.2 Imunogenost), da „Stimulacijski sev za v nadaljevanju opisani preskus se izbere tako, da se zagotovi stimulacija z vsemi toksini Ap, ki jih tvorijo serotipi, navedeni na označevanju…“.
English: It was noted by the Committee that the lack of compliance with the GCP requirements weakened the content of the surveillance study essentially.
Slovenian: Odbor je izpostavil, da neskladnost z zahtevami GCP v osnovi zmanjša jakost vsebine študije spremljanja organizmov.
English: Consequently, there do not appear to be additional safety concerns relating to the levels of formaldehyde that may result from administration of product containing formaldehyde at the levels proposed.
Slovenian: Posledično je videti, da ni drugih varnostnih zadržkov glede ravni formaldehida, ki bi lahko nastali pri dajanju zdravila, ki vsebuje formaldehid v predlaganih ravneh.
English: The data have been collected over a number of years (at least 2004-2008) and included a total of 163,061 pigs, of which 93,460 had been vaccinated with APPM Respipharm, 37,541 had been treated with an APP vaccine without P.multocida, and 32,060 pigs had not been vaccinated.
Slovenian: V podatke, zbrane v več letih (vsaj v obdobju 2004-2008), je vključenih skupno 163 061 prašičev, od tega 93 460 cepljenih s cepivom APPM Respipharm, 37 541 cepljenih s cepivom APP brez komponente P. multocida in 32 060 necepljenih prašičev.
English: In addition, Spain considered that an adequate justification had not been provided for including the different serotypes of A.pleuropneumoniae and P. multocida into the same vaccine.
Slovenian: Poleg tega je Španija menila, da ni bila predložena ustrezna utemeljitev vključitve posameznih serotipov A.pleuropneumoniae in P. multocida v isto cepivo.
English: Consequently it was agreed that the APP serotypes in the product are relevant and therefore inclusion of the APP components in the vaccine was adequately justified.
Slovenian: Zaradi tega je bilo sklenjeno, da so serotipi APP v zdravilu pomembni, zato je bila vključitev komponent APP v cepivo ustrezno utemeljena.
English: The applicant has provided supporting opinions from EDQM and the Chairman of Group 15V which supports this interpretation.
Slovenian: Predlagatelj je v podporo predložil mnenji Evropskega direktorata za kakovost zdravil in predsednika skupine 15V, ki podpirata to interpretacijo.
English: The Note for Guidance on field trials with veterinary vaccines3 indicates “The environment in which the two groups of animals are housed shall be as equivalent as possible (i.e. same farm/barn/batch) or at least as similar as possible (e.g. same farm/different barn/same batch).” It was confirmed that according to the study protocol the groups of pigs vaccinated with the different vaccines had been housed at the same farm in different halls (barns) which is acceptable.
Slovenian: Navodila o terenskih preskušanjih s cepivi za uporabo v veterinarski medicini3 določajo: „Okolje, v katerem sta nastanjeni obe skupini živali, mora biti čimbolj enakovredno (tj. ista kmetija/hlev/serija) ali vsaj čimbolj podobno (npr. ista kmetija/drug hlev/ista serija).“ Potrjeno je bilo, da so bile po protokolu študije skupine prašičev, ki so bile cepljene z različnimi cepivi, nastanjene na isti kmetiji v različnih halah (hlevih), kar je sprejemljivo.
English: Requirements for combined veterinary vaccines http://www.emea.europa.eu/pdfs/vet/iwp/005297en.pdf CVMP Note for guidance: Field trials with veterinary vaccines - http://www.emea.europa.eu/pdfs/vet/iwp/085299en.pdf
Slovenian: Navodilo CVMP: Terenska preskušanja s cepivi za uporabo v veterinarski medicinihttp://www.emea.europa.eu/pdfs/vet/iwp/085299en.pdf
English: It was noted that all three Apx toxigenic groups are represented in the vaccine.
Slovenian: Izpostavljeno je bilo, da so v cepivu zastopane vse tri toksigenske skupine Apx.
English: The field data were deficient and it was not clear that the presence of PMA in the vaccine had any specific benefit.
Slovenian: Terenski podatki so bili pomanjkljivi in ni bilo jasno, ali ima prisotnost PMA v cepivu specifičen koristni učinek.
English: This differentiation is based on identification of characteristic lesions by experienced veterinary staff at slaughterhouses.
Slovenian: Ta razlika temelji na identifikaciji značilnih lezij s strani izkušenih veterinarjev v klavnicah.
English: Spain raised objections which have led to the present referral procedure as it was considered that the authorisation of this veterinary medicinal product may present a potential serious risk to human or animal health or to the environment on the grounds of concerns over Quality and Efficacy.
Slovenian: Španija pa je ugovarjala, kar je sprožilo ta napotitveni postopek, saj je menila, da lahko odobritev tega zdravila za uporabo v veterinarski medicini predstavlja možno resno tveganje za javno zdravje ljudi, živali in okolje na osnovi zadržkov glede kakovosti in učinkovitosti.
English: In brief, concerns were raised that the composition of Actinobacillus pleuropneumoniae serotypes in the vaccine (2, 9 and 11) were not based on the epizoological situation in Spain, where the most prevalent serotypes are 2, 4 and 7.
Slovenian: Na kratko: do zadržkov je prišlo, ker sestava serotipov Actinobacillus pleuropneumoniae v cepivu (2, 9 in 11) ne temelji na epizoološki situaciji v Španiji, kjer so najpogostejši serotipi 2, 4 in 7.
English: However, in view of the deficiencies in these data (see below) a justification for inclusion of PMA in the product could not be accepted.
Slovenian: Vendar z vidika pomanjkljivosti teh podatkov (glejte nadaljevanje) utemeljitve za vključitev PMA v cepivo ni bilo mogoče sprejeti.
English: In addition, it is considered that on animal welfare grounds, additional challenge studies with APP Serotype 11 are unnecessary and should not be requested.
Slovenian: Poleg tega se šteje, da so z vidika dobrobiti živali dodatne študije z APP serotipa 11 nepotrebne in naj se ne zahtevajo.
English: Therefore, in view of the fact that APPM Respipharm has met the efficacy requirements of the Ph.Eur.
Slovenian: Zato se z vidika dejstva, da je zdravilo APPM Respipharm izpolnilo zahteve glede učinkovitosti iz Ph.
English: The Apx toxins present in the product (Apx I, Apx II and Apx III) are appropriate to providing protection against the serotypes present in the Member States where the product is intended to be used.
Slovenian: Toksini Apx, ki jih vsebuje zdravilo (Apx I, Apx II in Apx III), so primerni za zagotavljanje zaščite proti serotipom, ki so prisotni v državah članicah, kjer naj bi se zdravilo uporabljalo.
English: NAME, PHARMACEUTICAL FORM, STRENGTH OF THE VETERINARY MEDICINAL PRODUCT, ANIMAL SPECIES, ROUTES OF ADMINISTRATION, WITHDRAWAL PERIOD AND APPLICANT/MARKETING AUTHORISATION HOLDER IN THE MEMBER STATES
Slovenian: SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVILA ZA UPORABO V VETERINARSKI MEDICINI, ŽIVALSKIH VRST, POTI UPORABE ZDRAVILA, KARENC IN PREDLAGATELJEV/IMETNIKOV DOVOLJENJA ZA PROMET Z ZDRAVILOM V DRŽAVAH ČLANICAH
English: In addition, argumentation has been presented which supports the importance of Apx toxins as important antigens in mediating protection, which is also supported by the requirements of the specific Ph. Eur.
Slovenian: Poleg tega je predstavil argumente, ki podpirajo pomen toksinov Apx kot pomembnih antigenov pri posredovanju zaščite, kar podpirajo zahteve specifične monografije Ph. Eur.
English: or P.multocida.
Slovenian: ali P. multocida.
English: Furthermore, there was a need to clarify the relevance of the APPM Respipharm vaccine batch(es) used in the field studies.
Slovenian: Poleg tega je obstajala potreba po pojasnitvi pomena serije (serij) cepiva APPM Respipharm, uporabljenih v terenskih študijah.
English: The applicant has shown that product containing the proposed upper limit of formaldehyde has not given rise to significant adverse reactions during single, repeated and overdose studies or during field use, nor during safety studies in pregnant sows.
Slovenian: Predlagatelj je dokazal, da zdravilo, ki je vsebovalo predlagano zgornjo mejno vrednost formaldehida, ni sprožilo pomembnih neželenih učinkov v študijah enkratnega, ponovljenega in prekomernega odmerjanja, med terensko uporabo ali v študijah varnosti pri brejih svinjah.
English: However, in these particular studies a serological response was induced but a correlation between efficacy (clinical signs) and potency could not be shown.
Slovenian: V omenjenih študijah so spodbudili seroloških odziv, vendar korelacije med učinkovitostjo (kliničnimi znaki) in jakostjo ni bilo možno dokazati.
English: Specific challenge studies had not been conducted using APP serotype 11 as challenge, therefore Spain had requested confirmation of efficacy of the APP 11 component.
Slovenian: Specifične izzivne študije z APP serotipa 11niso bile opravljene, zato je Španija zahtevala potrditev učinkovitosti komponente APP 11.
English: It was shown that all comparator products contain the same range of Apx antigens as the current product, therefore a comparison could be justified on this basis.
Slovenian: Dokazano je bilo, da vsa primerjalna cepiva vsebujejo enak razpon antigenov Apx kot zadevno cepivo, zato je na podlagi tega mogoča utemeljitev primerjave.
English: Marketing Authorisation granted
Slovenian: Dovoljenje za promet z zdravilom odobreno
English: In particular the Applicant/MAH should clarify to what extent they could be considered to meet the criteria of minimum potency for P.multocida.
Slovenian: Predlagatelj/imetnik dovoljenja za promet z zdravilom bi zlasti moral pojasniti, v kakšnem obsegu se lahko šteje, da izpolnjujejo merila najmanjše učinkovitosti proti P. multocida.
English: Based on an interpretation of the specific monograph that is supported by EDQM it was considered that the applicant has met these requirements through the use of the challenge strains used.
Slovenian: Na podlagi interpretacije specifične monografije, ki jo podpira Evropski direktorat za kakovost zdravil, se šteje, da je predlagatelj izpolnil te zahteve z uporabljenimi stimulacijskimi sevi.
English: The data provided was not considered adequate to support a claim for the P.multocida component (discussed below) therefore a link between production parameters and efficacy for PMA could not be accepted.
Slovenian: Predloženi podatki se niso šteli za zadostne za podporo trditve glede komponente P. multocida (razprava v nadaljevanju), zato povezava med parametri izdelave in učinkovitostjo komponente PMA ni bila sprejeta.
English: According to the provided data only batches clearly above the minimum potency were used.
Slovenian: Predloženi podatki kažejo, da so bile uporabljene le serije nad najmanjšo jakostjo.
English: The applicant has provided data which confirm that the APP serotypes contained within the product are present in the Member States involved.
Slovenian: Predlagatelj je predložil podatke, ki potrjujejo, da so serotipi APP, ki jih vsebuje zdravilo, prisotni v vpletenih državah članicah.
English: In principle the Applicant/MAH's justification for the absence of specific challenge studies was accepted.
Slovenian: Načeloma je bila utemeljitev predlagatelja/imetnika dovoljenja za promet z zdravilom glede odsotnosti specifičnih izzivnih študij sprejeta.
English: In addition, published literature was presented to support the view that P.multocida is involved in worsening of disease caused by APP.
Slovenian: Poleg tega je bila predložena objavljena literatura v podporo mnenju, da je bakterija P. multocida vpletena v poslabšanje bolezni, ki jo povzroča APP.
English: These tests (Modified Agglutination Test for APP and optical density at 540nm for PMA) had been validated, however further questions were raised concerning the link between the initial antigen levels before inactivation (CFU/ml for all components), the post inactivation specifications (MAT for APP and OD540nm for PM) and the serological potency assay.
Slovenian: Ti preskusi (modificiran aglutinacijski preskus za APP in optična gostota pri 540 nm za PMA) so bili potrjeni, vendar so bila postavljena dodatna vprašanja o povezavi med začetnimi ravnmi antigena pred inaktivacijo (CFU/ml za vse komponente), specifikacijami po inaktivaciji (modificiran aglutinacijski preskus za APP in optična gostota pri 540 nm za PM) ter serološkim preskusom učinkovitosti.
English: Some of the field data presented by the Applicant/MAH confirmed that the antigen levels were in those studies at or below the antigen levels proposed as the product minima.
Slovenian: Nekateri terenski podatki, ki jih predložil predlagatelj/imetnik dovoljenja za promet z zdravilom, so potrdili, da so ravni antigena v teh študijah na ravneh ali pod ravnmi antigena, predlaganimi v minimalnih zahtevah za zdravilo.
English: Due to concerns related to correlation between serological response against P. multocida and protection, Spain considers that because of a lack of correlation there is also no proven correlation between the batch potency test in rabbits and efficacy in pigs for this antigen.
Slovenian: Glede zadržkov v zvezi s korelacijo med serološkim odzivom proti P. multocida in zaščito Španija meni, da zaradi odsotnosti korelacije ni dokaza za korelacijo med serijskim preskusom učinkovitosti pri kuncih in učinkovitostjo pri prašičih za ta antigen.
English: Efficacy issues:
Slovenian: Vprašanja glede učinkovitosti:
English: Whilst these lesions are not specific for the pathogen in question they provide a basis for differentiation in terms of the specificity of respiratory lesions which have different pathology and are supported in questionable cases by bacterial isolation.
Slovenian: Čeprav te lezije niso specifične za zadevne patogene, predstavljajo podlago za razlikovanje v smislu specifičnosti lezij v dihalih, ki imajo različno patologijo.
English: and considering the additional data in support of a close antigenic relationship between APP Serotypes 9 and 11 it is considered that a request for further challenge studies is not justified.
Slovenian: Eur., in ob upoštevanju dodatnih podatkov v podporo ozki antigenski sorodnosti med APP serotipa 9 in 11 šteje, da zahteva po dodatnih izzivnih študijah ni utemeljena.
English: the CVMP has recommended the refusal of granting the Marketing Authorisations and the suspension of the existing Marketing Authorisation.
Slovenian: CVMP je priporočil zavrnitev odobritve dovoljenj za promet z zdravilom ter zadržanje obstoječega dovoljenja za promet z zdravilom.
English: Consequently it was agreed that the level of formaldehyde included in the product was acceptable.
Slovenian: Zaradi tega je bilo doseženo soglasje, da je raven formaldehida v zdravilu sprejemljiva.
English: requirement was considered met by challenge studies with serotype 2 and 9.
Slovenian: šteje za izpolnjeno z izzivnimi študijami s serotipoma 2 in 9.
English: For immunization of piglets the first dose (2ml) should be given at age 6-8 weeks, followed by a second dose (2ml) 14-21 days later.
Slovenian: Za imunizacijo prašičkov je treba prvi odmerek (2 ml) dati pri starosti 6-8 tednov, ki mu sledi drugi odmerek (2 ml) 14-21 dni pozneje.
English: - consequently, the CVMP considered that in the absence of any demonstrated benefit of this component the risk-benefit analysis for the P. multocida serotype A component must be negative, therefore presenting an unacceptable serious risk to human or animal health or to the environment.
Slovenian: - Posledično CVMP meni, da je zaradi odsotnosti dokazanih koristi analiza tveganja in koristnih učinkov komponente P. multocida serotipa A negativna, ker predstavlja nesprejemljivo resno tveganje za zdravje ljudi in živali ter okolje.
English: Additional information supporting the close antigenic relationship between APP Serotype 9 and 11 have also been presented.
Slovenian: Predloženi so bili tudi dodatni podatki v podporo ozki antigenski sorodnosti med APP serotipa 9 in 11.
English: Pregnant sows: Vaccine dose: 3 ml
Slovenian: Breje svinje: Odmerek cepiva: 3 ml
English: The efficacy of the P.multocida component should be demonstrated through the provision of appropriate controlled studies clearly demonstrating that the presence of PMA in the vaccine has a specific benefit.
Slovenian: Treba je dokazati učinkovitost komponente P. multocida z zagotovitvijo primerno nadzorovanih študij, ki jasno kažejo specifične koristne učinke prisotnosti PMA v cepivu.
English: The product is indicated for use in pigs (sows and weaned piglets) from 6 weeks of age, intended to induce active immunization of sows and piglets against pleuropneumonia caused by Actinobacillus pleuropneumoniae and against secondary infection by Pasteurella multocida.
Slovenian: Zdravilo je indicirano za uporabo pri prašičih (svinjah in odstavljenih prašičkih) od 6. tedna starosti za sprožitev aktivne imunizacije svinj in prašičkov proti plevropnevmoniji, ki jo povzroča Actinobacillus pleuropneumoniae, ter proti sekundarni okužbi s Pasteurella multocida.
English: The Applicant/Marketing Authorisation Holder (MAH) had developed additional in-process tests to control antigen levels after inactivation.
Slovenian: Predlagatelj/imetnik dovoljenja za promet z zdravilom je razvil dodatne medprocesne preskuse za nadzor ravni antigena po inaktivaciji.
English: However, the committee had significant concerns related to the quality and validity of the field studies provided in support of the efficacy of P.multocida.
Slovenian: Vendar je imel Odbor pomembne zadržke glede kakovosti in veljavnosti terenskih študij, ki so bile predložene v podporo učinkovitosti komponente P. multocida.
English: Concerning the absence of challenge with APP serotype 11, part of the applicant's view is that all three Apx groups are represented in the vaccine.
Slovenian: Del predlagateljevega stališča v zvezi z odsotnostjo izzivnega preskusa z APP serotipa 11 je, da so v cepivu zastopane vse tri skupine Apx.
English: This opinion was supported by opinions gathered by the Applicant/MAH from EDQM and the Chairman of Group 15V.
Slovenian: To mnenje podpirata mnenji, ki jih je predlagatelj/imetnik dovoljenja za promet z zdravilom pridobil od Evropskega direktorata za kakovost zdravil in predsednika skupine 15V.
English: The Applicant/MAH provided the requested clarification, which confirmed the statistical analysis that had been applied.
Slovenian: Predlagatelj/imetnik dovoljenja za promet z zdravilom je predložil zahtevana pojasnila, ki so potrdila, da je bila statistična analiza opravljena.
English: Notwithstanding the committees reservations concerning the deficiencies in the studies it was also noted that the Applicant/MAH had not provided data in support of the claimed onset and duration of protection for P. multocida.
Slovenian: Kljub zadržkom Odbora glede pomanjkljivosti študij je bilo izpostavljeno tudi, da predlagatelj/imetnik dovoljenja za promet z zdravilom ni predložil podatkov v podporo zatrjevanega nastopa in trajanja zaščite proti P. multocida.
English: In view of the fact that the Applicant/MAH intended to demonstrate the efficacy of the PMA component by comparison of the efficacy of APPM Respipharm compared to comparator products there was a need to clarify the composition of the other vaccine (containing A. pleuropneumoniae only).
Slovenian: Ob upoštevanju dejstva, da je predlagatelj/imetnik dovoljenja za promet z zdravilom nameraval dokazati učinkovitost komponente PMA s primerjavo učinkovitosti cepiva APPM Respipharm in primerjalnih cepiv, je bilo potrebno pojasnilo sestave drugega cepiva (ki vsebuje le A. pleuropneumoniae).
English: APPM Respipharm is a multi-component formaldehyde inactivated whole-cell bacterial vaccine containing three strains of Actinobacillus pleuropneumoniae (Serotypes 2, 9 and 11) and one strain of Pasteurella multocida (Serotype A), and includes aluminium hydroxide gel as adjuvant.
Slovenian: Zdravilo APPM Respipharm je večkomponentno, s formaldehidom inaktivirano bakterijsko cepivo s celimi celicami, ki vsebuje tri seve Actinobacillus pleuropneumoniae (serotipe 2, 9 in 11) in en sev Pasteurella multocida (serotip A) ter aluminijev hidroksid v gelu kot adjuvans.
English: There had been initial concerns related to whether the control parameters in place during production and on the finished product could ensure consistency of production.
Slovenian: Obstajali so začetni zadržki v zvezi z zagotavljanjem doslednosti izdelave s kontrolnimi parametri, ki so vzpostavljeni pri izdelavi in v končnem zdravilu.
English: The Applicant/MAH had justified the absence of specific challenge studies with P.multocida on the basis that there are recognised difficulties in conducting meaningful challenge studies.
Slovenian: Predlagatelj/imetnik dovoljenja za promet z zdravilom je utemeljil odsotnost specifičnih izzivnih študij s P. multocida, ker obstajajo priznane težave pri izvedbi pomenljivih izzivnih študij.
English: Administration is by two intramuscular injections separated by 2-3 weeks.
Slovenian: Cepivo se daje z dvema intramuskularnima injekcijama, med katerima je presledek 2-3 tednov.