natgillin/translations-raw huggingface dataset:
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.
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.
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.
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.
However, in view of the deficiencies in these data (see below) a justification for inclusion of PMA in the product could not be accepted.
Vendar z vidika pomanjkljivosti teh podatkov (glejte nadaljevanje) utemeljitve za vključitev PMA v cepivo ni bilo mogoče sprejeti.
In addition, it is considered that on animal welfare grounds, additional challenge studies with APP Serotype 11 are unnecessary and should not be requested.
Poleg tega se šteje, da so z vidika dobrobiti živali dodatne študije z APP serotipa 11 nepotrebne in naj se ne zahtevajo.
Therefore, in view of the fact that APPM Respipharm has met the efficacy requirements of the Ph.Eur.
Zato se z vidika dejstva, da je zdravilo APPM Respipharm izpolnilo zahteve glede učinkovitosti iz Ph.
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.
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.
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
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
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.
Poleg tega je predstavil argumente, ki podpirajo pomen toksinov Apx kot pomembnih antigenov pri posredovanju zaščite, kar podpirajo zahteve specifične monografije Ph. Eur.
or P.multocida.
ali P. multocida.
Furthermore, there was a need to clarify the relevance of the APPM Respipharm vaccine batch(es) used in the field studies.
Poleg tega je obstajala potreba po pojasnitvi pomena serije (serij) cepiva APPM Respipharm, uporabljenih v terenskih študijah.
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.
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.
However, in these particular studies a serological response was induced but a correlation between efficacy (clinical signs) and potency could not be shown.
V omenjenih študijah so spodbudili seroloških odziv, vendar korelacije med učinkovitostjo (kliničnimi znaki) in jakostjo ni bilo možno dokazati.
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.
Specifične izzivne študije z APP serotipa 11niso bile opravljene, zato je Španija zahtevala potrditev učinkovitosti komponente APP 11.
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.
Dokazano je bilo, da vsa primerjalna cepiva vsebujejo enak razpon antigenov Apx kot zadevno cepivo, zato je na podlagi tega mogoča utemeljitev primerjave.
Marketing Authorisation granted
Dovoljenje za promet z zdravilom odobreno
In particular the Applicant/MAH should clarify to what extent they could be considered to meet the criteria of minimum potency for P.multocida.
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.
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.
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.
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.
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.
According to the provided data only batches clearly above the minimum potency were used.
Predloženi podatki kažejo, da so bile uporabljene le serije nad najmanjšo jakostjo.
The applicant has provided data which confirm that the APP serotypes contained within the product are present in the Member States involved.
Predlagatelj je predložil podatke, ki potrjujejo, da so serotipi APP, ki jih vsebuje zdravilo, prisotni v vpletenih državah članicah.
In principle the Applicant/MAH's justification for the absence of specific challenge studies was accepted.
Načeloma je bila utemeljitev predlagatelja/imetnika dovoljenja za promet z zdravilom glede odsotnosti specifičnih izzivnih študij sprejeta.
In addition, published literature was presented to support the view that P.multocida is involved in worsening of disease caused by APP.
Poleg tega je bila predložena objavljena literatura v podporo mnenju, da je bakterija P. multocida vpletena v poslabšanje bolezni, ki jo povzroča APP.
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.
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.
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.
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.
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.
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.
Efficacy issues:
Vprašanja glede učinkovitosti:
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.
Čeprav te lezije niso specifične za zadevne patogene, predstavljajo podlago za razlikovanje v smislu specifičnosti lezij v dihalih, ki imajo različno patologijo.
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.
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.
the CVMP has recommended the refusal of granting the Marketing Authorisations and the suspension of the existing Marketing Authorisation.
CVMP je priporočil zavrnitev odobritve dovoljenj za promet z zdravilom ter zadržanje obstoječega dovoljenja za promet z zdravilom.
Consequently it was agreed that the level of formaldehyde included in the product was acceptable.
Zaradi tega je bilo doseženo soglasje, da je raven formaldehida v zdravilu sprejemljiva.
requirement was considered met by challenge studies with serotype 2 and 9.
šteje za izpolnjeno z izzivnimi študijami s serotipoma 2 in 9.
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.
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.
- 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.
- 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.
Additional information supporting the close antigenic relationship between APP Serotype 9 and 11 have also been presented.
Predloženi so bili tudi dodatni podatki v podporo ozki antigenski sorodnosti med APP serotipa 9 in 11.
Pregnant sows: Vaccine dose: 3 ml
Breje svinje: Odmerek cepiva: 3 ml
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.
Treba je dokazati učinkovitost komponente P. multocida z zagotovitvijo primerno nadzorovanih študij, ki jasno kažejo specifične koristne učinke prisotnosti PMA v cepivu.
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.
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.
The Applicant/Marketing Authorisation Holder (MAH) had developed additional in-process tests to control antigen levels after inactivation.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je razvil dodatne medprocesne preskuse za nadzor ravni antigena po inaktivaciji.
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.
Vendar je imel Odbor pomembne zadržke glede kakovosti in veljavnosti terenskih študij, ki so bile predložene v podporo učinkovitosti komponente P. multocida.
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.
Del predlagateljevega stališča v zvezi z odsotnostjo izzivnega preskusa z APP serotipa 11 je, da so v cepivu zastopane vse tri skupine Apx.
This opinion was supported by opinions gathered by the Applicant/MAH from EDQM and the Chairman of Group 15V.
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.
The Applicant/MAH provided the requested clarification, which confirmed the statistical analysis that had been applied.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je predložil zahtevana pojasnila, ki so potrdila, da je bila statistična analiza opravljena.
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.
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.
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).
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).
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.
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.
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.
Obstajali so začetni zadržki v zvezi z zagotavljanjem doslednosti izdelave s kontrolnimi parametri, ki so vzpostavljeni pri izdelavi in v končnem zdravilu.
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.
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.
Administration is by two intramuscular injections separated by 2-3 weeks.
Cepivo se daje z dvema intramuskularnima injekcijama, med katerima je presledek 2-3 tednov.
The Applicant/MAH had conducted further analysis and validation in support of the in-process and finished product testing specifications, which could be considered adequate, provided some points of clarification were adequately addressed.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je opravil dodatno analizo in potrditev v podporo specifikacijam medprocesnih preskusov in preskusov končnega zdravila, ki se lahko šteje za zadostno ob upoštevanju, da so bile nekatere točke ustrezno pojasnjene.
ANNEX III CONDITIONS FOR THE LIFTING OF THE MARKETING AUTHORISATION SUSPENSION
DODATEK III POGOJI ZA PREKLIC ZADRŽANJA DOVOLJENJA ZA PROMET Z ZDRAVILOM
However, whilst these provided more detailed information than had been previously available these were not sufficient to confirm the validity of the studies for the purposes of supporting a efficacy claim for P.multocida.
Čeprav so ta dala podrobnejše podatke od tistih, dostopnih pred tem, pa niso bila zadostna za potrditev veljavnosti študij za podporo trditve o učinkovitosti komponente P. multocida.
Concerns over A.pleuropneumoniae efficacy related to a lack of confirmation of Apx toxins in the finished product and absence of specific challenge studies with APP serotype 11.
Zadržki glede učinkovitosti komponente A. pleuropneumoniae so se pojavili, ker ni niti potrditve prisotnosti toksinov Apx v končnem zdravilu niti specifičnih izzivnih študij z APP serotipa 11.
ANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR REFUSAL OF THE GRANTING OF THE MARKETING AUTHORISATIONS AND FOR THE SUSPENSION OF EXISTING MARKETING AUTHORISATION
DODATEK II ZNANSTVENI ZAKLJUČKI IN PODLAGA ZA ZAVRNITEV ODOBRITVE DOVOLJENJA ZA PROMET Z ZDRAVILOM IN ZADRŽANJE OBSTOJEČEGA DOVOLJENJA ZA PROMET Z ZDRAVILOM
In view of the fact that Serotypes 9 and 11 belong to the same toxigenic group (Group 1, producing Apx1 and Apx2) and Serotype 2 belongs to Toxigenic Group 2, producing Apx2 and Apx3, then this Ph. Eur.
Glede na to, da serotipa 9 in 11 spadata v isto toksigensko skupino (skupina 1, ki tvori Apx1 in Apx2), serotip 2 pa v toksigensko skupino 2, ki tvori Apx2 in Apx3, se ta zahteva Ph. Eur.
The major point of refusal related to the lack of evidence to support the efficacy of the P.multocida component.
Poglavitna točka zavrnitve se je nanašala na pomanjkanje dokazov v podporo učinkovitosti komponente P. multocida.
The Applicant considers that the pathological changes seen in the lungs are different due to Actinobacillus pleuropneumoniae compared to Pasteurella multocida.
Predlagatelj meni, da se patološke spremembe zaradi Actinobacillus pleuropneumoniae v pljučih razlikujejo od sprememb zaradi Pasteurella multocida.
In view of the fact that the Applicant/MAH proposed to support the efficacy of the P. multocida component with data from the field the Applicant/MAH was requested to clarify whether animals vaccinated with APPM Respipharm, competitor vaccine and unvaccinated controls had been housed together on each site, which could have allowed a valid comparison of the efficacy of the respective vaccines.
Ker je predlagatelj/imetnik dovoljenja za promet z zdravilom predlagal podporo učinkovitosti komponente P. multocida s terenskimi podatki, je bil naprošen, da pojasni, ali so bile živali, cepljene s cepivom APPM Respipharm, konkurenčnim cepivom, in necepljene živali na vsaki lokaciji nastanjene skupaj, kar bi omogočilo veljavno primerjavo učinkovitosti cepiv.
For immunization of sows the first dose (3ml) should be given 4-5 weeks before the expected farrowing date, with the second injection (3ml) at least 2 weeks before the expected farrowing date.
Za imunizacijo svinj je treba prvi odmerek (3 ml) dati 4-5 tednov pred pričakovano kotitvijo, drugo injekcijo (3 ml) pa najmanj 2 tedna pred pričakovano kotitvijo.
There were concerns as to how the results had been assessed, in particular how mortality and lung confiscations had been definitively assigned to A.pleuropneumoniae.
Izraženi so bili zadržki o vrednotenju rezultatov, zlasti o gotovosti pripisa smrtnosti in pljučnih zapletov bakterijama A. pleuropneumoniae.
The analysis had looked at the frequency of mortality and lung confiscations at slaughter (indicative of the presence of lesions) caused by either APP or P.multocida in pigs vaccinated with APPM Respipharm.
V analizi so pregledali smrtnost in pogostnost zaplemb pljuč pri zakolu (ki so kazale prisotnost lezij) zaradi APP ali P. multocida pri prašičih, cepljenih s cepivom APPM Respipharm.
Consequently, there were concerns that batch to batch consistency could not be ensured.
Posledično so se pojavili zadržki glede zagotovitve doslednosti med serijami.
The Applicant/MAH provided information on the antigen content of the batches of vaccine used in the field studies.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je predložil podatke o vsebnosti antigena v serijah cepiva, uporabljenih v terenskih študijah.
The Applicant/MAH confirmed that the diagnosis was conducted by experienced veterinary practitioners based on previous clinical history and on post mortem findings in cases of mortality.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je potrdil, da so diagnoze postavljali izkušeni veterinarji na podlagi klinične anamneze in ugotovitev obdukcij v primeru smrti živali.
Concerning the link to the efficacy of P.multocida the Applicant/MAH was requested to provide further information on the batches of vaccine used during the field studies and further clarification on the details of the studies sufficient to substantiate a claim for the efficacy of the P.multocida component.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je bil glede povezave z učinkovitostjo komponente P. multocida naprošen, da predloži dodatne podatke o serijah cepiva, ki so bile uporabljene v terenskih študijah, ter dodatno pojasnilo o podrobnostih študije, ki so zadostovale za utemeljitev trditve o učinkovitosti komponente P. multocida.
The applicant provided field data, supplemented with bibliographical data, to indicate that P.multocida causes frequent co-infections with APP in pigs with respiratory disease.
Predlagatelj je predložil terenske podatke, dopolnjene z bibliografskimi podatki, za prikaz, da P. multocida povzroča pogoste okužbe sočasno z APP pri prašičih z boleznimi dihal.
- the CVMP considered that these deficiencies are such that it is considered that no data have been provided in support of the efficacy of the P. multocida serotype A component.
- CVMP šteje, da je posledica teh pomanjkljivosti, da ni predloženih podatkov v podporo učinkovitosti komponente P. multocida serotipa A.
Concerning the surveillance field study the Applicant/MAH gave additional data about the batches used, which were by mistake omitted.
V zvezi s terensko študijo spremljanja organizmov je predlagatelj/imetnik dovoljenja za promet z zdravilom predložil dodatne podatke o uporabljenih serijah, ki so bili pomotoma izpuščeni.
Whereas: - the CVMP considered that there are significant deficiencies in the data provided by the Applicant in support of the efficacy of the Pasteurella multocida serotype A component.
- CVMP je menil, da obstajajo pomembne pomanjkljivosti v podatkih, ki jih je predlagatelj predložil v podporo učinkovitosti komponente Pasteurella multocida serotipa A.
Regarding justification of the P. multocida component in the vaccine the Applicant/MAH has provided field data from a surveillance study, supplemented with bibliographical data, to indicate that P.multocida causes frequent co-infections with APP in pigs with respiratory disease.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je v zvezi z utemeljitvijo komponente P. multocida v cepivu predložil terenske podatke iz študije spremljanja organizma, dopolnjene z bibliografskimi podatki, za prikaz, da P. multocida povzroča pogoste okužbe sočasno z APP pri prašičih z boleznimi dihal.
The Applicant/MAH clarified the composition of the other comparator products and confirmed that they had been administered according to the recommended schedule.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je pojasnil sestavo primerjalnih cepiv ter potrdil, da so bila cepiva uporabljena po priporočenem režimu.