natgillin/translations-raw huggingface dataset:
These include effects on male and female fertility, mating, conception, implantation, ability to maintain pregnancy to term, parturition, lactation, survival, growth and development of the offspring from birth through to weaning, sexual maturity and the subsequent reproductive function of the offspring as adults.
Običajno se na učinkovinah izvede standardni sklop in vitro ter in vivo preskusov genotoksičnosti v skladu z uveljavljenimi smernicami.
At least three dose levels shall be used.
V nekaterih primerih je morda potrebno preskusiti tudi enega ali več metabolitov, ki se pojavljajo v živilih kot ostanki.
The maximum dose should be selected so as to bring harmful effects to light.
Rakotvornost
Study of developmental toxicity
Pri odločitvi o tem, ali so potrebni preskusi rakotvornosti, se upoštevajo rezultati preskusov genotoksičnosti in razmerij med strukturo in dejavnostjo ter ugotovitve sistemskih preskusov toksičnosti, ki so morda relevantni za neoplastične lezije v dolgoročnih študijah.
In the case of pharmacologically active substances or veterinary medicinal products intended for use in food-producing animals, tests on developmental toxicity shall be performed.
Upoštevajo se mehanizmi toksičnosti, ki so specifični za vrsto, ter vse razlike v presnovi poskusne vrste, ciljne živalske vrste in ljudi.
These tests shall be designed to detect any adverse effects on the pregnant female and development of the embryo and foetus consequent to exposure of the female from implantation through gestation to the day before predicted birth.
Kadar so potrebni preskusi rakotvornosti, se na splošno izvedeta dveletna študija na podganah in 18-mesečna študija na miših.
Such adverse effects include enhanced toxicity relative to that observed in non-pregnant females, embryo-foetal death, altered foetal growth, and structural changes to the foetus.
Študije rakotvornosti se lahko z ustrezno znanstveno utemeljitvijo izvedejo na eni vrsti glodavcev, po možnosti na podgani.
A developmental toxicity test in the rat is required.
Izjeme
Depending on the results, a study in a second species may have to be performed, in accordance with established guidance.
Kadar je zdravilo za uporabo v veterinarski medicini namenjeno za lokalno uporabo, se pri ciljni živalski vrsti preuči sistemska absorpcija.
In the case of pharmacologically active substances or veterinary medicinal products not intended for use in food producing animals, a study of developmental toxicity shall be performed in at least one species, which may be the target species, if the product is intended for use in female animals which may be used for breeding.
Če je dokazano, da je sistemska absorpcija zanemarljiva, se lahko izpustijo preskus toksičnosti pri večkratnih odmerkih, preskus toksičnosti za razmnoževanje ter preskus rakotvornosti, razen če:
However, where the use of the veterinary medicinal product would result in significant exposure to users, standard developmental toxicity studies shall be performed.
se pod predvidenimi pogoji predpisane uporabe lahko pričakuje, da žival zdravilo za uporabo v veterinarski medicini zaužije skozi usta, ali
Genotoxicity
se pod predvidenimi pogoji predpisane uporabe lahko pričakuje, da je uporabnik zdravila za uporabo v veterinarski medicini zdravilu izpostavljen po poteh, ki niso kožna pot, ali
Tests for genotoxic potential shall be performed to reveal changes which a substance may cause in the genetic material of cells.
učinkovina ali metabolit lahko vstopi v živilo, pridobljeno iz zdravljene živali.
Any substance intended to be included in a veterinary medicinal product for the first time must be assessed for genotoxic properties.
Druge zahteve
A standard battery of in vitro and in vivo genotoxicity tests in accordance with established guidance shall usually be carried out on the active substance(s).
Posebne študije
In some cases, it may also be necessary to test one or more metabolites that occur as residues in foodstuffs.
Za posebne skupine snovi ali če se v študijah z večkratnim odmerkom pri živalih pojavijo spremembe, ki nakazujejo npr. imunotoksičnost, nevrotoksičnost ali motnjo hormonske funkcije, so zahtevani nadaljnji preskusi, kot so študije občutljivosti ali preskusi pozne nevrotoksičnosti.
Carcinogenicity
Glede na naravo zdravila je morda treba izvesti dodatne študije za oceno mehanizma, ki povzroča toksični učinek ali lahko draži.
The decision on whether carcinogenicity testing is required shall take into account the results of genotoxicity tests, structure-activity relationships and the findings in systemic toxicity tests that may be relevant to neoplastic lesions in longer term studies.
Te študije se običajno izvedejo s končno formulacijo.
Any known species specificity of the mechanism of toxicity shall be considered, as well as any differences in metabolism between the test species, target animal species, and human beings.
Pri načrtovanju teh študij ter oceni rezultatov se upoštevajo trenutna znanstvena spoznanja in uveljavljene smernice.
Where carcinogenicity testing is necessary, generally a two-year rat study and an 18-month mouse study are required.
Mikrobiološke lastnosti ostankov
With appropriate scientific justification, carcinogenicity studies may be carried out in one rodent species, preferably the rat.
Mogoči učinki na črevesno floro človeka
Exceptions
V skladu z uveljavljenimi smernicami se preuči mogoče mikrobiološko tveganje, ki ga za črevesno floro človeka predstavljajo ostanki protimikrobnih spojin.
Where a veterinary medicinal product is intended for topical use, systemic absorption shall be investigated in the target animal species.
Mogoči učinki na mikroorganizme, ki se uporabljajo v industrijski predelavi živil
If it is proved that systemic absorption is negligible, the repeated dose toxicity tests, the tests for reproductive toxicity and the carcinogenicity tests may be omitted, unless:
V nekaterih primerih je morda treba izvesti preskuse za ugotovitev, ali mikrobiološki aktivni ostanki morda vplivajo na tehnološke postopke v industrijski predelavi živil.
under the intended conditions of use laid down, oral ingestion of the veterinary medicinal product by the animal is to be expected, or
Ugotovitve pri ljudeh
under the intended conditions of use laid down, exposure of the user of the veterinary medicinal product by other routes than the dermal route is to be expected, or
Predložijo se informacije o tem, ali se farmakološke učinkovine v zdravilu za uporabo v veterinarski medicini uporabljajo kot zdravila pri zdravljenju ljudi; če je tako, se pripravi poročilo o vseh ugotovljenih učinkih (vključno s neželenimi reakcijami) pri ljudeh ter o vzrokih učinkov, ki je lahko pomembno za oceno varnosti zdravila za uporabo v veterinarski medicini, in v katerega se po potrebi vključijo rezultati iz objavljenih študij; kadar se sestavine zdravila za uporabo v veterinarski medicini same ne uporabljajo ali se ne uporabljajo več kot zdravila pri zdravljenju ljudi, se navedejo razlogi za to.
the active substance or metabolites may enter foodstuffs obtained from the treated animal.
Razvoj odpornosti
Other requirements
Za zdravila za uporabo v veterinarski medicini so potrebni podatki o mogočem razvoju odpornih bakterij, pomembnih za zdravje ljudi.
Special studies
Pri tem je zlasti pomemben mehanizem razvoja te odpornosti.
For particular groups of substances or if the effects observed during repeated dose studies in animals include changes indicative of e.g. immunotoxicity, neurotoxicity- or, endocrine dysfunction, further testing shall be required, e.g. sensitisation studies or delayed neurotoxicity tests.
Po potrebi se predlagajo ukrepi za omejitev razvoja odpornosti zaradi predvidene uporabe zdravila za uporabo v veterinarski medicini.
Depending on the nature of the product, it may be necessary to conduct additional studies to assess the underlying mechanism of the toxic effect or the irritation potential.
V skladu z delom 4 se preuči odpornost, ki je pomembna za klinično uporabo zdravila.
Such studies shall usually be conducted with the final formulation.
Po potrebi se navedejo sklicevanja na podatke iz dela 4.
The state of scientific knowledge and established guidance shall be taken into account when designing such studies and evaluating their results.
Varnost uporabnikov
Microbiological properties of residues
Ta oddelek vključuje razpravo o učinkih, ugotovljenih v predhodnih oddelkih, povezanih z vrsto in obsegom izpostavljenosti ljudi zdravilu, da se lahko oblikuje ustrezno opozorilo uporabnikom in določijo drugi ukrepi za obvladovanje tveganja.
Potential effects on the human gut flora
Ocena tveganja za okolje
The potential microbiological risk presented by residues of antimicrobial compounds for the human intestinal flora shall be investigated in accordance with established guidance.
Ocena tveganja za okolje pri zdravilih za uporabo v veterinarski medicini, ki ne vsebujejo gensko spremenjenih organizmov ali niso iz njih sestavljena
Potential effects on the microorganisms used for industrial food processing
Ocena tveganja za okolje se izvede, da se ocenijo mogoči škodljivi učinki, ki jih ima lahko uporaba zdravila za uporabo v veterinarski medicini na okolje, in določi tveganje teh učinkov.
In certain cases, it may be necessary to carry out tests to determine whether microbiologically active residues may interfere in technological processes in the industrial processing of foodstuff.
V oceni se navedejo vsi previdnostni ukrepi, ki so morda potrebni za zmanjšanje takega tveganja.
Observations in humans
Ta ocena se po navadi izvede v dveh stopnjah.
Information shall be provided showing whether the pharmacologically active substances of the veterinary medicinal product are used as medicinal products in human therapy; if this is so, a compilation shall be made of all the effects observed (including adverse reactions) in humans and of their cause, to the extent that they may be important for the assessment of the safety of the veterinary medicinal product, where appropriate including results from published studies; where constituents of the veterinary medicinal products are themselves not used or are no longer used as medicinal products in human therapy, the reasons shall be stated.
Prva stopnja ocene je vedno obvezna.
Development of resistance
Podrobnosti ocene se predložijo v skladu s sprejetimi smernicami.
Data on the potential emergence of resistant bacteria of relevance for human health are necessary in the case of veterinary medicinal products.
Vključujejo mogočo izpostavljenost okolja zdravilu in stopnjo tveganja zaradi tovrstne izpostavljenosti ob upoštevanju zlasti naslednjih točk:
The mechanism of the development of such resistance is particularly important in this regard.
ciljne živalske vrste in predlaganega vzorca uporabe,
Where necessary, measures to limit resistance development from the intended use of the veterinary medicinal product shall be proposed.
načina uporabe, še zlasti verjetnega obsega, v katerem bo zdravilo neposredno prišlo v okoljske sisteme,
Resistance relevant for clinical use of the product shall be addressed in accordance with Part 4.
možnega izločanja zdravila, njegovih učinkovin ali ustreznih metabolitov v okolje prek zdravljenih živali; obstojnosti v teh izločkih,
Where relevant, cross reference shall be made to the data set out in Part 4.
odstranjevanja neuporabljenih zdravil za uporabo v veterinarski medicini ali drugih odpadnih proizvodov.
User safety
Na drugi stopnji se v skladu z uveljavljenimi smernicami izvedejo nadaljnje specifične raziskave o vplivu in učinkih proizvoda na posebne ekosisteme.
This section shall include a discussion of the effects found in the preceding sections and relate this to the type and extent of human exposure to the product with a view to formulating appropriate user warnings and other risk management measures.
Upoštevajo se obseg izpostavitve okolja zdravilu in razpoložljive informacije o fizikalno/kemijskih, farmakoloških in/ali toksikoloških lastnosti zadevnih snovi, vključno z metaboliti v primeru ugotovljenega tveganja, ki so bile pridobljene pri izvajanju drugih preskusov in preskušanj, ki jih zahteva ta direktiva.
Environmental risk assessment
Ocena tveganja za okolje pri zdravilih za uporabo v veterinarski medicini, ki vsebujejo gensko spremenjene organizme ali so iz njih sestavljena
Environmental risk assessment of veterinary medicinal products not containing or consisting of genetically modified organisms
Vlogi za pridobitev dovoljenja z zdravilom za uporabo v veterinarski medicini, ki vsebuje gensko spremenjene organizme ali je iz njih sestavljeno, se priložijo dokumenti, ki so zahtevani v skladu s členom 2 in delom C Direktive 2001/18/ES.
An environmental risk assessment shall be performed to assess the potential harmful effects, which the use of the veterinary medicinal product may cause to the environment and to identify the risk of such effects.
Poglavje II
The assessment shall also identify any precautionary measures which may be necessary to reduce such risk.
Predložitev podrobnih podatkov in dokumentov
This assessment shall normally be conducted in two phases.
Dokumentacija o preskusih varnosti vključuje:
The first phase of the assessment shall always be performed.
navedbo vseh študij, vključenih v dokumentacijo,
The details of the assessment shall be provided in accordance with accepted guidance.
izjavo, ki potrjuje, da je predlagatelj vključil vse ugodne in neugodne podatke, ki so mu bili znani ob predložitvi,
It shall indicate the potential exposure of the environment to the product and the level of risk associated with any such exposure taking into account in particular the following items:
utemeljitev izpustitve katere koli vrste študije,
the target animal species, and the proposed pattern of use,
obrazložitev vključitve nadomestne vrste študije,
the method of administration, in particular the likely extent to which the product will enter directly into environmental systems,
razpravo o tem, kako na celotno oceno tveganja vplivajo študije, ki so bile izvedene pred študijami, izvedenimi v skladu z dobro laboratorijsko prakso (DLP) v skladu z Direktivo 2004/10/ES.
the possible excretion of the product, its active substances or relevant metabolites into the environment by treated animals; persistence in such excreta,
Vsako poročilo o študiji vključuje:
the disposal of unused veterinary medicinal product or other waste product.
kopijo načrta študije (protokola),
In the second phase, further specific investigation of the fate and effects of the product on particular ecosystems shall be conducted, in accordance with established guidance.
po potrebi izjavo o upoštevanju dobre laboratorijske prakse,
The extent of exposure of the product to the environment, and the available information about the physical/chemical, pharmacological and/or toxicological properties of the substance(s) concerned, including metabolites in case of an identified risk, which has been obtained during the conduct of the other tests and trials required by this Directive, shall be taken into consideration.
opis uporabljenih metod, naprav in materialov,
Environmental risk assessment for veterinary medicinal products containing or consisting of genetically modified organisms
opis in utemeljitev sistema preskusa,
In the case of a veterinary medicinal product containing or consisting of genetically modified organisms the application shall also be accompanied by the documents required under Article 2 and Part C of Directive 2001/18/EC.
opis dobljenih rezultatov, ki je dovolj podroben, da omogoči neodvisno kritično oceno ne glede na razlago avtorja,
Chapter II
po potrebi statistično analizo rezultatov,
Presentation of particulars and documents
razpravo o rezultatih s pripombami o ugotovljenih ali neugotovljenih ravneh učinka in o nenavadnih ugotovitvah,
The dossier of safety tests shall include the following:
podroben opis ter temeljito razpravo o rezultatih študije o varnosti učinkovine ter njeni pomembnosti za oceno mogočih tveganj, ki jih predstavljajo ostanki za ljudi.
an index of all studies included in the dossier,
B. TESTI OSTANKOV
a statement confirming that all data known by the applicant at the time of submission, whether favourable or unfavourable, are included,
Uvod
a justification for the omission of any type of study,
V tej prilogi se uporabljajo opredelitve iz Uredbe Sveta (EGS) št. 2377/90.
an explanation of the inclusion of an alternative type of study,
Namen preučevanja izločanja ostankov iz užitnih tkiv ali jajc, mleka in meda, pridobljenih od zdravljenih živali, je ugotoviti, pod katerimi pogoji in v kakšni količini lahko ostanki ostanejo v živilih, proizvedenih od teh živali.
a discussion of the contribution that any study that pre-dates studies performed in line with good laboratory practice (GLP) according to Directive 2004/10/EC can make to the overall risk assessment.
Poleg tega je namen študij določiti karenco.
Each study report shall include:
Za zdravila za uporabo v veterinarski medicini, namenjena za uporabo pri živalih za proizvodnjo živil, se v dokumentaciji o ostankih navede naslednje:
a copy of the study plan (protocol),
količina ostankov in kako dolgo ostanki zdravil za uporabo v veterinarski medicini ali njihovi metaboliti ostanejo v tkivih zdravljene živali ali v mleku, jajcih in/ali medu, ki so pridobljeni iz te živali;
a statement of compliance with good laboratory practice, where applicable,
da je mogoče določiti realno karenco, ki jo je mogoče ugotoviti pod praktičnimi pogoji kmetovanja, zato da se prepreči tveganje za zdravje potrošnika živil, pridobljenih od zdravljenih živali, ali težave pri industrijski predelavi živil;
a description of the methods, apparatus and materials used,
da so analitske metode, uporabljene pri študijah izločanja ostankov, zadostno potrjene, tako da se lahko z zadostno gotovostjo potrdi primernost uporabe predloženih podatkov o ostankih kot podlage za določanje karence.
a description and justification of the test system,
Metabolizem in kinetika ostankov
a description of the results obtained, in sufficient detail to allow the results to be critically evaluated independently of their interpretation by the author,
Farmakokinetika (absorpcija, porazdelitev, metabolizem, izločanje)
a statistical analysis of the results where appropriate,
Povzetek farmakokinetičnih podatkov se predloži s sklicevanjem na farmakokinetične študije na ciljni vrsti, navedene v delu 4.
a discussion of the results, with comment on observed and no-observed-effect levels, and on any unusual findings,
Celega poročila o študiji ni treba predložiti.
a detailed description and a thorough discussion of the results of the study of the safety profile of the active substance, and its relevance for the evaluation of potential risks presented by residues to humans.
Namen farmakokinetičnih študij ostankov zdravil za uporabo v veterinarski medicini je ocena absorpcije, porazdelitve, presnove ter izločanja zdravila v ciljni vrsti.
B. RESIDUE TESTS
Končno zdravilo ali formulacija, ki ima primerljive lastnosti glede biološke uporabnosti, se ciljni živalski vrsti daje v največjem priporočenem odmerku.
Introduction
Glede na način uporabe zdravila se podrobno opiše obseg absorpcije zdravila za uporabo v veterinarski medicini.
For the purposes of this Annex, the definitions of Council Regulation (EEC) No 2377/90 shall apply.
Če se dokaže, da je sistemska absorpcija zdravil za lokalno uporabo zanemarljiva, nadaljnje študije o ostankih niso potrebne.
The purpose of studying the depletion of residues from the edible tissues or of eggs, milk and honey derived from treated animals is to determine under what conditions and to what extent residues may persist in foodstuffs produced from these animals.
Opiše se porazdelitev zdravila za uporabo v veterinarski medicini v ciljni živali; upoštevajo se možnost vezave na plazemske beljakovine, prenos v mleko ali jajca ter kopičenje lipofilnih spojin.
In addition, the studies shall enable the determination of a withdrawal period.
Opišejo se poti izločanja zdravila iz ciljne živali.
In the case of veterinary medicinal products intended for use in food-producing animals, the residue documentation shall show:
Navedejo se glavni metaboliti in opišejo se njihove lastnosti.
to what extent, and how long, do residues of the veterinary medicinal product or its metabolites persist in the edible tissues of the treated animal or in milk, eggs and/or honey obtained therefrom;
Izločanje ostankov
that in order to prevent any risk to the health of the consumer of foodstuffs from treated animals, or difficulties in the industrial processing of foodstuffs, it is possible to establish realistic withdrawal periods which can be observed under practical farming conditions;
Namen tovrstnih študij, ki merijo hitrost izločanja ostankov iz ciljne živali po zadnjem dajanju zdravila, je določitev karence.
that the analytical method(s) used in the residues depletion study are sufficiently validated to provide the necessary reassurance that the residues data submitted are suitable as the basis for a withdrawal period.
S potrjeno analitsko metodo se z zadostno pogostostjo določi količina ostankov, prisotnih v preskusni živali po tem, ko je prejela zadnji odmerek zdravila za uporabo v veterinarski medicini; opišejo se tehnični postopki ter zanesljivost in občutljivost uporabljenih metod.
Metabolism and residue kinetics
Analitska metoda za ostanke
Pharmacokinetics (absorption, distribution, metabolism, excretion)
Podrobno se opišejo analitske metode, uporabljene v študijah izločanja ostankov, in njihove potrditve.
A summary of the pharmacokinetic data shall be submitted with cross reference to the pharmacokinetic studies in target species submitted in Part 4.
Opišejo se naslednje lastnosti:
The full study report does not need to be submitted.
specifičnost,
The purpose of pharmacokinetic studies with respect to residues of veterinary medicinal products is to evaluate the absorption, distribution, metabolism and excretion of the product in the target species.
natančnost,
The final product, or a formulation, which has comparable characteristics in terms of bioavailability as the final product, shall be administered to the target animal species at the maximum recommended dose.
točnost,
Having regard to the method of administration, the extent of absorption of the veterinary medicinal product shall be fully described.
meja zaznavnosti,
If it is demonstrated that systemic absorption of products for topical application is negligible, further residue studies will not be required.
meja določljivosti,
The distribution of the veterinary medicinal product in the target animal shall be described; the possibility of plasma protein binding or passage into milk or eggs and of the accumulation of lipophilic compounds shall be considered.
praktičnost in uporabnost v običajnih laboratorijskih pogojih,
The pathways for the excretion of the product from the target animal shall be described.
dovzetnost za motnje,
The major metabolites shall be identified and characterised.
stabilnost nastalih ostankov.
Depletion of residues
Primernost predlaganih analitskih metod se oceni glede na trenutna znanstvena in tehnična spoznanja ob predložitvi vloge.
The purpose of these studies, which measure the rate at which residues deplete in the target animal after the last administration of the medicinal product, is to permit the determination of withdrawal periods.
Analitska metoda se predloži v mednarodno dogovorjeni obliki.
At a sufficient number of times after the test animal has received the final dose of the veterinary medicinal product, the quantities of residues present shall be determined by validated analytical methods; the technical procedures and the reliability and sensitivity of the methods employed shall be specified.
Identifikacija zdravila
Residue analytical method
Predloži se identifikacija zdravil za uporabo v veterinarski medicini, ki vključuje:
The analytical method(s) used in the residues depletion study (studies) and its (their) validation shall be described in detail.
sestavo,
The following characteristics shall be described:
rezultate fizikalnih in kemijskih preskusov (potenca in čistost) za ustrezne serije,
specificity,
identifikacijo serije,
accuracy,
povezanost s končnim zdravilom,
precision,
specifično aktivnost ter radiokemijsko čistost označenih snovi,