natgillin/translations-raw huggingface dataset:
A description of the traceability system that the marketing authorisation holder intends to establish and maintain to ensure that the individual product and its starting and raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the hospital, institution or private practice where the product is used, shall be provided.
Predloži se opis sistema sledljivosti, ki ga namerava vzpostaviti in vzdrževati imetnik dovoljenja za promet z zdravili, da se prek virov, izdelave, pakiranja, shranjevanja, transporta in dostave bolnišnici, instituciji ali zasebni praksi, v kateri se izdelek uporablja, zagotovi sledljivost posameznega izdelka ter vhodnih snovi in surovin, vključno z vsemi snovmi, ki prihajajo v stik s celicami ali tkivi, ki jih lahko vsebuje.
Specific requirements for gene therapy medicinal products
Posebne zahteve za zdravila za gensko zdravljenje
Introduction: finished product, active substance and starting materials
Uvod: končni izdelek, zdravilna učinkovina in vhodne snovi
Gene therapy medicinal product containing recombinant nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es)
Zdravilo za gensko zdravljenje, ki vsebuje rekombinantna zaporedja nukleinskih kislin ali gensko spremenjene mikroorganizme ali viruse.
The finished medicinal product shall consist of nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es) formulated in their final immediate container for the intended medical use.
Končno zdravilo vsebuje zaporedja nukleinskih kislin ali gensko spremenjene mikroorganizme ali viruse, ki so pripravljeni v končnem stičnem vsebniku za predvideno medicinsko uporabo.
The finished medicinal product may be combined with a medical device or active implantable medical device.
Končno zdravilo se lahko kombinira z medicinskim pripomočkom ali aktivnim medicinskim pripomočkom za vsaditev.
The active substance shall consist of nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es).
Zdravilna učinkovina vsebuje zaporedja nukleinskih kislin ali gensko spremenjene mikroorganizme ali viruse.
Gene therapy medicinal product containing genetically modified cells
Zdravilo za gensko zdravljenje, ki vsebuje gensko spremenjene celice
The finished medicinal product shall consist of genetically modified cells formulated in the final immediate container for the intended medical use.
Končno zdravilo vsebuje gensko spremenjene celice, ki so pripravljene v končnem stičnem vsebniku za predvideno medicinsko uporabo.
The active substance shall consist of cells genetically modified by one of the products described in section 3.2.1.1 above.
Zdravilna učinkovina je sestavljena iz celic, ki jih gensko spremeni eden od izdelkov, opisanih v oddelku 3.2.1.1.
In the case of products consisting of viruses or viral vectors, the starting materials shall be the components from which the viral vector is obtained, i.e. the master virus vector seed or the plasmids used to transfect the packaging cells and the master cell bank of the packaging cell line.
Če izdelki vsebujejo viruse ali virusne vektorje, so vhodne snovi sestavine, iz katerih se pridobi virusni vektor, tj. glavni sev virusnega vektorja ali plazmidi, ki se uporabljajo za transfekcijo pakirnih celic, in glavna celična banka celične linije za pakiranje.
In the case of products consisting of plasmids, non-viral vectors and genetically modified microorganism(s) other than viruses or viral vectors, the starting materials shall be the components used to generate the producing cell, i.e. the plasmid, the host bacteria and the master cell bank of recombinant microbial cells.
Če vsebujejo izdelki plazmide, nevirusne vektorje in gensko spremenjene mikroorganizme, ki niso virusi ali virusni vektorji, so vhodne snovi sestavine, ki se uporabljajo za pridobitev celice proizvajalke, tj. plazmid, bakterije gostiteljice in glavna celična banka rekombinantnih mikrobnih celic.
In the case of genetically modified cells, the starting materials shall be the components used to obtain the genetically modified cells, i.e. the starting materials to produce the vector, the vector and the human or animal cells.
Če so celice gensko spremenjene, so vhodne snovi sestavine, ki se uporabljajo pri pridobivanju gensko spremenjenih celic, tj. vhodne snovi za pridobivanje vektorjev, vektorskih in človeških ali živalskih celic.
The principles of good manufacturing practice shall apply from the bank system used to produce the vector onwards.
Načela dobre proizvodne prakse se uporabljajo od sistema banke, ki se uporablja pri pridobivanju vektorja.
In addition to the requirements set out in sections 3.2.1 and 3.2.2 of Part I of this Annex, the following requirements shall apply:
Poleg zahtev iz oddelkov 3.2.1 in 3.2.2 dela I te priloge se uporabljajo tudi naslednje zahteve:
information shall be provided on all the starting materials used for the manufacture of the active substance, including the products necessary for the genetic modification of human or animal cells and, as applicable, subsequent culture and preservation of the genetically modified cells, taking into consideration the possible absence of purification steps;
Predložijo se informacije o vseh vhodnih snoveh, ki se uporabljajo pri izdelavi zdravilnih učinkovin, vključno z izdelki, ki so potrebni za gensko spremembo človeških ali živalskih celic ter, kadar je ustrezno, za nadaljnje gojenje in shranjevanje gensko spremenjenih celic, pri čemer se upošteva, da se prečiščevanje morda ni izvedlo.
for products containing a microorganism or a virus, data on the genetic modification, sequence analysis, attenuation of virulence, tropism for specific tissues and cell types, cell cycle dependence of the microorganism or virus, pathogenicity and characteristics of the parental strain shall be provided;
Za izdelke, ki vsebujejo mikroorganizem ali virus, se navedejo podatki o genski spremembi, analizi zaporedja, slabljenju virulence, tropizmu za posebne vrste celic in tkiv, odvisnosti celičnega ciklusa od mikroorganizma ali virusa, patogenosti in lastnostih starševskega seva.
process-related impurities and product-related impurities shall be described in the relevant sections of the dossier, and in particular replication competent virus contaminants if the vector is designed to be replication incompetent;
V ustreznih delih vloge se opišejo nečistote, povezane s postopkom in izdelkom, ter zlasti virusni kontaminanti, sposobni za razmnoževanje, če vektor ni sposoben za razmnoževanje.
for plasmids, quantification of the different plasmid forms shall be undertaken throughout the shelf life of the product;
Pri plazmidih se med celotnim rokom uporabnosti izdelka določa količina različnih oblik plazmidov.
for genetically modified cells, the characteristics of the cells before and after the genetic modification, as well as before and after any subsequent freezing/storage procedures, shall be tested.
Pri gensko spremenjenih celicah se preskušajo lastnosti celic pred gensko spremembo in po njej ter pred postopkom zamrzovanja/hranjenja in po vsakem nadaljnjem takem postopku.
For genetically modified cells, in addition to the specific requirements for gene therapy medicinal products, the quality requirements for somatic cell therapy medicinal products and tissue engineered products (see section 3.3) shall apply.
Poleg posebnih zahtev za zdravila za gensko zdravljenje se za gensko spremenjene celice uporabljajo zahteve v zvezi s kakovostjo zdravil za somatsko celično zdravljenje in izdelke tkivnega inženirstva (glej oddelek 3.3).
Specific requirements for somatic cell therapy medicinal products and tissue engineered products
Posebne zahteve za zdravila za somatsko celično zdravljenje in izdelke tkivnega inženirstva
The finished medicinal product shall consist of the active substance formulated in its immediate container for the intended medical use, and in its final combination for combined advanced therapy medicinal products.
Končno zdravilo vsebuje zdravilno učinkovino, ki je pripravljena v končnem stičnem vsebniku za predvideno zdravstveno uporabo in končni kombinaciji za kombinirana zdravila za napredno zdravljenje.
The active substance shall be composed of the engineered cells and/or tissues.
Zdravilna učinkovina je sestavljena iz gojenih celic in/ali tkiv.
Additional substances (e.g. scaffolds, matrices, devices, biomaterials, biomolecules and/or other components) which are combined with manipulated cells of which they form an integral part shall be considered as starting materials, even if not of biological origin.
Dodatne snovi (npr. ogrodja, matrice, pripomočki, biomateriali, biomolekule in/ali druge sestavine), ki se kombinirajo z manipuliranimi celicami, katerih sestavni del so, se obravnavajo kot vhodne snovi, čeprav njihov izvor ni biološki.
Materials used during the manufacture of the active substance (e.g. culture media, growth factors) and that are not intended to form part of the active substance shall be considered as raw materials.
Materiali, ki se uporabljajo med izdelavo zdravilnih učinkovin (npr. mediji za gojenje, rastni faktorji) in za katere ni predvideno, da so del zdravilne učinkovine, se obravnavajo kot surovine.
Starting materials
Vhodne snovi
Summary information shall be provided on donation, procurement and testing of the human tissue and cells used as starting materials and made in accordance with Directive 2004/23/EC.
V skladu z Direktivo 2004/23/ES se pripravi in predloži povzetek informacij o darovanju, preskrbi in preskušanju človeškega tkiva in celic, ki se uporabljajo kot vhodne novi.
If non-healthy cells or tissues (e.g. cancer tissue) are used as starting materials, their use shall be justified.
Če se kot vhodne snovi uporabljajo nezdrave celice ali tkiva (npr. rakasto tkivo), se njihova uporaba utemelji.
If allogeneic cell populations are being pooled, the pooling strategies and measures to ensure traceability shall be described.
Če se združujejo populacije alogenskih celic, se navedejo strategije združevanja in ukrepi za zagotovitev sledljivosti.
The potential variability introduced through the human or animal tissues and cells shall be addressed as part of the validation of the manufacturing process, characterisation of the active substance and the finished product, development of assays, setting of specifications and stability.
Morebitna variabilnost, vnesena prek človeških ali živalskih tkiv in celic, se obravnava kot del validacije postopka izdelave, opisa lastnosti zdravilne učinkovine in končnega izdelka, razvoja preskusov določanja vsebnosti, določanja specifikacij in stabilnosti.
For xenogeneic cell-based products, information on the source of animals (such as geographical origin, animal husbandry, age), specific acceptance criteria, measures to prevent and monitor infections in the source/donor animals, testing of the animals for infectious agents, including vertically transmitted micro-organisms and viruses, and evidence of the suitability of the animal facilities shall be provided.
Za izdelke, ki temeljijo na ksenogenskih celicah, se predložijo informacije o izvoru živali (kot so geografsko poreklo, reja živali, starost), posebnih merilih sprejemljivosti, ukrepih za preprečevanje in spremljanje okužb pri viru/živalih donatorkah, ter preskušanju živali na povzročitelje okužb, vključno z vertikalno prenosljivimi mikoorganizmi in virusi, ter dokazilo o primernosti objektov za živali.
For cell-based products derived from genetically modified animals, the specific characteristics of the cells related to the genetic modification shall be described.
Za izdelke, ki temeljijo na celicah in se pridobijo iz gensko spremenjenih živali, se navedejo posebne lastnosti celic, povezane z gensko spremembo.
A detailed description of the method of creation and the characterisation of the transgenic animal shall be provided.
Predloži se podroben opis metode nastanka transgene živali in opis njenih lastnosti.
For the genetic modification of the cells, the technical requirements specified in section 3.2 shall apply.
Za gensko spremembo celic se uporabljajo tehnične zahteve iz oddelka 3.2.
The testing regimen of any additional substance (scaffolds, matrices, devices, biomaterials, biomolecules or other components), which are combined with engineered cells of which they form an integral part, shall be described and justified.
Navede in utemelji se režim preskušanja vseh dodatnih snovi (ogrodij, matric, pripomočkov, biomaterialov, biomolekul ali drugih sestavin), ki se kombinirajo z inženirsko obravnavanimi celicami, katerih sestavni del so.
For scaffolds, matrices and devices that fall under the definition of a medical device or active implantable medical device, the information required under section 3.4 for the evaluation of the combined advanced therapy medicinal product shall be provided.
Za ogrodja, matrice in pripomočke, ki so zajeti v opredelitvi medicinskega pripomočka ali aktivnega medicinskega pripomočka za vsaditev, se predložijo informacije, ki se v skladu z oddelkom 3.4 zahtevajo za oceno kombiniranih zdravil za napredno zdravljenje.
Manufacturing process
Postopek izdelave
The manufacturing process shall be validated to ensure batch and process consistency, functional integrity of the cells throughout manufacturing and transport up to the moment of application or administration, and proper differentiation state.
Postopek izdelave se validira, da se zagotovijo konsistentnost serij in postopka, funkcijska neokrnjenost celic od izdelave in transporta do aplikacije ali dajanja ter ustrezna stopnja diferenciacije.
If cells are grown directly inside or on a matrix, scaffold or device, information shall be provided on the validation of the cell culture process with respect to cell-growth, function and integrity of the combination.
Če so celice gojene neposredno v matrici, ogrodju ali pripomočku ali na njih, se predložijo informacije o validaciji postopka gojenja celic v zvezi z rastjo celic, funkcijo in neokrnjenostjo kombinacije.
Characterisation and control strategy
Opis lastnosti in strategija nadzora
Relevant information shall be provided on the characterisation of the cell population or cell mixture in terms of identity, purity (e.g. adventitious microbial agents and cellular contaminants), viability, potency, karyology, tumourigenicity and suitability for the intended medicinal use.
Predložijo se ustrezne informacije v zvezi z opisom lastnosti celične populacije ali mešanice celic v smislu identitete, čistote (npr. naključnih mikrobnih agensov in celičnih kontaminantov), sposobnosti preživetja, učinkovitosti, kariologije, rakotvornosti in primernosti za predvideno medicinsko uporabo.
The genetic stability of the cells shall be demonstrated.
Dokaže se genska stabilnost celic.
Qualitative and, where possible, quantitative information on product- and process-related impurities, as well as on any material capable of introducing degradation products during production, shall be provided.
Predložijo se kvalitativne informacije in, če je mogoče, kvantitativne informacije o nečistotah, povezanih z izdelkom in postopkom, ter vseh materialih, ki so med izdelavo sposobni vnesti razpadne produkte.
The extent of the determination of impurities shall be justified.
Utemelji se obseg določanja nečistot.
If certain release tests cannot be performed on the active substance or finished product, but only on key intermediates and/or as in-process testing, this shall be justified.
Če na zdravilni učinkovini ali končnem izdelku ni mogoče opraviti nekaterih preskusov za sproščanje, ampak je to mogoče le na ključnih intermediatih in/ali kot preskus med izdelavo, se to utemelji.
Where biologically active molecules (such as growth factors, cytokines) are present as components of the cell-based product, their impact and interaction with other components of the active substance shall be characterised.
Kadar so biološko aktivne molekule (kot so rastni faktorji, citokini) prisotne kot sestavine izdelka na podlagi celic, se opredelijo njihov vpliv in medsebojno delovanje z drugimi sestavinami zdravilne učinkovine.
Where a three-dimensional structure is part of the intended function, the differentiation state, structural and functional organisation of the cells and, where applicable, the extracellular matrix generated shall be part of the characterisation for these cell-based products.
Kadar je tridimenzionalna struktura del predvidene funkcije, so stopnja diferenciacije, strukturna in funkcijska organizacija celic ter, kadar je primerno, pripravljena zunajcelična matrica del opisa lastnosti teh izdelkov na podlagi celic.
Where needed, non-clinical investigations shall complement the physicochemical characterisation.
Kadar je potrebno, neklinične raziskave dopolnijo fizikalno-kemijski opis lastnosti.
For excipient(s) used in cell or tissue-based medicinal products (e.g. the components of the transport medium), the requirements for novel excipients, as laid down in Part I of this Annex, shall apply, unless data exists on the interactions between the cells or tissues and the excipients.
Za pomožne snovi, uporabljene v zdravilih na podlagi celic ali tkiva (npr. sestavine transportnega gojišča), se uporabljajo zahteve za nove pomožne snovi iz dela I te priloge, razen če obstajajo podatki o medsebojnem delovanju celic ali tkiv in pomožnih snovi.
Developmental studies
Razvojne študije
The description of the development program shall address the choice of materials and processes.
Opis razvojnega programa obravnava izbiro materialov in postopkov.
In particular, the integrity of the cell population as in the final formulation shall be discussed.
Obravnava se zlasti neokrnjenost celične populacije, kakršna je v končni sestavi.
Reference materials
Referenčni materiali
A reference standard, relevant and specific for the active substance and/or the finished product, shall be documented and characterised.
Dokumentirajo in opredelijo se referenčni standardi, pomembni in značilni za zdravilne učinkovine in/ali končni izdelek.
Advanced therapy medicinal product containing devices as referred to in Article 7 of Regulation (EC) No 1394/2007
Zdravila za napredno zdravljenje, ki vključujejo pripomočke, kot so opredeljeni v členu 7 Uredbe (ES) št. 1394/2007
A description of the physical characteristics and performance of the product and a description of the product design methods shall be provided.
Predloži se opis fizikalnih lastnosti in učinkovitosti izdelka ter metod načrtovanja izdelka.
The interaction and compatibility between genes, cells and/or tissues and the structural components shall be described.
Opišeta se medsebojno delovanje in združljivost genov, celic in/ali tkiv ter strukturnih sestavin.
Combined advanced therapy medicinal products as defined in Article 2(1)(d) of Regulation (EC) No 1394/2007
Kombinirana zdravila za napredno zdravljenje, kot so opredeljena v členu 2(1)(d) Uredbe (ES) št. 1394/2007
For the cellular or tissue part of the combined advanced therapy medicinal product, the specific requirements for somatic cell therapy medicinal products and tissue engineered products set out in section 3.3 shall apply and, in the case of genetically modified cells, the specific requirements for gene therapy medicinal products set out in section 3.2 shall apply.
Za celični ali tkivni del kombiniranega zdravila za napredno zdravljenje se uporabljajo posebne zahteve za zdravila za somatsko celično zdravljenje in izdelke tkivnega inženirstva iz oddelka 3.3, v primeru gensko spremenjenih celic pa se uporabljajo posebne zahteve za zdravila za gensko zdravljenje iz oddelka 3.2.
The medical device or the active implantable medical device may be an integral part of the active substance.
Medicinski pripomoček ali aktivni medicinski pripomoček za vsaditev je lahko sestavni del zdravilne učinkovine.
Where the medical device or active implantable medical device is combined with the cells at the time of the manufacture or application or administration of the finished products, they shall be considered as an integral part of the finished product.
Kadar je medicinski pripomoček ali aktivni medicinski pripomoček za vsaditev med izdelavo, aplikacijo ali dajanjem končnega izdelka kombiniran s celicami, se te štejejo kot sestavni del končnega izdelka.
Information related to the medical device or the active implantable medical device (which is an integral part of the active substance or of the finished product) which is relevant for the evaluation of the combined advanced therapy medicinal product shall be provided.
Predložijo se informacije o medicinskem pripomočku ali aktivnem medicinskem pripomočku za vsaditev (ki je sestavni del zdravilne učinkovine ali končnega izdelka), pomembne za oceno kombiniranega zdravila za napredno zdravljenje.
information on the choice and intended function of the medical device or implantable medical device and demonstration of compatibility of the device with other components of the product;
informacije o izbiri in predvideni funkciji medicinskega pripomočka ali medicinskega pripomočka za vsaditev ter dokaz združljivosti pripomočka z drugimi sestavinami izdelka;
evidence of conformity of the medical device part with the essential requirements laid down in Annex I to Council Directive 93/42/EEC, or of conformity of the active implantable device part with the essential requirements laid down in Annex 1 to Council Directive 90/385/EEC;
dokazilo o skladnosti dela medicinskega pripomočka z bistvenimi zahtevami iz Priloge I k Direktivi Sveta 93/42/EGS ali dokazilo o skladnosti dela aktivnega pripomočka z bistvenimi zahtevami iz Priloge 1 k Direktivi Sveta 90/385/EGS;
where applicable, evidence of compliance of the medical device or implantable medical device with the BSE/TSE requirements laid down in Commission Directive 2003/32/EC;
kadar je primerno, dokazilo o skladnosti medicinskega pripomočka ali medicinskega pripomočka za vsaditev z zahtevami glede BSE/TSE iz Direktive Komisije 2003/32/ES;
where available, the results of any assessment of the medical device part or the active implantable medical device part by a notified body in accordance with Directive 93/42/EEC or Directive 90/385/EEC.
kadar so dostopni, rezultate vseh ocen dela medicinskega pripomočka ali dela aktivnega medicinskega pripomočka za vsaditev, ki jih je v skladu z Direktivo 93/42/EGS ali Direktivo 90/385/EGS izvedel priglašeni organ.
The notified body which has carried out the assessment referred to in point (d) of this section shall make available on request of the competent authority assessing the application, any information related to the results of the assessment in accordance with Directive 93/42/EEC or Directive 90/385/EEC.
Priglašeni organ, ki je izvedel oceno iz točke (d) tega oddelka, zagotovi na zahtevo organa, ki je pristojen za oceno vloge, vse informacije v zvezi z rezultati ocene v skladu z Direktivo 93/42/EGS ali Direktivo 90/385/EGS.
This may include information and documents contained in the conformity assessment application concerned, where necessary for the evaluation of the combined advanced therapy medicinal product as a whole.
To so lahko informacije in dokumenti iz zadevnih vlog v zvezi z oceno skladnosti, kadar je to potrebno za vrednotenje kombiniranega zdravila za napredno zdravljenje kot celoto.
SPECIFIC REQUIREMENTS REGARDING MODULE 4
POSEBNE ZAHTEVE V ZVEZI Z MODULOM 4
The requirements of Part I, Module 4 of this Annex on the pharmacological and toxicological testing of medicinal products may not always be appropriate due to unique and diverse structural and biological properties of advanced therapy medicinal products.
Zahteve iz dela I, modula 4, te priloge o farmakološkem in toksikološkem preskušanju zdravil niso vedno primerne zaradi edinstvenih ter raznolikih strukturnih in bioloških lastnosti zdravil za napredno zdravljenje.
The technical requirements in sections 4.1, 4.2 and 4.3 below explain how the requirements in Part I of this Annex apply to advanced therapy medicinal products.
Tehnične zahteve v oddelkih 4.1, 4.2 in 4.3 pojasnjujejo, kako se zahteve iz dela I te priloge uporabljajo za zdravila za napredno zdravljenje.