FrancophonIA/ELRC3.0 huggingface dataset:
English: However, confirmatory clinical trials with the biosimilar are usually not needed in every indication that has been approved for the reference medicine.
Danish: Der er dog normalt ikke behov for konfirmatoriske kliniske forsøg med det biosimilære lægemiddel i hver enkelt indikation, som er godkendt for referencelægemidlet.
English: This guide has therefore been prepared with the important objective of providing healthcare professionals with reference information on both the science and regulation underpinning the use of biosimilars.
Danish: Derfor har denne håndbog det vigtige formål at være et opslagsværk for sundhedspersoner om både videnskab og regulering vedrørende anvendelse af biosimilære lægemidler.
English: Example of variability between different batches of a biological medicine
Danish: Eksempel på variation mellem forskellige batches af et biologisk lægemiddel
English: Polysaccharides Low-molecular weight heparins
Danish: Polysaccharider Lavmolekylære hepariner
English: Biological medicines usually cause no or only a limited immune response (e.g. transient appearance of antibodies).
Danish: Biologiske lægemidler medfører sædvanligvis ingen eller kun en begrænset immunrespons (f.eks. midlertidig forekomst af antistoffer).
English: This is because of the intrinsic ability of proteins and other biological medicines to cause an unwanted immune response, which, in rare cases, could cause a serious adverse reaction (e.g. anaphylaxis or delayed hypersensitivity) or reduced efficacy.
Danish: Det skyldes proteiners og andre biologiske lægemidlers indbyggede evne til at forårsage et uønsket immunrespons, som i sjældne tilfælde kan medføre en alvorlig bivirkning (f.eks. anafylaksi eller forsinket hypersensibilitet) eller begrænset virkning.
English: It is important that healthcare professionals report any suspected ADR of a biosimilar even if the reaction is already listed in the reference medicine's SmPC.
Danish: Det er vigtigt, at sundhedspersoner indberetter alle formodede bivirkninger af et biosimilært lægemiddel, selv om reaktionen allerede er nævnt i produktresuméet for referencelægemidlet.
English: Table 2 lists the classes of biological medicines for which biosimilars have been approved in the EU.
Danish: Tabel 2 viser de kategorier af biologiske lægemidler, hvor biosimilære lægemidler er godkendt i EU.
English: The EU's regulation of biosimilars has shaped biosimilar development globally, by establishing the core principles that underpin biosimilar development in other highly regulated areas of the world.
Danish: EU's regulering af biosimilære lægemidler har været forbillede for udvikling af biosimilære lægemidler globalt ved at fastlægge de centrale principper, der ligger til grund for udvikling af biosimilære lægemidler i andre vel regulerede områder i verden.
English: For simpler molecules with well-established action (e.g. filgrastim) and where comparative quality data are solid, it may be sufficient to compare the effect of the biosimilar and reference medicine with PK and PD studies in healthy volunteers.
Danish: I tilfælde af simplere molekyler med veletableret virkemåde (f.eks. filgrastim), og hvor de sammenlignelige kvalitetsdata er robuste, kan det være tilstrækkeligt at sammenligne virkningen af det biosimilære lægemiddel og referencelægemidlet med PK- og PD-studier hos raske frivillige.
English: Pharmacokinetic/pharmacodynamic Efficacy + safety + immunogenicity
Danish: Sammenlignende kliniske studier Farmakokinetiske/farmakodynamiske Virkning + sikkerhed + immunogenicitet
English: This is done by adjusting the manufacturing process to guarantee that the active substance fits into the desired specifications range.
Danish: Derfor tilpasses fremstillingsprocessen, så det virksomme stof ligger inden for det ønskede specifikationsinterval.
English: A biosimilar is not regarded as a generic of a biological medicine.
Danish: Et biosimilært lægemiddel betragtes ikke som en generisk udgave af et biologisk lægemiddel.
English: These summaries (called ‘EPAR summaries'), are available on each medicine's landing page on EMA's website in the form of questions-andanswers documents in all official EU languages.
Danish: Resumeerne (“EPAR-sammendrag”) findes på hvert enkelt lægemiddels forside på EMA's websted i form af spørgsmål og svar-dokumenter på alle officielle EU-sprog.
English: Comparative clinical trials are specifically designed to rule out clinically relevant differences in safety or efficacy between the biosimilar and the reference medicine, and to confirm biosimilarity.
Danish: Sammenlignende kliniske forsøg er specifikt udformet til at udelukke klinisk relevante forskelle i sikkerhed eller virkning mellem det biosimilære lægemiddel og referencelægemidlet og til at bekræfte biosimilaritet.
English: Prescribers should include the tradename of the medicine in the prescription.
Danish: Ordinerende læger bør skrive lægemidlets handelsnavn på recepten.
English: Comparability is not a new regulatory concept, but a well-established scientific principle that has been used for decades in the manufacture of medicines made by biotechnology
Danish: Sammenlignelighed er ikke et nyt regulatorisk begreb, men et veldokumenteret videnskabeligt princip, der har været anvendt i årtier til bioteknologisk fremstilling af lægemidler3,4,5.
English: Extrapolation of data to other indications is always supported by scientific evidence generated in robust comparability studies (quality, non-clinical and clinical).
Danish: Ekstrapolering af data til andre indikationer er altid baseret på videnskabelige beviser, som er genereret i robuste studier af sammenlignelighed (kvalitet, nonkliniske og kliniske).
English: When any extra measure is applied to the reference medicine (e.g. educational material), it should also be considered for the biosimilar.
Danish: Ekstra foranstaltninger for referencelægemidlet (f.eks. undervisningsmateriale) bør også tages i betragtning for det biosimilære lægemiddel.
English: The manufacture of biological medicines tends to be more complex than for chemically-derived molecules.
Danish: Fremstilling af biologiske lægemidler er for det meste mere kompliceret end fremstilling af kemisk molekyler.
English: Key considerations on potential immunogenicity of biological medicines
Danish: Vigtigste overvejelser om biologiske lægemidlers mulige immunogenicitet
English: The experience over the past 10 years indicates that biosimilar competition can offer advantages to EU healthcare systems, as having more treatment alternatives available is expected to improve patients' access to biological medicines with proven pharmaceutical quality.
Danish: Erfaringen fra de sidste 10 år11 viser, at konkurrence inden for biosimilære lægemidler kan give fordele for EU's sundhedssystemer, da flere behandlingsmuligheder forventes at forbedre patienternes adgang til biologiske lægemidler med dokumenteret farmaceutisk kvalitet.
English: In most of these cases, regulators approve manufacturing changes based on comparability studies and clinical trials are not repeated for all indications.
Danish: I de fleste af disse tilfælde, godkender de regulerende myndigheder ændringerne af fremstillingsprocessen baseret på sammenlignelighedsstudier, og kliniske forsøg gentages ikke for alle indikationer.
English: Comprehensive comparability studies with the reference medicine
Danish: Omfattende sammenlignelighedsstudier med referencelægemidlet
English: International nonproprietary name
Danish: Internationalt fællesnavn
English: In cases where clinically relevant immunogenic responses have been observed (e.g. epoetins) immunogenicity testing is more frequent, there is a longer patient follow-up with intensified clinical monitoring, and specific post-marketing studies may be required.
Danish: I tilfælde, hvor der er observeret klinisk relevant immunogenrespons (f.eks. epoetiner), testes der hyppigere for immunogenicitet, der er en længere patientopfølgning med en intensiveret klinisk overvågning, og specifikke undersøgelser efter markedsføring kan være påkrævet.
English: Report that a company marketing medicines in the EU must submit to regulatory authorities periodically (e.g. every six months) that includes new reports of suspected adverse drug reactions.
Danish: En rapport, som en virksomhed, der markedsfører lægemidler i EU, periodisk skal indsende til de regulerende myndigheder (f.eks. halvårligt), og som omfatter nye indberetninger af formodede bivirkninger.
English: To date, the great majority of biosimilars approved in the EU contain proteins as active substances.
Danish: Indtil nu indeholder langt de fleste biosimilære lægemidler, der er godkendt i EU, proteiner som virksomme stoffer.
English: In most of these cases, clinical trials are not repeated for all indications and changes are approved based on quality and in vitro comparability studies.
Danish: I de fleste af disse tilfælde gentages de kliniske forsøg ikke for alle indikationer, og ændringer godkendes på baggrund af kvalitets- og in vitrostudier af sammenlignelighed.
English: Apart from reactions of an immunological nature, most adverse drug reactions (ADRs) can be predicted from the pharmacological action, and occur with both the reference medicine and the biosimilar (e.g. high haemoglobin levels with epoetins).
Danish: Bortset fra immunologiske reaktioner kan de fleste bivirkninger (ADR) forudsiges ud fra den farmakologiske virkemåde og forekommer ved både referencelægemidlet og det biosimilære lægemiddel (f.eks. et højt hæmoglobinniveau med epoetiner).
English: Extrapolation needs to be supported by all the scientific evidence generated in comparability studies (quality, non-clinical and clinical).
Danish: Ekstrapoleringen skal understøttes af alle de videnskabelige beviser, som er indsamlet i sammenlignelighedsstudier (kvalitet, non-kliniske og kliniske).
English: Comparing batches before and after a manufacturing change ensures consistency, so that there are no changes in safety or efficacy.
Danish: Sammenligning af batches før og efter en ændring sikrer ensartethed, så der ikke forekommer ændringer i lægemidlets sikkerhed eller virkning.
English: For any biological medicine with a new active substance, a positive benefit-risk balance is determined mainly from evidence of safety and efficacy in pivotal trials in humans (figure 4), supported by solid pharmaceutical quality data and non-clinical data.
Danish: For biologiske lægemidler med et nyt virksomt stof bestemmes et positivt benefit/riskforhold hovedsagelig ud fra beviser for sikkerhed og virkning i centrale forsøg på mennesker (figur 4), understøttet af solid dokumentation af den farmaceutiske kvalitet samt non-kliniske data.
English: The biosimilar has physical, chemical and biological properties highly similar to the reference medicine's.
Danish: Det biosimilære lægemiddel har fysiske, kemiske og biologiske egenskaber, som har høj grad af similaritet med referencelægemidlets.
English: Their assessment reports can be accessed on EMA's website, on the landing page of each medicine, under the tab ‘assessment history'.
Danish: Vurderingsrapporterne for disse kan findes på EMA's websted på startsiden for hvert lægemiddel, under fanen “assessment history”.
English: Mostly smaller molecules, easier to characterise In general, larger, structurally more complex molecules, which require multiple technologies for their characterisation
Danish: Generelt større og strukturelt mere komplekse molekyler, som kræver adskillige analytiske teknologier til karakterisering
English: Immunogenicity data required for approval include incidence, titre and persistence of antibodies against the biological medicine (ADAs), neutralisation assays (because neutralising antibodies may reduce the effect of the medicine), assessment of the clinical impact and measures to manage the potential risk of immunogenicity (e.g. special monitoring of immune-mediated adverse reactions or use of concomitant medication to mitigate infusion reactions).
Danish: De data om immunogenicitet, der kræves til godkendelse, omfatter forekomst, titer og persistens af antistoffer mod biologiske lægemidler (ADA), neutralisationstest (fordi neutraliserende antistoffer kan reducere lægemidlets virkning), vurdering af de kliniske konsekvenser og foranstaltninger til at håndtere den potentielle risiko for immunogenicitet (f.eks. særlig overvågning af immunrelaterede bivirkninger eller brug af samtidig medicinering for at afbøde infusionsreaktioner).
English: Information needs and feedback from EU healthcare professionals' organisations have been sought throughout the preparation of this document.
Danish: Under udarbejdelsen af dette dokument er der indhentet oplysninger og feedback fra sundhedsfaglige organisationer i EU.
English: When a company does not apply for all the indications of the reference medicine, efficacy data on the additional indications are not included in the biosimilar's SmPC, however safety data are reflected.
Danish: Når en virksomhed ikke ansøger om alle referencelægemidlets indikationer, medtages oplysninger om virkning for de yderligere indikationer ikke i produktresuméet for det biosimilære lægemiddel, men sikkerhedsoplysningerne medtages.
English: (step 1) is used to determine the extent and type of non-clinical (step 2) and clinical studies (step 3) required in the next step of development, always with the aim of ruling out differences in clinical performance between the biosimilar and the reference medicine.
Danish: Viden fra de indledende sammenligneligheds studier1 af kvalitet (trin 1) anvendes til at bestemme omfanget og typen af non-kliniske (trin 2) og kliniske studier2 (trin 3), som kræves på det næste trin i udviklingsprocessen, altid med sigte på at udelukke forskelle i kliniske resultater mellem det biosimilære lægemiddel og referencelægemidlet.
English: Data from a given indication (e.g. rheumatoid arthritis) may not be directly applicable in terms of safety or efficacy to an indication falling within another therapeutic area where the mode of action, posology or pharmacokinetics may be different (e.g. oncology).
Danish: Data fra en given indikation (f.eks. rheumatoid arthrit) kan måske ikke anvendes direkte, hvad angår sikkerhed eller virkning, på en indikation inden for et andet terapeutisk område, som kan have forskellig virkemåde, dosering eller farmakokinetik (f.eks. onkologi).
English: Thus, these differences are not clinically meaningful in terms of safety or efficacy.
Danish: Disse forskelle er således ikke klinisk relevante med hensyn til sikkerhed eller virkning.
English: Positive benefit-risk based on demonstrating biosimilarity (using comparability studies)
Danish: Et positivt benefit/risk-forhold baseret på dokumentation af biosimilaritet (ved hjælp af studier af sammenlignelighed)
English: Consecutive batches of the same biological medicine may show a small degree of variability (yellow shadow) within the accepted ranges, for example in glycosylation (sugar molecules attached to the protein, which are represented by small blue triangles).
Danish: Batches i rækkefølge af det samme biologiske lægemiddel kan vise en mindre grad af variation (gul skygge) inden for de tilladte intervaller, f.eks. glykosylering (sukkermolekyler knyttet til proteinet, vist som små blå trekanter).
English: Reference medicine A biological medicine approved in the EU, which is chosen by a company developing a biosimilar as a reference for the head-to-head comparison of quality, safety and efficacy.
Danish: Referencelægemiddel Et biologisk lægemiddel, som er godkendt i EU, og som er valgt af en virksomhed, der udvikler et biosimilært lægemiddel, som reference i head-tohead-sammenligningen af kvalitet, sikkerhed og virkning.
English: Development aims at demonstrating comparable safety and efficacy by establishing biosimilarity
Danish: Formålet med udviklingen er at påvise sammenlignelig sikkerhed og virkning ved at dokumentere biosimilaritet
English: Head-to-head comparison of a biosimilar with its reference medicine to rule out any significant differences between them in terms of structure and function.
Danish: Sammenlignelighed Head-to-head-sammenligning af et biosimilært lægemiddel med dets referencelægemiddel for at udelukke væsentlige forskelle mellem dem med hensyn til struktur og funktion.
English: Biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines approved in the EU.
Danish: Biosimilære lægemidler godkendes efter de samme standarder for farmaceutisk kvalitet, sikkerhed og virkning, som gælder for alle biologiske lægemidler godkendt i EU.
English: Amino acid sequence and folding are the main factors that determine biological activity, which must be the same for the biosimilar and the reference medicine.
Danish: Aminosyresekvens og proteinfoldning er de vigtigste bestemmende faktorer for biologisk aktivitet ogsom skal være de samme for det biosimilære lægemiddel og referencelægemidlet.
English: Contributors
Danish: Bidragydere
English: Full data requirements on pharmaceutical qualityFull data requirements on pharmaceutical quality, plus additional quality studies comparing the structure and biological activity of the biosimilar with the reference medicine
Danish: Krav om fuldstændige oplysninger om farmaceutisk kvalitet plus yderligere kvalitetsstudier, hvor strukturen og den biologiske aktivitet i det biosimilære lægemiddel sammenlignes med referencelægemidlet
English: The non-clinical and clinical data needed to approve a biosimilar are different from those needed for a biological medicine with a new active substance.
Danish: De non-kliniske og kliniske data, der kræves til godkendelse af et biosimilært lægemiddel, adskiller sig fra kravene til et biologisk lægemiddel med et nyt virksomt stof.
English: European Medicines Agency: Immunogenicity assessment of biotechnology-derived therapeutic proteins.
Danish: Immunogenicity assessment of biotechnologyderived therapeutic proteins.
English: Margins are established on the basis of knowledge of efficacy with the reference medicine, as well as on clinical judgement.
Danish: Marginerne fastsættes på grundlag af viden om referencelægemidlets virkning samt på baggrund af en klinisk vurdering.
English: Classes of biological medicines for which a biosimilar is currently approved in the EU Classes of biological medicines
Danish: Kategorier af biologiske lægemidler, hvor et biosimilært lægemiddel aktuelt er godkendt i EU Kategorier af biologiske lægemidler
English: Comparative trials are designed to confirm biosimilarity and clinical performance
Danish: Sammenlignende forsøg er konstrueret til at bekræfte biosimilaritet og klinisk effekt
English: Substitution (automatic), which is the practice of dispensing one medicine instead of another equivalent and interchangeable medicine at pharmacy level without consulting the prescriber.
Danish: Substitution (automatisk), dvs. at udlevere et lægemiddel i stedet for en andet tilsvarende og udskifteligt lægemiddel på apoteksniveau uden at konsultere den ordinerende læge.
English: Modification of a protein after its production, which involves the attachment of molecules or groups such as phosphates or carbohydrates (sugars).
Danish: Modifikation af et protein efter fremstilling, som indebærer tilføjelse af molekyler eller grupper, f.eks. fosfater eller kulhydrater (sukkergrupper).
English: Summary of product characteristics (the EU prescribing information)
Danish: Produktresumé (ordineringsoplysninger i EU)
English: Strict controls are always applied to ensure that, despite this variability, there is batch-to-batch consistency and that the differences do not affect safety or efficacy.
Danish: Der udføres altid streng kontrol for at sikre ensartethed mellem batches, trods denne variation, og for at sikre, at forskellene ikke påvirker sikkerheden eller virkningen.
English: Immunogenicity may be influenced by product characteristics (e.g. changes to the structure of the protein may occur during improper storage or transport, or proteins could form aggregates), but also by treatment-related factors (e.g. the risk may vary with subcutaneous versus intravenous administration or with continuous versus intermittent treatment regimen) and patient- or disease- related factors (e.g. age, genetic and immune status or concomitant treatments).
Danish: Immunogenicitet kan være påvirket af produktets egenskaber (f.eks. kan proteinets struktur ændre sig ved forkert opbevaring eller transport, eller proteinerne kan danne aggregater), men også af behandlingsmæssige faktorer (f.eks. kan risikoen variere mellem subkutan og intravenøs administration eller mellem kontinuerlig behandling og intervalbehandling) samt patient- eller sygdomsrelaterede faktorer (f.eks. alder, genetik og immunstatus eller samtidige behandlinger).
English: Biosimilars are approved according to the same strict standards of quality, safety and efficacy that apply to any other medicine.
Danish: Biosimilære lægemidler godkendes ifølge de samme strenge standarder for kvalitet, sikkerhed og virkning, som gælder for alle andre lægemidler.
English: Clinical studies Safety and efficacy PK/PD
Danish: Kliniske studier Sikkerhed og virkning PK/PD
English: Extension of the efficacy and safety data from a therapeutic indication for which the biosimilar has been clinically tested to another therapeutic indication approved for the reference medicine.
Danish: Udbredelse af virknings- og sikkerhedsdata fra en terapeutisk indikation, for hvilken det biosimilære lægemiddel er blevet klinisk testet, til en anden terapeutisk indikation godkendt for referencelægemidlet.
English: Pharmacovigilance and Risk Assessment Committee (EMA's scientific committee formed by EU experts on safety of medicines)
Danish: Udvalget for Risikovurdering inden for Lægemiddelovervågning (EMA's videnskabelige udvalg af EU-eksperter om lægemiddelsikkerhed)
English: As required by EU law, every medicine will have an invented name (tradename or brand name) together with the active substance name (i.e. the
Danish: Som krævet i EU-lovgivningen, har hvert lægemiddel et særnavn (handelsnavn eller mærke) samt det virksomme stofs navn (dvs. det almindelige internationale fællesnavn eller INN, som tildeles af WHO).
English: Information guide for healthcare professionals
Danish: Håndbog for sundhedspersonale
English: Extrapolation of immunogenicity data
Danish: Ekstrapolering af data om immunogenicitet
English: the type of biological medicine and its intended use product characteristics: the great majority of immunogenicity studies focus on how differences at product level may affect an immune response.
Danish: Produktkarakteristika: Langt de fleste immunogenicitetsstudier fokuserer på, hvordan forskelle på produktniveau kan påvirke et immunrespons.
English: The EU SmPC includes information and recommendations to enable healthcare professionals to prescribe the medicine and to give advice to patients on its use.
Danish: EU-produktresuméet indeholder oplysninger og anbefalinger til sundhedspersoner om ordinering af lægemidlet og om, hvordan de skal oplyse patienterne om dets brug.
English: Modification of a protein after its production, which involves the addition of carbohydrate (sugar) groups.
Danish: Modifikation af et protein efter fremstilling, som indebærer tilsætning af kulhydratgrupper (sukkergrupper).
English: Demonstration of high similarity to a reference biological medicine in terms of chemical structure, biological activity and efficacy, safety and immunogenicity profile, mainly based on comprehensive comparability studies.
Danish: Påvisning af stor lighed med et biologisk referencelægemiddel med hensyn til kemisk struktur og biologisk aktivitet, virkning, sikkerhed og immunogenicitetsprofil, hovedsagelig på grundlag af omfattende studier af sammenlignelighed.
English: IMS Health, The impact of biosimilar competition, June 2016. http://ec.europa.eu/ growth/tools-databases/newsroom/cf/itemdetail.
Danish: IMS Health, The impact of biosimilar competition, juni 2016. http://ec.europa.eu/ growth/content/impact-biosimilar-competitionprice-volume-and-market-share-updatedversion-2016-0_en.