natgillin/translations-raw huggingface dataset:
Hverken den eksplorative analyse af PDGFR-α-ekspression eller immunogenicitet synes at kunne forklare den manglende gavnlige effekt. 
Neither the exploratory analysis of PDGFR-α expression nor the immunogenicity appear to explain the absence of benefit.
Forekomsten er imidlertid højere i den eksperimentelle gruppe. 
However, this remains higher in the investigational arm.
• Som følge heraf vurderede udvalget, at Lartruvo mangler terapeutisk effekt, og at benefit/riskforholdet for Lartruvo er ugunstigt. 
• The Committee, as a consequence, concluded that Lartruvo lacks therapeutic efficacy and that the benefit-risk of Lartruvo is not favourable.
Samlet set er resultaterne af ANNOUNCE-studiet modne og robuste, så det kan konkluderes, at studiet påviser manglende terapeutisk effekt ved olaratumab-behandling i den godkendte indikation. 
Overall, the results of the ANNOUNCE study are mature and robust to draw the conclusion that the study showed lack of therapeutic efficacy associated with olaratumab treatment in the authorised indication.
Populationsstørrelsen, studiegennemførelsen, endepunkterne, de statistiske metoder eller randomiseringen ser ikke ud til at kunne forklare diskrepansen mellem ANNOUNCE-studiet og fase IIstudiet JGDG. 
The sample size, conduct of the study, endpoints, statistical methods or randomisation do not seem to explain the discrepancy between ANNOUNCE and the phase II JGDG.
Det var designet til at bekræfte den fordel, hvad angår samlet overlevelse, der tidligere er vist i det mindre fase 1b/2-studie JGDG. 
It was designed to confirm the OS benefit previously shown in the smaller phase 1b/2 study JGDG.
Der synes ikke at være en enkeltstående årsag, der kan forklare resultatdiskrepansen mellem fase IIstudiet JGDG og fase III-studiet ANNOUNCE. 
It seems no single reason can explain the discrepancy in results between phase II JGDG and phase III ANNOUNCE studies.
Desuden var forekomsten af (konsoliderede) smerter i bevægeapparatet sammenlignede i de 2 behandlingsgrupper. 
In addition, the rate of (consolidated) musculoskeletal pain was similar between the 2 treatment arms.
I henhold til protokollen skulle doxorubicin 75 mg/m2 administreres (efter olaratumab eller placebo) på dag 1 i serie 1-8 (a hver 3 uger). 
According to the protocol, doxorubicin 75 mg/m2 was to be administered (after olaratumab or placebo) on day 1 of cycles 1 to 8 (of 3 weeks each).
Når der ses bort fra ødemer, der ikke var forbundet med en bivirkning relateret til hjertedysfunktion eller signifikant nedsat funktion i venstre ventrikel, var den faktiske forekomst af hjertedysfunktion 9,3 % i den eksperimentelle gruppe og 6,8 % i kontrolgruppen. 
When excluding the event of oedema not associated with an AE suggestive of cardiac dysfunction or a significant decrease in left ventricular function, the true incidence of cardiac dysfunction was 9.3% in the investigational arm and 6.8% in the control arm.
Disse data synes at pege på forskellig tolerabilitet over for doxorubicin alt efter gruppe; tolerabiliteten ser ikke ud til at være den samme som i det tidligere fase II-studie, hvor eksponeringen for doxorubicin var højere hos patienter i den eksperimentelle gruppe end i kontrolgruppen (7 vs. 4). 
These data seem to suggest a different tolerability to doxorubicin depending on the group, which appears to be different from that observed in the previous phase II trial, where the exposure to doxorubicin was higher for patients in the investigational group as compared to the control group (7 vs 4).
Imidlertid var den mediane varighed af doxorubicinbehandlingen i den eksperimentelle gruppe og kontrolgruppen på hhv. 18 og 23 uger. 
However, the median duration of doxorubicin treatment was 18 weeks and 23 weeks for the investigational and control groups, respectively.
Forekomsten af hæmatologiske toksiciteter (neutropeni, trombocytopeni, anæmi og febril neutropeni) og gastrointestinale toksiciteter (kvalme, opkastning og diarré) var balanceret mellem behandlingsgrupperne. 
The rate of haematological toxicities (neutropenia, thrombocytopenia, anaemia and febrile neutropenia) and gastrointestinal toxicities (nausea, vomiting and diarrhoea) was balanced between the treatment arms.
Bløddelssarkom er en sygdom med mange varierende tumorhistologier, der har forskellige prognoser og kræver specifik behandling. 
STS is a disease which encompasses a wide range of different tumour histologies, some of them with different prognosis and specific treatments.
Alle følsomhedsanalyserne i ANNOUNCE-studiet peger i samme retning, både i ITT-populationen og LMS-gruppen (ingen gavnlig effekt af olaratumab). 
All the sensitivity analyses carried out in the ANNOUNCE study, both in the ITT population an in the LMS group, point in the same direction (no favourable effect of olaratumab).
• Udvalget behandlede sagen vedrørende Lartruvo i henhold til artikel 20 i forordning (EF) nr. 726/2004. 
• The Committee considered the procedure under Article 20 of Regulation (EC) No 726/2004 for Lartruvo.
Kvalme, neutropeni og træthed var de hyppigst indberettede behandlingsrelaterede uønskede hændelser. 
Nausea, neutropenia and fatigue were the most frequently reported TEAEs.
Det mediane antal gennemførte serier var højere i kontrolgruppen (6 vs. 7), og den mediane kumulative dosis pr. legemsoverflade (mg/m2) var også højere i kontrolgruppen (409 vs. 483). 
The median of the number of cycles received were higher in the control arm (6 vs 7) and the median of cumulative dose per body surface area (mg/m2) was also higher for the control group (409 vs 483).
Der foreligger heller ingen data vedrørende toksicitet hos patienter i den eksperimentelle gruppe ved vedligeholdelsesbehandling med olaratumab. 
There are also no data regarding the toxicity observed in subjects in the investigational arm when treated with olaratumab maintenance.
• Udvalget gennemgik resultaterne af ANNOUNCE (JGDJ)-studiet, der blev gennemført for at opfylde det specifikke krav om bekræftelse af det påberåbte gunstige benefit/risk-forhold i forbindelse med den betingede markedsføringstilladelse for Lartruvo, jf. artikel 14a, i forordning (EF) nr. 726/2004. 
• The Committee reviewed the results of the ANNOUNCE (JGDJ) study, which was conducted to fulfil the specific obligation with a view to confirming a favourable benefit-risk balance for the conditional marketing authorisation for Lartruvo, pursuant to Article 14-a of Regulation (EC) No
Der blev rapporteret om umiddelbare ikkeanafylaktiske reaktioner (grad 1/2) hos 9,3 % af patienterne. 
Immediate non-anaphylactic reactions were reported in 9.3% patients and were grade 1/2 in severity.
Studiets primære endepunkt var den samlede overlevelse i ITT-populationen og i LMS-populationen. 
The primary endpoint for this study was OS in the ITT population and in the LMS population.
Den 9. november 2016 fik Lartruvo en betinget markedsføringstilladelse med gyldighed i hele EU, jf. artikel 14, stk. 7, i forordning (EF) nr. 726/2004. 
Lartruvo was granted a conditional marketing authorisation under Article 14(7) of Regulation (EC) No. 726/2004, valid throughout the European Union, on 9 November 2016.
Doxorubicin blev administreret i maksimalt 8 serier hver 3. uge parallelt med olaratumab/placebo, der blev fortsat efter 8 serier indtil sygdomsprogression, uacceptabel toksicitet, død eller andre seponeringskriterier. 
Doxorubicin was administered for a maximum of 8 cycles every 3 weeks, along with olaratumab/placebo which was continued after 8 cycles until PD, unacceptable toxicity, death, or other withdrawal criteria.
Kaplan-Meier-kurverne for samlet overlevelse er overlappende. 
The Kaplan-Meier curves for OS are overlapping.
I alt 170 (66,1 %) vs. 158 (63,5 %) patienter døde i henholdsvis den eksperimentelle gruppe og kontrolgruppen, fortrinsvis som følge af deres sygdom (63,4 % vs. 61 %). 
A total of 170 (66.1%) vs 158 (63.5%) of patients died in the investigational vs control arm, respectively, mostly attributed to study disease (63.4% vs 61%).
Patientfordelingen i ANNOUNCE-studiet peger ikke på større forskelle mellem grupperne, hvad angår grundene til seponering. 
The patient disposition of the ANNOUNCE trial does not indicate major differences between arms in reasons for treatment discontinuation.
Forekomsten af dødsfald, der skyldtes uønskede hændelser, var omtrent den samme i de to grupper (7 [2,7 %] vs. 6 [2,4 %]). 
Deaths due to adverse events were overall similar in both arms (7[2.7%] vs 6 [2.4%]).
Da ANNOUNCE-studiet blev gennemført for at opfylde det specifikke krav om at bekræfte virkningen og sikkerheden ved olaratumab i den godkendte indikation, bør den betingede markedsføringstilladelse for Lartruvo derfor tilbagekaldes. 
Consequently, as the ANNOUNCE study was imposed as a specific obligation to confirm the efficacy and safety of olaratumab in the authorised indication, the conditional marketing authorisation for Lartruvo should be revoked.
Selvom ANNOUNCE-studiet ikke gav anledning til nye sikkerhedsmæssige betænkeligheder, betyder eventuelle sikkerhedsmæssige betænkeligheder ved olaratumab, at benefit/risk-forholdet for Lartruvo er negativt, for så vidt angår den manglende terapeutiske effekt, der er observeret i studiet. 
Even though no new safety concerns arose from the ANNOUNCE study, any safety concerns associated with olaratumab render the benefit-risk balance of Lartruvo negative in view of the lack of therapeutic efficacy observed in the study.
Som bekræftelsesstudie var ANNOUNCE specifikt designet til at påvise forskelle i samlet overlevelse. 
ANNOUNCE as the confirmatory trial was specifically designed to show differences in OS.
Analyserne i ANNOUNCE-studiet viste, at PDGFR-α-status ikke havde nogen prædiktiv rolle for responset på olaratumab, hvad angår samlet overlevelse eller progressionsfri overlevelse, og at PDGFR-α-status udgjorde en ringe prognostisk faktor, hvilket er konsistent med litteraturens data. 
The analyses of ANNOUNCE study showed that PDGFR-α status did not have any predictive role of the response to olaratumab in terms of OS or PFS, and that PDGFR-α was a poor prognostic factor, consistently with literature data.
Selvom studiets primære endepunkt (progressionsfri overlevelse) ikke viste en tydelig forsinkelse i tumorprogression i den eksperimentelle gruppe, understøttede den længere overlevelse ved olaratumab-kombinationsbehandling udstedelsen af en betinget markedsføringstilladelse. 
Even though the primary endpoint of that study (PFS) did not reveal a clear delay in the tumour progression for the experimental arm, the longer survival associated with the olaratumab combination treatment supported the granting of a conditional marketing authorisation.
Forekomsten af potentielle umiddelbare overfølsomhedsreaktioner (dvs. som opstår på infusionsdagen) var højere i den eksperimentelle gruppe for hændelser af alle grader (11,7 % vs. 7,2 %) og hændelser af grad ≥ 3 (2,3 % vs. 0,8 %), men der sås ingen hændelser med dødelig udgang. 
The rate of potential immediate (i.e. occurring on the day of infusion) hypersensitivity reactions was higher in the investigational arm for all grade events (11.7% vs. 7.2%) and Grade ≥3 events (2.3% vs 0.8%) but no fatal events were reported.
I alt 509 patienter var randomiseret til behandling med enten Lartruvo + doxorubicin (efterfulgt af Lartruvo alene indtil progression) eller placebo + doxorubicin (efterfulgt af placebo alene indtil progression). 
In total, 509 patients were randomised to treatment either with Lartruvo + doxorubicin (followed by Lartruvo monotherapy until progression) or with placebo + doxorubicin (followed by placebo monotherapy until progression).
• Udvalget bemærkede, at der ikke sås nogen gavnlig virkning ved tilføjelse af Lartruvo til doxorubicin ved behandling af patienter med fremskredent bløddelssarkom, sammenholdt med doxorubicin alene. 
• The Committee noted that no benefit was observed from adding Lartruvo to doxorubicin in the treatment of patients with advanced soft tissue sarcoma, when compared to doxorubicin alone.
Derefter blev der stillet specifikt krav om gennemførelse af ANNOUNCE (JGDJ)-studiet for at bekræfte virkningen og sikkerheden ved olaratumab i den population, som Lartruvo aktuelt er indiceret til. 
The ANNOUNCE (JGDJ) study was then requested as a specific obligation to confirm the efficacy and safety of olaratumab in same population for whom Lartruvo is currently indicated.
Bilag Videnskabelige konklusioner 
Annex Scientific conclusions
"Lartruvo i kombination med doxorubicin er indiceret til behandling af voksne patienter med avanceret bløddelssarkom, som ikke er egnede til kurativ behandling med kirurgi eller strålebehandling, og som ikke tidligere er blevet behandlet med doxorubicin." 
‘in combination with doxorubicin, for the treatment of adult patients with advanced soft tissue sarcoma who are not amenable to curative treatment with surgery or radiotherapy and who have not been previously treated with doxorubicin'.
2 af de behandlingsrelaterede uønskede hændelser, der havde dødelig udgang, ansås for at være forbundet med forsøgslægemidlet i den eksperimentelle gruppe (pneumoni og aspiration) vs. ingen i kontrolgruppen. 
Of those, 2 TEAE leading to deaths were considered related to study treatment in the investigational arm (pneumonia and aspiration) vs none in the control arm.
Sammenholdt med den aktuelt anbefalede dosering af olaratumab (15 mg/kg på dag 1 og 8 i hver 3ugers serie) blev der anvendt en støddosis på 20 mg/kg på dag 1 og 8 i serie 1 for at minimere antallet af patienter, der blev eksponeret for subterapeutiske olaratumab-serumniveauer, uden øget risiko for toksicitet, baseret på farmakokinetik og matchet case-kontrolanalyse ud fra eksponeringsrelaterede kvartilresultater. 
Compared to the currently recommended posology of olaratumab (15 mg/kg on days 1 and 8 of each 3 week cycle), a loading cycle of 20 mg/kg on day 1 and day 8 of cycle 1 was used, to minimize the number of patients exposed to sub-therapeutic olaratumab serum levels without an increased risk of toxicity, based on PK and matched case-control analysis by exposure quartiles results.
For at bekræfte virkningen og sikkerheden ved olaratumab var indehaveren af markedsføringstilladelsen specifikt forpligtet til senest i januar 2020 at indsende den kliniske studierapport fra et randomiseret, dobbeltblindet fase III-bekræftelsesstudie til sammenligning af doxorubicin plus olaratumab versus doxorubicin hos patienter med fremskredent eller metastatisk bløddelssarkom (studie I5B-MCJGDJ [JGDJ]; ANNOUNCE), herunder eksplorative biomarkørdata. 
In order to confirm the efficacy and safety of olaratumab, the marketing authorisation holder was required to submit as specific obligation, by January 2020, the clinical study report of a phase III randomised double-blind confirmatory study comparing doxorubicin plus olaratumab versus doxorubicin in patients with advanced or metastatic soft tissue sarcoma (Study I5B-MCJGDJ [JGDJ]; ANNOUNCE), including exploratory biomarker data.
Overordnet set sås der ingen fordel ved tilføjelse af Lartruvo til doxorubicin hos patienter med fremskredent bløddelssarkom i ANNOUNCE-studiet. 
In summary, no benefit of adding Lartruvo to doxorubicin in patients with advanced STS was observed in the ANNOUNCE study.
Forekomsten af dødsfald, der skyldes uønskede hændelser i forbindelse med behandling, eller som indtraf inden for 30 dage efter den sidste dosis forsøgslægemiddel, var 5 (1,9 %) vs. 3 (1,2 %) (den eksperimentelle gruppe: lungeemboli hos 2 patienter og akut respirationssvigt, aspiration og pneumoni hos én patient hver; kontrolgruppen: cerebrovaskulær hændelse, iskæmisk slagtilfælde og sepsis, hver hos én patient). 
Death due to AEs on therapy or within 30 days from the last dose of study drug were 5 (1.9%) vs 3 (1.2%) (investigational arm: pulmonary embolism in 2 subjects, acute respiratory failure, aspiration and pneumonia in one patient each; control arm: cerebrovascular accident, ischemic stroke and sepsis, each in one patient).
I LMS-populationen var den objektive responsrate i kontrolgruppens favør (ingen statistisk signifikans), og sygdomskontrolraten var i kontrolgruppens favør (statistisk signifikant). 
In the LMS population, ORR was in favour of the control arm (no statistical significance) and DCR was statistically significant in favour of the control arm.
ANNOUNCE-studiet gav ikke anledning til nye sikkerhedsmæssige betænkeligheder. 
No new safety concerns arose from the ANNOUNCE study.
Der sås heller ingen forskel i samlet overlevelse i LMS-populationen. 
No difference was seen in OS in the LMS population either.
ANNOUNCE (I5B-MC-JGDJ) er et randomiseret, dobbeltblindet, placebo-kontrolleret fase 3-studie til undersøgelse af olaratumab plus doxorubicin versus placebo plus doxorubicin hos patienter med lokalt fremskredent eller metastatisk bløddelssarkom. 
ANNOUNCE (I5B-MC-JGDJ) was a randomized, double-blind, placebo-controlled, phase 3 trial of olaratumab plus doxorubicin versus placebo plus doxorubicin in patients with locally advanced or metastatic soft tissue sarcoma.
I alt 509 voksne patienter med fremskredent eller metastatisk bløddelssarkom, der ikke var modtagelige over for kurativ behandling i form af kirurgi eller stråleterapi (234 af patienterne havde leiomiosarkom (LMS)), blev randomiseret i forholdet 1:1 - og stratificeret ud fra antallet af tidligere systemiske behandlinger for fremskreden/metastatisk sygdom, histologisk tumortype og ECOGperformancestatus - til den eksperimentelle gruppe (n = 258; LMS n = 119) med olaratumab plus doxorubicin eller til kontrolgruppen (n = 251; LMS n = 114) med placebo plus doxorubicin. 
Overall, 509 adult patients with advanced or metastatic soft tissue sarcoma not amenable to treatment with surgery or radiotherapy with curative intent (of those 234 were leiomiosarcoma, LMS) were randomized 1:1, stratified by number of prior systemic therapies for advanced/metastatic disease, histological tumour type, and ECOG PS, to the investigational arm (n=258; LMS n=119) with olaratumab plus doxorubicin or the control arm (n=251; LMS n=114) with placebo plus doxorubicin.
Der sås ingen signifikant forskel i progressionsfri overlevelse mellem behandlingsgrupperne i LMS-populationen. 
No significant difference in PFS between the treatment arms in the LMS population was found.
Forekomsten af behandlingsrelaterede uønskede hændelser, der førte til seponering, var næsten den samme i de to grupper (4,3 % vs. 4,4 %). 
Frequency of patients with TEAE leading to treatment discontinuation was similar in both arms (4.3% vs 4.4%).
Lartruvo blev godkendt på grundlag af et åbent, randomiseret, klinisk fase 1b/2-studie af doxorubicinnaive patienter med fremskredent bløddelssarkom, der ikke var modtagelige over for behandling med kirurgi og stråleterapi (studie JGDG). 
Lartruvo was authorised based on a single open-label, randomised phase 1b/2 clinical trial which enrolled doxorubicin-naïve subjects with advanced soft tissue sarcoma not amenable to treatment with surgery and radiotherapy (study JGDG).
Forekomsten af behandlingsrelaterede uønskede hændelser var generelt sammenlignelige i de to behandlingsgrupper (98,1 % vs. 99,2 %). 
The rate of TEAE was overall similar in both treatment arms (98.1% vs 99.2%).
Der foreligger ingen data om uønskede hændelser justeret i forhold til eksponering. 
No data on AE adjusted by exposure are available.
I alt 6 patienter i den eksperimentelle gruppe udviklede en anafylaktisk reaktion vs. ingen i kontrolgruppen. 
Overall, 6 patients in the investigational vs none in the control arm developed an anaphylactic reaction.
Den mediane progressionsfri overlevelse var 5,42 måneder i den eksperimentelle gruppe og 6,77 måneder i kontrolgruppen (HR = 1,231 [95 %-KI: 1,009-1,502]; p = 0,042). 
The median PFS was 5.42 months in the investigational arm and 6.77 months in the control arm (HR=1.231 [95% CI: 1.009, 1.502]; p=0.042).
Forekomsten af hændelser af alle grader i kategorien af hændelser af særlig interesse var 18,3 % i den eksperimentelle gruppe og 13,7 % i kontrolgruppen, idet der i de fleste tilfælde var tale om perifert ødem (13,2 vs. 9,2 %) og ødem (1,2 % vs. 0 %). 
The incidence for all grades of events in the cardiac dysfunction AESI category was 18.3% in the investigational arm and 13.7% in the control arm, the majority being events of peripheral oedema (13.2 vs 9.2%) and oedema (1.2% vs 0%).
Der sås ingen statistisk signifikant forskel i objektiv responsrate eller sygdomskontrolrate i ITTpopulationen mellem den eksperimentelle gruppe og kontrolgruppen, og begge rater var i kontrolgruppens favør. 
No statistically significant difference in ORR or DCR in the ITT population was observed between the investigational arm and control arms, and both rates favoured the control arm.
Der sås en signifikant forskel i progressionsfri overlevelse i ITT-populationen i henhold til investigators vurdering, men det var i kontrolgruppens favør. 
There was a significant difference in PFS in the ITT population based on investigator assessment, but in favour of the control arm.
I ITT-populationen var den mediane samlede overlevelse 20,37 måneder i den eksperimentelle gruppe og 19,75 måneder i kontrolgruppen (HR = 1,047 [95 %-KI: 0,841-1,303]; p = 0,69), og KM-kurverne for samlet overlevelse var fuldstændigt overlappende, hvilket tyder på, at tilføjelsen af Lartruvo til doxorubicin ikke havde nogen gavnlig effekt på den samlede overlevelse. 
In the ITT population, the median OS was 20.37 months in the investigational arm and 19.75 months in the control arm (HR=1.047 [95% CI: 0.841, 1.303]; p=0.69), and the OS KM curves are completely overlapping, indicating that adding Lartruvo to doxorubicin had no favourable effect on OS. Further OS analyses showed that in most subgroups HR estimates ranged from 0.9 to 1.1, consistent with the overall OS results.
Den eneste signifikante forskel i progressionsfri overlevelse, der blev konstateret, sås i ITT-populationen, men i kontrolgruppens favør. 
The only significant difference found in PFS was in the ITT population, but in favour of the control arm.
Der blev oftere rapporteret om hjertearytmier i den eksperimentelle gruppe (alle grader: 12,8 % vs. 9,6 %; grad ≥ 3: 2,7 % vs. 0,8 %). 
Cardiac arrhythmia events were more commonly reported in the investigational arm (any grade 12.8% vs 9.6%; grade >=3 2.7% vs 0.8%).
Med hynsyn til PDGFR-β sås der ingen signifikant sammenhæng mellem PDGFR-β-status og responset på olaratumab, hvad angår samlet overlevelse eller progressionsfri overlevelse. 
With regard to PDGFR-β, no significant association was found between PDGFR-β status and response to olaratumab in terms of OS or PFS. PDGFR-β did not seem to have a clear prognostic role in STS either.
en uafhængig vurdering; 6,6 vs. 4,1 måneder, hazard ratio (HR) 0,672 [95 %-KI: 0,442-1,021], p = 0,0615 iht. 
In this trial, treatment with olaratumab in combination with doxorubicin resulted in an improvement in progression-free survival (PFS) (8.2 vs. 4.4 months according to independent assessment; 6.6 vs. 4.1 months, hazard ratio (HR) 0.672 [95% CI: 0.442, 1.021], p = 0.0615 according to investigator assessment) and overall survival (OS) (26.5 months vs. 14.7 months, HR = 0.463; p = 0.0003).
Febril neutropeni var den hyppigst forekommende alvorlige uønskede hændelse; hyppigheden var sammenlignelig i de to grupper (12,8 % vs. 13,3 %). 
Few more SAE (38.9% vs 34.9%) occurred in the investigational arm than in the control arm. Febrile neutropenia was the most frequently SAE occurring with similar frequency in both arms (12.8% vs 13.3%).
De rå data blev gjort tilgængelige som separat dokumentation. 
The raw data were made available as separate documentation.
Produkterne til anvendelse hos hunde har siden december 2011 været godkendt i referencemedlemsstaten, Tjekkiet, hvor produktet til katte blev godkendt i maj i 2012. 
The presentations for use in dogs have already been authorised in the reference Member State, the Czech Republic, since December 2011 and the cat product was more recently authorised there in May 2012.
Ansøgninger om markedsføringstilladelse blev indgivet i de berørte medlemsstater via den gensidige anerkendelsesprocedure. 
Applications for marketing authorisation were submitted to the concerned Member States using the mutual recognition procedure.