qanastek/EMEA-V3 huggingface dataset:
The CHMP adopted the following harmonised wording: • Hypersensitivity to the active substance, to any of the excipients or any other ACE (Angiotensin Converting Enzyme) inhibitors (see section 6.1) • History of angioedema (hereditary, idiopathic or due to previous angioedema wit ACE inhibitors or AIIRAs(Angiotensin II Receptor Antagonists)) • Extracorporeal treatments leading to contact of blood with negatively charged surfaces (see section 4.5) • Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney • 2nd and 3rd trimester of pregnancy (see section 4.4 and 4.6) • Lactation (see section 4.6) Page 2/ 3 • Severe impairment of renal function with a creatinine clearance below 30 ml/ min in undialysed patients • Clinically relevant electrolyte disturbances which may worsen following treatment with TRITAZIDE (see section 4.4) • Severe impairment of liver function, hepatic encephalopathy
Paġna 2/ 3 • Kuri ekstrakorporali (extracorporeal) li jwasslu għal kuntatt ta ’ demm ma ’ uċuħ iċċarġjati b’ mod negattiv (ara sezzjoni 4. 5) • Stenożi tal- arterja renali bilaterali sinifikanti jew stenożi tal- arterja renali f’ kilwa waħda funzjonanti • It- tieni u t- tielet trimestru ta ’ tqala (ara sezzjonijiet 4. 4 u 4. 6) • Treddigħ (ara sezzjoni 4. 6) • Indeboliment qawwi tal- funzjoni renali bit- tneħħija ta ’ kreatinina taħt it- 30 ml/ min f’ pazjenti li mhumiex dijalizzati • Disturbi elettrolitiċi klinikament rilevanti li jistgħu jmorru għall- agħar wara kura bi TRITAZIDE (ara sezzjoni 4. 4) • Indeboliment qawwi tal- funzjoni tal- fwied, enċefalopatija epatika
The CHMP included under this session the warning about primary hyperaldosteronism, therefore adopted the following harmonised wording:
Is- CHMP inkluda f’ din is- sezzjoni it- twissija dwar l- iperaldosteroniżmu primarju, u għaldaqstant adotta l- kliem armonizzat li ġej:
The combination ramipril + hydrochlorothiazide does not represent a treatment of choice for primary hyperaldosteronism.
Il- kombinazzjoni ramipril + hydrochlorothiazide ma tirrappreżentax kura ta ’ għażla għall- iperaldosteroniżmu primarju.
If ramipril + hydrochlorothiazide is used in a patient with primary hyperaldosteronism, then careful monitoring of plasma potassium level is required.
Jekk ramipril + hydrochlorothiazide jintuża f’ pazjent b’ iperaldosteroniżmu primarju, ikun meħtieġ monitoraġġ preċiż tal- livell tal- potassju fil - plażma.
The CHMP included also new warnings for: pregnancy, surgery, electrolyte disturbances, and cough.
Is- CHMP inkluda wkoll twissijiet ġodda għal: tqala, intervent kirurġiku, disturbi elettrolitiċi u sogħla.
The CHMP endorsed the current list of products which interact or may interact with Tritazide, including additional text reinforcing lithium toxicity.
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
This is in line with the recommendation of the CHMP’ s Pharmacovigilance Working Party on use of ACE inhibitors in pregnancy.
Is- CHMP approva l- lista attwali ta ’ prodotti li ma jaqblux jew li jistgħu jinteraġixxu ma ’ Tritazide, inkluż test addizzjonali li jirrinforza t- tossiċità tal- litju.
The European Commission issued a decision on 6 March 2009.
4. 6 Tqala u treddigħ
Company responses provided on:
Tweġibiet tal- kumpanija pprovduti nhar:
Opinion date:
28 ta ’ April 2008, 24 ta ’ Ottubru 2008 Data tal- opinjoni:
Dr Ian Hudson (UK) Prof János Borvendég (HU) 24 January 2008 28 April 2008, 24 October 2008 18 December 2008
18 ta ’ Diċembru 2008
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS AND MARKETING AUTHORISATION HOLDER IN THE MEMBER STATE
LISTA TA` L- ISMIJIET, GĦAMLA FARMAĊEWTIKA (GĦAMLIET FARMAĊEWTIĊI), QAWWA (QAWWIET) TAL- PRODOTT( I) MEDIĊINALI, MNEJN JINGĦATA, L - APPLIKANT( I), ID- DETENTUR( I) TA` L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ FL- ISTATI MEMBRI
(Invented) Name Strength
Isem Ivvintat
Solution for injection
UMAN BIG 180 180 UI/ ml
Intramuscular use
Użu għal ġol -
Denmark
muskoli
Loc Ai Conti 55051 Castelvecchio Pascoli, Barga (Lucca) - ITALY
Loc Ai Conti 55051 Castelvecchio Pascoli, Barga (Lucca) - ITALJA
Umanbig 180 NE/ ml
għall- injezzjoni
180 IU/ ml
540UI/ 3ml
Solution for injection
Umanbig 180 180 UI/ ml
UMAN BIG
muskoli
(Invented) Name Strength
Loc Ai Conti 55051 Castelvecchio Pascoli, Barga (Lucca) - ITALJA
Route of administration
muskoli
Sweden
Il- Portugall
Umanbig 180
UMAN BIG 180 UI/ ml
180 IU/ ml
Soluzzjoni
Solution for
180 UI/ ml
Intramuscular use
għall- injezzjoni
180 IU/ ml
Umanbig 180
IU/ ml solution for injection
180 UI/ ml
injection
180 UI/ ml
540IU/ 3ml
540UI/ 3ml
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF UMAN BIG
SOMMARJU ĠENERALI TAL- EVALWAZZJONI XJENTIFIKA TA ’ UMAN BIG
UMAN BIG is a plasma derived medicinal product preparation of immunoglobulins (mainly IgG) with a specifically high content of antibodies against the hepatitis B virus surface antigen (HBsAg).
UMAN BIG huwa preparat mediċinali ta ’ immunoglobulini (prinċipalment IgG) derivat mill- plażma b’ kontenut speċifikament għoli ta ’ antikorpi kontra l- antiġene ta ’ superfiċje tal- virus tal- epatite B (HBsAg).
UMAN BIG belongs to the pharmacological class of immune sera and human specific immunoglobulins for intramuscular administration and contains 100-180 g/ l of plasma proteins with at least 90% of them representing Immunoglobulin G (IgG).
UMAN BIG jappartjeni għall- klassi farmakoloġika ta ’ sera immuni u ta ’ immunoglobulini speċifiċi umani għal għoti ġol- muskoli u fih 100- 180 g/ l ta ’ proteini tal- plażma b’ għallinqas 90% minnhom jirrappreżentaw Immunoglobulina G (IgG).
Specific neutralizing antibodies against the Hepatitis B virus are present at a concentration of not less than 180 IU/ ml.
Antikorpi newtralizzaturi speċifiċi kontra l- virus tal- epatite B huma preżenti f’ konċentrazzjoni ta ’ mhux inqas minn 180 IU/ ml.
It has been marketed since 1979, for intramuscular use.
Il- prodott ilu fis- suq mill- 1979, għal użu ġol- muskoli.
Eur. requirements, as well as reproducibility of quality characteristics, hence consistency of the biological response.
UMAN BIG huwa prodott minn ġabriet kbar ta ’ plażma umana, permezz ta ’ proċess industrijali kkonsolidat u konvalidat li jiżgura l- konformità mar- rekwiżiti tal - Farmakopea Ewropea kif ukoll ir- riproduċibilità tal- karatteristiċi tal- kwalità, għaldaqstant il - konsistenza tar- rispons bijoloġiku.
The application for UMAN BIG 180 IU/ ml solution for injection was submitted through the Mutual Recognition Procedure, on the basis of the marketing authorisation granted by the RMS (Italy) on the 2nd of June 1979.
L- applikazzjoni għal UMAN BIG 180 IU/ ml soluzzjoni injettabbli ppreżentata permezz tal- Proċedura ta ’ Rikonoxximent Reċiproku, fuq il- bażi tal- awtorizzazzjoni għat - tqegħid fis- suq u ngħatat mill- RMS (Italja) nhar it- 2 ta ’ Ġunju 1979.
The objecting member state Greece raised a potentially serious risk to public health related to the design of the submitted PK study designed to support the initial application, since the population enrolled in the PK study represents a different patient population from the population intended for the use of UMAN BIG and because the dosage administered was different from the posology indicated in the SPC.
Il- Greċja, l- Istat Membru li oġġezzjona, qajjem riskju potenzjalment gravi għas- saħħa pubblika relatat mal- mod kif inhu mfassal l- istudju farmakokinetiku ppreżentat sabiex jappoġġja l- applikazzjoni inizjali, billi l- popolazzjoni reklutata fl- istudju farmakokinetiku tirrappreżenta popolazzjoni ta ’ pazjenti differenti mill- popolazzjoni intenzjonata għall- użu ta 'UMAN BIG u minħabba li d- dożaġġ mogħti kien differenti mill- pożoloġija indikata fl- SPC.
Greece considered that a change in liver function is a common cause of altered drug pharmacokinetics and that the dosage in the PK study was much higher than that recommended in the relevant core SPC and proposed SPC.
Il- Greċja kkunsidrat li bidla fil- funzjoni epatika hija kawża komuni ta 'alterazzjonijiet tal- karatteristiċi farmakokinetiċi tal- mediċini u li d- dożaġġ fl - istudju farmakokinetiku kien ħafna ogħla minn dak rakkomandat mill- SPC ewlieni rilevanti u mill - SPC propost.
Therefore the results of the study can not be extrapolated to the population intended for use and consequently, the protective anti-HBs level in the population intended for use is not known and neither whether the recommended dose in the core SPC could guarantee an appropriate antibody level to prevent hepatitis B in adults and hemodialysed patients as well as newborns of a hepatitis B virus carrier-mother.
Għalhekk ir- riżultati tal- istudju ma jistgħux jiġu estrapolati għall- popolazzjoni intenzjonata biex tużaha u konsegwentement, il- livell tal- anti- HBs protettivi fil- popolazzjoni intenzjonata biex tużaha mhux magħruf u lanqas ma hu magħruf jekk id- doża rakkomandata fl- SPC ewlieni tistax tiggarantixxi livell xieraq ta ’ antikorpi biex tipprevjeni l- epatite B fl- adulti u f’ pazjenti emodijalizzati kif ukoll trabi tat- twelid minn omm li ġġorr il- virus tal- epatite B.
During the RMS procedure, the Applicant committed to carry out an observational study on newborns with mothers carrying the hepatitis B virus.
Matul il- proċedura tal- RMS, l- Applikant intrabat li jwettaq studju ta 'osservazzjoni fuq trabi tat- twelid minn omm li ġġorr il- virus tal- epatite B.
The study protocol was submitted to the RMS and all CMSs.
Il- protokoll tal- istudju ġie ppreżentat lill- RMS u lis- CMSs kollha.
Although the Reference Member State concluded that the objections raised had been resolved, the Objecting Concerned Member State was still of the opinion that a potential serious risk to public health was identified for this particular product, with regards to safety and efficacy.
Għalkemm l- Istat Membru ta 'Referenza ikkonkluda li l- oġġezzjonijiet imqajma issolvew, l- Istat Membru kkonċernat li kien qed joġġezzjona kien għadu tal- opinjoni li kien identifikat riskju potenzjali gravi għas- saħħa pubblika għal dan il- prodott partikolari, f’ termini ta ’ sigurtà u effikaċja.
The procedure was therefore referred to the CHMP in October 2008.
Għalhekk, il - proċedura ġiet riferuta lis- CHMP f’ Ottubru 2008.
Following the referral to the CHMP, the Committee noted the position of the RMS and the objecting CMS and decided to adopt a List of Questions addressed to the Blood Products Working Party (BPWP), in order to receive the view of the working party, on both specific issues related to this specific product and on issues related to immunoglobulins in general.
Wara li din ġiet riferuta lis- CHMP, il- Kumitat innota l- pożizzjoni tal- RMS u tal- CMS li kien qed joġġezzjona u ddeċieda li jadotta Lista ta ’ Mistoqsijiet indirizzati lill- Grupp ta ’ Ħidma għall- Prodotti tad- Demm (BPWP), sabiex jirċievi l - opinjoni tal- grupp ta ’ ħidma, fuq iż- żewġ kwistjonijiet speċifiċi relatati ma ’ dan il- prodott speċifiku u fuq kwistjonijiet relatati ma ’ immunoglobulini b’ mod ġenerali.
Summary of the report from the BPWP and CHMP position:
Sommarju tar- rapport mill- pożizzjoni tal- BPWP u tal- CHMP:
Is a single PK study conducted in a population and dose regimen different from the one intended for the Marketing Authorisation adequate and sufficient to support efficacy in all indications foreseen in the European core SPC for immunoglobulins, with no specific efficacy clinical trial?
Studju farmakokinetiku wieħed magħmul f’ popolazzjoni u reġim ta ’ dożaġġ differenti minn dak intenzjonat għall- Awtorizzazzjoni għat- Tqegħid fis- Suq huwa xieraq u biżżejjed biex isostni l- effikaċja fl- indikazzjonijiet kollha previsti fl- SPC ewlieni Ewropew għall - immunoblobulini, mingħajr prova klinika speċifika fir- rigward tal- effikaċja?
The Applicant stated that the only relevant measure of efficacy for this kind of product is the level of protective anti-HBs achieved in the plasma, since after the introduction of vaccination it is no longer feasible to assess the efficacy of the product on the basis of the incidence of new infections.
L- Applikant iddikjara li l- unika miżura rilevanti tal- effikaċja għal dan it- tip ta ’ prodott hija l- livell ta ’ anti- HBs protettivi miksubin fil- plażma, billi wara l- introduzzjoni ta ’ tilqima, ma jibqax fattibbli li tiġi valutata l- effikaċja tal- prodott fuq il- bażi tal- inċidenza ta ’ infezzjonijiet ġodda.
In addition, the Applicant submitted several clinical studies conducted in populations that are representative of the populations indicated in the SPC as bibliographic reference, which confirm the efficacy of UMAN BIG in the claimed indications.
Barra minn hekk, l - Applikant issottometta diversi studji kliniċi mwettqa f' popolazzjonijiet li huma rappreżentattivi tal - popolazzjonijiet indikati fl- SPC bħala referenza bibljografika, li jikkonfermaw l- effikaċja ta ’ UMAN BIG fl- indikazzjonijiet iddikjarati.
The Applicant also demonstrated the impossibility to perform any clinical study in any of the populations included in the indication, apart from newborns, after the introduction of the vaccination.
L- Applikant wera wkoll l- impossibbiltà li jwettaq xi studju kliniku f’ xi waħda mill- popolazzjonijiet inkluża fl- indikazzjoni, apparti t- trabi tat- twelid, wara l- introduzzjoni tat- tilqima.
5 immunoglobulins in HBs-Ag-Negative patients who have received liver transplantation (OLT patients) in order to support the efficacy of the product.
5 L- Applikant ippreżenta dejta minn studju farmakokinetiku KB- 036, li jevalwa l- profil farmakokinetiku tal- immunoblobulini tal- epatite B f’ pazjenti HBs- Ag- negattivi li rċevew trapjant tal - fwied (pazjenti sottoposti għal trapjant ortotopiku tal- fwied, OLT) sabiex isostni l- effikaċja tal - prodott.
The study was performed in different populations and in much higher posology than recommended in the relevant core SPC because the Applicant considered that the indications, posology and pharmacokinetic information reported in the core SPC are not product specific, but rather that they apply to products complying with the relative European Pharmacopoeia monograph, such as UMAN BIG.
L- istudju sar f’ popolazzjonijiet differenti u f’ pożoloġija ħafna ogħla minn dik speċifikata fl - SPC ewlieni għax l- Applikant ikkunsidra li l- indikazzjonijiet, il- pożoloġija u l- informazzjoni farmakokinetika rrappurtata fl- SPC ċentrali mhumiex speċifiċi għall- prodott, iżda li japplikaw għal prodotti li huma konformi mal- monografija tal- Farmakopea Ewropea relattiva, bħal UMAN BIG.
The Applicant provided bibliographic data showing that the pharmacokinetics of UMAN BIG in the population in which the PK study was carried out is super-imposable to that of healthy volunteers; therefore the population of study KB 036, although representing a specific subset of patients, did not influence the results obtained.
L - Applikant ipprovda dejta bibljografika li turi li l- farmakokinetika ta ’ UMAN BIG fil- popolazzjoni li fiha sar l- istudju farmakokinetiku tista 'toqgħod għal dik tal- voluntiera b' saħħithom; għalhekk il - popolazzjoni tal- istudju KB 036, għalkemm tirrappreżenta sottogrupp speċifiku ta ’ pazjenti, ma influwenzatx ir- riżultati miksuba.
Literature references show also that the pharmacokinetic profile of UMAN BIG is comparable to that of other intramuscular Hepatitis B immunoglobulin products.
Ir- referenzi mil- letteratura juru wkoll li l- profil farmakokinetiku ta ’ UMAN BIG huwa komparabbli għal dak ta ’ prodotti oħra ta ’ immunoglobulina għall- epatite B intramuskolari.
The Applicant provided comprehensive published data on the use of UMAN BIG in the prophylaxis of hepatitis B in newborns from HBsAg carrier mothers, demonstrating its efficacy in this particular subset of population.
L- Applikant ipprovda dejta komprensiva ppubblikata fuq l- użu ta ’ UMAN BIG fil- profilassi ta ’ epatite B fi trabi tat- twelid minn omm infettata b’ HbsAg, li turi l- effikaċja tagħha f’ dan is- sottogrupp partikolari tal- popolazzjoni.
More than 1,000 Italian newborns included in the studies (published between 1983 and 2001) received UMAN BIG and the dose regimen and protective threshold (10 mIU/ ml) are consistent with the provisions of the current core SPC and proposed SPC.
Aktar minn 1, 000 tarbija tat- twelid Taljana inklużi fl- istudji (ippubblikati bejn l- 1983 u l- 2001) rċevew UMAN BIG u r- reġim tad- doża u l- limitu protettiv (10mlU/ ml) huma konsistenti mad- dispożizzjonijiet tal- SPC ewlieni attwali u mal- SPC propost.
There are enough data regarding the safety and PK of UMAN BIG in newborns, administered for the prevention of HBV transmission from HBsAg infected mothers.
Hemm biżżejjed dejta rigward is- sigurtà u l- proprjetajiet farmakokinetiċi ta ’ UMAN BIG fit- trabi tat- twelid, meħud għall - prevenzjoni tat- trasmissjoni tal- HBV minn ommijiet infettati bl- HBsAg.
There is also convincing evidence that UMAN BIG, along with active anti-HBV immunization, prevented transmission of HBV to newborns from anti- HBe+ mothers.
Jeżistu wkoll provi konvinċenti li UMAN BIG, flimkien ma 'tilqim attiv kontra l- HBV, ipprevjena t- trasmissjoni tal- HBV lit- trabi tat- twelid minn omm anti- HBe+.
Finally, the papers quoted by the Applicant indicate that UMAN BIG prevented newborns from HBeAg infected mothers from becoming chronic HBsAg carriers.
Finalment, id- dokumenti kkwotati mill- Applikant jindikaw li UMAN BIG ipprevjena t- trabi tat- twelid minn ommijiet infettati bl- HBeAg milli jsiru ġarriera tal - HbsAg b’ mod kroniku.
Monograph (0722) and has shown a PK and safety profile within the expected ranges of an immunoglobulin, in a study in stabilized HBsAg/ HBeAg negative post-liver transplant patients.
Il- BWPB ikkunsidra li UMAN BIG jaderixxi mal- monografija tal- Farmakopea Ewropea (0722) u wera profil farmakokinetiku u ta ’ sigurtà fi ħdan il- livelli mistennija ta 'immunoglobulina, fi studju fuq pazjenti wara t- trapjant tal- fwied b’ HbsAg/ HbeAg negattivi stabbilizzati.
Levels of antibodies of ≥ 100IU/ ml were achieved.
Intlaħqu livelli ta ’ antikorpi ta ’ ≥100IU/ ml.
Furthermore, published data from non-sponsor driven studies using UMAN BIG in the prophylaxis of hepatitis B in approximately 1000 newborns of HBsAg carrier mothers was submitted.
Barra minn hekk, ġiet ippreżentata dejta ppubblikata minn studji, li mhumiex sponsorizzati minn xi sostenitur, bl- użu ta ’ UMAN BIG fil- profilassi tal- epatite B f’ bejn wieħed u ieħor 1000 tarbija tat- twelid minn ommijiet li jġorru l- HbsAg.
The dose regimen and protective threshold were consistent with the current core SPC.
Ir- reġim pożoloġiku u l- limitu protettiv kienu konsistenti mal- SPC ewlieni preżenti.
Based on the proof-of-principle applied to all immunoglobulins, the BPWP considered that submitting a single PK study is acceptable.
Skont il- prova tal- prinċipju applikata għall - immunoglobulini kollha, il- BPWP ikkunsidra li s- sottomissjoni ta ’ studju farmakokinetiku wieħed hija aċċettabli.
Monographs is well established.
Il- CHMP innota li UMAN BIG huwa prodott minn ġbir kbir ta ’ plażma umana, permezz ta ’ proċess industrijali konsolidat u konvalidat u li l- konformità ta ’ UMAN BIG mal- monografiji tal- Farmakopea Ewropea hija stabbilita sew.
The PK KB-036 study demonstrates that the anti-HBsAg antibodies in UMAN BIG maintain the kinetic profile of the natural antibodies and that the entire production process does not affect their characteristics or the integrity of the immunoglobulin molecule and therefore does not alter the biological response.
L- istudju farmakokinetiku KB- 036 juri li l- antikorpi anti- HbsAg f’ UMAN BIG iżommu l- profil kinetiku tal- antikorpi naturali u li l- proċess ta ’ produzzjoni kollu ma jaffettwax il- karatteristiċi tagħhom jew l- integrità tal- molekula tal- immunoglobulina u għalhekk ma jbiddilx ir- rispons bijoloġiku.
The PK behaviour, especially in terms of half life of the anti HB antibodies and maintenance of a protective antibody level titre can be considered as an acceptable surrogate marker of efficacy.
L- imġiba farmakokinetika, b’ mod speċjali f’ termini ta ’ half life tal - antikorpi kontra l- HB u ż- żamma ta ’ titolu (titre) ta ’ livell protettiv tal- antikorp, tista ’ titqies bħala markatur sostitut aċċettabbli tal- effikaċja.
The CHMP also noted the commitment to carry out an observational study on newborns with mothers carrying the hepatitis B virus.
Is- CHMP innota wkoll l- impenn li jsir studju ta 'osservazzjoni fuq trabi tat- twelid b' ommijiet ġarriera tal- virus tal- epatite B.
Eur. requirements in terms of potency and the long lasting experience in clinical use, support the efficacy of the product and the indications applied for in the SPC and considered that submitting a single PK study is acceptable.
Għalhekk, is- CHMP ikkunsidra li dawn ir- riżultati, flimkien mal- konformità mal- ħtiġiet tal- Farmakopea Ewropea. f’ termini ta ’ effikaċja u l- esperjenza fit- tul fl- użu kliniku, isostnu l- effikaċja tal- prodott u l- indikazzjonijiet li saret applikazzjoni għalihom fl- SPC u ikkunsidra li s- sottomissjoni ta 'studju farmakokinetiku wieħed huwa aċċettabbli.
Are Post Marketing Safety (PMS) data generated in only one EU country adequate to define the safety profile of the product?
Id- dejta dwar is- Sigurtà ta ’ Wara t- Tqegħid fis- Suq (PMS) iġġenerata f’ pajjiż wieħed biss tal - UE hija adegwata biex tiddefinixxi l- profil ta ’ sigurtà tal- prodott?
The Applicant provided a summary of the available post-marketing experience data for both UMAN BIG and IMMUNOHBs (a different brand name an identical product with the same pack sizes and concentration, produced by the same manufacturing sites, using the same manufacturing process), indicating that approximately 143,381,160 IU of IMMUNOHBs and approximately 11,695,680 IU of UMAN BIG have been sold worldwide between June 1995 and December 2007.
L- Applikant ipprovda sommarju tad- dejta disponibbli dwar l- esperjenza wara t- tqegħid fis- suq kemm għal UMAN BIG kif ukoll għal IMMUNOHBs (isem ta ’ ditta differenti iżda prodott identiku bl- istess daqs tal- pakketti u konċentrazzjonijiet, prodotti mill- istess siti ta ’ produzzjoni, bl- użu tal- istess proċess ta ’ produzzjoni), biex jindika li bejn Ġunju 1995 u Diċembru 2007 inbiegħu madwar 143, 381, 160 IU
The Applicant also provided exposure data, stating that a total of about 143,589 injections were given to patients.
L- Applikant ipprovda wkoll dejta dwar l- espożizzjoni u ddikjara li bħala total ingħataw madwar 143, 589 injezzjoni lill - pazjenti.
During this period, no notification of any adverse reaction related to the products IMMUNOHBs and UMAN BIG was received by the Applicant, either through the literature or the Regulatory Authorities,
Matul dan il- perjodu, l- Applikant ma rċieva l- ebda notifika ta ’ xi reazzjoni avversa relatata mal- prodotti IMMUNOHBs u UMAN BIG, jew permezz tal- letteratura jew tal- Awtoritajiet Regolatorji, Tobba, Spiżjara jew Pazjenti.
A literature search on specific immunoglobulins for intramuscular administration has shown, in general, a satisfactory profile of tolerability and safety, even if mild to moderate adverse events have been observed.
Tfittxija fil- letteratura fuq immunoglobulini speċifiċi għal amministrazzjoni ġol- muskoli, b' mod ġenerali wriet profil sodisfaċenti ta 'tollerabilità u sigurtà, anke jekk ġew osservati avvenimenti avversi ħfief għal moderati.
Limited cases of nausea, vomiting, hypotension, tachycardia, allergic or anaphylactic reactions have also been reported.
Ġew ukoll rappurtati każijiet limitati ta ’ nawżea, remettar, ipotensjoni, takikardija, reazzjonijiet allerġiċi jew anafilattiċi.
Moreover, the potential risk of transmitting infective agents through administration of anti hepatitis B immunoglobulins is only theoretical due to the state of the art knowledge and procedures for quality control.
Barra minn hekk, ir - riskju potenzjali li jiġu trasmessi aġenti infettivi permezz tat- teħid ta ’ immunoglobulini kontra l - epatite B huwa biss teoriku minħabba l- għarfien u l- proċeduri mill- aktar moderni għall- kontroll tal - kwalità.
The Applicant concluded that no new information on tolerability is available to suggest a modification of the safety profile of UMAN BIG.
L- Applikant ikkonkluda li m’ hemm l- ebda informazzjoni ġdida disponibbli dwar it- tollerabilità biex tiġi suġġerita modifika tal- profil ta ’ sigurtà ta ’ UMAN BIG.
According to the Applicant, the characteristics of the product, the available safety data, and the overall safety system in place do not warrant any recommendations for further risk minimisation activities.
Skont l- Applikant, il- karatteristiċi tal - prodott, id- dejta disponibbli dwar is- sigurtà, u s- sistema ta 'sigurtà globali fis- seħħ ma jeħtiġux rakkomandazzjonijiet għal attivitajiet oħra għat- tnaqqis tar- riskji.
The BPWP considered that post marketing safety data generated in only one EU member state can be adequate to define the safety profile of the product provided that the quality of the data and the Pharmacovigilance system is sufficient.
Il- BPWP ikkunsidra li d- dejta ta ’ sigurtà wara t- tqegħid fis- suq iġġenerata fi Stat Membru tal- UE wieħed biss tista 'tkun xierqa biex tiddefinixxi l- profil ta' sigurtà tal- prodott sakemm il- kwalità tad - dejta u s- sistema ta 'Farmakoviġilanza ikunu biżżejjed.
The CHMP noted that an active pharmacovigilance system is in place in Italy since 1975 guaranteeing a strict control of the adverse events linked to medicinal products and that the Italian pharmacovigilance database does not contain a single suspected adverse reaction signal related to UMAN BIG, which is consistent with the statement of the Applicant of the safety of UMAN BIG.
Is- CHMP innota li fl- Italja teżisti sistema ta ’ farmakoviġilanza attiva li ilha fis- seħħ sa mill- 1975 li tiggarantixxi kontroll strett tal- avvenimenti avversi marbuta ma ’ prodotti mediċinali u li d- database ta ’ farmakoviġilanza Taljana ma fihiex sinjal wieħed ta ’ reazzjoni avversa suspettata relatata ma ’ UMAN BIG, li hi konsistenti mad- dikjarazzjoni tal- Applikant dwar is- sigurtà ta ’ UMAN BIG.
Therefore, the CHMP was of the opinion that the submitted post marketing safety data are adequate to assess the safety profile of the product, even if they originate from a single EU member state.
Għalhekk is - CHMP kien tal- opinjoni li d- dejta ta ’ sigurtà wara t- tqegħid fis- suq sottomessa hija xierqa biex tevalwa l- profil ta ’ sigurtà tal- prodott, anke jekk din toriġina minn Stat Membru tal- UE wieħed.
Should non-clinical product-specific safety data be submitted for this product, in line with point 5.3 the Core SPC for human Immunoglobulin for IV administration?
Għandha tkun sottomessa dejta dwar is- sigurtà mhux klinika speċifika għall- prodott, skont il - punt 5. 3 tal- SPC ewlieni għall- Immunoglobulina umana għal amministrazzjoni IV.
And if yes, what kind of non-clinical studies shall be performed?
U jekk iva, x’ tip ta ’ studji mhux kliniċi għandhom isiru?
The BPWP considered that data from pre-clinical studies do not provide any additional information concerning the actual immunoglobulin and that often, data on the excipients are necessary.
Il- BPWP ikkunsidra li d- dejta minn studji prekliniċi ma tipprovdix xi informazzjoni addizzjonali li tikkonċerna l- immunoglobulina attwali u li spiss, id- dejta dwar is- sustanzi mhux attivi hija neċessarja.
UMAN BIG contains glycine as the excipient, a natural amino acid and therefore not expected to cause any problems.
UMAN BIG fih il- gliċina bħala s- sustanza mhux attiva, amminoaċidu naturali u għalhekk mhux mistenni li jikkawża xi problema.
The CHMP considered that based on the 28 years of clinical experience with the existing formulation of UMAN BIG, the safety in humans can be considered to have been extensively assessed.
Is- CHMP ikkunsidra li abbażi tat- 28 sena esperjenza klinika bit- test eżistenti ta ’ UMAN BIG, is - sigurtà fil- bnedmin tista ’ titqies li ġiet valutata b’ mod estensiv.
The CHMP was also of the opinion that a new pre-clinical investigation would not be justified at the moment, based on the extensive clinical use and the supporting pharmacovigilance data.
Is- CHMP kien ukoll tal- opinjoni, ibbażata fuq l- użu kliniku estensiv u d- dejta ta ’ sostenn dwar il- farmakoviġilanza, li investigazzjoni preklinika ġdida ma tkunx iġġustifikata f’ dan il- mument.
Does the BPWP consider necessary the development of a specific Note for Guidance on the Clinical Investigation of Human Plasma derived Hepatitis-B Immunoglobulins to outline requirements particularly with regard to the design of the clinical studies and the required safety data for the claimed indications?
Il- BPWP jikkunsidra neċessarju l- iżvilupp ta ’ Nota speċifika għal Gwida dwar l - Investigazzjoni Klinika tal- Immunoglobulini tal- Epatite B derivata mill- Plażma Umana biex jiġu deskritti r- rekwiżiti partikolarment fir- rigward tad- disinn tal- istudji kliniċi u d- dejta dwar is- sigurtà meħtieġa għall- indikazzjonijiet iddikjarati?
The BPWP noted that a guideline would not be helpful for currently ongoing applications but that a combined Guideline on the data expected to support applications for specific immunoglobulins against hepatitis B, varicella, tetanus, tick-borne encephalitis and rabies, for which there is currently only a core SPC.
Il- BPWP innota li linja gwida ma tkunx ta ’ għajnuna għall- applikazzjonijiet li għaddejjin bħalissa iżda Linja Gwida kombinata dwar id- dejta mistennija li ssostni applikazzjonijiet għal immunoglobulini speċifiċi kontra l- epatite B, il- ġidri r- riħ, it- tetnu, l- enċefalite minn qurdien u r- rabbja, li għalihom s’ issa hemm biss SPC ewlieni biss.
The CHMP fully endorses the development of a combined Guideline on specific immunoglobulins, in order to harmonise the requirements for granting marketing authorization.
Is- CHMP awtorizza kompletament l- iżvilupp ta ’ Linja Gwida kombinata dwar immunoglobulini speċifiċi, sabiex jiġu armonizzati r- rekwiżiti għall- għoti ta ’ awtorizzazzjoni għal tqegħid fis- suq.
In conclusion, the CHMP sought advice from the Blood Products Working Party on the four questions raised for discussion and noted the positive recommendation in favour of UMAN BIG expressed by the BPWP in a report dated 27 November 2008.
7 Bħala konklużjoni, is- CHMP talab konsulenza mingħand il- Grupp ta ’ Ħidma għall- Prodotti tad- Demm fuq l- erba ’ mistoqsijiet imqajma għad- diskussjoni u nnota r- rakkomandazzjoni pożittiva favur UMAN BIG imfissra mill- BWPW f’ rapport datat is- 27 ta ’ Novembru 2008.
The CHMP noted that no safety issues were raised in over 28 years of extensive clinical practice, following extensive use in the pre-and-post vaccination era and that the Italian pharmacovigilance database does not contain a single signal of any suspect
Is- CHMP innota li ma tqajmet l - ebda kwistjoni dwar is- sigurtà f’ aktar minn 28 sena prattika klinika estensiva, wara użu estensiv fl- era ta ’ qabel u ta ’ wara t- tilqim u li d- database dwar il- farmakoviġilanza Taljana ma fihiex sinjal wieħed ta ’ xi suspett ta ’ reazzjoni avversa relatata ma ’ UMAN BIG.
The CHMP also noted the commitment to carry out an observational study on newborns with mothers carrying the hepatitis B virus.
Is- CHMP innota wkoll l- impenn li jitwettaq studju ta 'osservazzjoni fuq trabi tat- twelid b' ommijiet li qed iġorru l- virus tal- epatite B.
The CHMP considered that efficacy in the sought indications has been demonstrated, based on the submitted PK study and the literature data.
Is - CHMP ikkunsidra li l- effikaċja fl- indikazzjonijiet imfittxija ġiet murija, ibbażata fuq l- istudju famakokinetiku u d- dejta dwar il- letteratura sottomessa.
Therefore, the CHMP is of the opinion that the benefit/ risk balance of the product can be considered to be positive and that the product is approvable.
Għalhekk, is- CHMP huwa tal- opinjoni li l - bilanċ tal- benefiċċju/ riskju tal- prodott jista ’ jitqies bħala wieħed pożittiv u li l- prodott għandu jiġi approvat.
GROUNDS FOR OPINION
RAĠUNIJIET GĦAL OPINJONI
- the CHMP considered that the post marketing safety data submitted are adequate to establish the
- is- CHMP ikkunsidra li d- dejta dwar is- sigurtà wara t- tqegħid fis- suq sottomessa hija adegwata biex
positive safety profile of UMAN BIG,
tistabbilixxi profil ta ’ sigurtà pożittiv ta ’ UMAN BIG,
- the CHMP considered the efficacy profile of UMAN BIG to be satisfactory for the indications
- is- CHMP ikkunsidra l- profil tal- effikaċja ta ’ UMAN BIG bħala wieħed sodisfaċenti għall -
applied for in the SPC,
indikazzjonijiet li saru applikazzjonijiet għalihom fl- SPC,
- the CHMP considered that the benefit/ risk of UMAN BIG is positive,
- is- CHMP ikkunsidra li l- benefiċċju/ riskju ta ’ UMAN BIG huwa wieħed pożittiv,
the CHMP has recommended the granting of the Marketing Authorisations for which the Summary of Product Characteristics, labelling and package leaflet remain as per the final versions achieved during the Coordination Group procedure as mentioned in Annex III for UMAN BIG.
is- CHMP irrakkomanda l- għoti tal- Aworizzazzjonijiet għat- Tqegħid fis- Suq li għalihom is- Sommarju tal- Karatteristiċi tal- Prodott, it- tikketta u l- fuljett ta 'tagħrif jibqgħu skont il- verżjonijiet finali miksuba waqt il- proċedura tal- Grupp ta' Koordinament kif imsemmija fl- Anness III għal UMAN BIG.
9 The valid Summary of Product Characteristics, labelling and package leaflet are the final versions achieved during the Coordination group procedure.
9 Is- Sommarju tal- Karatteristiċi tal- Prodott, l- ittikkettar u l- fuljett ta ’ tagħrif validi huma l- verżjonijiet finali miksuba waqt il- proċedura tal- Grupp tal- Koordinazzjoni.
Ref.
Londra, 9 ta ’ Marzu 2009 Dok. ta ’ Ref.
EMEA/ CHMP/ 173455/ 2009
EMEA/ CHMP/ 173447/ 2009
Questions and answers on the referral for Uman Big Human Hepatitis B Immunoglobulins, 180 IU/ ml, solution for injection
Mistoqsija u tweġiba dwar ir- referenza għal Uman Big Human Hepatitis B Immunoglobulins, 180 IU/ ml, soluzzjoni għal injezzjoni
The European Medicines Agency (EMEA) has completed a referral procedure following a disagreement among Member States of the European Union regarding the authorisation of the medicine Uman Big 180 IU/ ml, solution for injection.
L- Aġenzija Ewropea għall- Mediċini (EMEA) temmet proċedura ta ’ referenza wara nuqqas ta ’ ftehim fost Stati Membri tal- Unjoni Ewropea rigwar l- awtorizzazzjoni tal- mediċina Uman Big 180 IU/ ml, soluzzjoni għal injezzjoni.
The Agency’ s Committee for Medicinal Products for Human Use (CHMP) has concluded that the benefits of Uman Big outweigh its risks, and that the marketing authorisation granted in Italy can be recognised in other Member States of the European Union and the European Economic Area.
Il- Kumitat għall- prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) tal - Aġenzija ikkonkluda illi l- benefiċċji tal- Uman Big huma ogħola mir- riskji tiegħu, u illi l - awtorizzazzjoni għal fuq is- suq mogħtija fl- Italja tista ’ tiġi rikonoxxuta fl- Istati Membri l- oħra tal - Unjoni Ewropea u fiż- Żona Ekonomika Ewropea.
The review was carried out under an ‘ Article 29’ referral 1.
Ir- reviżjoni saret skont referenza ‘ tal- Artikolu 29 ’.
What is Uman Big?
X’ inhu Uman Big?
Uman Big is a solution of human hepatitis B immunoglobulins.
Uman Big huwa soluzzjoni ta ’ immunolgobulini tal- epatite umana B.
Immunoglobulins are blood proteins that have been extracted from donor plasma.
L- immunolglobulini huma proteini tad- demm li ġew estratti mill- plażma ta ’ donatur.
Hepatitis B immunoglobulins contain high levels of antibodies against the hepatitis B virus.
L- immunolgobuli tal- epatite B fihom livelli għolja ta ’ antikorpi kontra l- vajrus tal- epatite B.
Uman Big is given as an intramuscular (into the muscle) injection to prevent hepatitis B in the following cases: • in case of accidental exposure in people who have not been vaccinated against the hepatitis B virus; including those whose vaccination is incomplete or status unknown; • in haemodialysed patients (patients whose kidneys have failed and who rely on a blood purification technique called haemodialysis), until vaccination has become effective; • in the newborn of a hepatitis B virus carrier-mother; • in subjects who did not show an immune response after vaccination (and for whom a continuous prevention is necessary due to the continuous risk of being infected with hepatitis B.
L- Uman Big jingħata bħala injezzjoni intramuskolari (fil- muskolu) għal prevenzjoni tal- epatite B fil- każijiet li ġejjin: f’ każ ta ’ espożizzjoni aċċidentali f’ nies li kienu ġew vaċċinati kontra l- vajrus tal- epatite B; inklużi  dawk li l- vaċċinazzjoni tagħhom mhijiex sħiħa jew l- qagħda mhijiex magħrufa; f’ pazjenti emodjalizzati (pazjenti li l- kliewi tagħhom waqfu jew li huma dipendenti fuq il -  purifikazzjoni teknika msejħa emodijaliżi), sakemm il- vaċċinazzjoni ssir effikaċi; f’ tarbija li għadha kemm twieldet minn omm li ġġorr il- vajrus tal- epatite B;  f’ persuni li ma wrewx rispons immunitarju wara l- vaċċinazzjoni (u li għalihom hija meħtieġa  prevenzjoni kontinwa minħabba r- riskju kontinwu li jiġu infettati bl- epatite B.
Why was Uman Big reviewed?
Għaliex ġie rivedut l- Uman Big?
Kedrion S. p. A. submitted Uman Big for mutual recognition on the basis of the initial authorisation granted by Italy on 2 June 1979.
Kedrion S. p. A. issottomettiet Uman Big għar- rikonoxximent reċiproku abbażi tal- awtorizzazzjoni inizjali mogħtija mill- Italja fit- 2 ta ’ Ġunju 1979.
The company wanted the authorisation to be recognised in Austria, Denmark, Germany, Greece, Hungary, Poland, Portugal and Sweden (the concerned Member States).
Il- kumpanija ried li l- awtorizzazzjoni tiġi rikonoxxuta fl- Awstrija, fid- Danimarka, fil- Ġermanja, fil- Greċja, fl- Ungerija, fil- Polonja, fil- Portugall u fl- Iżvezja (l- Istati Membri konċernati).
These member states were not able to reach an agreement.
Dawn l- Istati Membri ma kienux kapaċi jilħqu ftehim.
On 31 October 2008, the Italian medicines agency, Agenzia Italiana del Farmaco, referred the matter to the CHMP.
Fil- 31 ta ’ Ottubru 2008, l- Aġenzija Taljana għall- Mediċini, l- Agenzia Italiana del Fármaco, irreferiet il- każ quddiem is- CHMP.
The grounds for the referral were concerns over the insufficiency of the clinical data submitted to establish the efficacy of the product.
Ir- raġunijiet għar- referenza kienu tħassib dwar l- insuffiċjenza ta ’ dejta klinika sottomessa sabiex tiġi stabbilita l- effikaċja tal- prodott.
In addition, the absence of product specific safety data or post- marketing safety data was raised as a concern.
Barra minn hekk, in- nuqqas ta ’ dejta speċifika dwar is- sigurtà tal - prodott jew dejta dwar is- sigurtà ta ’ wara l- awtorizzazzjoni ġiet imqajma bħala tħassib.
Based on evaluation of the currently available data and the scientific discussion within the Committee and at the CHMP’ s Blood Products Working Party, the CHMP concluded that the benefits of Uman Big outweigh its risks, and that therefore the marketing authorisation for Uman Big should be granted in all concerned member states.
Abbażi ta ’ evalwazzjoni tad- dejta disponibbli attwalment u d- diskussjoni xjentifika fi ħdan il- Kumitat u fil- Grupp tax- Xogħol ghal Prodotti tad- Demm CHMP, is- CHMP ikkonkluda li l- benefiċċji tal- Uman Big huma ogħla mir- riskji tiegħu, u li għalhekk l- awtorizzazzjoni għat- tqegħid fuq is- suq għal Uman Big għandha tingħata fl- Istati Membri konċernati kollha.
The European Commission issued a decision on 06 March 2009.
Il- Kummissjoni Ewropea adottat deċiżjoni fis- 6 ta ’ Marzu 2009.
Referral start date:
Data ta ’ bidu tar- referenza:
Antonio Addis (Italy) Dr Catherine Moraiti (Greece) 20 November 2008 18 December 2008
Antonio Addis (Italja) Dott. ssa Catherine Moraiti (Greċja) 20 ta ’ Novembru 2008 18 ta ’ Diċembru 2008
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCT, ROUTE OF ADMINISTRATION, APPLICANT AND MARKETING AUTHORISATION HOLDER IN THE MEMBER STATES
LISTA TA ’ L- ISMIJIET, GĦAMLA FARMAĊEWTIKA, IL- QAWWA TAL- PRODOTT MEDIĊINALI, MNEJN JINGĦATA, APPLIKANT U D- DETENTUR TA ’ L - AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ FL- ISATI MEMBRI Stat Membru
Marketing Authorisation Holder
Id- Detentur ta ’ l- Awtorizazzjoni għat- Tqegħid fis- Suq
Pharmaceutica l form
Għamla farmaċewtika
Content (concentration)
Kontenut (konċentrazzjoni
25-28 North Wall Quay, Dublin, Ireland
25- 28 North Wall Quay, Dublin, l- Irlanda
Subcutaneous
Taħt il- ġilda
United Kingdom
Ir- Remju Unit
3 SCIENTIFIC CONCLUSIONS
3 KONKLUŻONIJIET XJENTIFIĊI
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF VANTAS (see Annex I)
SOMMARJU GLOBALI TA ’ L- EVALWAZZJONI TA ’ VANTAS (Ara Anness I)
Early in its natural cycle, prostate cancer is androgen dependent.
Kmieni fiċ- ċiklu naturali tiegħu, il- kanċer tal- prostata huwa dipendenti fuq l- androġeni.
Late in the clinical course, it is androgen independent, and is refractory to hormonal therapy.
Tard fil- kors kliniku, huwa indipendenti mill- androġeni, u huwa refrattarju għal terapija ormonali.
However, even in the androgen- independent state, prostate cancer is likely to contain subpopulations of cells that are androgen dependent.
Madankollu, anke fl- istat indipendenti mill- androġeni, il- kanċer tal- prostata x’ aktarx fih sotto- popolazzjonijiet ta ’ ċelloli li huma dipendenti fuq l- androġeni.
On the basis of these limited data, continued androgen suppression in men with androgen- independent prostate cancer (AIPC) is the current standard of care.
Fuq il- bażi ta ’ dan it- tagħrif ristrett, soppressjoni mtennija ta ’ l- androġeni f’ irġiel b’ kanċer tal- prostata indipendenti mill- androġeni (AIPC) hija l- istandard ta ’ kura attwali.
In the past, testosterone suppression was achieved by bilateral orchiectomy (surgical castration).
Fl- imgħoddi, soppressjoni ta ’ testosteron kienet tinkiseb permezz ta ’ orkidektomija bilaterali (kastrazzjoni kirurġika).
For the last two decades, injection of long-acting luteinizing hormone-releasing hormone agonists (LH-RHas) has been used to achieve androgen ablation.
Għal dawn l- aħħar għoxrin sena, injezzjoni ta ’ ormon li jerħi l - ormon lutejnizzanti li jaħdem fit- tul (LH- RHas) qegħda tintuża biex tikseb ablatazzjoni kirurġika.
In principle, it is important to achieve serum testosterone concentrations as low as possible for ADT to minimize stimulation of prostate cancer cells.
Fil - prinċipju, huwa importanti li jinkisbu konċentrazzjonijiet ta ’ testosteron fis- serum baxxi kemm jista ’ jkun għal ADT biex tiġi minimizzata l- istimulazzjoni ta ’ ċelloli tal- kanċer tal- prostata.
Serum testosterone concentrations that correspond to castration levels have generally been set at less than 50 ng/ dL (1.7 nmol/ L), given the known variability of values in reference laboratories.
Konċentrazzjonijiet ta ’ testosteron fis- serum li jikkorispondu ma ’ livelli ta ’ kastrazzjoni ġew iffissati b’ mod ġenerali għal inqas minn 50 ng/ dL (1. 7 nmol/ L), mogħtija l- varjabilità tal- valuri fil- laboratorji ta ’ referenza.
The achievement of castrate levels of testosterone is an acceptable surrogate endpoint in hormone sensitive advanced prostate cancer which can be translated into less pain from bone metastases, improvement in urinary flow, and in some cases slowing of tumour progression, although a clear-cut survival benefit has not been demonstrated.
Il- kisba ta ’ livelli ta ’ testosteron ta ’ kastrazzjoni hija punt ta ’ tmiem sostitut aċċettabbli f’ kanċer tal- prostata sensittiv għal ormoni avvanzat li jista ’ jiġi tradott f’ anqas uġigħ minn metastasi fl- għadam, titjib fil- passaġġ ta ’ l- awrina, u f’ xi każijiet ittardjar tal- progressjoni tat- tumur, għalkemm ma ntweriex benefiċċju ta ’ sopravivenza ċar.
Androgen ablation is considered to be a palliative treatment.
Ablatazzjoni ta ’ l- androġeni hija ikkunsidrata bħala trattament li jnaqqas l- uġigħ.
Furthermore, reduction of testosterone to castrate levels has been accepted as a valid surrogate for clinical efficacy in advanced prostate cancer by the CHMP in 2004 as part of scientific advice from the SAWP.
Barra dan, tnaqqis ta ’ testosteron għal- livelli ta ’ kastrazzjoni ġie aċċettat bħala sostitut validu għal effikaċja klinika f’ kanċer tal- prostata avvanzat mis- CHMP fl- 2004 bħala parti mill- parir xjentifiku mill- SAWP.
Thus, the documented pharmacological endpoint serum testosterone < 50 ng/ dL, documented for Vantas in studies 302, 301 and in addition in the Long Term Extension of Study 301 is an acceptable primary efficacy endpoint in patients with advanced prostate cancer.
Għalhekk il- punt ta ’ tmiem farmakoloġiku ta ’ testosteron fis - serum dokumentat ta ’ 50 ng/ dL (1. 7 nmol/ L), dokumentat għal Vantas fl- istudji 302, 301 u addizzjonalment fl- Istudju ta ’ Estensjoni 301 fuq Tul ta ’ Żmien huwa punt tat- tmiem ta ’ effikaċja primarja aċċettabbli f’ pazjenti b’ kanċer tal- prostata avvanzat.
With an efficacy of 98-100% in serum testosterone reduction further active comparator studies are redundant and thus not necessary.
B’ effikaċja ta ’ 98- 100% tnaqqis fit- testosteron fis- serum, aktar studji komparattivi attivi huma żejda u għalhekk mhux neċessarji.
Another LHRH agonist could be used, but this is superfluous considering the meta-analysis presented by Applicant, orchidectomy is not acceptable when reversible methods are available, DES is obsolete and non-steroidal anti-androgens may have inferior efficacy when used as monotherapy.
Jista ’ jintuża agonist LHRH ieħor, imma dan huwa superfluwu meta wieħed jikkonsidra l- meta- analiżi ppreżentata mill- Applikant, l- orkidektomija mhix aċċettabbli fejn hemm metodi riversibbli, DES m’ għadux jintuża u anti- androġeni mhux sterojdi jista ’ jkollhom effikaċja inferjuri meta użati bħala monoterapija.
The safety database seems limited, but no unexpected safety issues have occurred nor in the American post marketing surveillance neither in the trials.
Il- bażi tad- dejta dwar is- sigurtà tidher ristretta, iżda ma seħħet l- ebda kwistjoni importanti marbuta mas- sigurtà, la fis- sorveljanza ta ’ wara t- tqegħid fis- suq Amerikana u lanqas fil- provi.
The data of the Long Term Extension of Study 301 support long-term safety for patients treated with Vantas for two or more years.
Id- dejta ta ’ l - Istudju ta ’ Estensjoni 301 fuq Tul ta ’ Żmien tappoġġja sigurtà fuq tul ta ’ żmien f’ pazjenti ittrattati b’ Vantas għal sentejn jew aktar.
A distinction should be made between safety aspects of androgen suppression therapy in general and the (local) safety of this product.
Trid issir distinzjoni bejn l- aspetti ta ’ sigurtà ta ’ terapija ta ’ soppressjoni ta ’ androġeni in ġenerali u s- sigurtà lokali ta ’ dan il- prodott.
The safety of androgen suppression is well known and further information is not necessary for this product.
Is- sigurtà ta ’ soppressjoni ta ’ androġeni hija magħrufa sewwa u aktar tagħrif m’ huwiex neċessarju għal dan il- prodott.
The local safety of Vantas is sufficiently investigated and further comparative studies are not necessary.
Is- sigurtà lokali ta ’ Vantas hija mistħarrġa biżżejjed u aktar studji komparattivi m’ humiex meħtieġa.
The proposal of the applicant/ MAH to include five pharmacovigilance safety concerns in the Risk Management Plan is endorsed (two relate specifically to the unique Vantas formulation while the other three are classified as class effects: expulsions, cellulitis, flare, osteoporosis and QT prolongation).
Il- proposta ta ’ l- applikant/ MAH biex tinkludi ħames konsiderazzjonijiet dwar is- sigurtà fuq il- farmakoviġilanza fil- Pjan ta ’ Maniġment tar- Riskju hija awtorizzata (tnejn għandhom x’ jaqsmu speċifikament mal - formolazzjoni unika ta ’ Vantas waqt li t- tlieta l- oħra huma kklassifikati bħala effetti ta ’ klassijiet: espulsjonijiet, ċellulite, tħeġġiġ, osteoporożi u prolongazzjoni tal- QT).
In conclusion, the CHMP agrees that the responses submitted by the Applicant indicate that the issues are resolved.
Bħala konklużjoni, is- CHMP jaqbel li r- riposti ppreżentati mill- Applikant jindikaw li l- argumenti huma riżolti.
Vantas is a new LHRH agonist and this pharmacological class was introduced for the treatment of advanced prostate cancer more than 20 years ago.
Vantas huwa l- agonist LHRH ġdid u din il- klassi farmakoloġika ġiet introdotta għat - trattament ta ’ kanċer tal- prostata avvanzat aktar minn 20 sena ilu.