natgillin/translations-raw huggingface dataset:
Following submission of MAHs' responses, and whilst due consideration was given to every MAHs' replies, the arguments and data provided were classified into three categories.
Potem ko so imetniki dovoljenj za promet z zdravili predložili odgovore in so se ustrezno upoštevali odgovori vsakega od imetnikov dovoljenj, so bile predložene utemeljitve in dokazi razvrščeni v tri kategorije.
For the purpose of this report, GVK Biosciences Private Limited/Clinogent will be hereafter referred to as ‘GVK Bio'.
Za namene tega poročila se za družbo GVK Biosciences Private Limited/Clinogent v nadaljevanju uporablja ime GVK Bio.
Finally, The CHMP determined that GVK Bio did not provide evidence to demonstrate that the problem was confined to a specific time period or specific clinical trials or specific individuals and clinical activities.
Nazadnje je odbor CHMP ugotovil, da družba GVK Bio ni predložila dokaza, da je bila težava omejena na določeno časovno obdobje ali določena klinična preskušanja ali določene posameznike in klinične dejavnosti.
• Re-examination request for Levetiracetam and Dipyridamole:
• Ponovni pregled zahteve za levetiracetam in dipiridamol
The Committee therefore recommends that these marketing authorisations (Annex IB) should be suspended unless the medicinal product is considered critical by the relevant national competent authorities.
Odbor zato priporoča, da se ta dovoljenja za promet z zdravilom (Priloga IB) začasno umaknejo, razen v primeru, da je zadevno zdravilo po mnenju ustreznega nacionalnega pristojnega organa kritičnega pomena.
Neo-Balkanika submitted the bioequivalence study (PK-05-035) which had already been submitted during the referral procedure in support of marketing authorisations for Nebivolol 5 mg tablets, with the same qualitative and quantitative composition and same manufacturers.
Družba Neo Balkanika je predložila študijo biološke enakovrednosti (PK-05-035), ki je že bila predložena med napotitvenim postopkom v podporo dovoljenjem za promet z zdravilom Nebivolol 5 mg tablete z enako kakovostno in količinsko sestavo in enakimi proizvajalci.
According to article 10 of Directive 2001/83/EC, the bioequivalence vis-à-vis an EU reference medicinal product needs to be established and therefore the abovementioned studies can not be considered fulfilling the criteria of article 10.
V skladu s členom 10 Direktive 2001/83/ES je treba ugotoviti biološko enakovrednost z referenčnim zdravilom, odobrenim v EU, zato se za zgoraj navedene študije ne more šteti, da izpolnjujejo merila iz člena 10.
Heumann Pharma GmbH & co. Generica KG, and Torrent Pharma GmbH / Torrent Pharma SRL (for Irbesartan/hydrochlorothiazide and Irbesartan);
Heumann Pharma GmbH & co. Generica KG in Torrent Pharma GmbH/Torrent Pharma SRL (za irbesartan hidroklorotiazid in irbesartan);
In the light of these uncertainties and consequent potential efficacy, safety and tolerability concerns, the benefit-risk balance of the concerned medicinal products is not positive.
Ob upoštevanju teh negotovosti in posledičnih morebitnih pomislekov glede učinkovitosti, varnosti in prenašanja razmerje med tveganji in koristmi zadevnih zdravil ni pozitivno.
The following findings were reported in the French inspection report dated 02 July 2014, to which GVK Bio have responded on 18 July 2014 and in the final inspection report, which was issued on 21 July 2014: data manipulations of electrocardiograms (ECGs) were detected in each and every one of the 9 trials inspected by the ANSM.
V poročilu francoske agencije o inšpekcijskem pregledu z dne 2. julija 2014, na katerega se je družba GVK Bio odzvala 18. julija 2014, in v končnem poročilu o inšpekcijskem pregledu, ki je bilo izdano 21. julija 2014, so bile navedene naslednje ugotovitve: v vseh devetih preskušanjih, ki jih je pregledala agencija ANSM, je bilo ugotovljeno prirejanje podatkov o elektrokardiogramih (EKG).
Having taken into account the ANSM's inspection report, the available data and all arguments presented in the MAHs' replies, the CHMP concluded in its plenary meeting on January 2015 that in the absence of demonstration of bioequivalence to an EU Reference Medicinal Product, the efficacy, safety and tolerability of the concerned medicinal product cannot be established.
Ob upoštevanju poročila agencije ANSM o inšpekcijskem pregledu, razpoložljivih podatkov in vseh utemeljitev, ki so jih imetniki dovoljenj za promet z zdravilom podali v svojih odgovorih, je odbor CHMP na svojem plenarnem zasedanju januarja 2015 zaključil, da ob odsotnosti dokazov o biološki enakovrednosti z referenčnim zdravilom, odobrenim v EU, učinkovitosti, varnosti in prenašanja zadevnega zdravila ni mogoče ugotoviti.
According to the MAH, this is only mentioned in the Guideline on the Investigation of Bioequivalence.
Po mnenju imetnika dovoljenja za promet z zdravilom je to navedeno samo v Smernicah o raziskavah biološke enakovrednosti.
Based on the same argumentation as described above for Irbesartan, the MAH claims that the data obtained in the AU study are still applicable for the EU.
Na podlagi enakih utemeljitev, kot so opisani zgoraj za zdravilo Irbesartan, imetnik dovoljenja za promet z zdravilom trdi, da podatki, pridobljeni v avstralski študiji, še vedno veljajo za EU.
Further to the assessment, the CHMP noted that medicinal products containing Pravastatin were to be excluded of this procedure as out of the scope of the procedure.
Nadalje je odbor CHMP opozoril, da bi bilo treba zdravila, ki vsebujejo pravastatin, izključiti iz tega postopka, saj ne spadajo v njegov obseg.
However, the CHMP is of the opinion that the absence of the identification of any pharmacovigilance signals does not provide sufficient reassurance because it is not established that the pharmacovigilance activities may be designed to detect such a signal.
Vendar meni, da dejstvo, da farmakovigilančni signali niso bili ugotovljeni, ne zagotavlja zadostne gotovosti, saj ni ugotovljeno, da so farmakovigilančne dejavnosti zasnovane na način, ki omogoča zaznavanje tovrstnih znakov.
The MAH claimed that it had not received the official notification of the inclusion of the product in the Article 31 Referral procedure.
Imetnik dovoljenja za promet z zdravilom je trdil, da ni prejel uradnega obvestila o vključitvi zdravila v napotitveni postopek po členu 31.
The CHMP was asked to assess the potential impact of the findings on the benefit risk balance of products authorised on the basis of studies with clinical activities performed at the inspection site.
Odbor za zdravila za uporabo v humani medicini (CHMP) je bil naprošen, da oceni morebitni učinek ugotovitev na razmerje med tveganji in koristmi zdravil, odobrenih na podlagi študij, pri katerih so klinične dejavnosti potekale na pregledani lokaciji.
Submission of new scientific data: The MAHs informed the CHMP that they have initiated activities for a new bioequivalence study.
Predložitev novih znanstvenih podatkov: Imetniki dovoljenj za promet z zdravilom so odbor CHMP obvestili, da so začeli dejavnosti za izvedbo nove študije biološke enakovrednosti.
The CHMP therefore confirms that it cannot be ruled out beyond reasonable doubt that critical GCP violations at the site have not affected the integrity of the scientific data of other bioequivalence studies conducted at the site, and that the studies therefore remain unreliable.
Odbor CHMP zato potrjuje, da ni mogoče brez vsakega dvoma izključiti, da kritične kršitve dobre klinične prakse na zadevni lokaciji niso vplivale na neoporečnost znanstvenih podatkov drugih študij biološke enakovrednosti, opravljenih na lokaciji, in da študije zato ostajajo nezanesljive.
During September 2014 CHMP plenary meeting, the CHMP adopted a LoQ to the CRO to clarify whether the findings should be confined to the period 2008-2014, to specific clinical trials and/or specific clinical activities at the Hyderabad site.
Na plenarnem zasedanju odbora CHMP septembra 2014 je Odbor sprejel seznam vprašanj za pogodbeno raziskovalno organizacijo, da bi pojasnili, ali bi morali ugotovitve omejiti na obdobje 2008-2014, na določena klinična preskušanja in/ali določene klinične dejavnosti na lokaciji v Hyderabadu.
The systematic nature of the data manipulations of ECGs, the extended period of time during which they took place and the number of members of staff involved highlight critical deficiencies in the quality system in place at GVK Bio's clinic in Hyderabad.
Sistematičnost prirejanj podatkov o elektrokardiogramih, dolgo obdobje, v katerem so prirejanja potekala, in število sodelujočih zaposlenih kažejo na kritične pomanjkljivosti sistema zagotavljanja kakovosti na kliniki družbe GVK Bio v Hyderabadu.
The CHMP had already assessed this study and concluded that it can be considered as acceptable proof of bioequivalence and the benefit risk balance of the respective marketing authorisations can be considered positive.
Odbor CHMP je to študijo že ocenil in zaključil, da se lahko šteje za sprejemljivi dokaz biološke enakovrednosti in da je razmerje med tveganji in koristmi zadevnih dovoljenj za promet z zdravilom pozitivno.
During the November 2014 meeting, after GVK Biosciences' submission of responses as well as providing information relating to the matter before the CHMP on 22 October 2014, the CHMP determined that GVK Biosciences Pvt. Ltd. did not provide evidence to demonstrate that the problem was confined to a specific time period or specific clinical trials or specific individuals and clinical activities.
Potem ko je družba GVK Biosciences predložila odgovore ter 22. oktobra 2014 pred odborom CHMP podala informacije o zadevi, je odbor je na svojem zasedanju novembra 2014 odločil, da družba GVK Biosciences Pvt. Ltd. ni predložila dokazov, ki bi kazali, da je težava omejena na določeno časovno obdobje, določena klinična preskušanja ali določene posameznike in klinične dejavnosti.
In addition, the MAH claims that in art 10 of Directive 2001/83/EC there is ‘room for interpretation', and it is not specifically mentioned that an EU reference product must be used.
Poleg tega imetnik dovoljenja za promet z zdravilom trdi, da člen 10 Direktive 2001/83/ES „dopušča možnost razlage“ in da v njem ni izrecno navedeno, da je treba uporabiti referenčno zdravilo, odobreno v EU.
Indeed, any mentioned audits and inspections, including those that have been done at the site since the GCP findings by the ANSM's inspection, do not provide sufficient reassurance since they may not have detected serious GCP violations, even if present.
Nobeden od omenjenih inšpekcijskih pregledov ali revizij, vključno s tistimi, ki so bili na lokaciji opravljeni po ugotovitvah inšpekcijskega pregleda agencije ANSM v zvezi z dobro klinično prakso, ne ponuja zadostnih zagotovil, saj morda ni zaznal resnih kršitev dobre klinične prakse, tudi če so bile te prisotne.
The MAHs did not submit the above mentioned scientific data before the adoption of the initial opinion.
Imetniki dovoljenj za promet z zdravilom niso predložili zgoraj navedenih znanstvenih podatkov pred sprejetjem prvotnega mnenja.
The benefit-risk balance for the products of Annex IA remains positive and the CHMP recommends therefore the maintenance of the concerned marketing authorisations.
Za zdravila iz Priloge IA razmerje med tveganji in koristmi ostaja pozitivno, zato odbor CHMP priporoča, da se zadevna dovoljenja za promet z zdravilom ohranijo.
• Confirmed its previous recommendation to suspend the marketing authorisations for medicinal products for which bioequivalence vis-à-vis the EU reference medicinal product was not established.
• potrdil svoje prejšnje priporočilo za začasni umik dovoljenj za promet z zdravili, za katera biološka enakovrednost z referenčnim zdravilom, odobrenim v EU, ni bila ugotovljena.
The seriousness of the deficiencies identified and the lack of GCP compliance at GVK Bio's clinic in Hyderabad raise questions as to the reliability of studies conducted between 2008 and 2014 at the site inspected, as well as the clinical part of all other bioequivalence trials performed prior to 2008.
Zaradi resnosti ugotovljenih pomanjkljivosti na kliniki GVK Bio in pomanjkanja skladnosti z dobro klinično prakso se pojavljajo dvomi o zanesljivosti študij, opravljenih med letoma 2008 in 2014 na pregledani lokaciji, ter kliničnih delov drugih preskušanj biološke enakovrednosti, opravljenih pred letom 2008.
The benefit-risk balance for these medicinal products remains therefore positive.
Za ta zdravila razmerje med tveganji in koristmi tako ostaja pozitivno.
They also show a lack of GCP training, awareness and understanding of members of GVK Bio staff, a lack of understanding by them of the importance of data integrity and of the possible consequences of their acts, as well as a lack of overview of clinical trial activities by the investigators.
Prav tako kažejo, da so usposabljanje zaposlenih v družbi GVK Bio na področju dobre klinične prakse, seznanjenost s to prakso in njeno razumevanje pomanjkljivi ter da se ti zaposleni ne zavedajo pomena neoporečnosti podatkov in morebitnih posledic svojih dejanj, kažejo pa tudi na pomanjkanje pregleda raziskovalcev nad dejavnostmi v okviru kliničnih preskušanj.
Serious findings were identified at the clinical site where the study was carried out, and in view of the seriousness of the deficiencies identified, the obtained data at the clinical site are considered not reliable by the CHMP.
Na lokaciji, na kateri je bila izvedena študija, so prišli do resnih ugotovitev, zato odbor CHMP zaradi resnosti ugotovljenih pomanjkljivosti podatke, pridobljene na zadevni klinični lokaciji, šteje za nezanesljive.
• Request for re-examination for Irbesartan and Irbesartan/hydrochlorothiazide:
• Zahteva za ponovni pregled za irbesartan in irbesartan hidroklorotiazid
Therefore the CHMP is of the view that analysing the plasma samples at another CRO cannot overcome the fact that the generated data are unreliable.
Zato meni, da analiza vzorcev plazme na lokaciji druge pogodbene raziskovalne organizacije ne bo spremenila dejstva, da so pridobljeni podatki nezanesljivi.
• The Committee considered the grounds for re-examination provided by the MAHs in writing;
• odbor je proučil razloge za ponovni pregled, ki so jih v obliki pisne dokumentacije podali imetniki dovoljenj za promet z zdravilom;
The bioequivalence is therefore established and the benefit-risk balance for these products remains positive.
Biološka enakovrednost je tako ugotovljena in razmerje med tveganji in koristmi teh zdravil ostaja pozitivno.
The MAHs also state that they note the opinion regarding GCP audits conducted by GVK Bio's clients (i.e. implying that these audits were substandard as they did not identify any serious violations of GCP at the GVK Bio facility).
Imetniki dovoljenj za promet z zdravilom prav tako navajajo, da upoštevajo mnenje glede revizij dobre klinične prakse, ki so jih izvedle stranke družbe GVK Bio (kar pomeni, da so bile te revizije podstandardne, saj z njimi niso odkrili nobenih resnih kršitev dobre klinične prakse na lokaciji družbe GVK Bio).
However, the CHMP considers that the pharmacovigilance activities may likely have lacked the ability to detect a signal with regard to efficacy or safety and tolerability, and the lack of any pharmacovigilance signal does not offer sufficient reassurance to conclude on a positive benefit risk in the absence of the demonstration of bioequivalence with the EU reference medicinal product.
Vendar meni, da s farmakovigilančnimi dejavnostmi najverjetneje ni bilo mogoče odkriti znaka glede učinkovitosti ali varnosti in prenašanja, pomanjkanje vsakršnega farmakovigilančnega znaka pa ne zagotavlja zadostnega zagotovila za sklep o pozitivnem razmerju med tveganji in koristmi, če ne obstaja dokaz biološke enakovrednosti z referenčnim zdravilom, odobrenim v EU.
A list of questions to MAHs was adopted to request them to submit data to prove bioequivalence for their medicinal products vis-à-vis the EU reference medicinal product, as appropriate.
Sprejet je bil seznam vprašanj za imetnike dovoljenj za promet z zdravili, s katerim so bili pozvani, da predložijo podatke, ki dokazujejo biološko enakovrednost njihovih zdravil v primerjavi z referenčnim zdravilom, odobrenim v EU, kot je ustrezno.
The CHMP noted that pharmacovigilance data reported to the competent authorities have not indicated any problems which could be attributed to non-bioequivalence, such as reduced efficacy or worsened safety and tolerability.
Odbor CHMP je ugotovil, da farmakovigilančni podatki, o katerih so poročali pristojnim organom, niso pokazali nobenih težav, ki bi jih lahko pripisali odsotnosti biološke enakovrednosti, kot so zmanjšana učinkovitost ali slabša varnost ali prenašanje.
• Overall conclusion of the re-examination Based on the totality of the data available, including the information submitted during the original assessment procedure and the detailed grounds for re-examination put forward by the MAHs, the CHMP:
Na podlagi vseh razpoložljivih podatkov, vključno z informacijami, predloženimi med postopkom prvotne ocene in podrobnimi razlogi za ponovni pregled, ki so jih predložili imetniki dovoljenj za promet z zdravilom, je odbor CHMP:
Nevertheless many MAHs provided miscellaneous statements, as described in the previous section, concerning benefit risk balance of the medicinal products.
Kljub temu so številni imetniki dovoljenj za promet z zdravilom predložili razne izjave glede razmerja med tveganji in koristmi zdravil, kot je opisano v prejšnjem odstavku.
The CHMP therefore recommends by consensus the suspension of the Marketing Authorisations for the medicinal products referred to in Annex IB.
Odbor CHMP tako soglasno priporoča začasni umik dovoljenj za promet z zdravili, navedenimi v Prilogi IB.
• Concluded that the benefit risk of Nebivolol/Neo Balkanika is positive, therefore Nebivolol/Neo Balkanika is included in the list of medicinal products recommended for maintenance of the marketing authorisation;
• zaključil, da je razmerje med tveganji in koristmi za zdravilo Nebivolol družbe Neo Balkanika pozitivno in se zato lahko vključi na seznam zdravil, priporočenih za ohranitev dovoljenja za promet;
Where on the basis of these criteria the relevant national competent authorities of the Member States consider that a medicinal product is critical, the suspension of the concerned marketing authorisation(s) may be deferred by the period for which the medicinal product is considered critical (period which can not exceed twenty-four months from the Commission Decision).
Kadar na podlagi teh meril ustrezni nacionalni pristojni organi držav članic menijo, da je zdravilo kritičnega pomena, se lahko začasni umik zadevnih dovoljenj za promet z zdravilom odloži za obdobje, v katerem se zdravilo šteje za zdravilo kritičnega pomena (obdobje, ki ne sme presegati štiriindvajset mesecev od sklepa Komisije).
The CHMP conclusions on the points raised in the MAH's grounds are given below.
Zaključki odbora CHMP glede točk, ki jih je izpostavil imetnik dovoljenja za promet z zdravilom, so navedeni spodaj.
Following the adoption of the CHMP opinion during the January 2015 CHMP meeting, requests for re-examination were received from the following MAHs:
Mnenje je odbor CHMP sprejel na svojem zasedanju januarja 2015, nato pa je prejel zahteve za ponovni pregled od naslednjih imetnikov dovoljenj za promet z zdravilom:
For the remaining medicinal products in category 2 (i.e. products of Annex IB containing Donepezil), the following issues precluding the establishment of bioequivalence to an EU Reference Medicinal Product were raised:
Za preostala zdravila kategorije 2 (tj. zdravila v Prilogi IB, ki vsebujejo donepezil) so bila izpostavljena naslednja vprašanja, zaradi katerih ni mogoče ugotoviti biološke enakovrednosti z referenčnim zdravilom, odobrenim v EU:
Not all phases of the study performed at GVK Bio: For the original submission, the MAH had conducted a bioequivalence study that compared its test product Alendronate Sodium 70 mg Tablets with the European innovator, Fosamax 70 mg tablets in healthy, adult, male, human subjects under fasting condition.
Vse faze študije niso bile izvedene na lokaciji družbe GVK Bio: Imetnik dovoljenja za promet z zdravilom je za prvotno predložitev vloge izvedel študijo biološke enakovrednosti, v kateri so primerjali testno zdravilo Alendronate Sodium (natrijev alendronat) 70 mg tablete z inovatorskim zdravilom v EU, Fosamax 70 mg tablete, pri zdravih odraslih moških pri zaužitju na tešče.
• Re-examination request for Nebivolol Neo-Balkanika:
• Zahteva za ponovni pregled za zdravilo Nebivolol družbe Neo Balkanika
A number of MAHs have also argued that pharmacovigilance data collected on their medicinal products have not indicated any problems, which could be attributed to non-bioequivalence, such as reduced efficacy or worsened safety and tolerability.
Več imetnikov dovoljenj za promet z zdravili je tudi trdilo, da farmakovigilančni podatki, zbrani za njihova zdravila, niso pokazali nobenih težav, ki bi jih lahko pripisali odsotnosti biološke enakovrednosti, kot so zmanjšana učinkovitost ali slabša varnost ali prenašanje.
Where on the basis of these criteria the relevant national competent authorities of the Member States consider that a medicinal product is critical, the suspension of the concerned marketing authorisation(s) may be deferred by the period for which the medicinal product is considered critical.
Če na podlagi teh meril ustrezni nacionalni pristojni organi držav članic menijo, da je zdravilo kritičnega pomena, se lahko začasni umik zadevnih dovoljenj za promet z zdravili odloži za obdobje, v katerem se zdravilo šteje za zdravilo kritičnega pomena.
The provided study does not establish the bioequivalence with a reference medicinal product authorised in the EU.
S predloženo študijo ni mogoče ugotoviti biološke enakovrednosti z referenčnim zdravilom, odobrenim v EU.
Some MAHs have submitted bioequivalence data from a study associated with unresolved, critical GCP findings.
Nekateri imetniki dovoljenj za promet z zdravilom so predložili podatke o biološki enakovrednosti, ki izvirajo iz študij, povezanih z nerešenimi in kritičnimi ugotovitvami glede dobre klinične prakse.
• For medicinal products (Annex IA) for which other bioequivalence studies than the one(s) performed at GVK Biosciences Hyderabad site or claims that the medicinal products fulfil the criteria for a Biopharmaceutics Classification System (BCS)-based biowaiver as described in Appendix III of the Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98) were submitted, assessed and considered positive by the CHMP (i.e. medicinal products containing Bendroflumetiazid, Bosentan, Fexofenadine, Lansoprazole, Levetiracetam, Levocetirizine, Metoclopramide, Nebivolol and Venlafaxine), the CHMP is of the opinion that the bioequivalence has been established.
• Za zdravila (Priloga IA), za katera so bile predložene študije biološke enakovrednosti, ki niso bile opravljene na lokaciji družbe GVK Biosciences v Hyderabadu, ali zahtevki za priznanje, da zdravila izpolnjujejo merila za izvzetje iz obveznosti izvedbe študije biološke enakovrednosti na podlagi biofarmacevtskega sistema klasifikacije, kot je opisano v Prilogi III k Smernicam o raziskavah biološke enakovrednosti (CPMP/EWP/QWP/1401/98), ki jih je odbor CHMP ocenil in ki so po njegovem mnenju pozitivni (tj. za zdravila, ki vsebujejo bendroflumetiazid, bosentan, feksofenadin, lansoprazol, levetiracetam, levocetirizin, metoklopramid, nebivolol in venlafaksin), je odbor menil, da je biološka enakovrednost ugotovljena.
The MAH claims that the data obtained in the AU study are still applicable for the EU.
Imetnik dovoljenja za promet z zdravilom trdi, da podatki, pridobljeni v avstralski študiji, še vedno veljajo za EU.
New scientific data: The MAHs have submitted a biowaiver request for levetiracetam and a new bioequivalence study for dipyridamole.
Novi znanstveni podatki: Imetniki dovoljenj za promet z zdravilom so predložili zahtevek za izvzetje iz obveznosti izvedbe študije biološke enakovrednosti („biowaiver“) za levetiracetam in za novo študijo biološke enakovrednosti za dipiridamol.