natgillin/translations-raw huggingface dataset:
The device helps the medicine to reach a specific part of the brain. 
pomočjo pripomočka zdravilo doseže določen del v možganih.
Symptoms resolved over time or with administration of antipyretics, antihistamines and/or glucocorticosteroids. 
Simptomi so izzveneli sčasoma ali z dajanjem antipiretikov, antihistaminikov in/ali glukokortikosteroidov.
Tmax*, hr 
tmax*, ure
In patients less than 3 years of age the recommended dose is in accordance with the posology used in the ongoing clinical study 190-203, see section 5.1. 
Pri bolnikih, starih manj kot 3 leta, je priporočeni odmerek v skladu z odmerjanjem, ki ga uporabljajo v potekajoči klinični študiji 190-203, glejte poglavje 5.1.
Convulsions resolved with standard anti-convulsive therapies, and did not result in discontinuation of Brineura treatment. 
Konvulzije so izzvenele s standardnimi antikonvulzivnimi zdravljenji in niso povzročile prekinitve zdravljenja z zdravilom
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before treatment with this medicine. 
Nosečnost, dojenje in plodnost Če ste noseči ali dojite, menite, da bi lahko bili noseči, ali načrtujete zanositev, se posvetujte z zdravnikom, preden zdravljenjem s tem zdravilom.
Convulsions are a common manifestation of CLN2 disease and are expected to occur in this population. 
Konvulzije so pogosta manifestacija CLN2 in njihovo pojavljanje je pri tej populaciji pričakovano.
There is limited data in patients older than 8 years of age. 
Podatki za bolnike, starejše od 8 let, so omejeni.
Will have obvious instability, and may have intermittent falls. 
Očitna nestabilnost in možni občasni padci.
Upon completion of the infusion, the patient status should be clinically assessed and observation may be necessary for longer periods if clinically indicated, particularly in patients less than 3 years. 
Po koncu infuzije je treba klinično oceniti stanje bolnika; morda ga bo treba opazovati dlje časa, če je to klinično indicirano, zlasti pri bolnikih, starih manj kot 3 leta.
However, the results of these studies in dachshund dogs cannot reliably predict human safety, because the regimen of cerliponase alfa infusions was different and highly variable even within the same study due to difficulties with the indwelling catheter system and prominent hypersensitivity reactions. 
Vendar pa rezultati teh študij na psu jazbečarju ne morejo z gotovostjo napovedati varnosti pri človeku, saj je bil režim infundiranja cerliponaze alfa drugačen in se je zelo razlikoval tudi v okviru iste študije zaradi težav z vsajenim katetrskim sistemom in izrazitih preobčutljivostnih reakcij.
- If you or your child has had life-threatening allergic reactions to cerliponase alfa or any of the other ingredients of this medicine (listed in section 6), and the reactions continue to happen when cerliponse alfa is given again. 
- Če ste vi ali vaš otrok imeli življenje ogrožajočo alergijsko reakcijo na cerliponazo alfa ali katero koli sestavino tega zdravila (navedeno v poglavju 6) in se reakcija ob ponovni uporabi cerliponaze alfa ponovi.
In study 190201, 23 patients were treated for 48 weeks (1 patient withdrew after week 1 due to the inability to continue with study procedures). 
V študiji 190-201 je bilo 23 bolnikov zdravljenih 48 tednov (1 bolnik je po 1. tednu prekinil sodelovanje zaradi nezmožnosti nadaljevanja s študijskimi postopki).
Findings from studies 190-201 and 190-202 were compared with a natural history control group that included patients that satisfied the inclusion criteria for studies 190-201 and 190-202. 
Izsledke iz študij 190-201 in 190-202 so primerjali s kontrolno skupino z naravnim potekom, ki je vključevala bolnike, ki so izpolnili vključitvene kriterije za študiji 190-201 in 190-202.
This disease model primarily served to investigate the pharmacodynamic and pharmacokinetic properties of cerliponase alfa, but also aimed to evaluate the toxicity of the substance. 
Model bolezni je bil primarno namenjen proučevanju farmakodinamičnih in farmakokinetičnih lastnosti cerliponaze alfa, pa tudi oceni toksičnosti učinkovine.
Pharmacotherapeutic group: other alimentary tract and metabolism products, enzymes, ATC code: A16AB17. 
Farmakoterapevtska skupina: druga zdravila za bolezni prebavil in presnove, encimi, oznaka ATC: A16AB17.
In order to further evaluate the treatment effectiveness as a delay in progression of CLN2 motor-language clinical sale and to further evaluate the safety and tolerability of cerliponase alfa, the MAH will submit the results of study 190-203 including at least 5 patients below the age of 2 years. 
Za nadaljnjo oceno učinkovitosti zdravljenja kot zakasnitev napredovanja CLN2 na klinični lestvici za ocenjevanje motorično-govornih spretnosti in nadaljnjo oceno varnosti in prenašanja cerliponaze alfa, bo imetnik dovoljenja za promet z zdravilom predložil rezultate študije 190-203, v katero bo vključenih vsaj 5 bolnikov, mlajših od 2 let.
Patients who experienced moderate hypersensitivity adverse events were tested for drug-specific IgE and found to be negative. 
Bolnike, ki so imeli zmerne preobčutljivostne neželene učinke, so testirali za IgE, specifičen za zdravilo, in ugotovili, da so negativni.
Your doctor may lower the dose or the speed of the infusion based on your response during the treatment. 
Zdravnik lahko odmerek ali hitrost infundiranja zmanjša na podlagi vašega odziva med zdravljenjem.
After long periods of use, the access device may need to be replaced and will be determined by your doctor. 
Po daljšem času uporabe je treba pripomoček za dostop zamenjati, kar določi zdravnik.
The inline filter may be integral to the infusion set. 
Filter v liniji je lahko integriran v infuzijski set.
Each domain encompasses scores of 3 (grossly normal) to 0 (profoundly impaired), for a total possible score of 6, with unit decrements representing milestone events in the loss of previously attained functions of ambulation and speech. 
Vsaka domena je zajemala ocene od 3 (večinoma normalno) do 0 (skrajno okvarjeno), pri čemer je bila najvišja možna skupna ocena 6, s pojemki enot, ki so predstavljali mejnik dogodkov pri izgubi predhodno pridobljene funkcije mobilnosti in govora.
The observed treatment effect was considered clinically meaningful in light of the natural history of untreated CLN2 disease. 
Opaženi učinek zdravljenja se obravnava kot klinično pomemben v luči naravnega poteka nezdravljene CLN2.
frequency convention defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). 
Opaženi neželeni učinki so navedeni spodaj po organskih sistemih in pogostnosti, skladno z opredelitvijo pogostnosti po MedDRA, kot: zelo pogosti (≥1/10), pogosti (≥1/100 do <1/10), občasni (≥1/1.000 do <1/100), redki (≥1/10.000 do <1/1.000), zelo redki (<1/10.000), neznana pogostnost (ni mogoče oceniti iz razpoložljivih podatkov).
The European Medicines Agency has deferred the obligation to submit the results of studies with Brineura in one or more subsets of the paediatric population in CLN2 (see section 4.2 for information on paediatric use). 
Evropska agencija za zdravila je začasno odložila zahtevo za predložitev rezultatov študij z zdravilom Brineura za eno ali več podskupin pediatrične populacije s CLN2 (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
Cerliponase alfa is a recombinant form of human tripeptidyl peptidase-1 (rhTPP1). 
Mehanizem delovanja Cerliponaza alfa je rekombinantna oblika humane tripeptidil-peptidaze-1 (rhTPP1).
• Two single-use hypodermic syringe needles, (21 G, 25.4 mm). 
• Dve hipodermični igli za brizgo za enkratno uporabo, (21 G, 25,4 mm).
6.7 (first 4 doses) 10 (subsequent doses) 
6,7 (prvi 4 odmerki) 10 (poznejši odmerki)
Cerliponase alfa is taken up by target cells and translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor). 
Ciljne celice cerliponazo alfa privzemajo in prenesejo do lizosomov s pomočjo receptorja CI-MPR (Cation Independent Mannose-6Phosphate Receptor) (znan tudi kot receptor M6P/IGF2).
Mean (SD) 
Povprečje (SD)
Material degradation of the intracerebroventricular access device reservoir occurs after long periods of use according to preliminary results of benchtop testing and as observed in clinical trials with approximately 4 years of use. 
Degradacija materiala rezervoarja pripomočka za intracerebroventrikularni dostop se pojavi po daljšem obdobju uporabe v skladu s predhodnimi rezultati laboratorijskega testiranja in kot je bilo ugotovljeno v kliničnih preskušanjih po približno 4 letih uporabe.
Adverse reactions are presented in order of decreasing seriousness. 
Neželeni učinki so navedeni po padajoči resnosti.
A total of 15 patients out of 23 (65%) had no overall decline in CLN2 score, irrespective of baseline score, and 2 of these 15 patients increased their score by one point during the treatment period. 
Skupaj 15 od 23 bolnikov (65 %) ni imelo skupnega upada ocene CLN2, neodvisno od izhodiščne ocene, pri 2 od teh 15 bolnikov pa se je ocena v obdobju zdravljenja zvišala za eno točko.
The activated proteolytic enzyme (rhTPP1) cleaves tripeptides from the N-terminus of the target protein with no known substrate specificity. 
Aktivirani proteolitični encim (rhTPP1) cepi tripeptide na N-koncu ciljne beljakovine brez znane specifičnosti za substrat.
From a microbiological point of view, open vials or medicinal product held in syringes should be used immediately. 
Z mikrobiološkega vidika je treba odprte viale ali zdravilo v injekcijskih brizgah uporabiti takoj.
Continuation of long-term treatment should be subject to regular clinical evaluation whether the benefits are considered to outweigh the potential risks to individual patients. 
V nadaljevanju dolgotrajnega zdravljenja je treba s kliničnim ocenjevanjem redno preverjati, ali so koristi zdravljenja večje od možnih tveganj za posamezne bolnike.
Prior to the launch of BRINEURA in each Member State (MS), the Marketing Authorisation Holder (MAH) must agree about the content and format of the educational materials, including communication media, distribution modalities, and any other aspects of the programme, with the National Competent Authority (NCA). 
Pred prihodom zdravila BRINEURA na trg v vsaki državi članici se mora imetnik dovoljenja za promet z zdravilom s pristojnim nacionalnim organom dogovoriti o vsebini in obliki izobraževalnega gradiva, vključno s sredstvi obveščanja, načinom razdeljevanja in vsemi drugimi vidiki programa.
All pharmacokinetic parameters were similar following the initial infusion on Day 1 and following infusions at Week 5 and Week 13, indicating no apparent accumulation or time dependent PK of cerliponase alfa in CSF or plasma when administered at of dose of 300 mg once every other week. 
Vsi farmakokinetični parametri so bili podobni po začetni infuziji na 1. dan in po infuzijah v 5. tednu in 13. tednu, kar kaže, da ni očitnega kopičenja ali od časa odvisne FK cerliponaze alfa v CSL ali plazmi, če se daje v odmerku 300 mg enkrat vsak drugi teden.
Cerliponase alfa is a proteolytic inactive proenzyme (zymogen) that is activated in the lysosome. 
Cerliponaza alfa je proteolitični inaktivni proencim (cimogen), ki se aktivira v lizosomu.
In cardiac normal patients, regular 12-lead ECG evaluations should be performed every 6 months. 
Pri bolnikih z normalnim srcem je treba redno ocenjevanje z EKG-jem z 12 kanali izvajati vsakih 6 mesecev.
You or your child may get problems with the implanted device used during treatment with Brineura (see section 4 “Possible side effects”), including infection or a fault in the device. 
Vi ali vaš otrok imate lahko težave z vsajenim pripomočkom, ki se uporablja med zdravljenjem z zdravilom Brineura (glejte poglavje 4 "Možni neželeni učinki"), vključno z okužbo ali okvaro pripomočka.
Hypersensitivity reactions were reported in 14 out of 24 patients (58%) treated with Brineura. 
O preobčutljivostnih reakcijah so poročali pri 14 od 24 bolnikov (58 %), zdravljenih z zdravilom
Your doctor may give you or your child medicines, such as antipyretics to reduce fever or antihistamines to treat allergic reactions before each treatment with Brineura to reduce side effects that can occur during or shortly after treatment. 
Zdravnik lahko vam ali vašemu otroku da zdravila, kot so antipiretiki za znižanje telesne temperature ali antihistaminiki za zdravljenje alergijskih reakcij, pred vsakim zdravljenjem z zdravilom Brineura za zmanjšanje neželenih učinkov, ki se lahko pojavijo med zdravljenjem ali tik po njem.
Chemical and physical in-use stability has been demonstrated for up to 12 hours at room temperature (19-25°C). 
Kemična in fizikalna stabilnost za uporabo je bila dokazana za obdobje do 12 ur pri sobni temperaturi (19 °C do 25 °C).
Posology was based upon analysis of differences in brain mass values for children less than 3 years of age. 
Odmerjanje je temeljilo na analizi razlik v vrednosti možganske mase za otroke, stare manj kot 3 leta.
Brineura must be administered using aseptic technique to reduce the risk of infection. 
Za dajanje zdravila Brineura je treba uporabiti aseptično tehniko, da se zmanjša tveganje za okužbe.
Overall, 23 (96%) subjects who received cerliponase alfa experienced an event that mapped to the Convulsions Standardized MedDRA Query. 
Skupaj je 23 (96 %) oseb, ki so prejemale cerliponazo alfa, doživelo dogodek, ki je bil mapiran v standardizirano MedDRA poizvedbo za konvulzije (Convulsions Standardized MedDRA
A length of 150 to 206 cm (not to exceed 400 cm) and an inner diameter of 0.1 cm is recommended. 
Priporoča se dolžina od 150 do 206 cm (ne več kot 400 cm) in notranji premer 0,1 cm. • Potreben je 0,2 µm filter v liniji.
They are also responsible for disposing of any unused Brineura properly. 
Odgovorna sta tudi za pravilno odstranitev neporabljenega zdravila Brineura.
The flushing solution may contain particles that dissolve when the vial is fully thawed. 
Raztopina za izpiranje lahko vsebuje delce, ki se raztopijo, ko je viala do konca odtaljena.
If immediate use is not possible, unopened vials of Brineura or flushing solution should be stored at 2-8°C and used within 24 hours. 
Če vsebine ne morete uporabiti takoj, lahko neodprte viale zdravila Brineura ali raztopine za izpiranje shranite pri 2-8 °C, nato pa ju porabite v 24 urah.
Results from the natural history control group demonstrate CLN2 disease is a rapidly progressive neurodegenerative disease with predictable decline in motor and language function with an estimated mean rate of decline in the CLN2 score of 2 points per 48 weeks. 
Rezultati iz kontrolne skupine z naravnim potekom kažejo, da je CLN2 hitro napredujoča nevrodegenerativna bolezen z napovedljivim upadom motorične in govorne funkcije z ocenjeno povprečno stopnjo upada ocene za CLN2 2 točki na 48 tednov.
CSF (N=17) Mean (SD) 
CSL (N = 17)
Withdraw 0.5 ml to 1 ml of CSF to check patency of the intracerebroventricular access device. 
Izvlecite 0,5 ml do 1 ml CSL, da preverite prehodnost pripomočka za intracerebroventrikularni dostop.
There are no data on the presence of cerliponase alfa in human milk, the effects of cerliponase alfa on the breastfed child, or the effects of cerliponase alfa on milk production. 
Podatkov o prisotnosti cerliponaze alfa v materinem mleku pri ljudeh, učinkih cerliponaze alfa na dojenega otroka ali učinkih cerliponaze alfa na nastajanje mleka ni.
Brineura has not been given to patients with advanced disease at the start of treatment or in children younger than 2 years of age. 
Zdravila Brineura niso dajali bolnikom z napredovalo boleznijo ob začetku zdravljenja ali otrokom, mlajšim od 2 let.
The access devices were replaced and patients resumed treatment with Brineura. 
Pripomoček za dostop je bil zamenjan in bolniki so nadaljevali zdravljenje z zdravilom Brineura.
Electrocardiogram (ECG) monitoring during infusion should be performed in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with CLN2 disease may develop conduction disorders or heart disease. 
Spremljanje z elektrokardiogramom (EKG) med infundiranjem je treba izvajati pri bolnikih, pri katerih so v anamnezi bradikardija, motnje prevajanja ali strukturna bolezen srca, saj se lahko pri nekaterih bolnikih s CLN2 pojavijo motnje prevajanja ali bolezen srca.
The most commonly reported convulsion events include seizure, epilepsy and generalized tonic-clonic seizure. 
Najpogostejši poročani dogodki konvulzij vključujejo epileptični napad, epilepsijo in generaliziran tonično-klonični napad.
Dispose of the infusion components, needles, unused solutions and other waste materials in accordance with local requirements. 
Komponente za infundiranje, igle, neporabljeno raztopino in druge odpadne materiale odstranite v skladu z lokalnimi zahtevami.
Table 3: CLN2 Clinical Rating Scale 
Preglednica 3: Klinična ocenjevalna lestvica CLN2
Brineura contains sodium: 
Zdravilo Brineura vsebuje natrij:
If the infusion is interrupted due to a hypersensitivity reaction, it should be restarted at approximately onehalf the initial infusion rate at which the hypersensitivity reaction occurred. 
Pri prekinitvi infundiranja zaradi preobčutljivostne reakcije je treba nadaljevati s približno polovično začetno hitrostjo infundiranja, pri kateri se je pojavila preobčutljivostna reakcija.
Cerliponase alfa is a recombinant human protein and systemic exposure is limited due to intracerebroventricular administration, therefore interactions between cerliponase alfa and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur. 
Cerliponaza alfa je rekombinantni humani protein in sistemska izpostavljenost je omejena zaradi intracerebroventrikularnega dajanja, zato interakcije med cerliponazo alfa in zdravili, ki jih presnavljajo encimi citokroma P450, niso verjetne.
Treatment should be based on the benefits and risks to the individual patient as assessed by the physician. 
Zdravljenje mora temeljiti na zdravnikovi oceni koristi in tveganj za posamičnega bolnika.
The signs and symptoms of device-related infections may not be apparent, therefore, CSF samples should routinely be sent for testing to detect subclinical device infections. 
Znaki in simptomi okužb, povezanih s pripomočkom, morda ne bodo očitni, zato je treba vzorce CSL rutinsko pošiljati na testiranje za odkrivanje subkliničnih okužb pripomočka.
Life-threatening anaphylactic reaction to the active substance or to any of the excipients listed in section 6.1, if re-challenge is unsuccessful (see section 4.4). 
Življenje ogrožajoča anafilaktična reakcija na učinkovino ali katero koli pomožno snov, navedeno v poglavju 6.1, če ponovna uporaba ni uspešna (glejte poglavje 4.4).
Your doctor will check your or your child's heart rate, blood pressure, respiratory rate, and temperature before, during, and after treatment. 
Zdravnik bo preveril vaš ali otrokov srčni utrip, krvni tlak, hitrost dihanja in temperaturo pred zdravljenjem, med njim in po njem.
The most common manifestations included pyrexia with vomiting, pleocytosis, or irritability, which are inconsistent with classic immune mediated hypersensitivity. 
Najpogostejše manifestacije so vključevale pireksijo z bruhanjem, pleocitozo ali razdražljivost, kar je neskladno s klasično preobčutljivostjo, pri kateri posreduje imunski sistem.
The estimated volume of distribution of cerliponase alfa following intracerebroventricular infusion of 300 mg (Vz = 435 ml) exceeds the typical CSF volume (100 ml), suggesting distribution to tissues outside the CSF. 
Ocenjeni volumen distribucije cerliponaze alfa po intracerebroventrikularnem infundiranju 300 mg (Vz = 435 ml) presega običajni volumen CSL (100 ml), kar kaže na porazdelitev v tkiva zunaj CSL.
• Do not return CSF to the intracerebroventricular access device. 
• CSL ne vračajte v pripomoček za intracerebroventrikularni dostop.
An ongoing study provides experience with two patients aged 2 years of age treated with Brineura at 300 mg every other week (see section 5.1). 
Iz potekajoče študije obstajajo izkušnje z dvema bolnikoma, starima 2 leti, zdravljena z zdravilom Brineura 300 mg vsak drugi teden (glejte poglavje 5.1).
Intracerebroventricular administration of cerliponase alfa is not expected to result in therapeutic concentrations in the eye due to the limited access from the CSF to the affected cells of the retina and the presence of the blood-retinal barrier. 
Ne pričakuje se, da bi intracerebroventrikularno dajanje cerliponaze alfa povzročilo terapevtske koncentracije v očesu zaradi omejenega dostopa iz CSL do zadevnih celic mrežnice in prisotnosti krvno-mrežnične pregrade.
Thus, the non-clinical development is inconclusive with respect to the clinical safety of cerliponase alfa. 
Zato predklinični razvoj ne dopušča sklepanja glede klinične varnosti cerliponaze alfa.
Anti-drug antibodies (ADAs) were detected in both serum and CSF in 79% and 21%, respectively, of patients treated with cerliponase alfa for up to 107 weeks. 
Protitelesa proti zdravilu (ADA, anti-drug antibodies) so odkrili v serumu pri 79 % in v cerebrospinalnem likvorju (CSL) pri 21 % bolnikov, zdravljenih s cerliponazo alfa do 107 tednov.
The medicine is slowly pumped through the implanted device. 
Zdravilo se počasi črpa skozi vsajeni pripomoček.
Brineura has not been given to patients younger than 2 years of age or older than 8 years of age (at the start of the clinical trial). 
Zdravila Brineura niso dajali bolnikom, mlajšim od 2 let ali starejšim od 8 let (ob začetku kliničnega preskušanja).
There are no data on the use of Brineura in pregnant women. 
Podatkov o uporabi zdravila Brineura pri nosečnicah ni.
Brineura contains the active substance cerliponase alfa, which belongs to a group of medicines known as enzyme replacement therapies. 
Zdravilo Brineura vsebuje učinkovino cerliponazo alfa, ki sodi v skupino zdravil, znanih kot encimsko nadomestno zdravljenje.
Transport and distribute frozen (-85°C to -15°C). 
Prevažajte in distribuirajte zamrznjeno (-85 °C do -15 °C).
Contents of the pack and other information What Brineura contains 
Vsebina pakiranja in dodatne informacije Kaj vsebuje zdravilo Brineura
• A programmable syringe pump with appropriate delivery range, delivery rate accuracy, and alarms for incorrect delivery or occlusion. 
• Črpalka za injekcijsko brizgo, ki jo je mogoče programirati in ima ustrezen razpon dovajanja, natančno hitrost dovajanja in alarm za nepravilno dovajanje ali zamašitev.
This medicine replaces the missing enzyme, TPP1, which minimises the build-up of the lysosomal storage materials. 
To zdravilo nadomesti manjkajoči encim, TPP1, kar zmanjša lizosomsko kopičenje nerazgrajenih snovi.
The large CSF to plasma ratios in Cmax and AUC0-t (approximately 1000 and 400, respectively) suggest that the majority of administered cerliponase alfa remains localized within the CNS. 
Visoki razmerji CSL glede na plazmo pri Cmax in AUC0-t (približno 1000 oz. 400) kažeta, da ostane večina uporabljene cerliponaze alfa v CŽS.
These particles are removed via the 0.2 μm inline filter without having a detectable effect on the purity or strength of Brineura. 
Ti delci se odstranijo s filtrom velikosti 0,2 μm v liniji brez zaznavnega učinka na čistost ali jakost zdravila Brineura.
Genotoxicity, carcinogenicity and reproductive toxicity investigations have not been performed. 
Preiskav genotoksičnosti, kancerogenosti ali vpliva na sposobnost razmnoževanja niso opravili.
Access device replacement should be considered prior to 4 years of regular administration of Brineura, however it must always be ensured, that the intracerebroventricular access device is used in accordance with the provisions of the respective medical device manufacturer. 
Zamenjavo pripomočka za dostop je treba izvesti, preden potečejo 4 leta rednega dajanja zdravila Brineura, pri čemer je vedno treba zagotavljati, da se pripomoček za intracerebroventrikularni dostop uporablja v skladu z določbami izdelovalca ustreznega medicinskega pripomočka.
- The active substance is cerliponase alfa. 
- Učinkovina je cerliponaza alfa.