Pantobax

Pantoprazolas, 20mg, skrandyje neirios tabletės

Vartojimas: vartoti per burną
Registratorius: Ranbaxy (UK) Limited, Jungtinė Karalystė
Receptinis: Nereceptinis/Receptinis

Sudedamosios medžiagos: Pantoprazolas

Decentralised Procedure

RMS Day 210 Final Assessment Report

OVERVIEW

Pantobax 20 mg gastro-resistant tablets

Pantobax 40 mg gastro-resistant tablets

Pantoprazole sodium sesquihydrate

LT/H/0105/001-002/DC

Applicant: UAB “VVB”

Date: 23.05.2013

TABLE OF CONTENTS

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ADMINISTRATIVE INFORMATION

Names of the assessors:

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IRECOMMENDATION

Based on the review of the data on quality, safety and efficacy, the RMS considers that the application for:

Pantobax 20 mg gastro-resistant tablets, in the short-term treatment of reflux symptoms (e.g. heartburn, acid regurgitation) in adults

AND

Pantobax 40 mg gastro-resistant tablets, in the treatment of

Adults and adolescents 12 years of age and above

reflux oesophagitis

Adults

Eradication of Helicobacter pylori (H. pylori) in combination with appropriate antibiotic therapy in patients with H. pylori associated ulcers.

Gastric and Duodenal ulcer

Zollinger-Ellison syndrome and other pathological hypersecretory conditions

Is approvable.

IIEXECUTIVE SUMMARY

II.1Problem statement

Not applicable for generic application.

II.2About the product

Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific blockade of the proton pumps of the parietal cells.

Pantoprazole is converted to its active form in the acidic environment in the parietal cells where it inhibits the H+, K+-ATPase enzyme, i. e. the final stage in the production of hydrochloric acid in the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, freedom from symptoms is achieved within 2 weeks. As with other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole reduces acidity in the stomach and thereby increases gastrin in proportion to the reduction in acidity. The increase in gastrin is reversible. Since pantoprazole binds to the enzyme distal to the cell receptor level, it can inhibit hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the product is given orally or intravenously.

The active substance pantoprazole is indicated for disorders related to gastric acid hypersecretion including peptic ulcers, gastroesophageal reflux disease, NSAID related ulceration, Zollinger–Ellison Syndrome and Helicobacter pylori infection.

II.3General comments on the submitted dossier

This application is submitted under Article 10(1) of Directive 2001/83/EC, except for Poland where the application was submitted under Article 10(3), so called hybrid application (change in therapeutic indications), and refers to the reference medicinal product Pantozol 40 mg gastro-resistant tablets by Nycomed GmbH, Germany, which has been authorised in the Community since 23th August 1994.

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The submitted documentation in relation to the proposed product is of sufficient quality and is consistent with the current EU regulatory requirements. Satisfactory quality, non-clinical and clinical overviews have been submitted. They represent an adequate summary of the dossier.

In the case of Pantobax 20 mg gastro-resistant tablets, applicant may refer to the centrally authorized OTC product Controloc Control , since reference product Controloc 20 mg gastro-resistant tablets and mentioned product belong to same MAH and the law of Global marketing is applicable in this situation.

Documentation relating to a Pharmacovigilance system has been provided.

II.4 General comments on compliance with GMP, GLP, GCP and agreed ethical principles.

The RMS has been assured that acceptable standards of GMP are in place for these product types at all sites responsible for the manufacture and assembly of this product.

For manufacturing sites within the Community, the RMS has accepted copies of current manufacturer authorisations issued by inspection services of the competent authorities as certification that acceptable standards of GMP are in place at those sites.

IIISCIENTIFIC OVERVIEW AND DISCUSSION

III.1 Quality aspects

Drug substance

The active substance pantoprazole sodium sesquihydrate is described in Ph.Eur. Two manufacturers are declared for the drug substance:

One manufacturer is provided a Certificate of Suitability for pantoprazole sodium sesquihydrate.

The quality of the active substance is controlled by the current version of the Ph. Eur. monograph for pantoprazole sodium sesquihydrate and it is supplemented by the tests mentioned below, based on the analytical procedure(s) given in Annex to the CEP:

The documentation of other manufacturer on the active substance pantoprazole sodium sesquihydrate is presented as an Active Substance Master File (ASMF).

All the issues raised with regard the ASMF have been properly solved. The applied route of synthesis and the used starting materials are considered appropriate. The general properties and the elucidation of structure are well discussed.

The information provided for the control of potential impurities is considered sufficient. The control tests and specifications for drug substance product are adequately drawn up. The

analytical methods have been sufficiently validated. Batch analysis data demonstrating compliance with the proposed drug substance specification of the Applicant were provided for ten production scale batches of the drug substance.

Drug Product

The drug product corresponds to gastro-resistant tablets available in the strengths of 20 mg and 40 mg pantoprazole, corresponding to 22.557 and 45.113 mg pantoprazole sodium sesquihydrate, respectively. Proposed packaging materials is cold form blister pack comprises of aluminium foil/ polyamide/polyvinyl chloride film on one side and aluminium foil on the other side with heat seal coating.

The development of the product has been described, the choice of excipients is justified and their functions explained. Manufacturing process development was adequately explained.

Comparative dissolution profiles of test and reference product of the bioequivalence study as well as of test product of the bioequivalence study and batches of both strengths of pantoprazole gastro-resistant tablets were provided with the respective similarity factors. Similarity of dissolution profiles

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was shown acceptably. Similarity of dissolution profiles was proved for the drug product applied for in relation to reference medicinal products of different EU member states, too.

The information provided with regard to manufacturing process of the medicinal product is considered adequate.

The proposed specifications at release and shelf life are considered acceptable. The analytical methods are described and validated.

The conditions used in the stability studies are according to the ICH guideline. The proposed shelf-life of 36 months without any special labelled storage conditions is considered justified by stability data provided.

III.2 Non clinical aspects

Pharmacodynamis, pharmacokinetic and toxicological properties of pantoprazole are well known. As pantoprazole is a widely used, well-known actives substance, the applicant has not provided additional studies and further studies are not required. Overview based on literature review is, thus, appropriate.

Environmental Risk Assessment (ERA)

Since pantoprazole is intended for generic substitution, this will not lead to an increased exposure to the environment. An environmental risk assessment is therefore not deemed necessary.

Conclusions

There are no objections to approval Pantobax 20 mg gastro-resistant tablets and Pantobax 40 mg gastro-resistant tablets from a non-clinical point of view.

III.3 Clinical aspects

To support the application, the applicant has carried out a 3 single dose bioequivalence studies:

study BE-038-PANT-2006: 40 mg tablet under fasting conditions study 111_PANTO_06: 40 mg tablet under fed conditions

study BE-155-PANT-2008: 20 mg tablet under fasting conditions

The studies were performed in healthy volunteers. The GCP/GLP aspects of the clinical phases of the studies are sufficiently documented. Quality assurance documents were provided.

The study BE-038-PANT-2006 was an open label, randomized, two-treatment, two-sequence, four-period, cross-over single-dose bioequivalence study of pantoprazole under fasting conditions. Sixty healthy male subjects, aged 18 - 42 years, were included in this study. A single oral dose of Test or Reference product (one tablet, containing 40 mg Pantoprazole as pantoprazole sodium sesquihydrate) was administered in each period. Each treatment was separated by a washout period of 7 days. In accordance with the study protocol, bioequivalence was accepted if the 90% confidence intervals of the test to reference product of ln-transformed AUC and Cmax were within the acceptance range of 80% to 125%. The 90% CI ranges for AUC0-t was 91.96 – 97.78%. For AUC0-∞ was 91.98 – 97.74%, for Cmax the 90% CI range was 90.98 – 100.05%.

The study 111_PANTO_06 was an open label, randomized, two-treatment, two-period, two-sequence, cross-over, single-dose, bioequivalence study of 40 mg pantoprazole under fed conditions. Forty healthy male subjects, aged 19 - 43 years, were included in this study and 38 subjects completed the study. A single oral dose of Test or Reference product (one tablet, containing 40 mg Pantoprazole as pantoprazole sodium sesquihydrate) was administered. Subjects received the alternate ‘treatment’ in the subsequent periods, in such a way that each subject received both the products by the end of the study. The Test or Reference product was administered with 240 mL of drinking water, 30 minutes after start of high-fat, high-calorie breakfest under supervision of trained study personal. Each treatment was separated by a washout period of 6 days. In accordance with the study protocol, bioequivalence was accepted if the 90% confidence intervals of the test to reference

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product of ln-transformed AUC and Cmax were within the acceptance range of 80% to 125%. The 90% CI ranges for AUC0-t was 87,36 – 106,62%. For AUC0-∞ was 89,04 – 110,53%, for Cmax the 90% CI range was 85,02 – 118,21%.

The study BE-155-PANT-2008 was an open label, randomized, two-treatment, two-sequence, two-period, cross-over single-dose bioequivalence study of pantoprazole 20 mg tablets in forty healthy adult subjects under fasting conditions. Forty healthy male subjects, aged 18 - 42 years, were included in this study. A single oral dose of Test or Reference product (one tablet, containing 20 mg Pantoprazole as pantoprazole sodium sesquihydrate) was administered. Subjects received the alternate ‘treatment’ in the subsequent periods, in such a way that each subject received both the products by the end of the study. In accordance with the study protocol, bioequivalence was accepted if the 90% confidence intervals of the test to reference product of ln-transformed AUC and Cmax were within the acceptance range of 80% to 125%. The 90% CI ranges for AUC0-t was 97.71 – 105.27 %. For AUC0-∞ was 97.83 – 105.96 %), for Cmax the 90% CI range was 91.06 – 103.78 %.

Applicant’s product data meet the requirements mentioned in the relevant guidelines, it is appropriate to consider The biowaiver for a separate fed bioequivalence study on 20 mg strength meet the conditions of Note for guidance on the investigation Bioavailability and Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1/Corr).

Pharmacovigilance system (DDPS)

According to contractual agreement between CRO Biomapas and UAB VVB, CRO Biomapas is contracted by UAB VVB for a pharmacovigilance services, including the services of EUQPPV. However, a co-operation on pharmacovigilance activities between UAB VVB and Ranbaxy Laboratories Limitedhas been established for the pantoprazole medicinal product.

The applicant has provided documents that set out a detailed description of the system of pharmacovigilance. A statement signed by the applicant and the qualified person for pharmacovigilance, indicating that the applicant has the services of a qualified person responsible for pharmacovigilance and the necessary means for the notification of any adverse reaction occurring either in the Community or in a third country has been provided.

Risk Management Plan

The present procedure is a generic application. According to well established safety profile of the reference product and proved bioequivalence between this generic product and the reference product, no Risk Management Plan is needed.

No risk minimization activities additional to recommendations included in the proposed Summary of Products Characteristics and Patient Information Leaflet are necessary.

Periodic Safety Update Report (PSUR)

The PSUR submission cycle is in accordance with published EURD list, i.e. the Data Lock Point (DLP) of the next PSUR submission for pantoprazole sodium sesquihydrate will be on 23/08/2015. However PSUR submission is not required for pantoprazole products referred to in Articles 10 (1). Therefore for Pantobax 20 mg gastro-resistant tablets and Pantobax 40 mg gastro-resistant tablets the PSUR submission is not required.

The applicant should monitor the EURD list for any changes to the requirements for PSUR submission and changes in periodicity and Data Lock Point.

Common renewal date

The common renewal date is proposed as 5 years after the closing date of the procedure.

IVBENEFIT RISK ASSESSMENT

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The benefit risk of this product is at present negative since potential serious risks to public health have been identified from quality point of view as detailed in section V.

VLIST OF QUESTIONS as proposed by RMS

V.1Quality aspects

Potential serious risks to public health

Drug substance

None

Drug product

None

Points for clarification

Drug substance

None

Drug product

None

V.2Non clinical aspects

Potential serious risks to public health

None

Points for clarification

None

V.3Clinical aspects

Potential serious risks to public health

None

Points for clarification

None

Pharmacovigilance system

None

Risk Management Plan

The applicant should monitor the EURD list for any changes to the requirements for PSUR submission and changes in periodicity and Data Lock Point.

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VIRECOMMENDEDCONDITIONSFORMARKETING

AUTHORISATION AND PRODUCT INFORMATION

VI.1 Conditions for the marketing authorisation

Legal Status

Pantobax 20 mg gastro-resistant tablets

The proposed Legal status is OTC. The Summary of Product Characteristics (SPC), Package Leaflet (PL) and the Labelling are full copies of the published texts of the centrally approved OTC product Controloc Control 20 mg, gastro-resistant tablets.

Pantobax 40 mg gastro-resistant tablets

The prescription-only medicine (POM).

Follow-up measures

None

Specific obligations

None

National points

D 195 CMS-Poland had comment that the name of medicinal product is not agreed in Poland. Please be informed that the name of medicinal product in Poland could be agreed during national phase of procedure.

VI.2 Summary of Product Characteristics (SPC)

SPC is acceptable (see attached SmPC).

VI.3Package Leaflet (PL) and User Testing

VI.3.1Package Leaflet

PL is acceptable (see attached PL).

VI.3.2Assessment of User Testing

The applicant submited two Readability Testings of the Package Leaflets: one for Pantobax 20 mg gastro-resistant tablets (OTC) and second for Pantobax 40 mg gastro-resistant tablets (POM). The package leaflets were evaluated via a user consultation study in accordance with the requirements of Articles 59(3) of Directive 2001/83/EC as amended by Directive 2004/27/EC. The evaluation reports of the tests are in an acceptable quality. The conclusions are clear, concise and clearly presented.

The test consisted of two rounds with 10 participants each. Four participants were tested during the preliminary round of testing.

Inclusion and exclusion criteria for the test persons were specified in the protocol. The test was performed in English. Educational levels correspond with the inclusion criteria set in the protocol.

The test was performed by face-to-face interviews. Questions were designed to determine whether users can identify key information that is necessary for appropriate use of product.

There were sufficient questions about the critical sections and the areas traceability, comprehensibility and applicability were sufficiently covered. The test included 17 questions (18 for POM product) related to the content of the PL. Three questions were related to the format of the package leaflet.

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Participants were interviewed individually by one experienced and trained interviewer. The responses were digitally recorded and written down by hand. A satisfactory outcome was achieved when 90% of the participants were able to find information and answer each question correctly.

In round 1, at least 90% of the time the correct section was located to answer the question. Each question was correctly answered 100% of the time. No adjustments to the package leaflet were made between the first and the second round. In the second round 90% of the participants were able to locate the section and 100% were able to answer the questions. Therefore no further changes were considered to be required.

VI.4Labelling

The labelling is acceptable. See attached Labelling.

VIIAPPENDIX

QRD GUIDANCE AND CHECKLIST FOR THE REVIEW OF USER

TESTING RESULTS

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QRD GUIDANCE AND CHECKLIST FOR THE REVIEW

OF USER TESTING RESULTS

[Disclaimer: This guidance has been set up to provide practical information on how to evaluate user testing reports which are based on the readability testing method as described in Annex 1 of the EC Readability Guideline. This does not exclude the submission and evaluation of user testing reports based on other methods than the one outlined above, for which specific assessment guidance may be issued once experience has been gained

Useful links: More detailed practical guidance can be found in the following documents:

• EC Readability Guideline http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/c/2009_01_12_readability_guideline_final.pdf
• “Operational procedure on Handling of “Consultation with target patient groups” on Package

Leaflets (PL) for Centrally Authorised Products for Human Use http://www.emea.europa.eu/htms/human/qrd/qrdplt/27737805en.pdf “Consultation with Target Patient

Groups-meeting the requirements of Article 59(3) without the need for a full test-Recommendations for Bridging” http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/procedural_guidance/Consulation _PatientsGroups/CMDh_100_2007_Rev1_clean_April09.pdf

• “Position paper on user testing of package leaflets” http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/procedural_guidance/Consulation _PatientsGroups/CMDh_234_2011.pdf
• [MRP/DCP relevant document – link to be inserted]

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(In case of bridging report, multiple bridging is, in principle, not acceptable. However, a maximum of 3 bridging procedures could be accepted for one product: e.g. first bridging to address the scientific content, a second one to address the device and a last one to address the layout of the PL).

- Grounds for bridging based on a sound justification:

extensions for the same route of administration

reference to test on same class of medicinal product

reference to test with same safety issues other ______________________

(In case no full user testing or bridging report has been provided, a justification should be submitted.)

(The following are examples of what are not considered valid justifications for not performing User Testing:

• Administration in a hospital setting only,

• Administration by a healthcare professional only,

• Compliance with the QRD templates,

• Long established use of the product.

Reasons [assessor’s views on acceptability or not of the justification/bridging report – assessment of justification/bridging]

___________________________________________________________________________________

_______________________________________________________________________________________

_______________________________________________________________________________________

________________________________________________________________________

_______________________________________________________________________________________

_____________________________________________________________________________

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1TECHNICAL ASSESSMENT

• Recruitment

Comments/further details________________________________________________________________

Guidance regarding Recruitment

The following points should be taken into consideration when assessing recruitment methods:

• Is the recruitment method well defined? Is it clear that serious thought was given to the composition of the test group? (e.g. in terms of variables such as sex, age, education, experience with the medicinal product, existing knowledge of the complaint, etc.)

• How has the test group been recruited? Are they new users or patients, parents or carers?
• Is it clear how many people were involved in the test/test rounds?

• Is that number sufficient? (The PL should be tested in minimum 2 rounds of 10 participants each)

• Questionnaire

Is the number of questions ___20 (for 20 mg tablets) and 21 (for 40 mg tablets)____ sufficient?

yes no

Comments/further details The text is easily understandable to the respondent. Given questions are open and do not require a long list of answers.

• Time aspects

Comments/further details_ Each interview lasted not longer than 45 minutes.

• Procedural aspects

Rounds of testing including pilot ___3____

Comments/further details Testing was undertaken in the English. Experienced and appropriately trained interviewers personally interview all study subjects. The testing was conducted in 3 rounds including the pilot test.

• Interview aspects

Comments/further details Interviews were done with one subject at a time, in a private, quiet location. Clear instructions for the test instructors were given.

2EVALUATION OF RESPONSES

• Evaluation system

Comments/further details_ The assessment was based on a check list covering the following 2 basic areas: finding the information and understanding the information.

• Question rating system

Comments/further details The search for information was graded as “simple”, “easy”,“moderate” and “difficult”.

The understanding of information was evaluated as “Correct answer”, “Wrong answer”.

3DATA PROCESSING

Comments/further details_The data were recorded and processed satisfactory.

• QUALITY ASPECTS

• Evaluation of diagnostic questions

Comments/further details In both rounds 90% of participants were able to find each item of information and to show that they had understood correctly all questions.

• Evaluation of layout and design

Comments/further details The evaluation system is satisfactory.

• DIAGNOSTIC QUALITY/EVALUATION

Comments/further details No changes were suggested on the basis of the quantitative and qualitative results of the combined first and second rounds.

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Vaistinio preparato veiklioji medžiaga pantoprazolo natrio druska seskvihidratas aprašytas Europos farmakopėjoje. Registracijos byloje pateiktas vieno veikliosios medžiagos gamintojo pantoprazolo natrio druskos seskvihidrato kokybės atitikties Europos farmakopėjai sertifikatas bei kito gamintojo pantoprazolo natrio drusko seskvihidrato gamybos byla. Pantoprazolo natrio druskos seskvihidrato kokybė atitinka Europos farmakopėjos reikalavimus. Pantoprazolo natrio drusko seskvihidrato specifikacijoje reglamentuojmų parametrų nustatymui naudojamos analizės procedūros yra tokios pačios, kaip ir reglamentuoja Europos farmakopėja straipsnyje pantoprazolo natrio drusko seskvihidrato kokybei.

Vaistinis preparatas yra registruojamas dviejų stiprumų: 20 mg ir 40 mg. Galutinio produkto sudėties parinkimo duomenys pateikti. Siūlomo registruoti vaistinio preparato ir referencinio vaistinio preparato farmacinis ekvivalentiškumas įrodytas. Vidinės talpyklės Aliuminio/Poliamido/PVCir aliuminio folijos lizdinės plokštelės tinkamumas įrodytas stabilumo tyrimų metu.

Pagalbinės medžiagos pariktos tinkamai, jų kokybė kontroliuojama pagal galiojančios Europos farmakopėjos straipsnių reikalavimus. Galutinio produkto specifikacijos kokybė yra tinkama, joje reglamentuojami visi būti parametrai, kuriuos nurodo Europos farmakopėja ir ICH gairės. Galutinio produkto stabilumo tyrimai atlikti pagal ICH gairių reikalavimus. Stabilumo tyrimų duomenimis siūlomas vaistinio preparato tinkamumo laikas yra 3 metai. Jokių specialių šio vaistinio preparato laikymo sąlygų nėra reglamentuojama.

Trumpa ikiklinikinės ir klinikinės dalies apžvalga

Pantobax 20 mg skrandyje neirios tabletės yra nereceptinis vaistinis preparatas, skirtas vartoti suaugusiems pacientams, kurio vartojimo indikacija yra:

Trumpalaikis suaugusių žmonių refliukso simptomų (pvz., rėmens, rūgšties regurgitacijos) gydymas.

Pantobax 40 mg skrandyje neirios tabletės yra receptinis vaistinis preparatas, skirtas vartoti vyresniems nei 12 metų paaugliams ir suaugusiems. Jo vartojimo indikacijos yra:

Suaugę žmonės ir 12 metų bei vyresni paaugliai

 Refliuksinis ezofagitas

Suaugę žmonės

• Helicobacter pylori (H. pylori) išnaikinimas pacientams, kuriems yra su H. pylori susijusių opų (kartu skiriama tinkamų antibiotikų).

• Skrandžio ir dvylikapirštės žarnos opa.

• Zolingerio ir Elisono sindromas arba kitokios su patologine hipersekrecija susijusios būklės.

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Ši generinė paraiška buvo pateikta pagal direktyvos 2001/83/EB 10 str. 1d. ir pareiškėjas klinikiniais tyrimais įrodė, kad Pantobax 20 mg ir 40 mg skrandyje neirios tabletės yra iš esmės panašios į referencinį vaistinį preparatą Protium 20 ir 40 mg gastro-resistant tablets, RTT Altana Pharma AG, Vokietija.

Pantoprazolas yra pakeistas benzimidazolas, kuris, specifiškai blokuoja parietalinių skrandžio gleivinės ląstelių protonų siurblį, todėl slopina vandenilio chlorido rūgšties sekreciją skrandyje. Rūgščioje parietalinių ląstelių terpėje pantoprazolas virsta aktyvia forma cikliniu sulfenamidu, kuris slopina fermentą H+, K+-ATF-azę, t. y. galutinį vandenilio chlorido rūgšties gamybos skrandyje etapą.

Slopinimas priklauso nuo dozės dydžio, poveikis pasireiškia bazinei ir stimuliacijos sukeltai rūgšties sekrecijai. Daugumai pacientų rėmuo ir rūgšties refliukso simptomai išnyksta per savaitę. Pantoprazolas mažina rūgštingumą skrandyje, todėl proporcingai rūgštingumo sumažėjimui padaugėja gastrino. Gastrino kiekio padidėjimas yra laikinas. Kadangi pantoprazolas jungiasi prie fermento, esančio distaliau nuo receptoriaus, vandenilio chlorido rūgšties sekreciją jis slopina nepriklausomai nuo kitų medžiagų (acetilcholino, histamino, gastrino) sukeliamo stimuliavimo. Išgerto ar į veną injekuoto pantoprazolo poveikis nesiskiria.

Naujų ikiklinikinių tyrimų duomenų apie pantoprazolą pareiškėjas nepateikė, nes referencinis vaistinis produktas, į kurį referuoja ši „generinė“ paraiška rinkoje yra daugiau nei 10 metų. Išskyrus biologinio ekvivalentiškumo tyrimus, kitų klinikinių tyrimų atlikta nebuvo, atsižvelgiant į „generinės“ paraiškos reikalavimus. Bioekvivalentiškumo tyrimai buvo atlikti pagal geros klinikinės praktikos reikalavimus.

RMS ir CMS nusprendė, kad paraiška yra priimtina ir užbaigė šią rinkodaros teisės suteikimo procedūrą (210 dieną) 2012-05-23. Po nacionalinės fazės Lietuvoje rinkodaros teisė buvo suteikta

2013-07-31.

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