Public Assessment Report. Decentralised Procedure

Transcription

1 Public Assessment Report Decentralised Procedure FOSFOMYCIN 3G GRANULES FOR ORAL SOLUTION Procedure No: UK Licence No: PL 31513/0007 Temapharm Sp. z.o.o.

2 LAY SUMMARY On 17 April 2013, Czech Republic, Estonia, Hungary, Latvia, Poland, Slovak Republic and the UK agreed to grant a Marketing Authorisation to Temapharm Sp. z.o.o. for the medicinal product Fosfomycin 3g Granules for Oral Solution (PL 31513/0007; ). The licence was granted via the Decentralised Procedure (DCP), with the UK as Reference Member State (RMS). After the national phase, a Marketing Authorisation was granted in the UK on 31 May This is a prescription-only medicine that is used to treat or prevent infections of the bladder. Fosfomycin belongs to a group of medicines known as antibiotics. It works by killing bacteria, which can cause infections. No new or unexpected safety concerns arose from this application and it was therefore judged that the benefits of taking Fosfomycin 3g Granules for Oral Solution outweigh the risks; hence, a Marketing Authorisation was granted. 2

3 TABLE OF CONTENTS Module 1: Information about initial procedure Page 3 Module 2: Summary of Product Characteristics Page 4 Module 3: Patient Information Leaflets Page 22 Module 4: Labelling Page 24 Module 5: Scientific Discussion Page 28 1 Introduction 2 Quality aspects 3 Non-clinical aspects 4 Clinical aspects 5 Overall conclusions Module 6 Steps taken after initial procedure 3

4 Module 1 Information About Initial Procedure Product Name Fosfomycin 3g Granules for Oral Solution Type of Application Generic, Article 10(1) Active Substances Form Strength Fosfomycin trometamol Granules for Oral Solution 3g MA Holder Temapharm Sp. z o.o., ul. Żwirki i Wigury 81, Warszawa Reference Member State (RMS) Concerned Member States (CMS) Procedure Number UK Czech Republic, Estonia, Hungary, Latvia, Poland and Slovak Republic Timetable Day April

5 Module 2 Summary of Product Characteristics The current approved UK version of the Summary of Product Characteristics (SmPC) for this product is available on the MHRA website. 5

6 Module 3 Patient Information Leaflet The current approved UK version of the Patient Information Leaflet (PIL) for this product is available on the MHRA website. 6

7 Module 4 Labelling 7

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11 Module 5 Scientific discussion during initial procedure I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the member states considered that the application for Fosfomycin 3g Granules for Oral Solution (PL 31513/0007; ) could be approved. This application was submitted via the Decentralised Procedure, with the UK as Reference Member State (RMS), and Czech Republic, Estonia, Hungary, Latvia, Poland and Slovak Republic as Concerned Member States (CMS). This is a prescription-only medicine for the treatment of acute uncomplicated lower urinary tract infections in adults, caused by pathogens sensitive to fosfomycin. It is also indicated for periprocedural prophylaxis in diagnostic and surgical transurethral procedures. This was an application made under the Decentralised Procedure (DCP), according to Article 10(1) of Directive 2001/83/EC, as amended, a generic application claiming essential similarity to the originator product Monuril adulti 3g, granulato per soluzione orale, which was initially granted to Zambon France in July Fosfomycin exerts its antibacterial effect by inhibition of cell wall synthesis. Through covalent binding it inhibits the enzyme UPD-N-acetylglucosamine enolpyruvyl transferase, which catalyses the formation of the cell wall building block acetyl- uraminic acid, an early step in wall synthesis. Uptake into the bacterial cell occurs either via the L-α-glycerol phosphate transport system or, if glucose-6-phosphate is present, the hexose phosphate transport system. Fosfomycin is active against a range of Gram-positive and Gram-negative bacteria including some β-lactamase producing strains and those bacteria frequently isolated from urinary tract infection, such as Escherichia coli, Proteus spp., Klebsiella spp., Staphylococcus spp., and Enterococci. No new non-clinical or clinical data were provided with this application, which is satisfactory for this type of application. The RMS has been assured that acceptable standards of Good Manufacturing Practice are in place for these product types at all sites responsible for the manufacture, assembly and batch release of this product. The RMS and CMS considered that the application could be approved with the end of procedure (Day 210) on 17 April After a subsequent national phase, the licence was granted in the UK on 31 May

12 II. ABOUT THE PRODUCT Name of the product in the Reference Member State Name(s) of the active substance(s) (INN) Pharmacotherapeutic classification (ATC code) Pharmaceutical form and strength(s) Reference numbers for the Mutual Recognition Procedure Reference Member State Concerned Member States Fosfomycin 3g Granules for Oral Solution Fosfomycin trometamol Other antibacterials (J01XX01) 3g Granules for Oral Solution United Kingdom Czech Republic, Estonia, Hungary, Latvia, Poland and Slovak Republic Marketing Authorisation Number(s) PL 31513/0007 Name and address of the authorisation holder Temapharm Sp. z o.o., ul. Żwirki i Wigury 81, Warszawa 12

13 III SCIENTIFIC OVERVIEW AND DISCUSSION III.1 QUALITY ASPECTS S. Active substance Fosfomycin trometamol rinn: Fosfomycin trometamol Chemical name: 1,3-Dihydroxy-2-(hydroxymethyl)propan-2-aminium-(2R,3S)-(3- methyloxiran-2-yl) phosphonate Structure: Molecular formula: C 7 H 18 NO 7 P Molecular weight: Appearance: A white or almost white powder Solubility: Very soluble in water, slightly soluble in alcohol and in methanol, practically insoluble in acetone Fosfomycin trometamol is the subject of a European Pharmacopoeia monograph. Synthesis of the drug substance from the designated starting materials has been adequately described and appropriate in-process controls and intermediate specifications are applied. Satisfactory specification tests are in place for all starting materials and reagents and these are supported by relevant Certificates of Analysis. Appropriate proof-of-structure data have been supplied for the active substance. All potential known impurities have been identified and characterised. An appropriate specification is provided for the active substance. Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specifications. Satisfactory Certificates of Analysis have been provided for all working standards. Batch analysis data are provided and comply with the proposed specification. Suitable specifications have been provided for all packaging used. The primary packaging has been shown to comply with current guidelines concerning contact with food. Appropriate stability data have been generated supporting a suitable retest period when stored in the proposed packaging. P. Medicinal Product Other Ingredients Other ingredients consist of the pharmaceutical excipients, namely saccharine sodium, sucrose, calcium hydroxide and orange flavour (consisting of maltodextrin, dextrose monohydrate, acacia (E414), anhydrous citric acid (E330), butylhydroxyanisole (E320)). All excipients comply with their respective European Pharmacopoeia monograph, with the exception of the orange flavour, which complies with a suitable in-house specification. Suitable batch analysis data have been provided for all excipients, showing compliance with their respective specifications. None of the excipients are sourced from animal or human origin. No genetically modified organisms (GMO) have been used in the preparation of this product. 13

14 Pharmaceutical Development The objective of the development programme was to formulate a globally acceptable, stable product containing fosfomycin trometamol that could be considered a generic medicinal product of the reference product Monuril adulti 3g, granulato per soluzione orale (Zambon, France). A satisfactory account of the pharmaceutical development has been provided. Physico-chemical characteristics between this product and the reference product, including impurirty profiles and assay, confirm that the Manufacturing Process Satisfactory batch formulae have been provided for the manufacture of the finished product. The manufacturing process has been validated using six pilot-scale batches and has shown satisfactory results. The marketing authorisation holder has committed to completing validation studies for the first three commercial-scale batches produced post authorisation. Finished Product Specification The finished product specification proposed is acceptable. Test methods have been described and have been adequately validated. Batch data have been provided and comply with the release specifications. Certificates of Analysis have been provided for all working standards used. Container-Closure System The finished product is packaged in paper/low-density polyethylene/aluminium sachets, which are packed into cartons in pack sizes of one or two sachets containing 8g of product (which contain 3g of fosfomycin). The marketing authorisation holder has stated that not all pack sizes are intended for marketing. They have committed to providing the relevant licensing authority with the mock-ups for those pack sizes that will be marketed in that country. Satisfactory specifications and Certificates of Analysis have been provided for all packaging components. All primary packaging complies with the current European regulations concerning materials in contact with food. Stability of the product Stability studies were performed in accordance with current guidelines on batches of finished product packed in the packaging proposed for marketing. The data from these studies support a shelf-life of 3 years for the unopened sachets, with no specific storage conditions. After reconstitution the reconstituted solution should be used immediately. Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels The SmPC, PIL and labels are pharmaceutically acceptable. A package leaflet has been submitted to the MHRA along with results of consultations with target patient groups ( user testing ), in accordance with Article 59 of Council Directive 2001/83/EC, as amended. The results indicate that the package leaflet is well-structured and organised, easy to understand and written in a comprehensive manner. The test shows that the patients/users are able to act upon the information that it contains. Marketing Authorisation Application (MAA) form The MAA form is pharmaceutically satisfactory. 14

15 Quality Overall Summary (Expert report) The pharmaceutical expert report has been written by an appropriately qualified person and is a suitable summary of the pharmaceutical dossier. Conclusion The grant of a Marketing Authorisation is recommended. III.2 NON-CLINICAL ASPECTS This application for a generic medicinal product claims essential similarity to Monuril adulti 3g, granulato per soluzione orale (Zambon, France), which has been licensed within the EEA for over 10 years. No new non-clinical data have been supplied with this application and none are required for an application of this type. No environmental risk assessment has been provided with this application. As this product is intended for generic substitution with products that are already marketed, no increase in environmental burden is anticipated. There are no objections to the approval of this product from a non-clinical viewpoint. III.3 CLINICAL ASPECTS CLINICAL PHARMACOLOGY No new data have been submitted for this application and none are required for an application of this type. EFFICACY No new data have been provided and none are required. SAFETY No new data have been provided and none are required. EXPERT REPORT A clinical expert report has been written by a suitably qualified person and is satisfactory. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) This is consistent with the SmPC for the reference product and is satisfactory. PATIENT INFORMATION LEAFLET (PIL) This is consistent with that for the reference product and is satisfactory. LABELLING These are satisfactory PHARMACOVIGILANCE SYSTEM AND RISK MANAGEMENT PLAN The Pharmacovigilance System, as described by the applicant, fulfils the requirements and provides adequate evidence that the applicant has the services of a qualified person responsible for pharmacovigilance, and has the necessary means for the notification of any adverse reaction suspected of occurring either in the Community or in a third country. Suitable justification has been provided for not submitting a risk management plan for this product. 15

16 APPLICATION FORM (MAA) This is satisfactory. MEDICAL CONCLUSION The grant of a marketing authorisation is recommended for this application. IV OVERALL CONCLUSION AND BENEFIT-RISK ASSESSMENT QUALITY The important quality characteristics of Fosfomycin 3g Granules for Oral Solution are well-defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit/risk balance. Bioequivalence between this and the reference product has been shown by comparison of the physico-chemical characteristics of the two products. NON-CLINICAL No new non-clinical data were submitted and none are required for an application of this type. EFFICACY No new data have been submitted No new or unexpected safety concerns arose from this application. The SmPC, PIL and labelling are satisfactory and consistent with that for the reference product. BENEFIT/RISK ASSESSMENT The quality of the products is acceptable and no new non-clinical or clinical safety concerns have been identified. The bioequivalence study supports the claim that the applicant s products and the innovator products are interchangeable. Extensive clinical experience with fosfomycin trometamol is considered to have demonstrated the therapeutic value of the compound. The benefit/risk is, therefore, considered to be positive. 16

17 Module 6 STEPS TAKEN AFTER INITIAL PROCEDURE - SUMMARY Date submitted Application type Scope Outcome 17