Public Assessment Report

Public Assessment Report ALERTRIN anti-allergie 10mg tablets Loratadine BE licence no: BE401177 Applicant: MSD Belgium BVBA/SPRL Date: 19/07/2011 Page 1 of 13

This assessment report is published by the Federal Agency for Medicines and Health Products following Article 21 (3) and (4) of Directive 2001/83/EC, amended by Directive 2004/27/EC and Article 25 paragraph 4 of Directive 2001/82/EC as amended by 2004/28/EC. The report comments on the registration dossier that was submitted to the Federal Agency for Medicines and Health Products and its fellow organisations in all concerned EU member states. It reflects the scientific conclusion reached by the Federal Agency for Medicine s and Health Products and all concerned member states at the end of the evaluation process and provides a summary of the grounds for approval of a marketing authorisation. This report is intended for all those involved with the safe and proper use of the medicinal product, i.e. healthcare professionals, patients and their family and carers. Some knowledge of medicines and diseases is expected of the latter category as the language in this report may be difficult for laymen to understand. This assessment report shall be updated by a following addendum whenever new information becomes available. To the best of the Federal Agency for Medicines and Health Products knowledge, this report does not contain any information that should not have been made available to the public. The Marketing Autorisation Holder has checked this report for the absence of any confidential information. Page 2 of 13

TABLE OF CONTENTS Chapter 1: Administrative Information Page 4 Chapter 2: Scientific Discussion Page 5 1. Introduction 2. Quality aspects 3. Non-clinical aspects 4. Clinical aspects 5. Overall conclusion, benefit/risk assessment and recommendation Chapter 3: Steps taken after the initial procedure update Page 11 Page 3 of 13

ADMINISTRATIVE INFORMATION Name of the medicinal product INN (or common name) of the active substance(s) Pharmaco-therapeutic Group and ATC Code Pharmaceuticals form(s) Strength(s) Target Species Indications Type of application Legal Basis Type of active substance Prescription status Reference number for the procedure Reference Member State Concerned Member State Marketing Authorisation Holder Alertrin anti-allergie tablets Loratadine Antihistamines H 1 antagonist, ATC code: R06A X13 Tablets 10 mg NA Alertrin anti-allergie tablets are indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria. DCP - Know Active substance - Abridged Generics (article 10(1) of Directive 2001/83/EC) Chemical substance Non prescription (including OTC) BE UK MSD Belgium BVBA/SPRL Clos du Lynx 5 B-1200 Brussels Page 4 of 13

Public Assessment Report Scientific discussion ALERTRIN anti-allergie 10mg tablets Loratadine Page 5 of 13

This module reflects the scientific discussion for the approval of Alertrin anti-allergie. The procedure was finalised at 19/07/2011. For information on changes after this date please refer to the module Update. Page 6 of 13

I. INTRODUCTION This application is being made according to Article 28 of Directive 2001/83/EC as amended, granted by the Belgian Health Authorities on 19/07/2011 (MA number: BE401177). This application concerns an abridged application, submitted according to Article 10 (c) of Directive 2001/83/EC as amended, related to medicinal products that are essentially similar to a medicinal product authorized in the Member State concerned by the application and that the holder of the marketing authorization for the original medicinal product has consented to the toxicological, pharmacological and/ or clinical references contained in the file on the original medicinal product being used for the purpose of examining the application in question. This medicinal product is essentially similar to Claritine 10 mg tablets of Schering-Plough SA/NV. Alertrin anti-allergie has the same composition and the same pharmaceutical form as Claritine 10 mg tablets, approved in Belgium since 1987-12-01 with Marketing Authorisation Holder Schering- Plough NV/SA (identical to the proposed MAH for Alertrin anti-allergie). Claritine 10 mg tablets has been authorised via the national procedure, but following the article 31 referral for loratadine containing products (EMEA/H/A-31/486), the SPC has been harmonised and the subsequent variations have been submitted through MRP BE/H/128/01, in which UK is CMS. Module 3 has been harmonised through variation BE/H/128/01/II/08. A letter of consent from Schering-Plough SA, dated 20 August 2010, has been submitted, which authorize use of the pharmaceutical, non-clinical and clinical documentation for Claritine 10 mg tablets in support of this application. Loratadine is indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria. II. QUALITY ASPECTS II.1 Introduction Alertrin anti-allergie is presented as a tablet containing 10mg of loratadine. The excipients are: Lactose monohydrate, maize starch and magnesium stearate. 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. II.2 Drug Substance Loratadine, the active ingredient in Alertrin anti-allergie tablets, is a tricyclic antihistamine with selective, peripheral H 1 -receptor activity. Loratadine is described in the Ph. Eur. No 2124 and is analysed by the manufacturers according to this monograph. It is produced as a micronised powder. Page 7 of 13

The drug substance loratadine provided is tested for compliance with the specifications of the Ph. Eur. monograph supplemented by additional requirements for residual solvents and particle size. The packaging material of the drug substance is described in the Ph. Eur. certificate (CEP): double PE bags in fibreboard drum. The re-test period of the drug substance is 5 years if stored in double PE bags placed in a fibreboard drum at a temperature not exceeding 30 C. II.3 Medicinal Product The tablet is white, to off-white, oval with flask and bowl, score and 10 on one side, plain on the other side. The scoreline of the tablet is only to facilitate breaking for ease of swallowing and not to divide into equal doses. The tablets are packed in Alu/PVC blister strips inserted in cartons. Discussion on The development of the drug product has been properly described regarding drug substance, compatibility, influence of polymorphism on product behaviour, manufacturing process and packaging materials. The manufacturing process of Alertrin anti-allergie 10mg tablets is a standard process using wet granulation and compression. The manufacturing process has been sufficiently validated at a production scale of 7,200,000 tablets. All used excipients comply with relevant Ph. Eur. monographs. Representative certificates of analysis for each excipient issued by the finished product manufacturer are presented. The tablets are manufactured, analysed, packed and released by Schering-Plough nv, Heist-op-denberg (Belgium). Analysis, packaging and release may alternatively be performed by Schering-Plough, Herouville Saint Clair (France). This medicinal product does not require any special storage conditions. Long-term and accelerated stability results are presented for at least 3 production batches. All results are within specification and there are no significant trends observed. Impurities are reported at levels between 0.05% and 0.1% for older batches. In the more recent batches, impurities have never exceeded 0.01%. A shelf life of 36 months without any special storage condition is acceptable. The drug product is not sensitive to light exposure as shown in the pharmaceutical development section. III. NON-CLINICAL ASPECTS Reference has been made to the original Claritine dossier and amendments by subsequent variations. No additional non-clinical studies have been provided. IV. CLINICAL ASPECTS IV.1 Introduction Loratadine, the active ingredient in Alertrin anti-allergie tablets, is a tricyclic antihistamine with selective, peripheral H1-receptor activity. It has no clinically significant sedative or anticholinergic properties in the majority of the population when used at the recommended dosage. Loratadine has no significant H2-receptor activity. It does not inhibit norepinephrine uptake and has practically no influence on cardiovascular function or on intrinsic cardiac pacemaker activity.alertrin anti-allergie tablets are indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria. Page 8 of 13

As Alertrin anti-allergie tablets is an informed consent application no new clinical data were submitted and consent has been given to the clinical data of the medicinal product Claritine 10 mg tablets. The SPC as provided is an ad verbatim copy of the SPC as approved for the reference product. No issues were raised during review. The PIL as provided is an ad verbatim copy of the SPC as approved for the reference product. No issues were raised during review. The RMS considers that 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. The clinical use of the active substance Loratadine is well established and there are many years of experience to enable safety monitoring via routine risk minimisation. No risk management plan has been provided. This is satisfactory V. OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION Alertrin anti-allergie 10mg tablets has the exact same risk/benefit profile as the reference product Claritine 10 mg tablets. The benefit/risk ratio is therefore considered positive. Loratadine, an H 1 agonistic antihistamin intended for use in this indication, has been on the market for some time in various forms including tablets and has shown to have a positive benefit/risk ratio. Periodic Safety Update Report (PSUR): The applicant has not requested a different PSUR cycle upon approval. The RMS considers the submission of 6-monthly PSURs not necessary and recommends PSUR submissions to be aligned with the EU Harmonised Birthday and related Data Lock Points as published on the HMA website. The applicant has confirmed this. With regard to PSUR submission, the Applicant/MAH should take into account the following: In accordance with the revised legislation on pharmacovigilance (Directive 2010/84/EU), the list of European Union Reference Dates (the EURD list) of PSURs has been established and published by EMA. Marketing authorisation holders shall continuously check the EMA webportal for the DLP and frequency of submission of the next PSUR. For medicinal products authorized under the legal basis of Article 10(1) or Article 10a of Directive 2001/83/EC, no routine PSURs need to be submitted, unless otherwise specified in the EURD list. For medicinal products that do not fall within the categories waived of the obligation to submit routine PSURs by the revised pharmacovigilance legislation, the MAH should follow the DLP according to the EURD list. The International Birth Date (IBD) is 19/07/2011 Page 9 of 13

The Common Renewal Date will be 19/07/2016. In March 2008 the Applicant submitted a bridging report for the Clarityn range, including the tablets PL 00201/0175. That leaflet has been approved by the MHRA on 20 August 2010, after extensive MHRA scrutiny. The leaflet submitted with this dossier is identical to this current approved leaflet with the exception of the Marketing Authorisation Holder's name and address. The bridging report of and a letter of application to the MHRA of March 2008 + the letter of approval of August 2010 were present in the submitted dossier. For this reason no further readability testing is needed. Page 10 of 13

Public Assessment Report Update ALERTRIN Allergy 10mg tablets Loratadine Page 11 of 13

This module reflects the procedural steps and scientific information after the finalisation of the initial procedure. Page 12 of 13

Scope Procedure number Product infomation affected < Type II analytical or clinical procedure; renewal; < sections of SmPC and line extention > PL modified > < Title of variation or line extention> Date of start of the procedure Date of end of procedure Approval/ non approval Assessment report attached <Y/N (version: date of report) + conclusions of AR attached> Page 13 of 13