Decentralised Procedure. Public Assessment Report

Transcription

1 Decentralised Procedure Public Assessment Report Aspirin Complex Hot drink 500 mg / 30 mg granules for oral suspension Acetylsalicylic acid / pseudoephedrine DE/H/3635/001/DC Applicant: Bayer Vital GmbH Reference Member State DE

2 TABLE OF CONTENTS I. INTRODUCTION... 4 II. EXECUTIVE SUMMARY... 4 II.1 Problem statement... 4 II.2 About the product... 4 II.3 General comments on the submitted dossier... 4 II.4 General comments on compliance with GMP, GLP, GCP and agreed ethical principles. 4 III. SCIENTIFIC OVERVIEW AND DISCUSSION... 4 III.1 Quality aspects... 4 III.2 Non-clinical aspects... 5 III.3 Clinical aspects... 5 IV. BENEFIT RISK ASSESSMENT... 6 Aspirin Complex, DE/H/3635/DC Public AR Page 2/6

3 ADMINISTRATIVE INFORMATION Proposed name of the medicinal product(s) in the RMS INN (or common name) of the active substance(s): Pharmaco-therapeutic group (ATC Code): Pharmaceutical form(s) and strength(s): Reference Number(s) for the Decentralised Procedure Reference Member State: Member States concerned: Applicant (name and address) Aspirin Complex Heissgetränk 500 mg / 30 mg Granulat zur Herstellung einer Suspension zum Einnehmen Acetylsalicylic acid / pseudoephedrine N02AB01 + R01BA02 granules for oral suspension, 500 mg /30 mg DE/H/3635/001/DC DE AT, BG, HU, PL, RO, SK Bayer Vital GmbH Leverkusen, Germany Aspirin Complex, DE/H/3635/DC Public AR Page 3/6

4 I. INTRODUCTION Based on the review of the data on quality, safety and efficacy, the application for Aspirin Complex, in the proposed indication Symptomatic treatment of nasal congestion with cold-related pain and fever is approved. II. EXECUTIVE SUMMARY II.1 Problem statement Aspirin Complex (Acetylsalicylic acid (ASA) 500mg/pseudoephedrine (PSE) 30mg granules for oral suspension) was first registered by Bayer Vital GmbH in Germany With Germany as the Reference Member State in this Decentralized Procedure, Bayer Vital GmbH is applying for the Marketing Authorisations for Aspirin Complex Hot drink in AT, BG, HU, PL, RO, SK as CMS. The legal basis of this application is Article 10b fixed combination, extension application to Aspirin Complex (DE/H/2228/001) as the existing marketing authorisation to which this extension applies. The differences between the innovator and the applied product are: differences in the flavour system (sucralose, vanilla- / peppermint-menthol-eucalyptus - flavour instead of saccharin, citric acid & orange-flavour) the applied product is dissolved with hot water instead of lukewarm water II.2 About the product Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are well known substances with analgesic, antipyretic and anti-inflammatory properties (ASA) and congestive properties (PSE). The combination of the two active ingredients represents a simplification of therapy of target symptoms in common cold. ASA and PSE have been used as an over-the-counter (OTC) drug for about 10 years. The product will be used as a hot drink in the symptomatic treatment of nasal congestion with coldrelated pain and fever. II.3 General comments on the submitted dossier This decentralised application concerns a fixed combination of acetylsalicylic acid and Pseudoephedrine under the trade name Aspirin Complex Hot drink, 500 mg / 30 mg granules for oral suspension. In this Assessment Report, the name Aspirin Complex is used. Both safety and efficacy of the two active substances from single products as well as from the combination product are well known. The active substances are not considered new active substances. 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. III. SCIENTIFIC OVERVIEW AND DISCUSSION III.1 Quality aspects Drug substance The chemical-pharmaceutical documentation and Quality Overall Summary in relation are of sufficient quality in view of the present European regulatory requirements. Both drug substances of the drug product acetylsalicylic acid (ASA) and pseudoephedrine hydrochloride (PSEH) are considered suitable to produce a pharmaceutical product of the proposed quality. Both substances are described in the Ph. Eur.. Recent CEP s of the EDQM are available for ASA and PSEH. Aspirin Complex, DE/H/3635/DC Public AR Page 4/6

5 The control tests and specifications for drug substances are adequately drawn up. Stability studies have been performed with the drug substance. No significant changes in any parameters were observed. ASA: The proposed retest period of 24 months is justified when the active substance is stored in polyethylene bags inside cardboard drums or big bags. PSEH: The proposed retest period of 60 months for PSEH is justified when the active substance is stored protected from light in double polyethylene bags. Drug Product The development of the product has been described, the choice of excipients is justified and their functions explained. Detailed dissolution studies have been carried out. The ingredients and the manufacturing process of the drug product are considered suitable to produce a pharmaceutical product of the proposed quality. Most of the ingredients are described in the Ph. Eur. The used substances are well known and documented. The product specifications cover appropriate parameters for this dosage form. Validation reports of the analytical methods have been carried out. Batch analysis has been performed on three batches. The batch analysis results show that the finished products meet the specifications proposed. The relevant quality characteristics of the drug substance and the drug product (release and shelf-life) are specified. The proposed limits are accepted. The conditions used in the stability studies are according to the ICH stability guideline. The control tests and specifications for drug product are adequately drawn up. A shelf-life of 3 years (without label claim) is accepted. III.2 Non-clinical aspects Pharmacology, Pharmacokinetics, Toxicology Pharmacodynamic, pharmacokinetic and toxicological properties of acetylsalicylic acid (ASA) and of pseuodephedrine (PSE) are well known. As ASA and PSE are widely used, well-known active substances, a non-clinical overview based on a literature review is thus appropriate. In this regard, the Applicant (i) makes reference to the non-clinical overview provided for the originator product Aspirin Complex (DE/H/2228/001/MR), dated September 2005 (ii) provides an updated review of published evidence for ASA and PSE together with an assessment by a non-clinical expert, showing that no new non-clinical information that would negatively impact the risk assessment of the fixed combination product with respect to human use has been obtained during the last 10 years. The approach chosen by the Applicant is considered adequate. Environmental Risk Assessment The applicant provided justification for an absence of an ERA according to the Questions & Answers on the Guideline on the environmental risk assessment of medicinal products for human use Question 2 based on the explanation of the minor differences, like flavour system and the temperature of the media to be dissolved in, between the reference product and the new product only. The RMS agrees with the applicant that no ERA is necessary. III.3 Clinical aspects Pharmacokinetics No new own clinical efficacy study reports are provided. To show that the changed flavour as well as the way of preparation with hot water do not influence the pharmacokinetic profile, the applied Aspirin Complex Hot drink was compared to the reference product Aspirin Complex, which is the innovator product (Trial IMPACT Number/Bay Number: / Bay , Bay-E4465). Aspirin Complex, DE/H/3635/DC Public AR Page 5/6

6 Both the mean ratio 90% confidence intervals for Aspirin Complex of the pharmacokinetic variable Cmax for ASA (93.5%-120.0%) as well as for PSE (99.3.%-117.2%) fall within the limit of bioequivalence. Also for the variables AUC0-inf for ASA (95%-100.1%) as well as for PSE (93.5% %) as characteristics of the rate and extent of absorption of ASA/PSE the conventional bioequivalence range of % were met. Therefore it can be concluded that the change of excipients doesn t change the pharmacokinetic behaviour of the drug. Pharmacodynamics Not applicable. Clinical efficacy Not applicable. Clinical safety The observed AEs in study / Bay , Bay-E4465) are in line with those expected after administration of Aspirin complex and as labelled in the SmPC of the reference drug. User Testing No new User testing has been provided. This strategy is accepted as the provided package leaflet is nearly identical with the one currently approved for Aspirin Complex. Pharmacovigilance system The Applicant/Proposed Future MAH has submitted a signed Summary of the Applicant's/Proposed Future MAH's Pharmacovigilance System and asked the RMS to replace the previously submitted DDPS with the new Summary of Pharmacovigilance System. Provided that the Pharmacovigilance System Master File fully complies with the new legal requirements as set out in the Commission Implementing Regulation and as detailed in the GVP module, the RMS accepts this substitution. Risk Management Plan No risk management plan has been provided. The respective justification of absence of risk management plan is acceptable. Periodic Safety Update Report (PSUR) The PSUR cycle should follow the list of Union reference dates and frequency of submission of periodic safety update reports (EURD-list). IV. BENEFIT RISK ASSESSMENT The overall benefit-risk ratio for Aspirin Complex Hot drink, 500 mg / 30 mg granules for oral suspension, in the proposed indication "Symptomatic treatment of nasal congestion with cold-related pain and fever" is positive. It can be concluded that the differences in the flavour system and the different resolving (with hot water instead of lukewarm water) between Aspirin Complex Hot drink and Aspirin Complex does not change the pharmacokinetic behaviour of the drug. The application is approved. For intermediate amendments see current product information. Aspirin Complex, DE/H/3635/DC Public AR Page 6/6