Document: Risedronate Cipla film-coated tablet ENG PAR change

• Risedronate Cipla film-coated tablet PL
• Risedronate Cipla film-coated tablet ENG PL
• Risedronate Cipla film-coated tablet SmPC
• Risedronate Cipla film-coated tablet ENG SmPC
• Risedronate Cipla film-coated tablet ENG PAR
• Risedronate Cipla film-coated tablet sPAR
• Risedronate Cipla film-coated tablet ENG sPAR

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Public Assessment Report Scientific discussion

Risedronate Cipla (risedronate sodium)

SE/H/1369/01/DC

INTRODUCTION

The application for Risedronate Cipla, 35 mg, film-coated tablet, is a generic application made according to Article 10(1) of Directive 2001/83/EC. The applicant, Cipla Europe NV, applies through the Decentralised Procedure with Sweden acting as reference member state (RMS) and ES, FR, IT, PL and PT as concerned member states (CMS).

The reference medicinal product chosen for the purposes of establishing the expiry of the data protection period is Optinate Septimum (SE/H/192/03), 35 mg, film-coated tablet authorised in SE since 2002, with sanofi-aventis AB as marketing authorisation holder.

The reference product used in the bioequivalence study is Actonel, 35 mg, film-coated tablet from UK with Warner Chilcott UK as marketing authorisation holder.

For approved indications, see the Summary of Product Characteristics.

II.    QUALITY ASPECTS

11.1    Introduction

Risedronate Cipla is presented in the form of film-coated tablets containing 35 mg risedronate sodium (as hemipentahydrate). The excipients are anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, macrogol, yellow iron oxide and red iron oxide. The tablets are packed in PVC/Aluminum blisters.

11.2    Drug Substance

Risedronate sodium 2.5-hydrate has a monograph in the Ph. Eur. Risedronate sodium 2.5-hydrate is a white to almost white crystalline powder which is soluble in water and hydrochloric acid. It is partly soluble in methylene chloride and insoluble in sodium hydroxide, methanol, acetone and DMSO. A discussion on polymorphism has been given.

The route of synthesis has been adequately described and satisfactory specifications have been provided for starting materials, reagents and solvents.

The active substance specification includes relevant tests and the limits for impurities/degradation products have been justified. The analytical methods applied are suitably described and validated.

Batch analysis data as analysed by the drug product manufacturer have been provided and are acceptable. Information on the reference standards for risedronate and impurities as used by the drug product manufacturer has been provided and is acceptable.

Stability studies under ICH conditions have been conducted and the data provided are sufficient to confirm the retest period.

11.3    Medicinal Product

Risedronate Cipla film-coated tablets are formulated using excipients described in the current Ph. Eur., except for iron oxide which is controlled according to NF/JP. All raw materials used in the product has demonstrated compliance with Commission Directive 2003/63/EC and the

NfG on Minimising the risk of transmitting Animal Spongiform Encephalopathy Agents via human and veterinary medicinal products (EMEA/410/01).

The product development has taken into consideration the physico-chemical characteristics of the active substance, such as solubility, polymorphism and stability.

The manufacturing process has been sufficiently described and critical steps identified. Results from the process validation studies confirm that the process is under control and ensure both batch to batch reproducibility and compliance with the product specification.

The tests and limits in the specification are considered appropriate to control the quality of the finished product in relation to its intended purpose.

Stability studies under ICH conditions have been performed and data presented support the shelf life claimed in the SPC, with no special storage precautions.

III. NON-CLINICAL ASPECTS

III.1 Discussion on the non-clinical aspects

Since this product has been shown to be essentially similar and refer to a product approved based on a full application with regard to preclinical data, no further such data have been submitted or are considered necessary.

IV.    CLINICAL ASPECTS

IV.1    Pharmacokinetics

Bioequivalence was evaluated in one single-dose, two-treatment, four-period, two-sequence replicate crossover study conducted in 100 healthy volunteers, comparing Risedronate Cipla, 35 mg, tablet with Actonel, 35 mg, tablet under fasting conditions. The study was conducted at Lambda Therapeutics, Ahmedabad, India between 11 Nov 2009 and 09 Jan 2010. Blood samples were collected pre-dose and up to 72 hours post-dose. The study design is considered acceptable. Plasma concentrations of risedronic acid were determined with a validated LC/MS/MS method. For AUC_0-t and C_max the 90% confidence interval for the ratio of the test and reference products fell within the conventional acceptance range of 80.00-125.00%.

Bioequivalence has been sufficiently shown.

IV.2    Discussion on the clinical aspects

Since this product has been shown to be essentially similar and refer to a product approved based on a full application with regard to clinical efficacy/safety data, no further such data have been submitted or are considered necessary.

OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION

User consultation

The package leaflet has been evaluated via a user consultation study in accordance with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose of user testing the PIL was English

The results show that the package leaflet meets the criteria for readability as set out in the Guideline on the readability of the label and package leaflet of medicinal products for human use.

The risk/benefit ratio is considered positive and Risedronate Cipla, 35 mg, film-coated tablet is recommended for approval.

VI. APPROVAL

The Decentralised procedure for Risedronate Cipla, 35 mg, film-coated tablet was successfully finalised on 2014-09-22.

Public Assessment Report - Update

Scope	Procedure number	Product Information affected	Date of start of the procedure	Date of end of procedure	Approval/ non approval	Assessment report attached
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