Public Assessment Report Scientific discussion. Ciprofloxacin Pfizer (Ciprofloxacin hydrochloride) SE/H/803/01-03/DC

Transcription

1 Public Assessment Report Scientific discussion Ciprofloxacin Pfizer (Ciprofloxacin hydrochloride) SE/H/803/01-03/DC This module reflects the scientific discussion for the approval of Ciprofloxacin Pfizer. The procedure was finalised at For information on changes after this date please refer to the module Update. Postadress/Postal address: P.O. Box 26, SE Uppsala, SWEDEN Besöksadress/Visiting address: Dag Hammarskjölds väg 42, Uppsala Telefon/Phone: +46 (0) Fax: +46 (0) Internet: Template version:

2 I. INTRODUCTION Pfizer AB, Sweden has applied for a marketing authorisation for Ciprofloxacin Pfizer, filmcoated tablets, 250 mg, 500 mg and 750 mg claiming essential similarity to Ciproxin, filmcoated tablets, 250 mg, 500 mg and 750 mg respectively marketed the EU by Bayer Schering Pharma AG. The product contains ciprofloxacin hydrochloride as active substance. For approved indications see the Summary of Product Characteristics. The reference product used in the bio-equivalence study is Ciproxin, film-coated tablet marketed by Bayer plc in UK. II. II.1 QUALITY ASPECTS Introduction Ciprofloxacin Pfizer is presented in the form of tablets containing 250, 500 and 750 mg of ciprofloxacin as ciprofloxacin hydrochloride. The excipients are cellulose microcrystalline, sodium starch glycolate, Povidone (K-30), silica colloidal anhydrous, magnesium stearate and Opadry white Y The film-coated tablets are packed in PVC/PVdC-aluminium foil blister pack. II.2 Drug Substance Ciprofloxacin hydrochloride has a monograph in the Ph Eur. The drug substance manufacturer holds a Certificate of Suitability for ciprofloxacin hydrochloride. Ciprofloxacin hydrochloride is a pale yellow, crystalline powder which is soluble in water, slightly soluble in methanol, very slightly soluble in ethanol, practically insoluble in acetone, ethyl acetate and methylene chloride. The structure of ciprofloxacin hydrochloride has been adequately proven and its physico-chemical properties sufficiently described. The drug substance has no asymmetric carbon present and no polymorphic forms. The active substance specification includes relevant tests and the limits for impurities and degradation products. Stability studies under ICH conditions have been conducted and the data provided are sufficient to confirm the retest period of 4 years. II.3 Medicinal Product Ciprofloxacin Pfizer film-coated tablets are formulated using excipients described in the current Ph Eur. All raw materials used in the product are of vegetable origin. Compliance is demonstrated with 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. 2/5

3 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. III.1 NON-CLINICAL ASPECTS 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. IV.1 CLINICAL ASPECTS Pharmacokinetics Bioequivalence was evaluated in one single-dose two-way crossover, bioequivalence study in 24 healthy volunteers under fasting conditions comparing Ciprofloxacin 750 mg film-coated tablets with Ciproxin 750 mg film-coated tablets. A single-dose, fasting study with one tablet strength is appropriate from a pharmacokinetic point of view, as the application concerns an immediate-release formulation, the pharmacokinetics of ciprofloxacin is linear over the clinical dose range and is unaffected by food. Ciprofloxacin in plasma was determined with a validated HPLC- method. The 90% confidence interval of ln-transformed C max, AUC 0-t and AUC 0-inf were within the prespecified limits of %. Bioequivalence has been sufficiently demonstrated. 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. V. OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION User consultation A user consultation with target patient groups on the package information leaflet (PIL) has been performed on the basis of a bridging report making reference to Ciprofloxacin Bayer 3/5

4 FR/H/416/01-03/MR. The bridging report submitted by the applicant has been found acceptable. The results of the conducted bioequivalence study can be extrapolated to other strengths since the criteria for biowaiver for additional strengths are fulfilled according to the Note for Guidance on the Investigation of Bioavailability and Bioequivalence. The risk/benefit ratio is considered positive and Ciprofloxacin Pfizer, film-coated tablet, 250 mg, 500 mg and 750 mg is recommended for approval. VI. APPROVAL The Decentralised procedure for Ciprofloxacin Pfizer, film-coated tablets, 250 mg, 500 mg and 750 mg was successfully finalised on /5

5 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 Y/N (version) Postadress/Postal address: P.O. Box 26, SE Uppsala, SWEDEN Besöksadress/Visiting address: Dag Hammarskjölds väg 42, Uppsala Telefon/Phone: +46 (0) Fax: +46 (0) Internet: Template version: