CO-CODAMOL 30MG/500MG TABLETS PL …

1 MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 1 - CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 11 Steps taken after authorisation summary Page 12 Summary of Product Characteristics Page 13 Patient Information Leaflet Page 18 Labelling Page 20 MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 2 - CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 LAY SUMMARY The Medicines and Healthcare products Regulatory Agency granted Bristol Laboratories Limited a Marketing Authorisation (licence) for the medicinal product CO-CODAMOL 30MG/500MG TABLETS (PL 17097/0235 on 23rd May 2011.)

2 This is a prescription-only medicine (POM). CO-CODAMOL 30MG/500MG TABLETS contain two active ingredients-codeine and paracetamol both of which belong to a group of medicines called painkillers (analgesics). CO-CODAMOL TABLETS are a compound analgesic and are used to provide relief from severe pain. No new or unexpected safety concerns arose from this application and it was, therefore, judged that the benefits of taking CO-CODAMOL 30MG/500MG TABLETS outweigh the risks; hence a Marketing Authorisation has been granted. MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 3 - CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 SCIENTIFIC DISCUSSION TABLE OF CONTENTS Introduction Page 4 Pharmaceutical assessment Page 5 Preclinical assessment Page 8 Clinical assessment Page 9 Overall conclusions and risk benefit assessment Page 10 MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 4 - INTRODUCTION The UK granted a Marketing Authorisation for the medicinal product CO-CODAMOL 30MG/500MG (PL 17907/0235) to Bristol Laboratories Limited on 23rd May 2011.

3 This product is a prescription-only medicine. This application was submitted as an abridged application according to Article 10(1) of Directive 2001/83/EC. The applications refer to the originator product, Solpadol 30MG/500MG Caplets (PL 11723/0071), authorised to Sanofi Aventis on 12 September 1989. The reference product has been authorised in the EEA for over 10 years. Paracetamol is an analgesic which acts peripherally, probably by blocking impulse generation at the bradykinin sensitive chemo-receptors which evoke pain. Paracetamol also exhibits antipyretic activity. Codeine is a centrally acting analgesic which produces its effect by its action at opioid-binding sites ( -receptors) within the CNS. It is a full agonist. CO-CODAMOL TABLETS are indicated in the relief of severe pain. The pharmacovigilance system, as described by the MAH, fulfils the requirements and provides adequate evidence that the MAH 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.

4 The MAH has provided adequate justification for not submitting a Risk Management Plan (RMP). As the application is for a generic version of an already authorised reference product, for which safety concerns requiring additional risk minimisation have not been identified, a risk minimisation system is not considered necessary. The reference product has been in use for many years and the safety profile of the active is well established. No new pre-clinical or clinical studies were performed, which is acceptable given that the proposed product is a generic medicinal product of the reference product that have been licensed for over 10 years. No new or unexpected safety concerns arose during the review of information provided by the Marketing Authorisation Holder (MAH) and it was, therefore, judged that the benefits of taking product CO-CODAMOL 30MG/500MG TABLETS outweigh the risks; hence a Marketing Authorisation has been granted.

5 MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 5 - PHARMACEUTICAL ASSESSMENT DRUG SUBSTANCE (1) Paracetamol INN: Paracetamol Ph Eur 500mg Chemical name: Paracetamol Acetaminophen N-Acetyl-p-aminophenol Paracetamolum 4 -hydroxyacetanilide N-(4-hydroxyphenyl)acetanilide Structure: Molecular mass: Molecular formula: C8H9N02 General Properties Description: White odourless crystalline powder. Paracetamol is the subject of a European Pharmacopoeia monograph (Ph Eur). Manufacture All aspects of the manufacture and control of the active substance paracetamol are covered by a European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability.

6 DRUG SUBSTANCE (2) Codeine INN: Codeine phosphate hemihydrate Molecular mass: Molecular formula: C18H21NO3 H2O MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 6 - General Properties Description: White odourless crystalline powder. Codeine is the subject of a European Pharmacopoeia monograph (Ph Eur). Manufacture All aspects of the manufacture and control of the active substance codeine phosphate hemihydrate are covered by a European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability. DRUG PRODUCT Description and Composition CO-CODAMOL 30MG/500MG TABLETS are presented as a white to off white capsule shaped biconvex uncoated plain TABLETS . Each tablet contains 30mg of codeine phosphate hemihydrate and 500mg of paracetamol. Other ingredients consist of pharmaceutical excipients, namely pregelatinised maize starch, microcrystalline cellulose, sodium starch glycollate Type A, sodium metabisulfite, and magnesium stearate.

7 Appropriate justification for the inclusion of each excipient has been provided. All excipients used comply with their relevant European Pharmacopoeia (Ph. Eur) monographs. Satisfactory Certificates of Analysis have been provided for all excipients. The applicant has provided a declaration confirming that there are no materials of human or animal origin contained in or used in the manufacturing process of the proposed product. None of the excipients are sourced from genetically modified organisms. Pharmaceutical Development Details of the pharmaceutical development of the medicinal product have been supplied and are satisfactory. The objective was to develop robust, stable, generic formulation, bioequivalent to the innovator product Solpadol 30MG/500MG Caplets. Comparative impurity and dissolution profiles were provided for the test and reference products and were found to be similar.

8 Manufacture A description and flow-chart of the manufacturing method has been provided. In-process controls were considered appropriate considering the nature of the product and the method of manufacture. Process validation studies have been conducted and are accepted. Finished Product Specification The finished product specification is satisfactory. Acceptance limits have been justified with respect to conventional pharmaceutical requirements and, where appropriate, safety. Test methods have been described and have been adequately validated, as appropriate. Satisfactory batch analysis data are provided and comply with the release specification. Certificates of Analysis have been provided for any reference standards used. MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 7 - Container Closure System The finished product is presented in blisters composed of opaque polyvinylidene chloride (PVdC), polyvinyl (PVC) and aluminium which are packed with the Patient Information Leaflet (PIL) into cardboard outer cartons in pack sizes of 8, 10, 16, 20, 30, 32 and 100 TABLETS .

9 The MA Holder (MAH) has stated that not all pack sizes may be marketed however, the MAH has committed to submitting the proposed packaging/labelling for any pack size before it is marketed. Satisfactory specifications and Certificates of Analysis for all packaging components used have been provided. All primary product packaging complies with EU legislation, Directive 2002/72/EC (as amended), and is suitable for contact with foodstuffs. In addition compliance with BS 8404 for child resistant containers has been confirmed. Stability Finished product stability studies have been conducted in accordance with current guidelines and results were within the proposed specification limits. Based on the results, a shelf-life of 3 years has been set which is satisfactory. Storage conditions for the medicinal product in blister packs are as follows: Do not store above 25oC and Store in the original package.

10 Bioequivalence Study No bioequivalence studies have been submitted with this application; however; a suitable biowaiver, in accordance with CPMP guidelines, has been submitted and is acceptable. Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL), Labels The approved SmPCs, PILs and labelling are pharmaceutically acceptable. Mock-ups of the package leaflet and labelling have been provided. The labelling fulfils the statutory requirements for Braille. Expert Report The pharmaceutical expert report has been written by an appropriately qualified person and is a suitable summary of the pharmaceutical dossier. The CV of the expert has been provided. Conclusion It is recommended that a Marketing Authorisation is granted for this application. MHRA-UKPAR CO-CODAMOL 30MG/500MG TABLETS PL 17907/0235 - 8 - PRECLINICAL ASSESSMENT This application was submitted as an abridged, application, according to Article of Directive 2001/83/EC, as amended.