UK Public Assessment Report

1 UKPAR Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 1 Chlorhexidine Gluconate 2% w/v Impregnated Pad (chlorhexidine gluconate) PL 27821/0004 UK Public Assessment Report TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for Assessment Page 20 Steps taken after authorisation Page 21 Summary of Product Characteristics Page 22 Product Information Leaflet Page 26 Labelling Page 28 UKPAR Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 2 Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 LAY SUMMARY The Medicines and Healthcare products Regulatory Agency (MHRA)

2 Granted Baggerman FarmaNet NV a Marketing Authorisation (licence) for the medicinal product Chlorhexidine Gluconate 2% w/v Impregnated Pad (PL 27821/0004) on 7th July 2010. This is a medicine available on the General Sales List (GSL), and can be purchased at pharmacies, supermarkets and other retail outlets without the supervision of a pharmacist. The active ingredient in these pads is chlorhexidine gluconate 2% (equivalent to 500mg chlorhexidine gluconate per pad), which has antibacterial properties, fighting and killing bacteria.

3 These pads should only be used for disinfecting the skin and can be used before surgery on the advice of your doctor. They can also be used to disinfect your skin generally. No new or unexpected safety concerns arose from this application and it was, therefore, judged that the benefits of Chlorhexidine Gluconate 2% w/v Impregnated Pad outweigh the risks; hence a Marketing Authorisation (MA) has been granted. UKPAR Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 3 Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 SCIENTIFIC DISCUSSION TABLE OF CONTENTS Introduction Page 4 Pharmaceutical Assessment Page 5 Pre-clinical Assessment Page 8 Clinical Assessment Page 9 Overall conclusion and benefit-risk Assessment Page 19 UKPAR Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 4 INTRODUCTION Based on the review of the data on quality, safety and efficacy.

4 The MHRA granted Baggerman FarmaNet NV a Marketing Authorisation for the medicinal product Chlorhexidine Gluconate 2% w/v Impregnated Pad (PL 27821/0004) on 7th July 2010. The product is available on a General Sales Licence (GSL). This is an abridged application for Chlorhexidine Gluconate 2% w/v Impregnated Pad, submitted under Article of 2001/83 EC, as amended. This hybrid application makes reference to the UK product, Hibiscrub (PL 21855/0002), a 4% w/v solution of chlorhexidine gluconate, authorised to Regent Medical Oversees Ltd in December 2004.

5 The cross-referenced product was originally awarded a default conversion licence in November 1993, as Hibiscrub Solution, to Imperial Chemical Industries plc (PL 00029/0129), and subsequently underwent a series of Change of Ownership (CoA) procedures to the current Regent Medical Oversees Ltd licence in December 2004. The reference product has been authorised in the UK for more than 10 years, so the period of data exclusivity has expired. Chlorhexidine Gluconate 2% w/v Impregnated Pads are indicated for skin antisepsis as part of an advance pre-operative cleansing regimen, as well as general skin antisepsis.

6 Chlorhexidine gluconate is a disinfectant which is effective against a wide range of vegetative Gram-positive and Gram-negative bacteria. The wide range of microorganisms against which chlorhexidine gluconate is active makes it suitable for broad-spectrum disinfection of skin prior to surgery to reduce risk of infection. It is effective against MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococcus), Acinetobacter baumannii, Pseudomonas aeruginosa and various Streptococcus species. Chlorhexidine gluconate significantly reduces the number of microorganisms on intact skin and demonstrates continued anti-microbial activity for up to 6 hours after application.

7 Chlorhexidine gluconate is inactive against bacterial spores. The application is supported by a series of clinical studies, which are discussed in the Clinical Assessment section of this Report . No new pre-clinical studies were submitted. The pharmacovigilance system, as described by the Marketing Authorisation Holder (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.

8 The MAH has provided adequate justification for not submitting a Risk Management Plan (RMP). The active ingredient, chlorhexidine gluconate, is well-established, with a good safety profile. The MAH has submitted an Environmental Risk Assessment (ERA) in accordance with current guidelines. UKPAR Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 5 PHARMACEUTICAL Assessment ACTIVE SUBSTANCE Chlorhexidine gluconate (solution) Nomenclature: INN: Chlorhexidine gluconate Structure: Molecular formula: C22H30Cl2N10 , 2C6H12O7 Molecular weight: 898 g/mol CAS No: 18472-51-0 Physical form: Almost colourless or pale-yellowish liquid Solubility.

9 Miscible with water, with not more than 3 parts of acetone, and with not more than 5 parts of ethanol (96%) The active substance, chlorhexidine gluconate, is the subject of a European Pharmacopeia (Ph. Eur.) monograph. All aspects of the manufacture and control of chlorhexidine gluconate are supported by a European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability (CEP). This certificate is accepted as confirmation of the suitability of chlorhexidine gluconate for inclusion in this medicinal product. UKPAR Chlorhexidine Gluconate 2% w/v Impregnated Pad PL 27821/0004 6 MEDICINAL PRODUCT Description and Composition The medicinal product is presented as a polyester pad impregnated with chlorhexidine gluconate 2% w/v solution (equivalent to 500mg chlorhexidine gluconate per pad).

10 Other ingredients of the solution impregnated into the polyester pad consist of pharmaceutical excipients, namely aloe vera gel (containing sodium benzoate and potassium sorbate), dimeticone, fragrance F750485, gluconolactone, glycerol, nonoxinol 9, polysorbate 20, propylene glycol and purified water. Appropriate justification for the inclusion of each excipient has been provided. All excipients used comply with their respective European Pharmacopoeia monographs, with the exception of gluconolactone, which complies with the requirements of the US Pharmacopoeia, and the aloe vera gel and fragrance, which comply with satisfactory in-house specifications.