UKPAR Metformin 500 mg and 850 mg Tablets BP PL 17907/0178-79

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Metformin 500 mg and 850 mg Tablets BP

(Metformin hydrochloride)

PL 17907/0178-79

UKPAR

TABLE OF CONTENTS Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

Page 11

Summary of Product Characteristics

Page 12

Patient Information Leaflet

Page 13

Labelling

Page 14

UKPAR Metformin 500 mg and 850 mg Tablets BP PL 17907/0178-79

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Metformin 500 mg and 850 mg Tablets BP

PL 17907/0178-79

LAY SUMMARY

On 10th October 2013, the MHRA granted Marketing Authorisations (licences) for the medicinal products Metformin 500 mg and 850 mg Tablets BP (PL 17907/0178-79). These medicines are only available on prescription from your doctor. Metformin is a medicine to treat diabetes. It belongs to a group of medicines called biguanides. Insulin is a hormone produced by the pancreas that makes the body take in glucose (sugar) from the blood. The body uses glucose to produce energy or stores it for future use. If the patient has diabetes, the pancreas does not make enough insulin or the body is not able to use properly the insulin it produces. This leads to a high level of glucose in the blood. Metformin Tablets helps to lower the blood glucose to as normal level as possible. If the patient is an overweight adult when diet and exercise alone have not been sufficient in adequate glycaemic control, taking Metformin Tablets over a long period of time also helps to lower the risk of complications associated with diabetes. What Metformin Tablets are used for? Metformin Tablets are used to treat patients with type 2 diabetes (also called’non-insulin dependent diabetes’) when diet and exercise alone have not been enough to control the blood glucose levels. It is used particularly in overweight patients. Adults can take Metformin on its own or together with other medicines to treat diabetes (medicines taken by mouth or insulin). Children 10 years and over and adolescents can take Metformin on its own or together with insulin. No new or unexpected safety concerns arose from these applications and it was, therefore, judged that the benefits of taking Metformin 500 mg and 850 mg Tablets BP outweigh the risks; hence Marketing Authorisations have been granted.

UKPAR Metformin 500 mg and 850 mg Tablets BP PL 17907/0178-79

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Metformin 500 mg and 850 mg Tablets BP

PL 17907/0178-79

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 4

Pharmaceutical assessment

Page 5

Non-clinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusion and risk benefit assessment Page 10

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INTRODUCTION

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Marketing Authorisations (licences) for the medicinal products Metformin 500 mg and 850 mg Tablets BP (PL 17907/0178-79) to Bristol Laboratories Limited on 10th October 2013. These prescription only medicines (POM) are indicated for the treatment of type 2 diabetes mellitus, particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycaemic control.

• In adults, Metformin film-coated tablets may be used as monotherapy or in combination with other oral anti-diabetic agents, or with insulin.

• In children from 10 years of age and adolescents, Metformin film-coated tablets may be used as monotherapy or in combination with insulin.

A reduction of diabetic complications has been shown in overweight type 2 diabetic adult patients treated with metformin as first-line therapy after diet failure. These are national abridged applications for Metformin 500 mg and 850 mg Tablets BP submitted under Article 10c of Directive 2001/83/EC, as amended. These applications cross-refer to Metformin 500 mg and 850 mg tablets (PL 17907/0080-81), authorised to Bristol Laboratories Ltd on 18th December 2007. A pharmacovigilance system has been provided with these applications and is satisfactory. A suitable justification for non-submission of the Risk Management Plan has been provided.

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PHARMACEUTICAL ASSESSMENT

LICENCE NO: PL 17907/0178-79 PROPRIETARY NAME: Metformin 500 mg and 850 mg Tablets BP COMPANY NAME: Bristol Laboratories Limited E.C. ARTICLE: Article 10c of Directive 2001/83/EC LEGAL STATUS: POM 1 INTRODUCTION These are informed consent applications for Metformin 500 mg and 850 mg Tablets BP, submitted under Article 10c of Directive 2001/83/EC as amended. The applications cross-refer to Metformin 500 mg and 850 mg tablets (PL 17907/0080-81), also authorised to Bristol Laboratories Ltd on 18th December 2007. The current applications are considered valid. 2 MARKETING AUTHORISATION APPLICATION (MAA) 2.1 Name(s) The proposed names of the products are Metformin 500 mg and 850 mg Tablets BP. The products have been named in line with current requirements. 2.2 Strength, pharmaceutical form, route of administration, container and pack sizes The products are tablets for oral use and contain 500 mg and 850 mg of the active ingredient metformin hydrochloride, equivalent to 390 mg and 662.9 mg of Metformin base respectively. The tablets are packed either in blisters of aluminium and clear transparent PVC coated with PVDC containing in 14, 28, 56 or 84 tablets. or in White opaque HDPE tablet containers in pack sizes of 100, 250, 300 or 500 tablets. The packaging and pack sizes are the same as those for the cross-reference products. The proposed shelf-life is 4 years. The proposed storage conditions for blisters are “Do not store above 25°C”, “Store in the original package” and “Keep the blister in the outer carton”. The storage conditions for tablets containers are “Do not store above 25°C”, “Store in the original container” and “Keep the container tightly closed”. The shelf-life and storage conditions are identical to those for the cross-reference products and are satisfactory. 2.3 Legal status These products are Prescription Only Medicines (POM).

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2.4 Marketing Authorisation Holder/Contact Persons/Company The proposed Marketing Authorisation holder is Bristol Laboratories Limited, Unit 3, Canalside, Northbridge Road, Berkhamsted, Herts, HP4 1EG, United Kingdom 2.5 Manufacturers The proposed manufacturing sites are consistent with those registered for the cross-reference products and evidence of Good Manufacturing Practice (GMP) compliance has been provided. 2.6 Qualitative and quantitative composition The proposed compositions are consistent with the details registered for the cross-reference products. 2.7 Manufacturing process The proposed manufacturing process is consistent with the details registered for the cross-reference products and the maximum full scale batch size is stated. 2.8 Finished product specifications The proposed finished product specifications, at release and shelf-life, are in line with the details registered for the cross-reference products. 2.9 Drug substance specification The proposed drug substance specification conforms to the current European Pharmacopoeia monograph for of metformin hydrochloride and is in-line with that for the cross-reference products. An European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability for the manufacturer of metformin hydrochloride has been provided. The active substance manufacturer is the same as that for the cross-reference products. 2.10 TSE Compliance No materials of human or animal origin have been used in the manufacture of these products. 2.11 Bioequivalence No bioequivalence data are required to support these informed consent applications, as the proposed products are manufactured to the same formula utilising the same process as the cross-reference products Metformin 500 mg and 850 mg tablets (PL 17907/0080-81). 3 EXPERT REPORTS The applicant cross-refers to the data for cross-reference products Metformin 500 mg and 850 mg tablets (PL 17907/0080-81), to which it claims to be identical. This is acceptable. The applicant has included expert reports of the applications. Signed declarations and copies of the experts’ CVs are enclosed for the quality, non-clinical and clinical experts. All are considered to have sufficient experience for their responsibilities.

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4. PRODUCT NAME & APPEARANCE See 2.1 for details of the proposed product names. The appearance of the products is identical to those of the cross-reference products. 5. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) The proposed SmPCs are consistent with the details registered for the cross-reference products. 6. PATIENT INFORMATION LEAFLET (PIL)/LABELLING As these applications are for products which are in the same drug class and have the same pharmaceutical form and format of package leaflet as an already approved leaflet, consultation with target patient groups is not considered necessary. The package leaflet for the consent application is exactly the same as the reference package leaflet. In addition, the product information and the design and layout are identical. The proposed artwork complies with the relevant statutory requirements. In line with current legislation the applicant has also included the name of the product in Braille on the outer packaging and sufficient space for a standard UK pharmacy dispensing label. 7. CONCLUSION The data submitted with the applications are acceptable. The grant of marketing authorisations is recommended.

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NON-CLINICAL ASSESSMENT

No new non-clinical data have been supplied with these applications and none are required for applications of this type.

UKPAR Metformin 500 mg and 850 mg Tablets BP PL 17907/0178-79

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CLINICAL ASSESSMENT

No new clinical data have been supplied with these applications and none are required for applications of this type.

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OVERALL CONCLUSION AND RISK BENEFIT ASSESSMENT

QUALITY The data for these applications are consistent with those previously assessed for the cross-reference products and, as such, have been judged to be satisfactory. NON-CLINICAL No new non-clinical data were submitted and none are required for applications of this type. EFFICACY These applications are identical to the previously granted applications for Metformin 500 mg and 850 mg tablets (PL 17907/0080-81)) also authorised to Bristol Laboratories Ltd on 18th December 2007. SAFETY No new or unexpected safety concerns arise from these applications. PRODUCT LITERATURE The SmPCs, PIL and labelling are satisfactory and consistent with those for the cross-reference products. RISK BENEFIT ASSESSMENT The quality of the product is acceptable and no new non-clinical or clinical concerns have been identified. The applicant’s products are identical to the cross-reference products. Extensive clinical experience with metformin hydrochloride is considered to have demonstrated the therapeutic values of the compounds. The risk benefit is, therefore, considered to be positive.

UKPAR Metformin 500 mg and 850 mg Tablets BP PL 17907/0178-79

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Metformin 500 mg and 850 mg Tablets BP

PL 17907/0178-79

STEPS TAKEN FOR ASSESSMENT

1 The MHRA received the Marketing Authorisation applications on 3rd December

2012

2 Following standard checks and communication with the applicant the MHRA considered the applications valid on 11th December 2012

3 Following assessment of the application the MHRA requested further information relating to the quality dossier on 14th January 2013 and 29th May 2013

4 The applicant responded to the MHRA’s requests, providing further information to the quality section on 15th February 2013 and 10th September 2013

5 The applications were determined on 10th October 2013.

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Module 2

Summary of Product Characteristics In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC) for products that are granted Marketing Authorisations at a national level are available on the MHRA website.

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Module 3

Patient Information Leaflet

In accordance with Directive 2010/84/EU the Patient Information Leaflets (PIL) for products that are granted Marketing Authorisations at a national level are available on the MHRA website.

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LABELLING

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