Public Assessment Report Decentralised Procedure …

1 Public Assessment Report Decentralised Procedure Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (Melphalan hydrochloride) Procedure No: UK/H/6713/001/DC UK Licence Number: PL 00289/2173 TEVA UK Limited PAR Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion UK/H/6713/001/DC 2 LAY SUMMARY Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (Melphalan hydrochloride, powder and solvent for injection /infusion) This is a summary of the Public Assessment Report (PAR) for Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (PL 00289/2173; UK/H/6713/001/DC). It explains how Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion was assessed and its authorisation recommended, as well as its conditions of use.

2 It is not intended to provide practical advice on how to use Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion. The product will be referred to as Melphalan throughout the remainder of this Public Assessment Report (PAR). For practical information about using Melphalan, patients should read the package leaflet or contact their doctor or pharmacist. What is Melphalan and what is it used for? Melphalan is a generic medicine . This means that Melphalan is similar to a reference medicine already authorised in the European Union (EU) called Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (Aspen Pharma Trading Limited, Ireland). Melphalan is used in the treatment for cancer and is used for: multiple myeloma a type of cancer that develops from cells in the bone marrow called plasma cells.

3 Plasma cells help to fight infection and disease by producing antibodies advanced cancer of the ovaries childhood neuroblastoma cancer of the nervous system malignant melanoma skin cancer soft tissue sarcoma cancer of the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. The patient should speak to their doctor if they would like more explanation about these diseases. How does Melphalan work? This medicine contains an active ingredient called melphalan (as hydrochloride). This belongs to a group of medicines called cytotoxics (also called chemotherapy). This medicine works by reducing the number of abnormal cells the body makes. How is Melphalan used? This medicine should only be prescribed for the patient by a specialist doctor who is experienced in treating blood problems or cancer.

4 This medicine contains ethanol, sodium and propylene glycol. This should be taken into account for pregnant and breastfeeding women, in children and high-risk groups of patients with liver disease or epilepsy. This medicine can be harmful to patients suffering from alcoholism. This medicine contains mmol (or mg) sodium per vial. This should be taken into consideration by patients on a controlled sodium diet. PAR Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion UK/H/6713/001/DC 3 Propylene glycol may cause alcohol-like symptoms The pharmaceutical form of this medicine is a powder and solvent for solution for injection and or infusion and can be given in the following ways: as an infusion into the patient s vein as a perfusion to a particular part of the patient s body through an artery.

5 The patient s doctor will decide how much of this medicine they will need. The amount of Melphalan depends on: the patient s body weight or body surface area (A specific measurement taking into account the patient s weight and their size) other drugs the patient is taking the patient s disease the patient s age whether or not the patient has kidney problems. When the patient is given this medicine, their doctor will take regular blood tests. This is to check the number of cells in the patient s blood. Their doctor may sometimes change the amount of medicine given as a result of these tests. Please read section 3 of the package leaflet for detailed dosing recommendations, the route of administration, and the duration of treatment. For further information on how Melphalan is used, refer to the package leaflet and Summary of Product Characteristics available on the Medicines and Healthcare products Regulatory Agency (MHRA) website.

6 This medicine can only be obtained with a prescription. What benefits of Melphalan have been shown in studies? No additional studies were needed as Melphalan is a generic medicine that after reconstitution is an aqueous solution that is given by injection or infusion and contains the same active substance as the reference medicine, Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (Aspen Pharma Trading Limited, Ireland). What are the possible side effects of Melphalan? Because Melphalan is a generic medicine, its benefits and possible side effects are taken as being the same as the reference medicine Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (Aspen Pharma Trading Limited, Ireland). For the full list of restrictions, see the package leaflet. For the full list of all side effects reported with Melphalan, see section 4 of the package leaflet available on the MHRA website.

7 Why was Melphalan approved? It was concluded that, in accordance with EU requirements, Melphalan has been shown to have comparable to Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (Aspen Pharma Trading Limited, Ireland); the benefits are greater than the risks and it is recommended that Melphalan can be approved for use. PAR Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion UK/H/6713/001/DC 4 What measures are being taken to ensure the safe and effective use of Melphalan? A risk management plan (RMP) has been developed to ensure that Melphalan is used as safely as possible. Based on this plan, safety information has been included in the Summary of Product Characteristics (SmPC) and the package leaflet for Melphalan including the appropriate precautions to be followed by healthcare professionals and patients.

8 Known side effects are continuously monitored. Furthermore, new safety signals reported by patients/healthcare professionals will be monitored/reviewed continuously. Other information about Melphalan Germany and the UK agreed to grant a Marketing Authorisation for Melphalan on 13 December 2017. A Marketing Authorisation was granted in the UK on 12 January 2018. The full PAR for Melphalan follows this summary. For more information about treatment with Melphalan, read the package leaflet, or contact your doctor or pharmacist. This summary was last updated in March 2018. PAR Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion UK/H/6713/001/DC 5 TABLE OF CONTENTS I Introduction Page 6 II Quality aspects Page 8 III Non-clinical aspects Page 10 IV Clinical aspects Page 10 V User consultation Page 11 VI Overall conclusion, benefit/risk Assessment and recommendation Table of content of the PAR update Page 11 Page 17 PAR Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion UK/H/6713/001/DC 6 I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products Regulatory Agency (MHRA) granted Teva UK Limited, a marketing authorisation for the medicinal product Melphalan (PL 00289/2173; UK/H/6713/001/DC).

9 This product is a prescription-only medicine (POM). Melphalan: at conventional intravenous dosage, is indicated in the treatment of multiple myeloma and ovarian cancer at high intravenous dosage, is indicated, with or without haematopoietic stem cell transplantation, for the treatment of multiple myeloma and childhood neuroblastoma administered by regional arterial perfusion, is indicated in the treatment of localised malignant melanoma of the extremities and localised soft tissue sarcoma of the extremities. In the above indications, Melphalan may be used alone or in combination with other cytotoxic drugs. This application was submitted using the Decentralised Procedure (DCP), with the UK as Reference Member State (RMS) and Germany (DE) as a Concerned Member State (CMS). The application was submitted under Article 10(1) of Directive 2001/83/EC, as amended, as a generic application.

10 The EU reference product for this application is Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (PL 39699/0039; Aspen Pharma Trading Limited, Ireland) and SOLVENT-DILUENT (for Melphalan injection ) [PL 39699/0040; Aspen Pharma Trading Limited, Ireland] which was first authorised to the Wellcome foundation Limited on 26 May 1993 as Alkeran injection (freeze dried) 50 mg (PL 00003/0323) and SOLVENT DILUENT (for Alkeran injection ) (PL 00003/0324) respectively. The reference product subsequently underwent changes of ownership procedures to Laboratories Genopharm (PL 26946/0001 and PL 26946/0002) on 19 January 2011 and to the current Marketing Authorisation Holder (MAH); Aspen Pharma Trading Limited, Ireland on 07 May 2012. The product names were changed by way of variation on 17 December 2012 to Melphalan 50 mg Powder and Solvent for Solution for injection /Infusion (PL 39699/0039) and SOLVENT-DILUENT (for Melphalan injection ) (PL 39699/0040).