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Public Assessment Report

Zenbumin 20, 200 g/l, solution for infusion

(Human Albumin)

UK Licence No: PL 08801/0037

BIO PRODUCTS LABORATORY LIMITED

PAR Zenbumin 20, 200 g/l, solution for infusion PL 08801/0037

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LAY SUMMARY

Zenbumin 20, 200 g/l, solution for infusion (human albumin)

This is a summary of the Public Assessment Report (PAR) for Zenbumin 20, 200 g/l, solution for infusion (PL 08801/0037). It explains how Zenbumin 20, 200 g/l, solution for infusion was assessed and its authorisation recommended, as well as its conditions of use. It is not intended to provide practical advice on how to use Zenbumin 20, 200 g/l, solution for infusion. The applicant has indicated that there are no intentions for a UK launch based on this licence as this licence will be used purely as a comparator pharmaceutical product. A comparator product is a pharmaceutical product with which a generic product is intended to be interchangeable in clinical practice. The product will be referred to as Zenbumin 20 throughout the remainder of this public assessment report (PAR). For practical information about using Zenbumin 20, patients should read the package leaflet (PIL) or contact their doctor or pharmacist. What is Zenbumin 20? This medicine is the same as for Zenalb 20 solution for infusion, PL 08801/0007, which is already authorised in the UK. The licences for both Zenbumin 20 and the reference product, Zenalb 20 solution for infusion, are held by the same company Bio Products Laboratory Ltd (BPL Ltd). The scientific data for the reference product, Zenalb 20 solution for infusion, (PL 08801/0007) has been used as a basis for the grant of an identical licence for Zenalb 20 PL 08801/0037 Zenbumin 20 is a solution containing the active substance called human albumin (a protein found naturally in your blood which is needed for many different functions). Human albumin is obtained from blood plasma from screened donors selected from the USA. How does Zenbumin 20 work? Zenbumin 20 is used to replace the blood or body fluids that you have lost because of bleeding, surgery, or kidney dialysis (blood “cleaning” by a machine). It contains four times the amount of albumin as normal blood. How is Zenbumin 20 used? Zenbumin 20 is given by injection into a vein (intravenous infusion) either undiluted or in a solution containing 5% glucose or 0.9% sodium chloride. It is only available on a doctor’s prescription. Zenbumin 20 is also suitable for premature babies and patients on kidney dialysis as it contains only very small quantities of aluminium. What benefits of Zenbumin 20 have been shown in studies? As Zenbumin 20 (PL 08801/0037) is considered to be identical to the reference product, Zenalb 20 solution for infusion (PL 08801/0007), its benefits and risks are taken as being the same as those for the reference product. What are the possible side effects of Zenbumin 20? Like all medicines, Zenbumin 20 can cause side effects, although not everybody gets them. Most complications that may result from Zenbumin 20 therapy are mild and include feeling sick, flushing and feeling feverish. For the full list of all side effects reported with Zenbumin 20, see section 4 of the package leaflet. For the full list of restrictions, see the package leaflet.

PAR Zenbumin 20, 200 g/l, solution for infusion PL 08801/0037

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Why was Zenbumin 20 approved? No new or unexpected safety concerns arose from this application. It was, therefore, considered that the benefits of Zenbumin 20 outweigh the risks, and the grant of a Marketing Authorisation was recommended. What measures are being taken to ensure the safe and effective use of Zenbumin 20? A risk management plan (RMP) has been developed for the cross-reference product to ensure that Zenbumin 20 is used as safely as possible. Based on this plan, safety information has been included in the Summary of Product Characteristics and the patient information leaflet for Zenbumin 20 including the appropriate safety precautions to be followed by healthcare professionals and patients. Furthermore, new safety signals reported by patients/healthcare professionals will be monitored/reviewed continuously. However, since there are no plans to launch this product in the UK, a RMP is not applicable in this case. Other information about Zenbumin 20 The marketing authorisation for Zenbumin 20 was granted on 30th January 2018. This medicine is subject to restricted medical prescription. For more information about treatment with Zenbumin 20, read the package leaflet or contact your doctor or pharmacist. This summary was last updated in March 2018. The full PAR for Zenbumin 20 follows this summary.

PAR Zenbumin 20, 200 g/l, solution for infusion PL 08801/0037

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TABLE OF CONTENTS

I Introduction P5 II Quality assessment P5 III Non-clinical assessment P6 IV Clinical assessment P6 V User consultation P8 VI Overall conclusions and risk benefit assessment P8 Table of content of the PAR update P12

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I INTRODUCTION Based on the review of data on safety and efficacy the UK granted a Marketing Authorisation to Bio Products Laboratory Limited (BPL Ltd) for the medicinal product Zenbumin 20, 200 g/l, solution for infusion (PL 08801/0037) on 30th January 2018. This product is a restricted prescription only medicine and is used for the restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated, and use of a colloid is appropriate. The choice of albumin rather than artificial colloid will depend on the clinical situation of the individual patient, based on official recommendations. This is an abridged simple national application submitted under Article 10(c) of Article 2001/83/EC, as amended. The reference marketing authorisation, Zenalb 20 Solution for Infusion, PL 08801/0007, is held by the same company (BPL Ltd) and was granted in April 1993 via a National Procedure. The applicant has indicated that there are no intentions for a UK launch based on this licence as this licence will be used purely as an international comparator pharmaceutical product. Nevertheless, full compliance with the requirements for a 10c submission is still required. Zenbumin 20 is a solution containing 200 g/l of total protein of which at least 95% is human albumin derived from screened human plasma donors. Albumin is a major normal constituent of human plasma and extravascular body fluids. It is a naturally occurring plasma protein consisting of a single polypeptide chain of 585 amino acids and, unlike most other plasma proteins, it is non-glycosylated. Albumin is a transport protein and is the most important plasma component in the maintenance of oncotic pressure and control of compartmental fluid balance. No new data were submitted nor were they necessary for these simple applications, as the data are identical to those of the previously granted cross-reference products. The MHRA has already been assured with regard to the cross-referenced product that acceptable standards of Good Manufacturing Practice (GMP) are in place for this product type at all sites responsible for the manufacture, assembly and release of the product. II QUALITY ASPECTS II.1 Introduction This is a simple (informed consent) application for Zenbumin 20, 20 g/l solution for infusion (PL 08801/0037), submitted under Article 10c of Directive 2001/83/EC, as amended. The applicant has cross-referred to Zenalb 20 solution for infusion, PL 08801/0007, which is also authorised by the same company, BPL Ltd. II.2 Drug substance The drug substance is the same as that for the cross-reference product. II.3 Medicinal Product Name The proposed name Zenbumin 20 is considered to be acceptable and no potential for confusion with currently authorised products could be found. Strength, pharmaceutical form, route of administration, container and pack size Zenbumin 20 is a solution containing 200 g/l of total protein of which at least 95% is human albumin. A vial of 100 mL contains 20 g of human albumin. It is a clear, slightly viscous liquid, almost colourless, yellow, amber or green. The solution is contained in glass bottles stoppered with a rubber bung. The bung is over-sealed with a tamper evident cap.

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The proposed shelf-life is 36 months unopened and 3 hours once opened. The proposed packaging, shelf-life and storage conditions are consistent with the details registered for the cross-reference product. Marketing Authorisation Holder/Contact Persons/Company Bio Products Laboratory Limited, Dagger Lane, Elstree, WD6 3BX. The Qualified Person (QP) responsible for pharmacovigilance is stated and a satisfactory Curriculum Vitae (CV) has been provided. Manufacturer The proposed manufacturing sites are consistent with those registered for the cross-referenced product and evidence of GMP compliance has been provided. Qualitative and quantitative composition The proposed composition is consistent with the details registered for the cross-reference product. Manufacturing process The proposed manufacturing process is consistent with the details registered for the cross-reference product and the maximum batch size is stated. Finished Product Specification The proposed finished product specifications are in line with the details registered for the cross-reference product. II.4 Discussion on chemical, pharmaceutical and biological aspects There are no objections to the approval of this application from a pharmaceutical viewpoint. III NON-CLINICAL ASPECTS As this is a simple (informed consent) application submitted under Article 10c of Directive 2001/83/EC, as amended, no new non-clinical data has been supplied and none are required. A suitable justification has been provided for not submitting an environment risk assessment. The grant of Marketing Authorisation is recommended. IV CLINICAL ASPECTS As this is a simple (informed consent) application submitted under Article 10c of Directive 2001/83/EC, as amended, no new non-clinical data has been supplied and none are required. Risk Management Plan (RMP) and Pharmacovigilance System The marketing authorisation holder (MAH) has provided a copy of the RMP for the reference product, Zenalb 20 solution for infusion (PL 08801/0007) in accordance with the requirements of Directive 2001/83/EC as amended, describing the pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to Zenalb 20 solution for infusion. A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, are listed below:

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Summary table of safety concerns:

Routine pharmacovigilance and routine risk minimisation are proposed. No additional pharmacovigilance or additional risk minimisation measures are proposed. Follow up forms are proposed in order to gather follow up information on any cases of pregnancy. This is considered a routine pharmacovigilance activity. Discussion on the clinical aspects There are no objections to the approval of this application from a clinical viewpoint.

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V User consultation User testing has not been performed as the product will not be launched in the UK. This is acceptable. VI Overall conclusion, benefit/risk assessment and recommendation The quality of the product is acceptable, and no new non-clinical or clinical safety concerns have been identified. Extensive clinical experience with Zenbumin 20 is considered to have demonstrated the therapeutic value of the compound. The product is bioequivalent to the marketed reference product and the benefit-risk balance is considered similar and positive. Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels In accordance with Directive 2010/84/EU the SmPCs and PILs for products granted Marketing Authorisations at a national level are available on the MHRA website.

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The following labelling is the approved label mock-ups for this medicine.

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PAR Zenbumin 20, 200 g/l, solution for infusion PL 08801/0037

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PAR Zenbumin 20, 200 g/l, solution for infusion PL 08801/0037

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Table of content of the PAR update Steps taken after the initial procedure with an influence on the Public Assessment

Report (Type II variations, PSURs, commitments)

Date submitted

Application type

Scope Outcome