UKPAR Naloxone Hydrochloride 1 mg/ml Injection
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`PL 12064/0125
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`EPIRUBICIN HYDROCHLORIDE 10 MG AND 50 MG POWDER FOR
`SOLUTION FOR INJECTION
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`PL 40378/0153-4
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`UKPAR
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`TABLE OF CONTENTS
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`Page 2
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`Page 3
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`Page 11
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`Page 12
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` Page 13
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` Page 13
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` Page 14
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`Lay Summary
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`Scientific discussion
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`Steps taken for assessment
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`Steps taken after authorisation – summary
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`Summary of Product Characteristics
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`Patient Information Leaflet
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`Labelling
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`Ex. 1060-0001
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`

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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`EPIRUBICIN HYDROCHLORIDE 10 MG AND 50 MG POWDER FOR
`SOLUTION FOR INJECTION
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`PL 40378/0153-4
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`
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`LAY SUMMARY
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`
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`On 4th October 2012, the MHRA granted Aptil Pharma Limited Marketing Authorisations
`(licences) for Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection.
`
`Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection contain the
`active ingredient epirubicin hydrochloride.
`
`Epirubicin hydrochloride belongs to a group of medicines called anthracyclines, which are
`used to treat cancer. Epirubicin hydrochloride is a medicine that acts upon cells that are
`actively growing (such as cancer cells) in such a way as to slow or stop their growth and
`increases the likelihood that the cells will die. This medicine helps to selectively kill the
`cancer tissue rather than normal, healthy tissue.
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`Epirubicin hydrochloride is used to treat a variety of cancers, either alone or in combination
`with other drugs. The way in which it is used depends upon the type of cancer that is being
`treated.
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`When injected into the bloodstream, epirubicin hydrochloride has been found to be useful in
`the treatment of cancers of the breast, ovaries, stomach, bowel and lung. Epirubicin
`hydrochloride can be given in the same way to treat cancers of the blood-forming tissues such
`as malignant lymphomas, leukaemias and multiple myeloma.
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`In addition, epirubicin hydrochloride can be injected into the bladder through a tube. This is
`sometimes used to treat abnormal cells or cancers of the bladder wall. It can also be used after
`other treatments to try to prevent such cells from growing again.
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`No new or unexpected safety concerns arose from these applications and it was therefore
`judged that the benefits of taking Epirubicin Hydrochloride 10 mg and 50 mg Powder for
`Solution for Injection outweigh the risks and Marketing Authorisations were granted.
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`2
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`Ex. 1060-0002
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`

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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`EPIRUBICIN HYDROCHLORIDE 10 MG AND 50 MG POWDER FOR
`SOLUTION FOR INJECTION
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`PL 40378/0153-4
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`SCIENTIFIC DISCUSSION
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`Page 4
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`Page 5
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`Page 8
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`Page 9
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`Page 10
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`TABLE OF CONTENTS
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`Introduction
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`Pharmaceutical assessment
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`Non-clinical assessment
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`Clinical assessment (including statistical assessment)
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`Overall conclusions and risk benefit assessment
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`3
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`Ex. 1060-0003
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`

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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`INTRODUCTION
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`The MHRA granted Marketing Authorisations for the medicinal products Epirubicin
`Hydrochloride 10 mg and 50 mg Powder for Solution for Injection (PL 40378/0153-4) to
`Aptil Pharma Limited on 4th October 2012. These prescription-only medicines (POM) have
`produced responses in a wide range of neoplastic conditions, including breast, ovarian,
`gastric, lung and colorectal carcinomas, malignant lymphomas, leukaemias and multiple
`myeloma.
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`Intravesical administration of Epirubicin Hydrochloride 10 mg and 50 mg Powder for
`Solution for Injection has been found to be beneficial in the treatment of superficial bladder
`cancer, carcinoma-in-situ and in the prophylaxis of recurrences after transurethral resection.
`
`These applications for Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for
`Injection were submitted according to Article 10c (informed consent application) of Directive
`2001/83/EC, as amended, cross-referring to Epirubicin Hydrochloride 10 mg and 50 mg
`Powder for Solution for Injection, licensed to Apsla Limited on 14th April 2011
`(PL 33410/0010-11).
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`It is considered that the pharmacovigilance system as described by the applicant fulfils the
`requirements and provides adequate evidence that the applicant has the services of a qualified
`person responsible for pharmacovigilance together with the necessary means for notification
`of any adverse reaction suspected of occurring.
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`Satisfactory justification was provided for the absence of a Risk Management Plan.
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`No new data were submitted nor were they necessary for these ‘informed consent’
`applications because the data are identical to those of the previously granted cross-reference
`products.
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`4
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`Ex. 1060-0004
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`

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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`PHARMACEUTICAL ASSESSMENT
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` PL 40378/0153-4
`LICENCE NO:
`PROPRIETARY NAME: Epirubicin Hydrochloride 10 mg and 50 mg Powder for
`Solution for Injection
`Epirubicin hydrochloride
` Aptil Pharma Limited
`Article 10c of Directive 2001/83/EC, as amended
` POM
`
`
`ACTIVE(S):
`COMPANY NAME:
`E.C. ARTICLE:
`LEGAL STATUS:
`
`1. INTRODUCTION
`These are ‘informed consent’ applications for Epirubicin Hydrochloride 10 mg and 50 mg
`Powder for Solution for Injection (PL 40378/0153-4) submitted under Article 10c of
`Directive 2001/83/EC, as amended. The proposed Marketing Authorisation Holder (MAH) is
`Aptil Pharma Limited, 9th Floor, CP House, 97 – 107 Uxbridge Road, Ealing, London
`W5 5TL.
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`These applications cross-refer to Epirubicin Hydrochloride 10 mg and 50 mg Powder for
`Solution for Injection, licensed to Apsla Limited on 14th April 2011 (PL 33410/0010-11).
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`MARKETING AUTHORISATION APPLICATION FORM
`2.
`2.1 NAME(S)
`The proposed names of the products are Epirubicin Hydrochloride 10 mg and 50 mg Powder
`for Solution for Injection. The products have been named in line with current requirements.
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`2.2 Strength, pharmaceutical form, route of administration, container and pack sizes
`The products contain 10 mg and 50 mg of epirubicin hydrochloride. The products are sterile,
`freeze-dried, orange-red coloured, lyophilised cakes (powder for solution for injection). After
`reconstitution, each vial contains 2 mg/ml epirubicin hydrochloride. The products Epirubicin
`Hydrochloride 10 mg and 50 mg Powder for Solution for Injection are for intravenous or
`intravesical administration.
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`The 10 mg strength presentation is packaged in a 10 ml Type I moulded flint glass vial with a
`20 mm bromo butyl rubber stopper and 20 mm aluminium flip-off, tear-off seal.
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`The 50 mg strength presentation is packaged in a 50 ml Type I moulded flint glass vial with a
`20 mm bromo butyl rubber stoppers and 20 mm aluminium flip-off tear-off seal.
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`There is 1 vial in each pack for both presentations.
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`The shelf-life of the products as packaged for sale is 2 years with storage conditions ‘Store
`below 30°C. Keep the container in the outer carton’.
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`The shelf-life of the products after reconstitution is according to directions:
`‘In-use stability has been demonstrated for 24 hours at 15°C - 25°C and for 48 hours at 2-8°C
`in water for injections and 0.9 % w/v sodium chloride solution. However from a
`microbiological point of view, it is recommended that the product should be used
`immediately. If not used immediately, in-use storage times and conditions prior to use are the
`responsibility of the user and would normally not be longer than 24 hours at 2 to 8ºC’.
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`5
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`Ex. 1060-0005
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`This is consistent with the information registered for the cross-reference products.
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`2.3 Legal status
`Prescription-only medicine (POM).
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`2.4 Marketing authorisation holder (MAH)/Contact Persons/Company
`The proposed MAH is Aptil Pharma Limited, 9th Floor, CP House, 97 – 107 Uxbridge Road,
`Ealing, London W5 5TL.
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`The QP responsible for pharmacovigilance is stated and a CV is included.
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`2.5 Manufacturers
`The manufacturing sites are consistent with those registered for the cross-reference products
`and evidence of GMP compliance has been provided.
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`2.6 Qualitative and quantitative composition
`The composition is consistent with the details registered for the cross-reference products.
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`2.7 Manufacturing process
`The manufacturing process is consistent with the details registered for the cross-reference
`products.
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`2.8 Finished product/shelf-life specifications
`The finished product specifications are in line with those registered for the cross-reference
`products.
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`2.9 Drug substance specification
`The drug substance specification is consistent with that registered for the cross-reference
`products.
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`2.10 TSE Compliance
`With the exception of lactose monohydrate, none of the excipients used contain material of
`animal or human origin. The applicant has provided a declaration that the milk used in the
`production of the lactose monohydrate is sourced from healthy animals under the same
`conditions as those intended for human consumption.
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`This information is consistent with that for the cross-reference products.
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`EXPERT REPORTS
`3.
`Quality, non-clinical and clinical expert statements have been provided in Module 2 of the
`application. Signed declarations and copies of the experts’ CVs are enclosed in Module 1.4
`for the quality, non-clinical and clinical experts. All are considered to have sufficient
`experience for their responsibilities.
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`PRODUCT NAME & APPEARANCE
`4.
`See Section 2.1 for details of the proposed product names. The appearance of the products is
`identical to the cross-reference products.
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`SUMMARY OF PRODUCT CHARACTERISTICS (SmPC)
`5.
`The SmPC is consistent with that registered for the cross-reference products.
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`6
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`Ex. 1060-0006
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`PATIENT INFORMATION LEAFLET (PIL)/LABELLING
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`6.
`PIL
`A satisfactory bridging report to previous ‘user testing’ of the readability of the PIL has been
`provided. The report cross-refers to the readability testing for the reference product PIL,
`which is acceptable since the content, layout, formatting and appearance of the proposed
`leaflet are identical to that of the reference PIL.
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`Labelling
`The artwork is comparable to the artwork registered for the cross-reference products and
`complies with statutory requirements.
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`CONCLUSIONS
`7.
`The data submitted with the applications are acceptable. The grant of these Marketing
`Authorisations is recommended.
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`7
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`Ex. 1060-0007
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`NON-CLINICAL ASSESSMENT
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`No new non-clinical data have been supplied with these applications and none are required
`for applications of this type.
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`An Environmental Risk Assessment was not submitted or required for these generic
`applications.
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`8
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`Ex. 1060-0008
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`CLINICAL ASSESSMENT
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`No new clinical data have been supplied with these applications and none are required for
`applications of this type.
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`9
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`Ex. 1060-0009
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`OVERALL CONCLUSION AND RISK BENEFIT ASSESSMENT
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`QUALITY
`The data for these applications are consistent with those previously approved for the
`cross-reference products and, as such, have been judged to be satisfactory.
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`NON-CLINICAL
`No new non-clinical data were submitted and none are required for applications of this type.
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`EFFICACY
`These applications are considered identical to the previously granted applications, Epirubicin
`Hydrochloride 10 mg and 50 mg Powder for Solution for Injection, licensed to Apsla Limited
`on 14th April 2011 (PL 33410/0010-11).
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`No new or unexpected safety concerns arose from these applications.
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`At the time of assessment, the SmPCs, PIL and labelling were satisfactory and consistent
`with those for the cross-reference products.
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`RISK BENEFIT ASSESSMENT
`The quality of the products is acceptable and no new non-clinical or clinical safety concerns
`have been identified. The applicant’s products are identical to the cross-reference products.
`Extensive clinical experience with epirubicin hydrochloride is considered to have
`demonstrated the therapeutic value of the compound. The risk-benefit balance is therefore
`considered to be positive.
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`10
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`Ex. 1060-0010
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`EPIRUBICIN HYDROCHLORIDE 10 MG AND 50 MG POWDER FOR
`SOLUTION FOR INJECTION
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`PL 40378/0153-4
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`STEPS TAKEN FOR ASSESMENT
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`The MHRA received the Marketing Authorisation Applications on 20th July
`2012.
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`Following standard checks and communication with the applicant the MHRA
`considered the applications valid on 26th July 2012.
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`The applications were determined on 4th October 2012.
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`1
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`2
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`3
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`11
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`Ex. 1060-0011
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`EPIRUBICIN HYDROCHLORIDE 10 MG AND 50 MG POWDER FOR
`SOLUTION FOR INJECTION
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`PL 40378/0153-4
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`STEPS TAKEN AFTER ASSESSMENT
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`Date
`submitted
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`Application
`type
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`Scope
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`Outcome
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`12
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`Ex. 1060-0012
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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`SUMMARY OF PRODUCT CHARACTERISTICS AND PATIENT INFORMATION
`LEAFLET
`
`
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`In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC)
`and Patient Information Leaflets (PIL) for products granted Marketing Authorisations at a
`national level are available on the MHRA website.
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`13
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`Ex. 1060-0013
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`

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`UKPAR Epirubicin Hydrochloride 10 mg and 50 mg Powder for Solution for Injection PL 40378/0153-4
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`LABELLING
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`14
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`Ex. 1060-0014