Public Assessment Report Scientific discussion Lionova Solution for injection and infusion 50 micrograms/ml, 0.5 mg/ml and 2 mg/ml (Baclofen) ...
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Public Assessment Report
Scientific discussion
Lionova
Solution for injection and infusion
50 micrograms/ml, 0.5 mg/ml and 2 mg/ml
(Baclofen)
DK/H/2487/001-003/DC
27 March 2017
This module reflects the scientific discussion for the approval of Lionova. The procedure was
finalised on 21 January 2016. For information on changes after this date please refer to the module
‘Update’.I. INTRODUCTION Based on the review of the quality, safety and efficacy data, the Member States have granted a marketing authorisation for Lionova solution for injection and infusion 50 micrograms/ml, 0.5 mg/ml and 2 mg/ml. The product is indicated in adult patients with severe chronic spasticity resulting from trauma, multiple sclerosis or other spinal cord disorders, who are unresponsive to oral baclofen or other orally administered antispastic medicinal products and/or those patients who experience unacceptable side- effects at effective oral doses. Lionova is effective in patients with severe chronic spasticity of cerebral origin, resulting e.g. from cerebral palsy, brain trauma or cerebrovascular accident. Baclofen intrathecal is indicated in patients aged 4 to
The product is supplied in type I clear colourless glass ampoules in pack sizes of 5 ampoules of 1 ml
(50 micrograms/ml), 1 ampoule of 20 ml (0.5 mg/ml) and 1 ampoule of 5 ml (2 mg/ml).
Lionova solution for injection and infusion contains sodium chloride and water for injections.
The RMS has been assured that acceptable standards of GMP (see Directive 2003/94/EC) are in place
for this product type at all sites responsible for the manufacturing of the active substance as well as for
the manufacturing and assembly of this product prior to granting its national authorisation.
II.2 Drug Substance
The active substance, baclofen, is described in the European Pharmacopoeia (monograph 0653). It is a
white or almost white powder. It is slightly soluble in water, very slightly soluble in ethanol (96%),
practically insoluble in acetone, chloroform and ether. It dissolves in dilute mineral acids and alkali
hydroxides.
Structure:
Molecular formula: C10H12ClNO2
Molecular weight: 213.66 g/mol
One asymmetric center is present, therefore two enantiomers are obtained during the synthesis. Baclofen
was tested according to the Ph. Eur. 5.11 method and was found to be hygroscopic. Baclofen shows
polymorphism.
The active substance manufacturer has obtained a Certificate of Suitability.
All the control tests and specifications for drug substance product are adequately drawn up. The active
substance is controlled according to the requirements of the Ph. Eur. monograph and CEP.
The proposed retest period is stated in the CEP.
II.3 Medicinal Product
The finished product is a solution for injection and infusion for intrathecal use.
The development of the product has been described and all excipients (sodium chloride and water for
injections) are described in Ph. Eur. The development of the product is based on investigations of the
reference product Lioresal and excipients used for the formulation have been chosen to resemble the
reference product.
The manufacturing process has been described and satisfactorily validated. In-process controls have
been provided and they are appropriate considering the nature of the product and the method of
manufacture.
3/5Adequate descriptions and validations are provided for the analytical methods included in the
specification. Batch analysis has been performed on three production batches for each strength. The
batch analysis results show that the finished products meet the specifications proposed.
The conditions used in the stability studies are according to the ICH stability guideline. A shelf-life of
36 months (0.05 and 2 mg/ml) and 48 months (0.5 mg/ml) with no special storage conditions is accepted.
III. NON-CLINICAL ASPECTS
III.1 Introduction
Pharmacodynamic, pharmacokinetic and toxicological properties of baclofen are well known. As
baclofen is a well-known active substances, the MAH has not provided additional studies and further
studies are not required. Overview based on literature review is, thus, appropriate.
The non-clinical overview report refers 93 publications up to year 2010. Addendum update report refers
59 publications up to year 2014.
The non-clinical overview on the pre-clinical pharmacology, pharmacokinetics and toxicology is
adequate.
III.2 Ecotoxicity/environmental risk assessment (ERA)
The product is intended as a substitute for other identical products on the market. The approval of this
product will not result in an increase in the total quantity of baclofen released into the environment. It
does not contain any component, which results in an additional hazard to the environment during
storage, distribution, use and disposal.
IV. CLINICAL ASPECTS
IV.1 Introduction
Baclofen is a well-known active substance with established efficacy and tolerability. As baclofen is a
widely used, well-known active substance, the MAH has not provided additional studies and further
studies are not required. Overview based on literature review is, thus, appropriate.
The clinical report refers 108 publications up to year 2010. Addendum update report refers 52
publications up to year 2014.
The clinical overview on the clinical pharmacology, efficacy and safety is adequate.
As Lionova is a product for parenteral use, it is exempted for biostudy (NfG CPMP/EWP/QWP
1401/98). The current product can be used instead of its reference product. Overview based on literature
review is, thus, appropriate.
4/5IV.2 Risk Management Plan
The MAH has submitted a risk management plan, 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 Lionova.
The following summary list of safety concerns has been agreed with no additional pharmacovigilance
or risk minimisation measures:
Table 1. Summary table of safety concerns as approved in RMP
V. USER CONSULTATION
A user consultation with target patient groups on the package information leaflet (PIL) has been
performed on the basis of a bridging report making reference to Baklofen “Alternova” 10 mg and 25 mg
tablets (with regard to content) and to Amiodaronhydrochlorid “Alternova” 50 mg/ml solution for
injection (with regard to layout).
The bridging report submitted by the MAH has been found acceptable.
VI. OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND
RECOMMENDATION
Lionova solution for injection and infusion 50 micrograms/ml, 0.5 mg/ml and 2 mg/ml has a proven
chemical-pharmaceutical quality and is comparable to Lioresal. Lioresal is a well-known medicinal
product with an established favourable efficacy and safety profile.
As Lionova is a product for parenteral use, it is exempted for biostudy (NfG CPMP/EWP/QWP
1401/98).
Agreement between Member States was reached during a written procedure. There was no discussion
in the CMD(h). The Concerned Member States, on the basis of the data submitted, considered that a
marketing authorisation for Lionova could be granted. The decentralised procedure was finalised on 21
January 2016. Lionova was authorised in Denmark on 18 February 2016.
PSURs should be submitted in accordance with the requirements set out in the list of Union reference
dates (EURD list) provided for under Article 107c (7) of Directive 2001/83/EC and published on the
European medicines web-portal. According to the EURD list, PSURs should be submitted every 5 years.
The next DLP is 31 January 2021.
The date for the first renewal will be: 21 January 2021.
There were no post-approval commitments made during the procedure.
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