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Decentralised Procedure
(aceclofenac)
LAY SUMMARY
Aceclofenac 100mg Film-coated Tablets
(aceclofenac)
This is a summary of the public assessment report (PAR) for Aceclofenac 100mg Film-coated Tablets
(PL 30306/0648; UK/H/5948/001/DC). It explains how Aceclofenac 100mg Film-coated Tablets were
assessed and their authorisation recommended, as well as their conditions of use. It is not intended to
provide practical advice on how to use Aceclofenac 100mg Film-coated Tablets.
These products will be referred to as Aceclofenac 100mg Film-coated Tablets throughout the lay
summary, for ease of reading.
For practical information about using Aceclofenac Tablets, patients should read the package leaflet or
contact their doctor or pharmacist.
What are Aceclofenac Tablets and what are they used for?
Aceclofenac Tablets is a generic medicine. This means that Aceclofenac Tablets are similar to a
‘reference medicine’ already authorised in the UK called Preservex® 100 mg film-coated tablets
(Almirall S.A.; PL 16973/0001).
Aceclofenac Tablets are used to relieve pain and inflammation in adult patients suffering from:
Arthritis of the joints (osteoarthritis). This commonly occurs in patients over the age of 50 and
causes the loss of the cartilage and bone tissue next to the joint
Autoimmune disease that causes chronic inflammation of the joints (rheumatoid arthritis).
Arthritis of the spine which can lead to the fusion of the vertebrae (ankylosing spondylitis).
The recommended dose in adults is 200 mg (two Aceclofenac tablets) daily, taken as one 100 mg tablets
in the morning and one in the evening.
Elderly patients will be prescribed the lowest effective dose over the shortest duration of time as they are
more likely to experience serious side effects.
For further information on how Aceclofenac Tablets are used, please see the Summary of Product
Characteristics and package leaflet available on the MHRA website.
What measures are being taken to ensure the safe and effective use of Aceclofenac Tablets?
A risk management plan has been developed to ensure that Aceclofenac Tablets are used as safely as
possible. Based on this plan, safety information has been included in the Summary of Product
Characteristics and the package leaflet for Aceclofenac Tablets, including the appropriate precautions to
be followed by healthcare professionals and patients.
The full PAR for Aceclofenac Tablets follows this summary. For more information about treatment with
Aceclofenac Tablets, read the package leaflet or contact your doctor or pharmacist.
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PAR Aceclofenac 100mg Film-coated Tablets UK/H/5948/001/DC
TABLE OF CONTENTS
I Introduction Page 5
II Quality aspects Page 6
III Non-clinical aspects Page 7
IV Clinical aspects Page 8
V User consultation Page 13
VI Overall conclusion, benefit/risk assessment and Page 13
recommendation
Table of content of the PAR update for MRP and DCP Page 17
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PAR Aceclofenac 100mg Film-coated Tablets UK/H/5948/001/DC
I INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the Reference Member State (RMS) and
Concerned Member States (CMSs) considered that the application for Aceclofenac 100mg Film-coated
Tablets (PL 30306/0648; UK/H/5948/001/DC) indicated for the relief of pain and inflammation in
osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults, is approvable.
The application was submitted using the Decentralised Procedure (DCP) with the UK as the RMS and
Hungary, Poland, Romania and Slovak Republic as CMSs. The application was submitted under Article
10.1 of Directive 2001/83/EC, as amended, and cross referred to Preservex® 100 mg Film-coated
Tablets, which was first licensed to Prodesfarma SA (PL 08448/0001) on 24th April 1995. This reference
licence underwent a change of ownership procedure to the current Marketing Authorisation Holder,
Almirall S.A. (PL 16973/0001), on 22nd May 2000. The reference product used for the bioequivalence
study was Cartrex® 100 mg Film-coated Tablets (Almirall S.A.S, France), which is considered to be in
the same global Marketing Authorisation as the originator product, Preservex® 100 mg Film-coated
Tablets.
The active substance, aceclofenac, is a non-steroidal agent with marked anti-inflammatory and analgesic
properties. The mode of action of aceclofenac is largely based on the inhibition to prostaglandin
synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclo-oxygenase, which is involved in the
production of prostaglandins.
One bioequivalence study was submitted to support this application comparing the test product
Aceclofenac 100mg Film-coated Tablets (Rivopharm SA., Switzerland) with the reference product
Cartrex® 100 mg Film-coated Tablets (Almirall S.A.S, France) in 35 healthy adult subjects under fasting
conditions. The applicant has stated that the bioequivalence study was carried out in accordance with
Good Clinical Practice (GCP).
With the exception of the bioequivalence study, no new non-clinical or clinical studies were conducted,
which is acceptable given that the application was based on being generic medicinal product of an
originator product that has been licensed for over 10 years.
The RMS has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in
place for this product type at all sites responsible for the manufacture, assembly and batch release of this
product.
For manufacturing sites within the Community, the RMS has accepted copies of current manufacturer
authorisations issued by inspection services of the competent authorities as certification that acceptable
standards of GMP are in place at those sites.
For manufacturing sites outside the Community, the RMS has accepted copies of current GMP
Certificates of satisfactory inspection summary reports, ‘close-out letters’ or ‘exchange of information’
issued by the inspection services of the competent authorities (or those countries with which the EEA
has a Mutual Recognition Agreement for their own territories) as certification that acceptable standards
of GMP are in place at those non-Community sites.
All involved Member States agreed to grant a Marketing Authorisation for the above product at the end
of the procedure (Day 150 – 17th September 2015). After a subsequent national phase, the UK granted a
Marketing Authorisation (PL 30306/0648) for this product on 16th October 2015.
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PAR Aceclofenac 100mg Film-coated Tablets UK/H/5948/001/DC
II QUALITY ASPECTS
II.1 Introduction
This product is a film-coated tablet and contains 100mg of aceclofenac, as active ingredient. The
excipients present are microcrystalline cellulose (E460i), croscarmellose sodium, copovidone (K28), talc
(E553b), silica colloidal anhydrous, glicerol distearate (Type I) making up the core, and the film-coating
is composed of Opadry O3A0280002 (HPMC 2910/hypromellose 6 mPa·s (E464), microcrystalline
cellulose, titanium dioxide (E171) and polyoxyl 40 (macrogol) stearate (Type I)). Appropriate
justification for the inclusion of each excipient has been provided.
All excipients used comply with their respective European Pharmacopoeia monographs with the
exception of Opadry O3A0280002 which complies with an in-house specification.
Satisfactory specifications and Certificates of Analysis have been provided for all packaging
components. All primary packaging complies with the current European regulations concerning
materials in contact with food.
Synthesis of the drug substance from the designated starting materials has been adequately described
and appropriate in-process controls and intermediate specifications are applied. Satisfactory
specification tests are in place for all starting materials and reagents, and these are supported by relevant
Certificates of Analysis.
An appropriate specification is provided for the drug substance. Analytical methods have been
appropriately validated and are satisfactory for ensuring compliance with the relevant specifications.
Certificates of Analysis for all working standards have been provided.
Batch analyses data are provided that comply with the proposed specification.
Satisfactory specifications and Certificates of Analysis have been provided for all packaging used to
store the drug substance. Confirmation has been provided that the primary packaging complies with
current guidelines concerning materials in contact with food.
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PAR Aceclofenac 100mg Film-coated Tablets UK/H/5948/001/DC
Appropriate stability data have been provided, supporting a suitable retest period when the drug
substance is stored in the packaging proposed.
Comparative dissolution and impurity profiles have been presented for the proposed and reference
products.
Based on the results a shelf-life of 24 months with no special storage conditions is set. This is
satisfactory.
Bioequivalence/bioavailability
Satisfactory Certificates of Analysis have been provided for the test and reference batches used in the
bioequivalence study.
The pharmacodynamic, pharmacokinetic and toxicological properties of aceclofenac are well known. As
aceclofenac is a widely used, well-known active substance, no new non-clinical data have been supplied
and none are required for applications of this type. The non-clinical overview has been written by an
appropriately qualified person and is a suitable summary of the non-clinical aspects of the dossier.
III.2 Pharmacology
No new data have been submitted and none are required for applications of this type.
III.3 Pharmacokinetics
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PAR Aceclofenac 100mg Film-coated Tablets UK/H/5948/001/DC
No new data have been submitted and none are required for applications of this type.
III.4 Toxicology
No new data have been submitted and none are required for applications of this type.
IV CLINICAL ASPECTS
IV.1 Introduction
This is a generic application submitted under the Decentralised Procedure according to Article 10.1 of
Directive 2001/83/EC, as amended, for Aceclofenac 100mg Film-coated Tablets.
The pharmacodynamic, pharmacokinetic, clinical efficacy and safety properties of aceclofenac are well
known. As aceclofenac is a widely used, well-known active substance, the applicant has not provided
additional studies and further studies are not required. An overview based on literature review is
considered appropriate.
With the exception of the bioavailability study, no new clinical data have been submitted and none are
required for applications of this type. The applicant’s clinical overview has been written by an
appropriately qualified person and is considered acceptable.
IV.2 Pharmacokinetics
In support of this application, the Marketing Authorisation Holder has submitted the following
bioequivalence study under fasting conditions.
This is a single centre, randomized, single-dose, open-label, 2-way, crossover bioequivalence study
comparing the pharmacokinetics of the test product Aceclofenac 100mg Film-coated Tablets
(Rivopharm SA., Switzerland) with the reference product Cartrex® 100 mg Film-coated Tablets
(Almirall S.A.S, France) in 35 healthy adult subjects, under fasting conditions.
Blood samples were collected pre-dose and at 0.333, 0.667, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50,
4.00, 5.00, 6.00, 8.00, 10.0 and 12.0 hours post-dose, in each period. The washout period was 7 days.
Pharmacokinetic parameters for aceclofenac (non-transformed values; arithmetic mean ± SD, tmax
median, range).
Treatment AUC0-t AUC0-∞ Cmax tmax
ng/ml/h ng/ml/h ng/ml h
Test 20270.28 + 2898.04 20814.17 + 3042.28 10700.18 + 1879.29 1.67 (0.667 – 4.00)
Reference 20680.55 + 3213.58 21270.94 + 3340.44 10058.71 + 2564.14 1.00 (0.667 – 4.00)
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Conclusion
The 90% confidence intervals for Cmax and AUC were within the pre-defined acceptance criteria
specified in “Guideline on the Investigation of Bioequivalence” (CPMP/EWP/QWP/1401/98 Rev 1/
Corr**). Bioequivalence has been shown for the test formulation (Aceclofenac 100mg Film-coated
Tablets) and the reference formulation (Cartrex 100 mg Film-coated Tablets) under fasting conditions.
IV.3 Pharmacodynamics
No new data have been submitted and none are required for applications of this type.
A summary of safety concerns and planned risk minimisation activities, as approved in the RMP,
is listed below:
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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 Aceclofenac 100 mg Film-coated
Tablets (UK/H/5382 &5667/001/DC). The bridging report submitted by the applicant is acceptable.
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PAR Aceclofenac 100mg Film-coated Tablets UK/H/5948/001/DC
Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and labelling
In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) and
Patient Information Leaflets (PILs) for products that are granted Marketing Authorisations at a national
level are available on the MHRA website.
Labelling
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