Benifema 150 Mikrogramm/30 Mikrogramm Filmtabletten

Österreich - Deutsch - AGES (Agentur für Gesundheit und Ernährungssicherheit)

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Gebrauchsinformation Gebrauchsinformation (PIL)

30-04-2020

Fachinformation Fachinformation (SPC)

30-04-2020

Wirkstoff:
DESOGESTREL; ETHINYLESTRADIOL
Verfügbar ab:
Actavis Group PTC ehf
ATC-Code:
G03AA09
INN (Internationale Bezeichnung):
DESOGESTREL; ethinylestradiol
Verschreibungstyp:
Arzneimittel zur wiederholten Abgabe gegen aerztliche Verschreibung
Produktbesonderheiten:
Abgabe durch eine (öffentliche) Apotheke
Zulassungsnummer:
135384
Berechtigungsdatum:
2014-02-18

Bundesamt für Sicherheit im Gesundheitswesen, Traisengasse 5, A-1200 Wien

www.ages.at, DVR: 2112611, Konto Nr.: 50670 871 619

BLZ: 12000, IBAN: AT971200050670871619; UID: ATU 54088605, BIC/SWIFT: BKAUATWW

1 von 1

Die gegenständliche Arzneispezialität wurde in einem europäischen Zulassungsverfahren

geprüft.

Die Vermarktung des Produktes in Österreich ist derzeit seitens des Zulassungsinhabers nicht

geplant, daher liegen zur Zeit keine deutschsprachigen Übersetzungen der Fach- und

Gebrauchsinformation vor.

Traisengasse 5, 1200 Wien

Bundesamt für Sicherheit im Gesundheitswesen, Traisengasse 5, A-1200 Wien

www.ages.at, DVR: 2112611, Konto Nr.: 50670 871 619

BLZ: 12000, IBAN: AT971200050670871619; UID: ATU 54088605, BIC/SWIFT: BKAUATWW

1 von 1

Die gegenständliche Arzneispezialität wurde in einem europäischen Zulassungsverfahren

geprüft.

Die Vermarktung des Produktes in Österreich ist derzeit seitens des Zulassungsinhabers nicht

geplant, daher liegen zur Zeit keine deutschsprachigen Übersetzungen der Fach- und

Gebrauchsinformation vor.

Traisengasse 5, 1200 Wien

CMDh/223/2005

February 2014

Public Assessment Report

Scientific discussion

Benifema 150 Mikrogramm/30 Mikrogramm

Filmtabletten

DESOGESTREL, ETHINYLESTRADIOL

AT/H/0800/002

Former NL/H/2752/002

Date of RMS Splitting: 29.09.2017

This module reflects the scientific discussion for the approval of Benifema 150

Mikrogramm/30 Mikrogramm Filmtabletten. The procedure was finalised on

15

September 2013

.

For information on changes after this date please refer to the module

‘Update’.

Public Assessment Report

Scientific discussion

Desogestrel/Ethinylestradiol Actavis 150/20

and 150/30 micrograms, film-coated tablets

(desogestrel/ethinylestradiol)

NL/H/2752/001-002/DC

Date: 9 April 2014

This

module

reflects

the

scientific

discussion

for

the

approval

of

Desogestrel/

Ethinylestradiol

Actavis

150/20

and

150/30

micrograms,

film-coated

tablets.

The

procedures were finalised on 15 September 2013 (higher strength) and 11 February

2014 (lower strength). For information on changes after this date please refer to the

module ‘Update’.

2/10

I.

INTRODUCTION

Based on the review of the quality, safety and efficacy data, the Member States have granted a

marketing authorisation for Desogestrel/Ethinylestradiol Actavis 150/20 and 150/30 micrograms, film-

coated tablets from Actavis Group PTC ehf.

The product is indicated for oral contraception.

A comprehensive description of the indication and posology is given in the SmPC.

This decentralised procedure concerns a generic application.

For the lowest strength the MAH claimed essential similarity with Mercilon 0.15/0.20 mg, tablets (NL

License RVG 11508) which has been registered in the Netherlands by N.V. Organon since 19

November 1987.

150/30

micrograms strength,

essential

similarity is

claimed

with

innovator

product

Marvelon tablets (NL License RVG 08859) which has been registered in the Netherlands by N.V.

Organon since 29 May 1981. In addition, reference is made to Mercilon and Marvelon authorisations

in the individual member states (reference product).

The concerned member states (CMS) involved in this procedure were Austria, Belgium, Germany,

Ireland,

Italy,

Luxembourg,

Malta

(150/30

micrograms

only),

Poland,

Slovakia

United

Kingdom.

The marketing authorisation has been granted pursuant to Article 10(1) of Directive 2001/83/EC.

II.

QUALITY ASPECTS

II.1

Introduction

Desogestrel/Ethinylestradiol

Actavis

150/20

contains

micrograms

desogestrel

micrograms of ethinylestradiol and is a white, round film-coated tablet of 5 mm diameter.

The tablets

are coded on one side “C” and on the reverse side “5”.

Desogestrel/Ethinylestradiol Actavis 150/30 micrograms contains 150 micrograms of desogestrel and

30 micrograms of ethinylestradiol and is a white, round film-coated tablet of 5 mm diameter. The

tablets are coded on one side “C” and on the reverse side “7”.

The tablets are packed in blisters of aluminium push-thru foil and clear to slight opaque PVC/PVDC

film. Each blister contains 21 tablets.

The excipients are:

Tablet core - lactose monohydrate, maize starch, povidone K-30 (E1201), RRR-Alpha-tocoferol

(E307), soybean oil, silica colloidal hydrated (E551), silica colloidal anhydrous (E551), stearic acid

(E570)

Film-coating - hypomellose 2910 (E464), triacetin (E1518), polysorbate, titanium dioxide (E171)

II.2

Drug Substances

Desogestrel

The active substance desogestrel is an established active substance described in the European

Pharmacopoeia (Ph.Eur.). The active substance is a white or almost white, crystalline powder, which

is practically insoluble in water. Desogestrel has six chiral centers, but does not exhibit polymorphism.

The CEP procedure is used for the desogestrel. Under the official Certification Procedures of the

EDQM of the Council of Europe, manufacturers or suppliers of substances for pharmaceutical use can

apply for a certificate of suitability concerning the control of the chemical purity and microbiological

quality of their substance according to the corresponding specific monograph, or the evaluation of

reduction

Transmissible

Spongiform

Encephalopathy

(TSE)

risk,

according

general

monograph, or both. This procedure is meant to ensure that the quality of substances is guaranteed

and that these substances comply with the European Pharmacopoeia.

3/10

Manufacturing process

A CEP has been submitted; therefore no details on the manufacturing process have been included.

Quality control of drug substance

The drug substance is tested in accordance with the Ph.Eur. monograph with additional tests on

residual solvents, any other impurity and particle size distribution. Certificates of analysis of three

batches have been provided, demonstrating compliance with the specification.

Stability of drug substance

The MAH submitted stability testing results in support of a retest period of 3 years when stored under

the stated conditions.

Ethinylestradiol

The active substance ethinylestradiol is an established active substance described in the Ph.Eur. It is

a white to practically white crystals or powder, which is practically insoluble in water, freely soluble in

ethanol and dissolves in dilute alkaline solutions. Ethinylestradiol exhibits polymorphism in the form of

solvates/hydrates. The consistency and control of the anhydrate/hemi-hydrate form manufactured was

adequately discussed.

The CEP procedure is used for ethinylestradiol.

Manufacturing process

A CEP has been submitted; therefore no details on the manufacturing process have been included.

Quality control of drug substance

The drug substance is tested in accordance with the Ph.Eur. monograph with additional tests on

residual solvents, any other impurity and particle size distribution. Batch analytical data demonstrating

compliance with this specification have been provided for two batches.

Stability of drug substance

A retest period of 5 years is applicable when stored under the stated conditions. Assessment thereof

was part of granting the CEP and has been granted by the EDQM.

II.3

Medicinal Product

Pharmaceutical development

The development of the product has been described, the choice of excipients is justified and their

functions explained. A direct compression process was chosen as the manufacturing process.

The necessity for inclusion of the antioxidant vitamin E and the efficacy of the proposed level have

been shown.

For the 150/30 micrograms strength the reference product used in the first bioequivalence study is

Microdiol®. Microdiol is the name of the reference product in Spain which corresponds to Marvelon.

The composition of innovator products is the same in most of the European countries, therefore, the

innovator product used in the bioequivalence study is representative for the innovator products from all

member states involved in this procedure.

Initially the MAH applied for a biowaiver for the 150/20 micrograms strength, which could however not

be granted as the reference products are based on different dossiers and because the similarity of the

in vitro dissolution profiles of the 150/20 micrograms strength with the 150/30 micrograms strength

biobatch has not satisfactorily been demonstrated. Moreover, based on the comparative in vitro

dissolution data, equivalence between the 150/20 micrograms test and reference product cannot be

concluded.

Therefore, the MAH decided to carry out a second study comparing the 150/20 microgram strength of

the test product with the reference product Suavuret, which is the Spanish trademark for the reference

product Mercilon. The use of the Spanish product has been sufficiently justified.

Although equivalence between the test and reference products of both strengths could be concluded

based on the comparative in vitro dissolution data, bioequivalence was shown in vivo, which prevails

over the in vitro data.

The pharmaceutical development of the product was adequately performed.

Manufacturing process

The drug product is manufactured by a direct compression process. The active substances are pre-

mixed separately before mixing. The premixes are then blended together and the blend is compressed

4/10

into tablet cores, coated and packed into blisters. The provided in-process controls are deemed

acceptable.

The manufacturing process has been adequately validated according to relevant European guidelines.

product

manufactured

using

conventional

manufacturing

techniques,

given

concentration of active substance in the drug product, the manufacturing process can be considered

as non-standard. Full-scale process validation results have been provided.

Control of excipients

The excipients are tested in accordance with their respective Ph.Eur. monograph. The coating

mixtures are controlled in-house. For vitamin E absorbed to silica specifications has been set for the

silica as per Ph.Eur. monograph. The vitamin E consists of a mixture of RRR-alpha-tocopherol with

soy bean oil. A specification has been set for this mixture in line with the USP monograph for vitamin E

preparations and additional requirements as stated in the Food Chemical Codex (USA). These

specifications are acceptable.

Quality control of drug product

The drug product specifications includes tests for appearance, identification, water content, hardness,

dissolution,

assay,

related

substances,

uniformity

dosage

units

(content

uniformity)

microbiological quality. The shelf-life specifications differ with respect to limits for assay (active

substances and vitamin E), related substances and water content.

The analytical methods have been adequately described and validated. Batch analytical data from the

proposed production site have been provided on three full-scale batches of each tablet strength,

demonstrating compliance with the release specifications.

Stability of drug product

Desogestrel/Ethinylestradiol Actavis 150/20 micrograms:

Stability data on the active drug product has been provided on three pilot-scale and three full-scale

batches, stored at 25°C/60% RH (pilot-scale batches for 24 and 36 months, full-scale batches for

three months),30°C/65% RH (pilot-scale batches for 12 months, full-scale batches for three months)

and 40°C/75%RH (pilot-scale batches for six months, full-scale batches for three months). The

conditions used in the stability studies are according to the ICH stability guideline. The batches were

stored in clear transparent PVC/PVDC-Al blisters. The accelerated conditions demonstrate that the

drug product is sensitive to elevated temperatures. Out of specification values are observed for

desogestrel assay after 6 months at accelerated conditions.

A photostability study has been performed in conformity with ICH topic Q1B, demonstrating that the

product is sensitive to light and the blister packaging suffices to protect the tablets from light

degradation. Based on the results provided, the approved shelf life for the 150/20 micrograms strength

is 24 months when stored below 30°C with the storage condition “store in the original packaging in

order to protect from light”.

Desogestrel/Ethinylestradiol Actavis 150/30 micrograms:

Stability data on the drug product has been provided on three full-scale batches, stored at 25°C/60%

RH (up to 35 months), 30°C/65%RH (12 months) and 40°C/75%RH (6 months). The conditions used

in the stability studies are according to the ICH stability guideline.

For both strengths the accelerated conditions demonstrate that the drug product is sensitive to

elevated temperatures. Out of specification values are observed for desogestrel assay after 6 months

at accelerated conditions. The results under long-term and intermediate storage conditions justify the

proposed shelf-life of 36 months with the storage condition “Do not store above 30°C”. A photostability

study has been performed in line with ICH topic Q1B. The results demonstrate that the drug product is

photostable when packed in the proposed clear transparent PVC/PVDC-Al blisters. Therefore, the

storage condition “Store in the original package in order to protect from light’ is also included for both

strengths.

Specific

measures

concerning

prevention

transmission

animal

spongiform

encephalopathies

A TSE declaration has been provided by the MAH for lactose monohydrate. It comes from milk of

healthy animals collected under the same conditions as milk suitable for human consumption.

Magnesium stearate is of vegetable origin.

II.4

Discussion on chemical, pharmaceutical and biological aspects

5/10

Based on the submitted dossier, the member states consider that Desogestrel/Ethinylestradiol Actavis

150/20 and 150/30 micrograms, film-coated tablets have a proven chemical-pharmaceutical quality.

Sufficient controls have been laid down for the active substance and finished product.

The following post-approval commitments were made:

The MAH committed to add at least one production batch, if manufactured, to the follow up

stability program yearly.

The MAH committed to continue the on-going stability studies with the 150/20 micrograms

strength on the first three development and bioequivalence batches up to at least 36 months.

The MAH committed to perform long-term stability studies up to at least 24 months on the first

three production batches of the 150/20 micrograms strength.

III.

NON-CLINICAL ASPECTS

III.1

Ecotoxicity/environmental risk assessment (ERA)

Since

Desogestrel/Ethinylestradiol Actavis is intended for generic substitution, this will not lead to an

increased exposure to the environment. An environmental risk assessment is therefore not deemed

necessary.

III.2

Discussion on the non-clinical aspects

These products are generic formulations of Mercilon and Marvelon, which are available on the

European market. Reference is made tot the preclinical data obtained with the innovator product. A

non-clinical overview on the pharmacology, pharmacokinetics and toxicology has been provided,

which is based on up-to-date and adequate scientific literature. The overview justifies why there is no

need

generate

additional

non-clinical

pharmacology,

pharmacokinetics

toxicology

data.

Therefore, the member states agreed that no further non-clinical studies are required.

IV.

CLINICAL ASPECTS

IV.1

Introduction

Desogestrel and ethinylestradiol are well-known active substances with established efficacy and

tolerability.

A clinical overview has been provided, which is based on scientific literature. The overview justifies

why there is no need to generate additional clinical data. Therefore, the member states agreed that no

further clinical studies are required.

IV.2

Pharmacokinetics

For this generic application, the MAH initially submitted one bioequivalence study in which the

pharmacokinetic profile of the test product Desogestrel/Ethinylestradiol Actavis 150/30 micrograms

(Actavis Group PTC ehf, Iceland) is compared with the pharmacokinetic profile of the reference

product Microdiol® 0.03/0.15 mg tablets (Merck Sharp & Dohme de España, S.A., Spain).

For the 150/20 micrograms product, the MAH initially applied for a biowaiver. This biowaiver could

however not be granted for the lower strength, as the reference products are based on different

dossiers (Mercilon and Marvelon). Moreover, the similarity of the in vitro dissolution profiles of the

150/20 micrograms strength with the 150/30 micrograms strength biobatch had not satisfactorily been

demonstrated.

Therefore,

decided

conduct

second

bioequivalence

study

with

Desogestrel/Ethinylestradiol Actavis 150/20 micrograms (Actavis Group PTC ehf, Iceland) versus

Suavuret® 0.02/0.15 mg tablets (Merck Sharp & Dohme de España, S.A., Spain).

The choice of the reference products in the bioequivalence studies has been justified by comparison

dissolution

results and compositions of

reference

products

different

member states.

analytical methods have been adequately validated and are considered acceptable for analysis of the

6/10

plasma samples. The methods used for the pharmacokinetic calculations and statistical evaluation are

considered acceptable.

The design and results of both studies are discussed below.

Bioequivalence studies

Study I – 150/20 micrograms

Design

A single-dose, randomised, two-period, two-treatment, two-sequence, crossover bioequivalence study

was carried out under fasted conditions in 60 healthy females of child bearing potential or non-post-

menopausal females with tubal ligation, aged 20-45 years. Each subject received a single dose

(150/20 micrograms) of one of the 2 desogestrel/ethinylestradiol formulations. There were 2 dosing

periods, separated by a washout period of 28 days.

Blood samples were collected pre-dose and at 0.3, 0.7, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12,

16, 24, 36, 48 and 72 hours after administration of the products.

Bioequivalence will be based on the active metabolite 3-keto-desogestrel.

Measurement of 3-keto-

desogestrel will be truncated at 72 hours as a result of its long half life.

The study design is acceptable. The sampling period and sampling scheme are adequate to properly

estimate pharmacokinetic parameters. Desogestrel is rapidly absorbed and completely converted into

3-keto-desogestrel. Measurement of the metabolite 3-keto-desogestrel is justified by the achievement

of non measurable plasma concentrations of the parent compound desogestrel in this study. Food

does not interact with the absorption of desogestrel and ethinylestradiol. A study under fasted

conditions is therefore sufficient.

Results

Fifty-six subjects were included in the statistical analyses. There was 1 subject who withdrew consent

and there were 2 subjects withdrawn due to impossibility to obtain blood samples and receiving

concomitant medication that could have impact on the pharmacokinetic profile of desogestrel. Another

subject was excluded from the analysis due to pre-dose levels of more than 5% of the C

reasons for drop-out are acceptable.

Table 1.

Pharmacokinetic parameters (non-transformed values; arithmetic mean ± SD, t

(median, range)) of ethinylestradiol under fasted conditions.

Treatment

N=56

AUC

0-72

pg.h/ml

AUC

0-∞

pg.h/ml

C

max

pg/ml

t

max

h

t

1/2

h

Test

463 ± 150

503 ± 166

45 ± 13

(1.0-2.5)

Reference

475 ± 164

514 ± 175

48 ± 16

(1.0-3.0)

*Ratio (90%

CI)

0.98

(0.95-1.01)

0.98

(0.95-1.02)

0.93

(0.90-0.96)

AUC

0-∞

area under the plasma concentration-time curve from time zero to infinity

AUC

0-72

area under the plasma concentration-time curve from time zero to 72 hours

C

max

maximum plasma concentration

t

max

time for maximum concentration

t

1/2

half-life

*ln-transformed values

Table 2.

Pharmacokinetic parameters (non-transformed values; arithmetic mean ± SD, t

(median, range)) of 3-keto-desogestrel under fasted conditions.

Treatment

N=56

AUC

0-72

pg.h/ml

AUC

0-∞

pg.h/ml

C

max

pg/ml

t

max

h

t

1/2

h

Test

9908 ± 3385

1421 ± 442

1.25

(1.0-4.0)

Reference

10471 ± 3499

1525 ± 433

7/10

(1.0-4.0)

*Ratio (90%

CI)

0.93

(0.91-0.97)

0.92

(0.87-0.97)

AUC

0-∞

area under the plasma concentration-time curve from time zero to infinity

AUC

0-72

area under the plasma concentration-time curve from time zero to 72 hours

C

max

maximum plasma concentration

t

max

time for maximum concentration

t

1/2

half-life

*ln-transformed values

Study II – 150/30 micrograms

Design

A single-dose, randomised, two-period, two-treatment, two-sequence, crossover bioequivalence study

was carried out under fasted conditions in 60 healthy females of childbearing potential or pre-

menopausal females with tubal ligation between 21 and 45 years of age. Each subject received a

single dose (150/30 micrograms) of one of the 2 desogestrel/ethinylestradiol formulations. There were

2 dosing periods, separated by a washout period of 28 days.

Blood samples were collected pre-dose and at 0.3, 0.7, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 12,

16, 24, 36, 48 and 72 hours after administration of the products.

Bioequivalence will be based on the active metabolite 3-keto-desogestrel. Measurement of 3-keto-

desogestrel is truncated at 72 hours as a result of its long half life.

The study design is acceptable. The sampling period and sampling scheme are adequate to properly

estimate pharmacokinetic parameters. Desogestrel is rapidly absorbed and completely converted into

3-keto-desogestrel. Measurement of the metabolite 3-keto-desogestrel is justified by the achievement

of non measurable plasma concentrations of the parent compound desogestrel in this study. Also the

fasted conditions are acceptable, as the product can be taken without reference to food intake.

Results

Fifty-eight subjects completed the study and were included in pharmacokinetic and statistical analysis.

The two drop-outs were a withdrawal during the first dosing period due to vomiting and 1 subject who

withdrew due to personal reasons before the start of the second period.

Table 3.

Pharmacokinetic parameters (non-transformed values; arithmetic mean ± SD, t

(median, range)) of ethinylestradiol under fasted conditions.

Treatment

N=58

AUC

0-t

pg.h/ml

AUC

0-∞

pg.h/ml

C

max

pg/ml

t

max

h

t

1/2

h

Test

710 ± 249

772 ± 356

69 ± 21

(1.0-2.5)

Reference

711 ± 215

754 ± 220

74 ± 22

(1.0-2.25)

*Ratio (90%

CI)

0.99

(0.95-1.03)

1.00

(0.95-1.05)

0.93

(0.89-0.96)

AUC

0-∞

area under the plasma concentration-time curve from time zero to infinity

AUC

0-t

area under the plasma concentration-time curve from time zero to 72 hours

C

max

maximum plasma concentration

t

max

time for maximum concentration

t

1/2

half-life

*ln-transformed values

Table 4.

Pharmacokinetic parameters (non-transformed values; arithmetic mean ± SD, t

(median, range)) of 3-keto-desogestrel under fasted conditions.

Treatment

N=58

AUC

0-t

pg.h/ml

AUC

0-∞

pg.h/ml

C

max

pg/ml

t

max

h

t

1/2

h

8/10

Test

9764 ± 3848

1340 ± 391

1.25

(0.7-3.0)

Reference

10229 ± 4526

1409 ± 490

(1.0-4.0)

*Ratio (90%

CI)

0.97

(0.94-0.99)

0.99

(0.91-1.04)

AUC

0-∞

area under the plasma concentration-time curve from time zero to infinity

AUC

0-t

area under the plasma concentration-time curve from time zero to 72 hours

C

max

maximum plasma concentration

t

max

time for maximum concentration

t

1/2

half-life

*ln-transformed values

Conclusion on bioequivalence studies:

The 90% confidence intervals calculated for AUC

and C

are within the bioequivalence acceptance

range of 0.80–1.25. Based on the submitted bioequivalence studies Desogestrel/Ethinylestradiol

Actavis 150/20 and 150/30 micrograms are considered bioequivalent with Microdiol® and Suavuret®

tablets, respectively.

There were no serious or significant adverse events reported during the studies. Both formulations

were well tolerated, with no major side effects.

The MEB has been assured that the bioequivalence studies have been conducted in accordance with

acceptable

standards

Good

Clinical

Practice

(GCP,

Directive

2005/28/EC)

Good

Laboratory Practice (GLP, see Directives 2004/9/EC and 2004/10/EC).

IV.3

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 Desogestrel/Ethinylestradiol Actavis 150/20

and 150/30 micrograms tablets.

The MAH has a pharmacovigilance system at their disposal, which is

based on the current European legislation.

The MAH has laid down the following safety concerns:

Important identified risks

Venous thromboembolism,

Arterial thromboembolism

Benign and malign liver tumours

Breast cancer, Cervical cancer

Effect on hereditary angioedema

Disturbances of liver function

Pancreatitis

Increased blood pressure

Important potential risks

Worsening of endogenous depression/depressed mood,

Crohn’s disease and ulcerative colitis

Important missing information

Routine pharmacovigilance activities will be applied. This is considered appropriate.

IV.4

Discussion on the clinical aspects

For this authorisation, reference is made to the clinical studies and experience with the innovator

products Mercilon and Marvelon. No new clinical studies were conducted. The MAH demonstrated

through a bioequivalence study that the pharmacokinetic profile of the product is similar to the

pharmacokinetic profile of this reference product.

Risk management is adequately addressed. This

generic medicinal product can be used instead of the reference product.

9/10

V.

USER CONSULTATION

The package leaflet has been evaluated via a user consultation study in accordance with the

requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The test consisted of a pilot test with

4 participants, followed by two rounds with 10 participants each. The questions covered the following

areas sufficiently: traceability, comprehensibility and applicability.

The results show that the package leaflet meets the criteria for readability as set out in the Guideline

on the readability of the label and package leaflet of medicinal products for human use.

VI.

OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND

RECOMMENDATION

Desogestrel/Ethinylestradiol Actavis 150/20 and 150/30 micrograms, film-coated tablets have a proven

chemical-pharmaceutical quality and are generic forms of Mercilon 0.02/0.15 mg and Marvelon

0.03/0.15 mg tablets. Mercilon and Marvelon are well-known medicinal products with an established

favourable efficacy and safety profile.

Bioequivalence has been shown to be in compliance with the requirements of European guidance

documents for both strengths.

The Board followed the advice of the assessors.

There was no discussion in the CMD(h). Agreement between member states was reached during a

written procedure. The member states, on the basis of the data submitted, considered that essential

similarity

been

demonstrated

Desogestrel/Ethinylestradiol

Actavis

150/20

150/30

micrograms, film-coated tablets with the reference products, and have therefore granted a marketing

authorisation. The decentralized procedure was finalised with a positive outcome on 15 September

2013 for the higher strength and on 11 February 2014 for the 150/20 micrograms strength.

10/10

STEPS TAKEN AFTER THE FINALISATION OF THE INITIAL PROCEDURE - SUMMARY

Scope

Procedure

number

Type of

modification

Date of start

of the

procedure

Date of

end of the

procedure

Approval/

approval

Assessment

report

attached

Public Assessment Report

Update

Benifema 150 Mikrogramm/30 Mikrogramm

Filmtabletten

DESOGESTREL, ETHINYLESTRADIOL

AT/H/0800/002

Former NL/H/2752/002

Date of RMS Splitting: 29.09.2017

This module reflects the procedural steps and scientific information after the finalisation

of the initial procedure.

Procedure number*

Scope

Product

Information

affected

Date of end

procedure

Approval/

approval

Summary/ Justification for

refuse

AT/H/0800/002/

RMS Splitting from NL/H/2752/002 to

AT/H/0800/002

29.09.2017

Approval

n.a.

AT/H/0800/002/R/001

Renewal procedure

12.04.2019

Approval

n.a.

*Only procedure qualifier, chronological number and grouping qualifier (when applicable)

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