Traisengasse 5, 1200 Wien

CMDh/223/2005
February 2014

Public Assessment Report

Scientific discussion

Soventol Hydrocortisonacetat 0,25 % Creme,

Soventol Hydrocortisonacetat 0,5 % Creme

HYDROCORTISONE ACETATE

AT/H/1221/001-002/DC

Date: November 2022

This module reflects the scientific discussion for the approval of Soventol
Hydrocortisonacetat 0,25 % Creme, Soventol Hydrocortisonacetat 0,5 % Creme. The
procedure was finalised on 03.10.2022. For information on changes after this date, please
refer to the module ‘Update’.

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I. INTRODUCTION

Based on the review of the quality, safety and efficacy data, the Member States have granted a
marketing authorisation for Soventol Hydrocortisonacetat 0,25 % Creme, Soventol
Hydrocortisonacetat 0,5 % Creme, from Medice Pharma GmbH & Co. KG.

The product is indicated for the treatment of moderately severe, erythematous, inflammatory or
allergic skin conditions in adults and children above 6 years of age, for which low potency, low
concentration corticosteroids are indicated.
A comprehensive description of the indications and posology is given in the SmPC.
Hydrocortisone acetate is a topical corticosteroid belonging to the weak class I corticosteroids acting
locally in the skin. It is a synthetic derivative of the natural adrenal hormone hydrocortisone and has a
mild anti-inflammatory effect.
In general, topical corticosteroids can be absorbed by normal intact skin. In case of inflammation or
other skin diseases where the keratin layer is negatively affected percutaneous absorption increases.
The applied products contain hydrocortisone acetate in a low concentration and potency of 0.25 % and
0,5 % to treat moderately severe inflammatory and allergic skin conditions. Therefore, their indication is
focused on the relief of inflammatory and pruritic manifestations of corticosteroid-responsive
dermatoses.
The active substance is a well-established compound used for decades in dermatology and can be
found on the European market in several products.
The marketing authorisation has been granted pursuant to Article 10(3) of Directive 2001/83/EC.

II. QUALITY ASPECTS

II.1 Introduction
Soventol Hydrocortisonacetat is a cream which is presented in aluminium tubes with 20 g, 30 g or
50 g cream (0.25 % strength) and 15 g, 20 g, 30 g cream (0.5 % strength), respectively.

II.2 Drug Substance

The active substance in Soventol Hydrocortisonacetat is hydrocortisone acetate. The specification of
the active substance meets the current scientific requirements. The adequate quality of the active
substance has been shown by submitting the appropriate control data. The stability of the active
substance has been tested under ICH conditions. The results of the stability studies support the
established retest-period.

II.3 Medicinal Product

Soventol Hydrocortisonacetat contains the following excipients:
Purified water, isopropyl alcohol, decyl oleate, macrogol 400, isopropyl myristate, paraffin liquid,
Carbopol 1382 polymer, perfume oil, ammonia solution conc. (25%) for pH adjustment, disodium
edetate
The development of the product has been sufficiently made and deemed appropriate. The usage of all
the excipients has been described.
The release specification includes the check of all parameters relevant to this pharmaceutical form.
Appropriate data concerning the control of the finished product support the compliance with the
release specifications.
The packaging of the medicinal product complies with the current legal requirements.
Stability studies under ICH conditions have been performed and data presented support the shelf life
claimed in the SmPC, with a shelf life of 3 years when stored below 25°C. The pharmaceutical quality
of Soventol Hydrocortisonacetat has been adequately shown.

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II.4 Discussion on chemical, pharmaceutical and biological aspects

Information on development, manufacture and control of active substance and medicinal product has
been presented in a satisfactory manner. The results of tests carried out indicate satisfactory
consistency and uniformity of important product quality characteristics.

III. NON-CLINICAL ASPECTS

III.1 Introduction
Pharmacodynamic, pharmacokinetic and toxicological properties of hydrocortisone acetate are well
known. As hydrocortisone acetate is a widely used, well-known active substance, the applicant has
not provided additional studies and further studies are not required. Overview based on literature
review is, thus, appropriate.

III.2 Ecotoxicity/environmental risk assessment (ERA)

Since Soventol Hydrocortisonacetat 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.
The applicant submitted data on the Environmental Risk Assessment of hydrocortisone acetate for the
strengths of 0,25 % and 0,5 % of Phase I (estimation of exposure) and Phase II (environmental fate and
effects analysis).
Summary of main study results
Substance (INN/Invented Name): hydrocortisone acetate

PBT screening Result Conclusion

Bioaccumulation potential - log REACH 2.21 Potential PBT: No
Kow
PBT-assessment – N/A
Phase I
Calculation Value Unit Conclusion
PEC surface water , default or refined 0.0058 g/L > 0.01 threshold:
(e.g. prevalence, literature) No
Other concerns (e.g. chemical No
class)
Phase II Physical-chemical properties and fate
Study type Test protocol Results Remarks
Ready Biodegradability Test OECD 301 69 % hydrocortisone
acetate is readily
bio-degradable
following OECD
301B/EU C.4-C.

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Phase II: Environmental Fate and Effects analysis

Ready biodegradability of hydrocortisone acetate was investigated in a study following OECD guideline
301B and EU method C.4-C.
The test item hydrocortisone acetate was tested using a concentration of nominally 20 mg organic
carbon/l (corresponding to 29.3 mg hydrocortisone acetate /l) in test medium. Aniline was chosen as
positive control. Activated sludge was used as inoculum (concentration in the test 25.0 mg dry
matter/l). The test was left running for 28 days. All validity criteria were met. Degradation of the
positive control was 63 % after 7 days. The following data were determined for the test item
hydrocortisone acetate:
10-day-window: day 5 — 15
degradation at the end of 10-day-window: 69 %
degradation at the end of the test: 78 %
pass level following guideline: 60 % at the end of 10-day-window for pure substances respective
60 % at the end of the test for mixtures
Therefore, when applying the 10-day-window, hydrocortisone acetate is readily bio-degradable
following OECD 301B/EU C.4-C.
Hence, it can be assumed that most of the hydrocortisone acetate from drug products will be
degraded in the sewage treatment plant and only negligible amounts of hydrocortisone acetate will
enter the environment where it will be degraded in a short time. Therefore, further investigations on
environmental fate and effects of hydrocortisone acetate are considered not necessary.
Since Soventol Hydrocortisonacetat 0,25 %/ 0,5 % are intended for generic substitution, this will not
lead to an increased exposure to the environment.
Conclusions on studies:
Hydrocortisone acetate PEC surface water value is below the action limit of 0.01 µg/L and is not a PBT
substance as log Kow does not exceed 4.5.

III.3 Discussion on the non-clinical aspects

The non-clinical overview on the pre-clinical pharmacology, pharmacokinetics and toxicology is
adequate.

IV. CLINICAL ASPECTS

IV.1 Introduction
The clinical pharmacodynamics, pharmacokinetics, efficacy and safety of hydrocortisone acetate are
well known.
Three clinical studies were submitted by the applicant. All of them were no currently performed trials.
Study 1: “Analysis of the efficacy of a 0.5 % hydrocortisone acetate containing cream compared to a
reference product, a placebo and a higher and lower potential corticoid in a monocentric, randomized,
double-blind phase I clinical vasoconstrictor study with an intraindividual comparison in a panel of 33
subjects with healthy skin at the test areas.”
Study 2: “A 41 day, randomized, monocentric, double-blind, phase I clinical study for the exclusion of
a sensitization potential and investigation of irritation potential of a hydrocortisone acetate containing
cream (0.5 % hydrocortisone acetate) and placebo in a human repeated epicutaneous (insult) patch
test (HRIPT) design in a panel of 55 healthy subjects.”
Study 3: “A phase II, multi-center, randomized, double-blind trial with intraindividual comparison to
assess superiority of topically applied Soventol HydroCort 0.5 % Cremogel versus vehicle on lesional
skin in patients with mild atopic eczema, seborrheic eczema or stasis dermatitis and to assess safety
of Soventol HydroCort 0.5 % Cremogel.”

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Because of the submission of a letter of identification during clock-stop phase, those trials should be
seen as supportive data, only. Due to the equality of the test and reference product, there is no need
to demonstrate therapeutic equivalence and safety by clinical studies.
The dossier contains an adequate review of published literature concerning aspects of pharmacology,
pharmacodynamics, efficacy and safety of hydrocortisone acetate.

IV.2 Pharmacodynamics
Pharmacotherapeutic group:
Corticosteroid, dermatological preparation, Corticosteroids, weak (group I)
ATC code: D07AA02

IV.3 Clinical efficacy and safety

The indications claimed are in accordance with those of the reference product Soventol
Hydrocortisonacetat 0,25 % Creme and Soventol Hydrocortisonacetat 0,5 % Creme, from MEDICE
Pharma GmbH & Co. KG (authorised in Germany).
During clock stop a letter of identification has been submitted. Due to the equality of the test and
reference product, there is no need to demonstrate therapeutic equivalence and safety by clinical
studies.

IV.4 Risk Management Plan and Summary of the Pharmacovigilance System Master
File
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 Soventol Hydrocortisonacetat 0,25 %
Creme and Soventol Hydrocortisonacetat 0,5 % Creme.
Summary table of safety concerns as approved in RMP
Important identified risks None
Important potential risks None
Missing information None
-
Summary of the Pharmacovigilance System Master File
The applicant submitted the summary of the pharmacovigilance system in the scope of this
procedure.
The summary includes the following elements:
 Proof that the applicant has at his disposal a qualified person responsible for
pharmacovigilance
 The Member States in which the qualified person resides and carries out his/her tasks
 The contact details of the qualified person
 A statement signed by the applicant to the effect that the applicant has the necessary means
to fulfil the tasks and responsibilities listed in Title IX of Directive 2001/83/EC

IV.5 Discussion on the clinical aspects

The clinical overview on the clinical pharmacology, efficacy and safety is adequate.

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 language used for the purpose
of user testing the PIL was English.

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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.
The test consisted of a pilot test with 3 test subjects and two rounds with 10 participants each.
Recruitment method, inclusion and exclusion criteria are well defined and acknowledged. The
questions covered the following areas sufficiently: traceability, comprehensibility and applicability.

VI. OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION

The pharmaceutical quality of Soventol Hydrocortisonacetat has been adequately shown, and no new
non-clinical or clinical concerns have been identified. From a clinical point of view, equality of the test
and the reference product has been demonstrated by the submission of a letter of identification by
the applicant during clock-stop phase.
The benefit/risk relation is considered positive.

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Public Assessment Report

Update

Soventol Hydrocortisonacetat 0,25 % Creme,

Soventol Hydrocortisonacetat 0,5 % Creme

HYDROCORTISONE ACETATE

AT/H/1221/001-002/DC

This module reflects the procedural steps and scientific information after
the finalisation of the initial procedure.

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Procedure Scope Product Information Date of end of Approval/ Summary/ Justification for refuse
number* affected procedure non approval

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