panitaz 5, 10 and 20 micrograms/h transdermal patches

PAR Panitaz 5, 10 and 20 micrograms/h Transdermal Patches PL 08553/0564-0566

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Public Assessment Report

UKPAR

Panitaz 5 micrograms/h Transdermal Patches



(Buprenorphine)

UK Licence Number: PL 08553/0564-0566

Dr. Reddy’s Laboratories (UK) Ltd

.


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LAY SUMMARY Panitaz 5 micrograms/h Transdermal Patches



(Buprenorphine)

This is a summary of the Public Assessment Report (PAR) for Panitaz 5, 10 and 20 micrograms/h

Transdermal Patches (PL 08553/0564-0566). It explains how Panitaz 5, 10 and 20 micrograms/h

Transdermal Patches were assessed and their authorisation recommended, as well as the conditions of

use. It is not intended to provide practical advice on how to use Panitaz 5, 10 and 20 micrograms/h

Transdermal Patches.

These products will be referred to as Panitaz Patches in the remainder of this lay summary, for ease of

reading.

For practical information about using Panitaz Patches , patients should read the package leaflet or

contact their doctor or pharmacist.

What are Panitaz Patches and what are they used for?

Panitaz Patches are ‘hybrid generic medicines’. This means that they are similar to a reference medicine

containing the same active substance but are available in different pharmaceutical form, strength and

route of administration. The reference medicine for these products is Temgesic 400 microgram

sublingual tablets (Indivior UK Limited; PL 36699/0005).

Panitaz Patches are used to relieve moderate, longlasting pain that requires the use of a strong painkiller.

This medicine should not be used to relieve acute pain.

How do Panitaz Patches work?

Panitaz patches contain the active ingredient buprenorphine, which belongs to a group of medicines

called strong analgesics or ‘painkillers’. After application, buprenorphine passes through the skin into

the blood and helps to relieve moderate, longlasting pain.

How are Panitaz Patches used?

Panitaz patches should be applied in an area of non-irritated, intact skin of the upper arm, outer arm,

upper chest, upper back or side of the chest. Panitaz should be applied to a relatively hairless or nearly

hairless skin site. If none are available, the hair at the site should be cut with scissors. The application

site must be dry and clean.

The patient must always use this product exactly as their doctor has told them. The patient must check

with their doctor or pharmacist if they are not sure.

In adults and elderly patients, one Panitaz patch should be attached in an area of non-irritated, intact skin

and it should be changed every seventh day, preferably at the same time of day. A doctor may wish to

adjust the dose after 3-7 days until the correct level of pain control has been found. If a doctor advised

patients to take other painkillers in addition to the patch, patients should strictly follow the doctor’s

instructions, otherwise they will not fully benefit from the treatment. The patch should be worn for 3 full

days before increasing the dose; this is when the maximum effect of a given dose is established.

Panitaz patches should not be used in patients below the age of 18 years.


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In patients with kidney disease, no change in dose is necessary.

In patients with liver disease, the effects and period of action of the Panitaz patch may be affected and a

doctor will therefore check on patients more closely.

Patients should not apply more than two patches at the same time, regardless of the patch strength.

This medicine can only be obtained with a prescription from a doctor.

Please read section 3 of the package leaflet for detailed information on dosing recommendations, the

route of administration, and the duration of treatment.

What benefits of Panitaz Patches have been shown in studies?

Because Panitaz Patches are hybrid applications and are considered to be bioequivalent, to the reference

products, Norspan®

5, 10 and 20 micrograms/h transdermal patches, their benefits and risks are taken as

being the same as those of the reference medicines.

What are the possible side effects of Panitaz Patches?

Like all medicines, Panitaz Patches can cause side effects, although not everybody gets them.

The most common side effects with Panitaz Patches (which may affect more than 1 in 10 people) are

headache, dizziness, drowsiness, constipation, dry mouth, feeling or actually being sick, itchy skin,

redness and itching at application site.

The common side effects with Panitaz Patches (which may affect up to 1 in 10 people) are loss of

appetite, confusion, depression, difficulty in sleeping, nervousness, tingling or numbness, flushing of the

skin, shortness of breath, abdominal pain or discomfort, diarrhoea, indigestion, sweating, rash, skin

eruptions, tiredness, a feeling of unusual weakness, muscle weakness, pain, chest pain, swelling of

hands, ankles or feet and redness or rash at the application site.

For the full list of all side effects reported with Panitaz Patches, see section 4 of the package leaflet. For

the full list of restrictions, see the package leaflet.

Why was Panitaz Patches approved?

The MHRA decided that the benefits of Panitaz Patches are greater than their risks and recommended

that they are approved for use.

What measures are being taken to ensure the safe and effective use of Panitaz Patches?

A risk management plan (RMP) has been developed to ensure that Panitaz Patches are used as safely as

possible. Based on this plan, safety information has been included in the Summaries of Product

Characteristics and the package leaflet for Panitaz Patches including the appropriate precautions to be

followed by healthcare professionals and patients.

Known side effects are continuously monitored. Furthermore new safety signals reported by

patients/healthcare professionals will be monitored/reviewed continuously.

Other information about Panitaz Patches

The MHRA agreed to grant Marketing Authorisations for Panitaz Patches on 15 June 2016.

The full PAR for Panitaz Patches follows this summary. For more information about treatment with

Panitaz Patches, read the package leaflet, or contact your doctor or pharmacist.


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This summary was last updated in August 2016.


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TABLE OF CONTENTS

I Introduction Page 6

II Quality aspects Page 7

III Non-clinical aspects Page 9

IV Clinical aspects Page 9

V User consultation Page 15

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 15

Table of content of the PAR update Page 22


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I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products

Regulatory Agency (MHRA) granted Dr. Reddy’s Laboratories (UK) Ltd, Marketing Authorisations for

the medicinal products Panitaz 5, 10 and 20 micrograms/h Transdermal Patches (PL 08553/0564-0566).

These products are prescription only medicines (POM), used in the treatment of non-malignant pain of

moderate intensity when an opioid is necessary for obtaining adequate analgesia.

Panitaz is not suitable for the treatment of acute pain.

These applications were submitted under Article 10(3) of Directive 2001/83/EC, as amended, as hybrid

applications. The applications represent a change in pharmaceutical form, strength and route of

administration with respect to the reference product. The applicant has cross-referred to Temgesic 400

microgram sublingual tablets which were originally authorised to Reckitt & Colman (PL 00044/0109)

on 25 October 1990. Following change of ownerships this reference licence was authorised to Reckitt

Benckiser Healthcare (UK) Limited (PL 00063/0009) on 24 April 1995, then to Schering-plough

Limited (PL 00201/0244) on 20 May 1998 and to the current Marketing Authorisation Holder (MAH),

Indivior UK Limited (PL 36699/0005), on 29 September 2010.

As the pharmaceutical form of Panitaz 5, 10 and 20 micrograms/h Transdermal Patches differs from the

reference product, Temgesic 400 microgram sublingual tablets, Norspan®

transdermal patches were used

for the assessment of bioavailability (Norspan®

20 micrograms/h transdermal patches) and adhesion

performance (Norspan®

5 micrograms/h transdermal patches) of the products.

Panitaz patches contain the active ingredient buprenorphine, which is a partial agonist opioid, acting at

the mu opioid receptor. It also has antagonistic activity at the kappa opioid receptor.

The applicant has submitted two pivotal bioequivalence studies and an adhesion performance study with

these applications. The bioequivalence studies were conducted in line with the guideline on the

pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CHMP/EWP/280/96

Rev. 1).

With the exception of the above studies, no new non-clinical or clinical data were submitted, which is

acceptable given that these applications were based on the products being bioequivalent to originator

products that have been in clinical use for over 10 years.

The Marketing Authorisation holder has provided adequate justification for not submitting an

Environmental Risk Assessment (ERA).

A Risk Management Plan (RMP) and summary of the pharmacovigilance system have been provided

with these applications, and are satisfactory.

No new or unexpected safety concerns arose during the review of information provided by the

Marketing Authorisation Holder and it was, therefore, judged that the benefits of taking Panitaz 5, 10

and 20 micrograms/h Transdermal Patches outweigh the risks and Marketing Authorisations were

granted.


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II QUALITY ASPECTS

II.1 Introduction

The products are described as a transdermal delivery device containing buprenorphine in a matrix

system. It is composed of a drug-containing patch, and an oversized, beige coloured overtape. Each

transdermal patch contains 5 mg, 10 mg or 20 mg buprenorphine, as active ingredient.

Other ingredients consist of the pharmaceutical excipients:

Adhesive matrix (containing buprenorphine):

povidone K90

levulinic acid

oleyl oleate

Poly[acrylic acid-co-butylacrylate-co-(2-ethylhexyl)acrylate-co-vinylacetate] (5:15:75:5)

Adhesive matrix (without buprenorphine):

Poly[(2-ethylhexyl)acrylate-co-glycidylmethacrylat-co-(2-hydroxyethyl)acrylate-co-vinylacetate]

(68:27:5:0,15)

Separating foil between adhesive matrices with and without buprenorphine: polyethylene terephthalate

(PET) film

Backing web: polyester

Release liner: PET film (to be removed before applying the patch)

Blue printing ink

All excipients comply with their respective European Pharmacopoeia monographs with the exception of

oleyl oleate which complies with the United States Pharmacopeia (USP) National Formulary as well as

with the German Pharmacopoeia (DAB). In addition, levulinic acid, acrylate polymers, polyester web

and PET film comply with in house specifications. Satisfactory Certificates of Analysis have been

provided for all excipients. Suitable batch analysis data have been provided for each excipient.

None of the excipients contain materials of animal or human origin.

No genetically modified organisms (GMO) have been used in the preparation of these products.

Each child-proof sachet is made of a composite layer material consisting of paper/PET/ polyethylene

(PE)/aluminium/surlyn. One sachet contains one transdermal patch. Each pack contains 4 individually

sealed transdermal patches.

Satisfactory specifications and Certificates of Analysis have been provided for all packaging

components.

II.2. Drug Substance

INN: Buprenorphine

Chemical name: [5-alpha, 7-alpha (S)]-6,14-ethanomorphinan-7-methanol, 17-(cyclopropyl-

methyl)-alpha-(1,1-dimethyl)-4,5-epoxy- 18,19-dihydro-3-hydroxy-6-

methoxy-alpha-methyl

(2S)-2-[17-cycloproylmethyl)-4,5-alpha-epoxy-3- hydroxy-6-methoxy-6-

alpha,14-ethano-14-alpha- morphinan-7-alpha-yl]-3,3-dimethylbutan-2-ol


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Structural formula:

Molecular formula: C29H41NO4

Molecular mass: 467.6 g/mol

Appearance: White or almost white crystalline powder.

Solubility: Buprenorphine is very slightly soluble in water; freely soluble in acetone; soluble

in methyl alcohol; slightly soluble in cyclohexane. Also dissolves in dilute

solutions of acids (Ph.Eur. monograph).

Buprenorphine is the subject of a European Pharmacopoeia monograph.

All aspects of the manufacture and control of the active substance, buprenorphine, are covered by the

European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability.

II.3. Medicinal Product

Pharmaceutical Development

The objective of the development programme was to develop a drug product equivalent to the

formulation of the innovator product in qualitative and quantitative composition comprising a drug-

containing matrix patch with a desired drug release profile and an overtape with adequate adhesion

properties. A satisfactory account of the pharmaceutical development has been provided.

Comparative in vitro skin permeation experiments were conducted and comparable permeation profiles

were obtained in all experiments.

Comparative dissolution profiles have been presented for the proposed and reference products.

Manufacture of the products

Satisfactory batch formulae have been provided for the manufacture of the products, along with an

appropriate account of the manufacturing processes. The manufacturing processes have been validated at

production scale and have shown satisfactory results.

Finished Product Specifications

The finished product specifications proposed are acceptable. The test methods have been described that

have been adequately validated. Batch data have been provided that comply with the release

specifications. Certificates of Analysis have been provided for all working standards used.

Stability of the Products

Finished product stability studies were performed in accordance with current guidelines on batches of

finished product in the packaging proposed for marketing. The data from these studies support a

shelf-life of 21 months (5 and 10 micrograms/h transdermal patches) and 30 months (20 micrograms/h

transdermal patch) with a storage condition “Do not store above 25°C”.

Suitable post approval stability commitments have been provided to continue stability testing on batches

of finished products.


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II.4 Discussion on chemical, pharmaceutical and biological aspects

There are no objections to the approval of these applications from a pharmaceutical viewpoint.

III NON-CLINICAL ASPECTS III.1 Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties of buprenorphine are

well-known, no new non-clinical studies are required and none have been provided. An overview based

on the literature review is, thus, appropriate.

The Marketing Authorisation Holder’s (MAH’s) non-clinical expert report has been written by an

appropriately qualified person and is satisfactory, providing an appropriate review of the relevant non-

clinical pharmacology, pharmacokinetics and toxicology.

III.2 Pharmacology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.3 Pharmacokinetics


III.4 Toxicology


III.5 Ecotoxicity/environmental risk assessment (ERA)

Since Panitaz 5, 10 and 20 micrograms/h Transdermal Patches are intended for generic substitution, their

use will not lead to an increased exposure to the environment. An environmental risk assessment is

therefore not deemed necessary.

III.6 Discussion on the non-clinical aspects

There are no objections to the approval of these applications from a non-clinical viewpoint.

IV CLINICAL ASPECTS IV.1 Introduction

The clinical pharmacology of buprenorphine is well-known. With the exception of data from the

bioequivalence studies and an adhesion performance study detailed below, no new pharmacodynamics

or pharmacokinetic data are provided or required for these applications.

No new efficacy or safety studies have been performed and none are required for this type of

application. A comprehensive review of the published literature has been provided by the applicant,

citing the well-established clinical pharmacology, efficacy and safety of buprenorphine.

Based on the data provided, Panitaz 5, 10 and 20 micrograms/h Transdermal Patches can be considered

bioequivalent to Norspan®

5, 10 and 20 micrograms/h transdermal patches (Mundipharma GmbH).

IV.2 Pharmacokinetics

In support of these applications, the applicant submitted two pivotal bioequivalence studies and an

adhesion performance study. Bioequivalence between the test and the reference patches with respect to

the rate and extent of buprenorphine exposure after single and multiple dose applications for the highest

strengths (20 micrograms/h) were invstigated. In addition to the bioavailability study, adhesive

behaviour of the applicant’s product was demonstrated with Norspan 5 micrograms/h transdermal patch.


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Single Dose Study

This is an open label, randomised, two-period, two-way, crossover, single dose pivotal

bioequivalence study to assess the bioequivalence, skin tolerance and adhesion performance of

Buprenorphine 20 micrograms/h transdermal patch and the reference product, Norspan®

20

micrograms/h transdermal patch, in healthy adult volunteers.

In this single dose study, 27 adult subjects received a single application of the test or the reference patch.

Following application, patches were removed after 168 hours and patients were hospitalised for 192

hours. Blood samples were collected for the pharmacokinetic comparison for 288 hours after

administration in each study period. The two applications were separated by a wash out period of 15

days.

Primary efficacy parameters, secondary parameter and %extrapolated AUC, AUC0-84.5, AUC84.5-t, T1/2,

and MRT were evaluated as additional equivalence criteria.

Results

Table 1: Pharmacokinetic parameters of buprenorphine following single application of a 20

micrograms/h transdermal patch

No significant differences in pharmacokinetic parameters were observed between the drug formulations.

Ratios and 90% confidence limits for all primary parameters were within the pre-defined acceptance

criteria specified in “Guideline on the Investigation of Bioequivalence” (CPMP/EWP/QWP/1401/98

Rev 1/ Corr**). No significant differences between the secondary parameters were observed.

Adhesion performance and skin tolerance were evaluated as further parameters in this study. Adhesion

performance was scored using an 11-point scale (from 0 = < 50% adhesion to 10 = > 95% adhesion)

according to the Draft Guideline on Quality of Transdermal Patches (EMA/CHMP/QWP/911254/2011).

Cumulative adhesion scores (CAS) were calculated by subject and treatment over the last 24 hours

before patch removal. In order to demonstrate non-inferiority of the test versus reference, for the mean

CAS, 90% confidence interval for the difference between the CAS of Test and CAS of Reference were

calculated (see table 2).

Table 2: Mean cumulative adhesion score (CAS) analysis

As the lower limit of the 90% CI of the test (mean CASTEST - 0.8 x mean CASREFERENCE) is ≥ 0, non-inferiority can be

concluded.

The test formulation is non-inferior to the reference product with regard to adhesion performance. Mean

adherence was higher than 90% for both test and reference formulations thus demonstrating that skin

adhesion of the two study products is similar and at the same time qualitatively adequate.


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Skin tolerance was assessed at the end of the application period using an 8-point scoring system and

photographic documentation. The volunteer´s own subjective opinion regarding tolerability was scored

by the subject using a 4-point scale.

Skin irritation was generally slight and similar after both treatments, with a mean total score of 8.63 for

the test and 7.85 for the reference. A one-sided t test was performed in order to show non-inferiority of

the test to the reference (see table 3).

Table 3: Total objective irritation score analysis

As the upper limit of the 90% CI of the test (mean TEST – 1.25 x mean REFERENCE) is ≤ 0, non-inferiority can be

concluded.

The analysis of the subject’s subjective score supports the conclusion that no statistically significant

difference between the formulations can be identified with respect to the subjects’ opinions on safety or

tolerability of the two patch formulations.

Both products were well tolerated. No deaths or serious adverse events occurred during the study period.

42 (10 mild and 32 moderate) systemic adverse events were reported by 16 subjects. Subjects fully

recovered from all adverse events by the end of the study. No other clinically relevant adverse events or

laboratory changes occurred. No subject’s vital signs and electrocardiograms (ECGs) were abnormal at

the end of the study period.

Conclusion

No significant difference in the pharmacokinetic parameters was detected between the formulations.

Statistical analysis of the pharmacokinetic data proved that Buprenorphine 20 μg/h transdermal patch

and the reference product, Norspan® 20 μg/h transdermal patch, are bioequivalent after a single dose.

Analysis of adhesion scores confirmed the non-inferiority of the test buprenorphine formulation with

respect to adhesion performance. Both formulations were well tolerated. Analysis of objective and

subjective skin irritation scores obtained during the study confirmed the non-inferiority of the test

product to reference product following single application.

Multiple Dose Study

This is an open, randomised, two-period, crossover, multiple dose pivotal bioequivalence study to

assess the bioequivalence, skin tolerance and adhesion performance of Buprenorphine 20

micrograms/h transdermal patch and the reference product, Norspan®

20 micrograms/h

transdermal patch, in healthy adult volunteers.

In this multiple-dose study, 32 healthy male subjects were randomised to receive test or reference patch

for three consecutive applications of 168 hours. Each individual patch was separated with a washout

period of 18 days between removal of the last patch of the first period and the first application of the

second period.

In each period, blood samples were collected for the pharmacokinetic comparison up to 504 hours post

first application of the period. Primary efficacy parameters were (AUC0-tau)ss, Cmax.ss and Cmin.ss, Tmax.ss,

Cav.ss and peak trough fluctuation (%PTF) were evaluated as secondary criteria. 21 subjects were

included in the statistical analysis of pharmacokinetic data.


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Table 4: Pharmacokinetic parameters of buprenorphine following multiple application of a 20

micrograms/h transdermal patch

No significant differences in pharmacokinetic parameters were observed between the drug formulations.

Ratios and 90% confidence limits for all primary parameters were within the pre-defined acceptance

criteria specified in “Guideline on the Investigation of Bioequivalence” (CPMP/EWP/QWP/1401/98

Rev 1/ Corr**). No significant differences between the secondary parameters were observed.

Skin tolerance was assessed at the end of the application period of the first and second patch (168 hours

each). For the third patch skin tolerance was assessed at 168 hours, 168 hours 5 minutes and 170 hours

after application. Skin tolerance was measured using an 8-point scoring system and photographical

documentation. The volunteer’s subjective tolerability assessment was scored using a 4-point scale. Skin

irritation was generally slight and similar after both treatments, with a mean score of 10.63 for the test

and 11.33 for the reference assessed for the third patch application. A one-sided t-test was performed in

order to show non-inferiority of the test to the reference (table 5).


As the upper limit of the 90% CI of the test (mean TEST – 1.25 x mean REFERENCE) is ≤ 0, non inferiority can be

concluded.

The analysis of the subject’s subjective score supports the conclusion that no statistically significant

difference between the formulations can be identified with respect to the subjects’ opinions on safety

and tolerability of the two patch formulations.

The test and reference products were well tolerated. No deaths or serious adverse events occurred during

the study period. 23 systemic adverse events were reported by 15 subjects. They were mild (7) or

moderate (15) in nature. The intensity of one event could not be verified. All known adverse events were

recovered at the end of study. No other clinically relevant adverse events or laboratory changes

occurred. No subject’s vital signs and ECGs were abnormal at the end of the study period.

Conclusion

No significant difference in the pharmacokinetic parameters was detected between the formulations.

Statistical analysis of the pharmacokinetic data proved that Buprenorphine 20 microgram/h transdermal

patch and Norspan® 20 microgram/h transdermal patch are bioequivalent at steady state.


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Satisfactory justification is provided for a biowaiver of the applicant’s 5 and 10 microgram/h

transdermal patches. As Panitaz 5, 10 and 20 micrograms/h Transdermal Patches meet the criteria

specified in the “for Guidance on modified release oral and transdermal dosage forms, section II

(pharmacokinetic and clinical evaluation) (CPMP/EWP/280/96, 28 July 1999) for a Transdermal

Delivery System (TDS), the results and conclusions of the bioequivalence studies for 20 microgram/h

transdermal patch formulation can be extrapolated to the other strengths, i.e. 5 and 10 microgram/h

transdermal patches.

Adhesion study of 5 microgram/h transdermal patch

This is an open, one-period, two-treatment, parallel administration, single dose pivotal study to

assess adhesion performance of Buprenorphine 5 microgram/h transdermal patches versus

Norspan® 5 microgram/h transdermal patch reference products in healthy adult volunteers.

In this adhesion performance study, 32 healthy subjects received the test and reference patch at about the

same time (one left, one right side) for 168 hours. The assignment of the application site was random. A

visual estimation (including photography) of patch detachment was performed immediately after

application and up to and including 167 hours 56 minutes, following application for both patches. All

subjects completed the study and were included in the statistical analysis.

The patch detachment was depicted on a transparent grid pattern by visual identification of areas where

lift-off occurred. According to the Draft Guideline on Quality of Transdermal Patches

(EMA/CHMP/QWP/911254/2011) detachment percentages calculated for each time point were

converted in to adhesion scores (0-10) at 5% steps. Cumulative adhesion scores (CAS) for statistical

analyses were performed over the last 24 hours before patch removal. In order to demonstrate non-

inferiority of the test versus reference, for the mean CAS, 90% confidence interval for the difference

between the CAS of test and CAS of reference was calculated. Statistical analysis demonstrated non-

inferiority of the test product compared with the reference product (table 6).

Table 6: Mean cumulative adhesion score (CAS) analysis

Non-inferiority is proven if the lower limit of the 95% CI for the test (mean CASTEST-0.8 x mean CASREFERENCE) is ≥ 0

Mean patch adhesion was higher than 90% for both study products (90.79% for reference and 91.84%

for test product).

Skin irritation during the study course (0 to 168 hours) was evaluated by visual assessment by the

physician using an 8-point scoring system and photographical documentation. Subjective tolerance was

estimated by the subject using a 4-point scale.

The test and reference products caused equal skin irritation during the dosing interval. Mean scores for

test and reference at the end of treatment were 10.66 and 10.25, respectively. There were no significant

differences between the products with respect to total objective skin irritation scores or in the subjective

irritation scores. The results of the tolerance estimation are given in table 7.


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As the upper limit of the 90% CI of the test (mean TEST – 1.25 x mean REFERENCE) is ≤ 0, non-inferiority can be

concluded.

The analysis of the subject’s subjective score supported the conclusion that no statistically significant

difference between the formulations can be identified with respect to the subjects’ opinions on safety or

tolerability of the two patch formulations.

Systemic Tolerance:

No serious adverse events were reported during the study course. 12 systemic adverse events of mild

intensity and 13 of moderate intensity occurred in 13 subjects during the study course. All subjects

recovered before the end of the study. No clinically relevant changes in vital signs or laboratory

parameters were observed.

Conclusion

It can be concluded that both study products showed adhesion performance that is superior to minimum

requirement of the Draft Guideline on Quality of Transdermal Patches

(EMA/CHMP/QWP/911254/2011), which states that a mean adhesion of greater than 90% is

satisfactory. With respect to area under the adhesion percentage curve and mean patch adhesion,

equivalence of test and reference was confirmed. A statistical analysis of the study data revealed non-

inferiority of the test patches as compared with the reference patch.

Both products were generally well tolerated. Statistical analysis of objective and subjective irritation

scores proved that the test formulation is non-inferior to the reference formulation.

IV.3 Pharmacodynamics

No new pharmacodynamic data were submitted and none were required for applications of this type.

IV.4 Clinical efficacy

No new efficacy data were submitted and none were required for applications of this type.

IV.5 Clinical safety

No new safety data were submitted and none were required for applications of this type.

IV.6 Risk Management Plan (RMP)

The Marketing Authorisation Holder (MAH) has submitted a risk management plan (RMP), 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 Panitaz 5, 10 and 20 micrograms/h Transdermal Patches.


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A summary of safety concerns and planned risk minimisation activities, as approved in the RMP,

is listed below:

Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns.

IV.7 Discussion on the clinical aspects

There are no objections to the approval of these applications from a clinical viewpoint.

The grant of Marketing Authorisations is recommended for these applications.

V User consultation A user consultation with target patient groups on the patient information leaflet (PIL) has been

performed on the basis of a bridging report making reference to BuTrans®

M 5, 10 and 20

micrograms/hour transdermal patches (DK/H/718/001-003/MR). The bridging report submitted by the

applicant is acceptable.

VI Overall conclusion, benefit/risk assessment and recommendation The quality of the products is acceptable, and no new non-clinical or clinical concerns have been

identified. Extensive clinical experience with buprenorphine is considered to have demonstrated the

therapeutic value of the compound. The benefit-risk is, therefore, considered to be positive.


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Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels

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.

The approved labelling for Panitaz 5, 10 and 20 micrograms/h Transdermal Patches is presented below:


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Table of content of the PAR update

Steps taken after the initial procedure with an influence on the Public Assessment Report (Type II

variations, PSURs, commitments)

Date

submitted

Application

type

Scope Outcome

panitaz 5, 10 and 20 micrograms/h transdermal patches

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