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WHOPAR GUIDANCE for APPLICANTS v 2.4

Guidance note to Applicants on the compilation of the WHO Public Assessment Report

(WHOPAR)

1. Purpose of Guidance

To provide background information on the WHO Public Assessment Report (WHOPAR) and to

provide detailed guidance to Applicants on the documentation required for the WHOPAR as part of

the submission of a product dossier to WHO for assessment under the WHO Prequalification

Programme1.

Note: This guidance should be seen in addition to the existing submission requirements as published

on the website of the Prequalification Programme. It addresses only those requirements related

to documentation necessary in support of a WHOPAR.

2. WHO Public Assessment Report

The purpose of the WHOPAR is to promote the most possible transparency on the procedure

following the assessment of a finished pharmaceutical product (FPP) for possible inclusion in the List

of prequalified products and manufacturers. In addition, the WHOPAR aims at providing relevant

information on the products quality, efficacy and safety. Also, the inspection status will be reflected

in the WHOPAR.

Publication of WHOPARs is based on Resolution WHA57.142

of 22 May 2004 in which the Director

General of WHO requests under point 3.(4):

to ensure that the prequalification review process and the results of inspection and

assessment reports of the listed products, aside from proprietary and confidential information,

are publicly available.

WHOPARs are published on the WHO Prequalification website3.

The structure and format of the WHOPAR are adapted from the European Public Assessment Report

(EPAR)4

as published by the European Medicines Evaluation Agency (EMEA)5

to best serve the

requirements of the WHO prequalification procedure.

The development of a WHOPAR will follow the steps set forth below:

2.1 Procedure

Step 1. The applicant submits documents required for the WHOPAR as part of the initialsubmission to WHO;

Step 2. WHO compiles the draft WHOPAR when the assessment is completed;Step 3. WHO sends6 the draft WHOPAR to the applicant for comments;St 4 Th li t i d t ( t t ) th l t t f th d ft WHOPAR

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WHOPAR GUIDANCE for APPLICANTS v 2.4

Step 7. If the product, as produced at the specified manufacturing site(s), has been found to meetthe recommended standards, WHO accepts the product for inclusion in the List of

prequalified products and manufacturers8

and publishes the WHOPAR; the applicant isinformed accordingly.

Step 8. Within within three months after acceptance/publication of the WHOPARs. Please note thatthe format should be in line with the recommendations as set out in the Guideline of the

readability of the labelling and the package leaflet of medicinal products for human use

(HTTP://EC.EUROPA.EU/ENTERPRISE/PHARMACEUTICALS/EUDRALEX/VOL-

2/C/2009_01_12_READABILITY_GUIDELINE_FINAL.PDF), which is also referred to in the

current WHOPAR guidance.

3. WHOPAR structure

The WHOPAR consists of 8 Parts:

1. Abstract2. All Accepted Presentations3. Package Leaflet in English4. Summary of Product Characteristics in English5. Labelling in English6. Discussion7. Steps taken for Prequalification8. Steps taken following Prequalification

The characteristics of the above mentioned WHOPAR parts are described in Appendix 1. The

applicant contributes relevant information for the respective parts, depending on the type of product as

detailed in section 4 of this guidance.

4. Requirements for submission

Required documentation as described in Appendix 2, is to be submitted as part of the initial

submission. Failure to include any of the required documentation may result in rejection of the

application.

The Procedure for Assessing the Acceptability, in principle, of Pharmaceutical Products for Purchaseby United Nations Agencies

9under paragraph 2.2 Submission of dossiers identifies two types of

submissions: for innovator products and for multisource (generic) products.

4.1 Innovator products

Detailed requirements for submission are provided on the website of the Prequalification

P10

With t t th b i i f d t i t f WHOPAR f t

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WHOPAR GUIDANCE for APPLICANTS v 2.4

The applicant should provide:

the Package Leaflet (Part 3), Summary of Product Characteristics (Part 4) and Labelling(Part 5) in accordance with the guidance provided in Appendix 3. An authorized Englishtranslation has to be provided, whenever the original texts were issued in another

language.

For each part of the WHOPAR referring to the public assessment report (parts 3, 4, 5 and6) the relevant links.

Information on international licensing status, stating countries and licensing numbers.2. No public assessment report as referred to above is available

12:

The applicant should provide: Package Leaflet (Part 3), Summary of Product Characteristics (Part 4) and Labelling (Part

5) as English language version in accordance with the guidance provided in Appendix 3.

Summary of Product Safety and Efficacy of the FPP as contribution to the Discussion(Part 6) (see Appendix 4

).

Information on international licensing status, stating countries and licensing numbers.4.2 Multisource or generic products

Detailed requirements for the submission are provided on the website of the PrequalificationProgramme

13. With respect to the submission of documents in support of a WHOPAR one of two

approaches will apply depending on the availability of an innovator or comparator / reference product:

1. A comparator / reference product acceptable to WHO is available:

The applicant should provide:

Package Leaflet (Part 3), Summary of Product Characteristics (Part 4) and Labelling (Part 5)in accordance with the guidance provided in Appendix 3.

The text should reflect the information as available for the innovator/comparator product.Especially the indication and safety profile should be the same as approved for the comparator

/ reference product(s) acceptable to WHO.

Information on international licensing status, stating countries and licensing numbers.A Summary on Product Safety and Efficacy is not considered necessary, as relevant information on

product safety and efficacy is generally available for this type of products.

2. An innovator or an acceptable comparator / reference product is not available e.g. new

combinations of existing products like fixed dose combinations or traditionally used multisource

products such as the artemisinines.

The applicant should provide:

Package Leaflet (Part 3), Summary of Product Characteristics (Part 4) and Labelling (Part 5)in accordance with the guidance provided in Appendix 3.

Comprehensive summary of Product Safety and Efficacy of the Finished Pharmaceutical

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WHOPAR GUIDANCE for APPLICANTS v 2.4

5. Additional Information

Additional information on this procedure may be obtained by email from Dr M. Stahl at

[email protected] to whom also comments may be submitted.

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.1 Appendix 1

Guidance note to Applicants (Manufacturers) on the compilation of the

WHO Public Assessment Report

Appendix 1

Characteristics of WHOPAR Parts.

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.1 Appendix 1

Appendix 1 Characteristics of WHOPAR Parts.

Responsibility for PurposePart Title

Drafting Submission Acceptance to provide :

1 Abstract WHO, Applicant Applicant WHO Overview of key information

2 All Accepted Presentations WHO WHO Tabulated product summary

3 All Package Leaflets in English Applicant Applicant WHO Practical, easily understandable information for

the user of the FPP such that, if necessary, he is

able to directly act on it

4 All Summaries of ProductCharacteristics in English

Applicant Applicant WHO All practical and essential medical (background) information on FPP for health care

providers

5 All Labelling in English Applicant Applicant WHO All text for packaging

6 Discussion WHO, based on

assessor reports on Qualityand Bioequivalence and

Summary of Product Safetyand Efficacy

Applicant1

WHO Outcome of quality and bioequivalence

evaluation and, if required, the overview of

current product safety and efficacy

7 Steps taken for Prequalification WHO WHO Chronological description of main steps

undertaken for assessment of the product and

by whom

8 Steps taken following

Prequalification

WHO WHO Chronological description of main steps

undertaken following assessment of the product

and by whom

1 As appropriate, see Requirements for Submission and Appendix 2

June 2006 WHO Prequalification of Medicines Programme 2

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.0 Appendix 2

Guidance note to Applicants (Manufacturers) on the compilation of the WHO

Public Assessment Report

Appendix 2

Documentation to submit together with the initial submission.

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.0 Appendix 2

Appendix 2 Documentation to submit together with the initial submission.

Applicants contribute relevant documentation on Parts 3, 4 and 5 of the WHOPAR and, if required, a

Summary of Product Safety and Efficacy to be included in Part 6. Submissions for a multisourceproduct for which no comparator / reference product exists, should include a bibliographic submission.

Documentation to submit for an:

Innovator product, for which a public assessment report has been issued by a

Drug Regulatory Authority from the ICH regions or associated countries

which is available:

Package Leaflet in English (Part 3), Summary of Product Characteristics in English (Part 4), Labelling in English (Part 5), Summary of Product Safety and Efficacy as contribution to the Discussion (Part 6)

may be voluntarily submitted; submission and subsequent publication of this summary

ensures availability of product information for all Finished Pharmaceutical Products

(FPPs) that are accepted for Prequalification on the WHO Prequalification web site.

Innovator product, for which no public assessment report is available: Package Leaflet in English (Part 3) Summary of Product Characteristics in English (Part 4) Labelling in English (Part 5) Summary of Product Safety and Efficacy (contribution to Part 6)

Multisource (generic) product, for which an innovator or comparator / reference product is

available:

Package Leaflet in English (Part 3)

Summary of Product Characteristics in English (Part 4) Labelling in English (Part 5)

Multisource product, for which an innovator or comparator / reference product is not

available:

Package Leaflet in English (Part 3) Summary of Product Characteristics in English (Part 4) Labelling in English (Part 5) Summary of Product Safety and Efficacy (contribution to Part 6) Bibliographic submission containing all literature, original clinical research (if carried

out) and other documentation in support of the information provided in the Package

Leaflet, Summary of Product Characteristics and Summary of Product Safety and

Efficacy in the Discussion.

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.0 Appendix 2

FDCs including evidence on the safety and efficacy of the equivalent combination of single

API products, original clinical research (if carried out) and other documentation in support of

the information provided in the Package Leaflet, Summary of Product Characteristics and

Summary of Product Safety and Efficacy in the Discussion.The format for presentation of information and data should follow the manual Marketing

Authorization of Pharmaceutical Products with special Reference to Multisource (Generic)

Products: a Manual for a Drug Regulatory Authority1.

Further useful guidance is provided in the draft WHO Guidelines for Registration of Fixed

Dose Combination Medicinal Products2

of September 2004 e.g. attachment 2, Principles for

determining whether data from scientific literature are acceptable.

Information, especially with respect to submissions according to the format of the Common

Technical Document (CTD) can be found at the website of the International Conference onHarmonization (ICH)3

as well as on those of the ICH Regulatory Bodies: EU (Commission4

and EMEA5), Japan (MHLW

6) and USA (FDA

7).

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.0 Appendix 3

Guidance note to Applicants (Manufacturers) on the compilation of the WHO

Public Assessment Report

Appendix 3

Guidance on Package Leaflet, Summary of Product Characteristics and

Labelling.

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WHOPAR GUIDANCE for APPLICANTS (MANUFACTURERS) v 2.0 Appendix 3

Appendix 3 Guidance on Package Leaflet, Summary of Product Characteristics and

Labelling.

Guidance documents on the Package Leaflet, Summary of Product Characteristics and Labelling are

listed below and attached for immediate reference. The documents are essentially as published by the

EMEA. Since these documents are subject to regular updates interested parties are advised to consult

the EMEA Quality Review of Documents (QRD) web pages as appropriate1, 2

.

Guidance documents to consult include:

Templates:

1.

Summary of Product Characteristics (template)Package Leaflet (template)

Labelling (template)

These are Word versions, which are directly usable

as a template to start developing the documents.

2. Annotated Summary of Product CharacteristicsAnnotated Package Leaflet template

Annotated Labelling template

3. Appendix I Statements for use in Section 4.6 Pregnancyand lactation of Summary of Product

Characteristics

4. Appendix II MedDRA terminology to be used in Section4.8 Undesirable effects of the Summary of

Product Characteristics

5. Appendix III New standards for required storage statements6. Appendix IV Terms for Batch number and Expiry date

QRD support documents:1. Convention to be followed for EMEA - QRD templates2. Compilation of QRD decisions on the use of terms3. Compilation of QRD decisions on stylistic matters in

product information.

4. Tables ofnon-standard abbreviations

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WHOPAR part 4 version 0.1

SUMMARY OF PRODUCT CHARACTERISTICS

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WHOPAR part 4 version 0.1

1. NAME OF THE MEDICINAL PRODUCT

{(Invented) name strength pharmaceutical form}

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

4.2 Posology and method of administration

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WHOPAR part 4 version 0.1

[MedDRA frequency convention and system organ class database, seeAppendix II]

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

4.9 Overdose

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: {group}, ATC code: {code}

5.2 Pharmacokinetic properties

5.3 Preclinical safety data

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

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WHOPAR part 4 version 0.1

6.5 Nature and contents of container

6.6 Special precautions for disposal

7. HOLDER

{Name and address}

8. AUTHORISATION NUMBER(S)

9. DATE OF FIRST / RENEWAL OF

THE

10. DATE OF REVISION OF THE TEXT

{MM/YYYY}

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{product name} WHOPAR part 3 version 0.1

PACKAGE LEAFLET

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{product name} WHOPAR part 3 version 0.1

PACKAGE LEAFLET: INFORMATION FOR THE USER

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

In this leaflet:

1. What {product name}is and what it is used for

2. Before you {product name}

3. How to {product name}

4. Possible side effects

5. How to store {product name}6. Further information

1. WHAT {PRODUCT NAME} IS AND WHAT IT IS USED FOR

2. BEFORE YOU {PRODUCT NAME}Do not {product name}

-

-

Take special care with {product name}

-

-

-

other medicines

{product name} with food and drink

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{product name} WHOPAR part 3 version 0.1

If you more {product name} than you should

If you forget to {product name}

If you stop {product name}

4. POSSIBLE SIDE EFFECTS

Like all medicines, {product name} can cause side effects, although not everybody gets them.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, pleasetell your .

5. HOW TO STORE {PRODUCT NAME}[For storage conditions statements seeAppendix III]

Keep out of the reach and sight of children.

,

Do not use {product name} after the expiry date which is stated on the

6. FURTHER INFORMATION

What {product name} contains

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{product name} WHOPAR part 3 version 0.1

For any information about this medicinal product, please contact the local representative of the

Holder:

{Country}

{Name}

tel: + {telephone number}

{Country}

{Name}

tel: + {telephone number}

This leaflet was last approved in {MM/YYYY}.

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WHOPAR part 5 version 0.1

LABELLING

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WHOPAR part 5 version 0.1

PARTICULARS TO APPEAR ON THE

{NATURE/TYPE}

1. NAME OF THE MEDICINAL PRODUCT

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

2. STATEMENT OF ACTIVE SUBSTANCE(S)

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUTOF THE REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

[For terms on Batch number and Expiry date seeAppendix IV]

9 SPECIAL STORAGE CONDITIONS

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WHOPAR part 5 version 0.1

12. NUMBER(S)

EU/0/00/000/000

13. BATCH NUMBER

[For terms on Batch number and Expiry date seeAppendix IV]

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

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WHOPAR part 5 version 0.1

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

{NATURE/TYPE}

1. NAME OF THE MEDICINAL PRODUCT

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

2. NAME OF THE

HOLDER

{Name}

3. EXPIRY DATE

[For terms on Batch number and Expiry date seeAppendix IV]

4. BATCH NUMBER

[For terms on Batch number and Expiry date seeAppendix IV]

5. OTHER

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WHOPAR part 5 version 0.1

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

{NATURE/TYPE}

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

{Route of administration}

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

[For terms on Batch number and Expiry date see Appendix IV]

4. BATCH NUMBER[For terms on Batch number and Expiry date see Appendix IV]

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6. OTHER

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Version 7

SUMMARY OF PRODUCT CHARACTERISTICS

[NOTE: the following are those items of information required by Article 11 of Directive 2001/83/EC, as

amended, and current practice in the centralised procedure. This guidance should be read in conjunction

with the relevant guidelines that can be found on the EMEA website (See also Convention for format and

layout): http://www.emea.eu.int/htms/human/qrd/qrdplt/qrdconvention.pdf, in particular the Guideline on

Summary of Product Characteristics as published on the Website of the European Commission in theNotice to Applicants, Volume 2C: http://pharmacos.eudra.org/F2/eudralex/vol-2/home.htm

During the evaluation process, applicants may present SPCs for different strengths in one document, clearly

indicating with grey-shaded titles the strength or presentation to which alternative text elements refer.

However, a separate SPC per strength and per pharmaceutical form, containing all pack-sizes related to the

strength and pharmaceutical form concerned will have to be provided by the applicant as follows:

- English language version: immediately after adoption of the opinion.- All other language versions: at the latest 22 days after adoption of the opinion (i.e. at

the latest after incorporation of Member States comments).

See also: The new Product Information linguistic review process for new applications in the Centralised

Procedure - http://www.emea.eu.int/pdfs/human/regaffair/554202en.pdf

Standard statements are given in the template, which must be used whenever they are applicable. If the

applicant needs to deviate from these statements to accommodate product-specific requirements alternative

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1. NAME OF THE MEDICINAL PRODUCT

{(Invented) name strength pharmaceutical form}

[no symbols attached here and throughout the text; tablets and capsules in the plural.]

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

[Name of the active substance(s) in the language of the text.]

[Qualitative and quantitative composition in terms of the active substances and constituents of the excipient,

knowledge of which is essential for proper administration of the medicinal product. The usual common name

or chemical description shall be used. See also the Guideline on excipients as published on the Website of

the European Commission in the Notice to Applicants, Volume 3B

http://pharmacos.eudra.org/F2/eudralex/vol-3/home.htm.]

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

[The pharmaceutical form should be stated according to the full Standard Terms published by the Council

of Europe, in the singular. Where the Council of Europe short standard term is used on small immediate

packaging materials, the short term should be added in brackets.]

[Include here a description of the visual appearance of the product pharmaceutical form as marketed,

including information on pH and osmolarity as required.

Information on appearance of reconstituted parenteral solution should appear under section 6.6.]

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

[Specify, if appropriate

If applicable, results of clinical trials to appear under section 5.1.]

4.2 Posology and method of administration[In case of restricted medical prescription start this section by specifying the conditions.

Method of administration: directions for proper use by healthcare professionals or by the patient. Further

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4.3 Contraindications

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Pregnancy and lactation

[For Pregnancy and lactation statements seeAppendix I.]

[Results from reproduction toxicology to be included under section 5.3 and cross-referenced here, if

necessary.]

4.7 Effects on ability to drive and use machines

on the ability to drive and use machines.> [describe effects where applicable]

4.8 Undesirable effects[MedDRA frequency convention and system organ class database, seeAppendix II.]

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

4.9 Overdose

[Describe the symptoms, emergency procedures, and antidotes (if available) in case of overdose.]

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: {group [lowest available level]}, ATC code: {code}

[For products approved under conditional approval, include the following statement:]

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5.2 Pharmacokinetic properties

5.3 Preclinical safety data

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

[Each to be listed on a separate line according to the different parts of the product.]

[Name of the excipient(s) in the language of the text.]

6.2 Incompatibilities

[if appropriate, e.g. for solid oral pharmaceutical forms.]

[e.g. for parenterals.]

6.3 Shelf life

[Information on the finished product shelf life and on the in-use stability after 1st opening and/or

reconstitution/dilution should appear here. Only one overall shelf life for the finished product is to be given

even if different components of the product may have a different shelf life (e.g. powder & solvent).]

6.4 Special precautions for storage

[For Storage condition statements seeAppendix III.]

[General storage conditions of the finished product should appear here, together with a cross-reference to

section 6.3 where appropriate: ]

6.5 Nature and contents of container[All pack sizes must be listed. If applicable, add:]

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7. MARKETING AUTHORISATION HOLDER

[Country name in the language of the text. Telephone, fax numbers or-e-mail addresses may be included (no

websites, no e-mails linking to websites).]

{Name and address}

8. MARKETING AUTHORISATION NUMBER(S)

[Item to be completed by the Marketing Authorisation Holder once the Marketing Authorisation has been

granted.]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[Item to be completed by the Marketing Authorisation Holder once the Marketing Authorisation has been

granted or renewed.

The date should correspond to the initial authorisation of the medicinal product concerned. It should not

reflect individual strength/presentation approvals introduced via subsequent variations and/or extensions.

Both the date of first authorisation and, if the authorisation has been renewed, the date of the (last) renewal

should be stated in the format given in the following example:

Date of first authorisation: 3 April 1985.

Date of last renewal: 3 April 2000.]

10. DATE OF REVISION OF THE TEXT

[Item to be completed by the Marketing Authorisation Holder at time of printing once a change to the SPC

has been approved e.g. the latest Commission Decision, implementation date of the Urgent Safety Restriction

or date of EMEA letter/notification.]

{MM/YYYY}

[It is recommended that the following reference to the WHO PQ Website is included:]

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Version 7

LABELLING AND PACKAGE LEAFLET

[The lay-out of the labelling and package leaflet presented in this template is intended for the word

document (Commission Decision Annex) only. Guidance on how to best present the actualprintedlabelling

and package leaflet (e.g. font size, use of colours, lay-out, etc.) is available in the the Guideline on the

Readability of the Label and Package Leaflet of Medicinal Products for Human Use as published on the

Website of the European Commission in the Notice To Applicants, Volume 2C

http://pharmacos.eudra.org/F2/eudralex/vol-2/home.htm]

[N.B.: boxed headings in Annex IIIA are provided to help applicants when completing the template; they

should remain in the opinion/decision. However, they are not to appear in the final printed packaging

materials (mock-ups/specimens).

A separate text for outer and innerpackaging labelling should be completed per strength and per

pharmaceutical form. Different pack-sizes of the same strength can be presented in one document. Upon

adoption by CHMP of a combined labelling text, the text does not need to be separated after adoption of the

opinion.

A separate package leaflet should be provided per strength and per pharmaceutical form. During the

evaluation process however, applicants may present package leaflets for different strengths in one document,

clearly indicating the strength or presentation to which alternative text elements refer. Where applicants

consider to also market a combined package leaflet, a detailed justification for such a combined package

leaflet will have to be included after the PL text and included in the application at submission or at the latest

at Day 121. The justification should take into account the QRD guidance as published in the Compilation

of QRD decisions on stylistic matters. Upon CHMP agreement (on a case-by-case basis) with a combined

package leaflet text, the text does not need to be separated after adoption.

However, in all other cases, a separate package leafletper strength and per pharmaceutical form,

containing all pack-sizes related to the strength and pharmaceutical form concernedwill have to be

provided by the applicant as follows:- English language version: immediately after adoption of the opinion.- All other language versions: at the latest 22 days after adoption of the opinion (i.e. at

the latest after incorporation of Member States comments).

Text which will not appear in the final printed material is to be presented as shadedtext.]

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PACKAGE LEAFLET

[NOTE: the following items must appear in the package leaflet as required by Title V of Directive

2001/83/EC, as amended. In exceptional cases, alternative headings may be acceptable, especially for those

headings containing or where a different wording would be more appropriate for the product

concerned e.g. to better reflect the user of the product. This should not in any case impact on the content

required for the section concerned. Applicants should justify the use of alternative headings (e.g. by

reference to user testing results). For certain medicinal products not all items may be relevant, in this case

the corresponding heading should not be included.

The leaflet must be readable for the patient; please refer to the Guideline on the Readability of the Label

and Package Leaflet of Medicinal Products for Human Use as published on the Website of the European

Commission in the Notice To Applicants, Volume 2C:

http://pharmacos.eudra.org/F2/eudralex/vol-2/home.htm

Throughout the text X stands for the (invented) name of the medicinal product.

Standard statements are given in the template which must be used whenever they are applicable. If the

applicant needs to deviate from these statements to accommodate product-specific requirements, alternative

or additional statements will be considered on a case-by-case basis.

Guidance notes in orange cross-refer to the section/information of the SPC which is to be reflected in that

particular section of the package leaflet.

Applicants shall ensure that, on request from patients' organisations, the package leaflet is made available

in formats appropriate for the blind and partially sighted.]

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PACKAGE LEAFLET: INFORMATION FOR THE USER

[Heading to be printed]

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

[The (invented) name of the medicinal product (referred to as X throughout this document) followed by the

strength and pharmaceutical form (i.e. as it appears in the SPC) should be stated here in bold. This should

be followed by the active substance(s) (as stated on the label section 1), which may be written on the line

below.]

[For medicinal products available only on prescription:]

In this leaflet:

1. What X is and what it is used for

2. Before you X

3. How to X

4. Possible side effects

5. How to store X6. Further information

1. WHAT X IS AND WHAT IT IS USED FOR[Pharmacotherapeutic group.]

[The pharmacotherapeutic group or type of activity should be stated here using patient understandable

language.]

[Therapeutic indications.]

[The therapeutic indications should be stated here, using patient understandable language. If appropriate,

specify that:]

2. BEFORE YOU X[Additional sub-headings within the headings given below may be included if needed to increase

readability.]

[List of information necessary before taking the medicinal product ]

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[Give information on absolute contraindications here in accordance with the SPC; this should be in patient

understandable language and should be strictly limited to contraindications, including contraindications due

to interactions with other medicinal products. Other precautions and special warnings should be made in the

next section.

Care must be taken to ensure that complex details are not omitted. It is not acceptable to state only thecommon or major contraindications. Belief that a patient cannot understand a contraindication is not a

reason for omitting it.]

[Appropriate precautions for use; special warnings.]

Take special care with X

-

-

- < Before treatment with X, >

[Information in patient understandable language, special warnings and appropriate precautions for use

should be provided here.]

[Interaction with other medicinal products.]

other medicines

[Describe the effects of other products on the product in question and vice versa. Reference should be made

to the intensification/weakening and the extension/shortening of effects.]

[Interactions with herbal or alternative therapies should be addressed where necessary.]

[Interactions with food and drink.]

X with food and drink

[Interactions not related to medicinal products should be mentioned here. For example, patients should not

consume milk in combination with tetracyclines and no alcohol should be consumed during treatment with

benzodiazepines. Where relevant, guidance should always be included to clarify if the medicine must be

taken with food, during/before meals, or clearly state if food/meals have no influence, etc.]

[Use by pregnant or breast-feeding women.]

Pregnancy and breast-feeding

[Where the information is significantly different, pregnancy and breast-feeding information can be presented

under separate headings.]

[Include conclusion summary of the information given in the SPC, in addition to the following optional

statement:]

[Information on teratogenicity in patient understandable language, should be included in the leaflet when

the product is contra-indicated during pregnancy.]

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Medicinal Products for Human Use (The rules governing medicinal products in the European Union,

Volume 3B), including relevant warnings for residues from the manufacturing process.]

3. HOW TO X[Additional sub-headings within the headings given below may be included if needed to increasereadability.]

[Instructions for proper use.]

[The following 4 items can be combined as one paragraph.]

[Dosage.]

[Method and/or route(s) of administration.]

[Method of administration: directions for a proper use of the medicinal product; e.g. Do not swallow,

Do not chew, Shake well before use.

Route(s) of administration according to Standard Terms published by the Council of Europe and an

additional patient-friendly explanation may be given if necessary.

When applicable, there should be descriptions (if useful with illustrations) of opening techniques for child-

resistant containers and other containers to be opened in an unusual way.

Where relevant, guidance should always be included to clarify if the medicine must be taken with food,

during/before meals, or clearly state if food/meals have no influence, etc.]

[Frequency of administration.]

[Specify if necessary the appropriate time(s) at which the medicinal product may or must be administered.]

[Duration of treatment.]

[If appropriate, especially for products available without prescription, precise statements should be included

on:

the usual duration of the therapy; the maximum duration of the therapy; the intervals with no treatment; the cases in which the duration of treatment should be limited.]

[Symptoms in case of overdose and actions to be taken.]

If you more X than you should

[Describe how to recognise if someone has taken an overdose and what to do.]

[Actions to be taken when one or more doses have been missed.]

If you forget to X

[Make clear to patients what they should do after irregular use of a product; e.g.:]

[Indication of the risk of withdrawal effects ]

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4. POSSIBLE SIDE EFFECTS

[Description of side effects (frequency according to MedDRA).]

[Begin this section with:]

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

[Describe, if necessary, the actions to be taken. If the patient needs to seek help urgently, the use of the term

is recommended; for less urgent conditions, can be used.]

[Close this section with:]

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your

.

5. HOW TO STORE X

Keep out of the reach and sight of children.

[Expiry date.]

[Where a specific abbreviation for Expiry date is used on the labelling, the full term should be mentioned

here as well as the abbreviation.]

Do not use X after the expiry date which is stated on the

[Storage conditions.]

[For Storage condition statements seeAppendix III.]

[Where applicable, shelf life after reconstitution, dilution or after first opening the container.]

[Please refer to Note for Guidance on Maximum Shelf Life for Sterile Products for Human Use after First

Opening or Following Reconstitution (CPMP/QWP/159/96/corr).]

[Where appropriate, warning against certain visible signs of deterioration.]

6. FURTHER INFORMATION

[Full statement of the active substance(s) and excipient(s).]

What X contains

[The active substance(s) (expressed qualitatively and quantitatively) and the other ingredients (expressed

qualitatively) should be identified using their names as given in the SPC and in the language of the text, e.g.]

- The active substance(s) is (are) [see guidance in section 2 of outer packaging.]- The other ingredient(s) is (are) [separate the excipients of the different parts of the medicinal

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[All pack sizes for this pharmaceutical form and strength should be detailed here; if appropriate indicate

that not all pack sizes may be marketed. A cross-reference to other pharmaceutical forms and strengths may

be included.]

[Name and address of the marketing authorisation holder and of the manufacturing authorisation holder

responsible for batch release, if different.]Marketing Authorisation Holder and Manufacturer

{Name and address}

[State the name and address of the Marketing Authorisation Holder and identify as such e.g. Marketing

Authorisation Holder: ABC Ltd, etc. (Full address: name of the country to be stated in the language of the

text. Telephone, fax numbers or e-mail addresses may be included (no websites, no e-mails linking towebsites).]

[State the name and address of the manufacturer responsible for batch release and identify as such e.g.

Manufacturer: DEF Ltd, etc. (Full address: name of the country to be stated in the language of the text.

Telephone or fax numbers, e-mail addresses or websites are not allowed).]

[If MAH and manufacturer are the same, the general heading Marketing Authorisation Holder and

Manufacturer can be used.]

[In cases where more than 1 manufacturer responsible for batch release is designated, all should be listed

here. However, the printed package leaflet of the medicinal product must clearly identify the manufacturer

responsible for the release of the concerned batch or mention only the specific manufacturer responsible forthe release of that batch.]

[List of local representatives, where applicable.

- Listing of local representatives is not a requirement, but where used they must be stated for allMember States. However, a representative may be designated for more than one country and may also

be the MAH where no other local representative is indicated.

In cases where the same representative is designated for more than one country, the representatives

details may be listed only once below the names of the countries concerned.

- Where a local representative is located outside the country concerned and where an address is given,the country name must be included in the address of the local representative and must be given in the

language(s) of the country for which the local representative is designated.

- ISO country codes* may be used to replace the full name of the country heading. ISO codes togetherwith the respective names of EU/EEA countries can be found at the following web site:

http://publications.eu.int/code/en/en-370101.htm.

- In order to save space in the printed package leaflet, local representatives may be presentedsequentially rather than in a tabulated format. In case of multi-lingual leaflets, the list of local

representatives can be printed only once at the end of the printed leaflet.

- The local representative may be indicated by name, telephone number and electronic e-mail address(optional) only. Postal address may be added space permitting. Website addresses or e-mails linking

to websites are not allowed.

- If a representative is outside the relevant country, indicate the name of the country.- For Belgium (Brussels) and Finland (Swedish speaking Finland) addresses may appear in two

languages respectively Dutch/French and Finnish/Swedish

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Country

{Nom/Naam/Name}

Tl/Tel: + {N de tlphone/Telefoonnummer/

Telefonnummer}

Country

{Nom}

Tl/Tel: + {N de tlphone/Telefonnummer}

This leaflet was last approved in {MM/YYYY}

[Date of granting of the Marketing Authorisation/approval of latest variation or transfer, e.g. the latest

Commission Decision, implementation date of the Urgent Safety Restriction or date of EMEA

letter/notification. Item to be completed by the Marketing Authorisation Holder at time of printing.]

[It is recommended that the following reference to the EMEA Website is included:]

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Version 7

LABELLING AND PACKAGE LEAFLET

[The lay-out of the labelling and package leaflet presented in this template is intended for the word

document (Commission Decision Annex) only. Guidance on how to best present the actualprintedlabelling

and package leaflet (e.g. font size, use of colours, lay-out, etc.) is available in the the Guideline on the

Readability of the Label and Package Leaflet of Medicinal Products for Human Use as published on the

Website of the European Commission in the Notice To Applicants, Volume 2C

http://pharmacos.eudra.org/F2/eudralex/vol-2/home.htm]

[N.B.: boxed headings in Annex IIIA are provided to help applicants when completing the template; they

should remain in the opinion/decision. However, they are not to appear in the final printed packagingmaterials (mock-ups/specimens).

A separate text for outer and innerpackaging labelling should be completed per strength and per

pharmaceutical form. Different pack-sizes of the same strength can be presented in one document. Upon

adoption by CHMP of a combined labelling text, the text does not need to be separated after adoption of the

opinion.

A separate package leaflet should be provided per strength and per pharmaceutical form. During the

evaluation process however, applicants may present package leaflets for different strengths in one document,

clearly indicating the strength or presentation to which alternative text elements refer. Where applicants

consider to also market a combined package leaflet, a detailed justification for such a combined packageleaflet will have to be included after the PL text and included in the application at submission or at the latest

at Day 121. The justification should take into account the QRD guidance as published in the Compilation

of QRD decisions on stylistic matters. Upon CHMP agreement (on a case-by-case basis) with a combined

package leaflet text, the text does not need to be separated after adoption.

However in all other cases a separate package leaflet per strength and per pharmaceutical form

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LABELLING

[NOTE: these are all mandatory items listed in Title V of Directive 2001/83/EC, as amended. The data

should be presented according to the template below, irrespectively of their sequence on the actual labelling

and their position and possible repetition on the individual sides/flaps of the packaging (e.g. top flap, front,

back etc.). Blue-boxes and their contents should not be included.

Where the same text for outer and inner packaging is used, this should be clearly indicated in the heading

and in {nature/type}. Text which is identical for different presentations should be provided only once e.g. text

of inner vial label where such vial is part of different pack-sizes.

On the printed outer packaging material, an empty space should be provided for the prescribed dose;

however, this should not appear in the Labelling text (Annex IIIA).]

[Boxed headings are provided to help applicants when completing the template; they should remain in the

opinion/decision annexes. However, they are not to appear in the final printed packaging materials (mock-

ups/specimens).]

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PARTICULARS TO APPEAR ON < THE OUTER PACKAGING>

{NATURE/TYPE}

1. NAME OF THE MEDICINAL PRODUCT

{(Invented) name strength pharmaceutical form} [as it appears in the SPC under section 1.]

{Active substance(s)}

[The reference to the active substance should correspond to the strength expressed in the name.

E.g. (invented) name 60 mg capsules

toremifene(since 60 mg corresponds to toremifene, even if the active substance is

actually present as toremifene citrate)

(invented) name 60 mg tablets

diltiazem hydrochloride

(since 60 mg corresponds to the hydrochloride salt)]

[For mock-ups and specimens, this information may be presented on different lines of text or in different font

sizes if necessary, provided that the appearance of the name is as an integrated item.

E.g. (invented) name Z mg/ml

Solution for injection]

[The international non-proprietary name (INN) of the active substance(s) shall be included, or, in absence of

INN name, the common names should be used.

In addition, the different strengths of fixed-combination products should be presented separated by a /.

The names of the active substances should be presented separated by a / and in the same order relating to

the strength.

E.g. (invented) name 150 mg/12.5 mg tablets

irbesartan/hydrochlorothiazide]

2. STATEMENT OF ACTIVE SUBSTANCE(S)

[Expressed qualitatively and quantitatively per dosage unit or according to the form of administration for a

given volume or weight. Where the active substance is present as a salt, this should be clearly indicated. E.g.for the examples given above: 60 mg toremifene (as citrate) or toremifene citrate equivalent to 60 mg

toremifene;60 mg diltiazem hydrochloride.]

3. LIST OF EXCIPIENTS

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[Pharmaceutical form according to the full Standard terms published by the Council of Europe.

Contents by weight, by volume or by number of doses or number of units of administration of the medicinal

product (i.e. pack size, including a reference to any ancillary items included in the pack such as needles,

swabs, etc.). In case of a combined labelling text covering different pack-sizes of the same strength, each

pack-size should be listed on a separate line in grey shading:e.g.

28 tablets

56 tablets

100 tablets]

5. METHOD AND ROUTE(S) OF ADMINISTRATION

[Method of administration: directions for proper use of the medicinal product, e.g. Do not swallow, Do

not chew, Shake well before use. In all cases, and especially if full details cannot be included on the

outer packaging itself, a reference to the package leaflet must be made:]

Read the package leaflet before use.

[Route of administration according to the Standard terms published by the Council of Europe.]

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF

THE REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

[For terms on Batch number and Expiry date seeAppendix IV.]

[The expiry date printed on medicinal products stating only month and year should be taken to mean the last

day of that month. Expiry dates should be expressed with the month given as 2 digits or at least 3 characters

and the year as 4 digits. E.g.: February 2007, Feb 2007, 02-2007.]

[Where applicable, shelf life after reconstitution, dilution or after first opening the container.Please refer to CHMP Note for Guidance on Maximum Shelf Life for Sterile Products for Human Use after

First Opening or Following Reconstitution (CPMP/QWP/159/96/corr).If however the maximum in-use

shelf life for the reconstituted product varies, depending on how, or with what, it is reconstituted, then there

should be a statement on the label, such as: read the leaflet for the shelf life of the reconstituted product.]

[E.g. radiopharmaceuticals, cytostatics.]

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[E.g. radiopharmaceuticals, cytostatics.]

[A reference to any appropriate collection system in place should be included in the Blue Box on the outer

packaging.]

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

[Including town, postal code (if available) and country name of the MAH in the language of the text

(Telephone, fax numbers or e-mail addresses may be included (no websites, no e-mails linking to websites).

Local representatives of the MAH, if mentioned in the leaflet, may be included in the Blue Box on the outer

packaging.]

{Name and address}

12. MARKETING AUTHORISATION NUMBER(S)

[Item to be completed by the Marketing Authorisation Holder once the Marketing Authorisation has been

granted.]

[In case of a combined labelling text covering different pack-sizes of the same strength, the respective pack-size should be included in grey shading after the corresponding EU Sub-Number and listed on a separate

line.

e.g.

EU/0/00/000/001 28 tablets

EU/0/00/000/002 56 tablets

EU/0/00/000/003 100 tablets]

EU/0/00/000/000

13. BATCH NUMBER

[For terms on Batch number and Expiry date seeAppendix IV.]

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

[Information that will appear in Braille on the printed outer packaging material should be mentioned here in

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[ f pp p p g g

normal text format (See also the Guidance concerning the Braille requirements for labelling and the

package leaflet published by the European Commission:

http://pharmacos.eudra.org/F2/pharmacos/docs/Doc2005/04_05/Braille_text20050411.pdf)]

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

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{NATURE/TYPE}

1. NAME OF THE MEDICINAL PRODUCT

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

[Active substance see guidance in section 1 of the outer packaging.]

[Pharmaceutical form short terms according to the current version of the Standard terms published by the

Council of Europe may be used in case of space limitation, if consistently used in all language versions.]

2. NAME OF THE MARKETING AUTHORISATION HOLDER

{Name} [Full/short name of the Marketing Authorisation Holder.]

3. EXPIRY DATE

[For terms on Batch number and Expiry date seeAppendix IV.]

4. BATCH NUMBER

[For terms on Batch number and Expiry date see Appendix IV.]

5. OTHER

[Space permitting, any other information necessary for the correct use and administration of the product can

be included here, e.g. calendar days.]

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

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{NATURE/TYPE}

[Small immediate packaging units are defined as containers sized up to and including 10 ml. On a case-by-

case basis the minimum particulars could also be considered for other containers where it is not be feasible

to include all the information. Such exceptional cases have to be justified, discussed and agreed with theCompetent Authority/EMEA.]

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

{(Invented) name strength pharmaceutical form}

{Active substance(s)}

{Route of administration}

[Pharmaceutical form short terms according to the current version of the Standard terms published by the

Council of Europe may be used in case of space limitation, if consistently used in all language versions.]

[Where different labels apply to different constituents of the pharmaceutical form, the pharmaceutical form

in the name on the specific label should only refer to the constituent concerned (e.g. separate label for

powder vial and solvent ampoule).]

2. METHOD OF ADMINISTRATION

[Method of administration: directions for proper use of the medicinal product, e.g. Do not swallow, Do

not chew, Shake well before use. If full details cannot be included on the immediate packaging itself, a

reference to the package leaflet should be made, e.g. Read the package leaflet before use.]

3. EXPIRY DATE

[For terms on Batch number and Expiry date see Appendix IV.]

[Where applicable, shelf life after reconstitution, dilution or after first opening the container.

Please refer to Note for Guidance on Maximum Shelf Life for Sterile Products for Human Use after First

Opening or Following Reconstitution (CPMP/QWP/159/96/corr).]

4. BATCH NUMBER

[For terms on Batch number and Expiry date see Appendix IV.]

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

Version 11

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TEMPLATE 1a

APPENDIX I

Statements for use in Section 4.6 Pregnancy and lactation of SPC

(Annex I to the Guideline on Summary of Product Characteristics)

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EN

[1]

[and if necessary] >

[2]

[These circumstances

should be specified]

[3]

[or]

[Trade name] should not be used during pregnancy unless clearly necessary [these circumstances should

be specified where possible].>

[4]

[5]

[or]

[6]

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[8]

[The subsequent two statements to be included as appropriate.]

[9] [In case of interaction with oral contraceptives information should also be given in 4.5]

[10] [In case of male-mediated effects on pregnancy outcome information should also be given in 4.4]

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2005 WHO Prequalification of Medicines Programme 1

[Version 05]

APPENDIX II

MedDRA terminology to be used in

Section 4.8 Undesirable effects of SPC

The table below shows the equivalent terminology in the EU official languages plus Icelandic and Norwegian as well asin the 2 official languages of Bulgaria and Romania

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Ref EN

[MedDRA frequency convention]

001 1/10)>

002 1/100, 003 1/1,000,

004 1/10,000,

005

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SUMMARY OF PRODUCT CHARACTERISTICS

6.4 Special precautions for storage

or

*

**

A. LABELLING

9. SPECIAL STORAGE CONDITIONS

or

*

**

B. PACKAGE LEAFLET

5. STORING X

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* The stability data generated at 25C/60%RH (acc) should be taken into account when deciding whether or not

transport under refrigeration is necessary. The statement should only be used in exceptional cases.

** The statement should be used only when critical.

*** The actual name of the container should be used (e.g. bottle, blister, etc.)

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APPENDIX IV

TERMS FOR BATCH NUMBER AND EXPIRY DATE TO BE USED ON

OUTER AND/OR INNER LABELLING

FULL TERM ABBREVIATION

Batch number

Batch

Lot

BN

Expiry date EXP

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Compilation of QRD decisions on the use of terms Version 7 - December 2005

d de

e

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Term

approved

preferred

acceptabl

in

PL

notto

be

used

Comments Go to

acetylsalicylic acid

X

According to the case, refer to ASA in package leaflets (e.g. for

interactions) as follows: acetylsalicylic acid or ".

Alternatively, as appropriate, use: " acetylsalicylic acid, a substance

present in many medicines used to relieve pain and lower fever, as well

as to prevent blood clotting "

For the translations of the ASA

statements in the EU official

languages, plus Icelandic and

Norwegian, please click

active ingredient X active substance

active substance X

adolescentsX

age 12 years to 17 years (Note for guidance on clinical investigation of

medicinal products in children, CPMP/EWP/462/97)

adverse effectsX

adverse events, adverse

reactions

adverse reactionsX

is to be used where there is a causal relationship with the use the

medicinal product

adverse events, adverse

reactionsadverse events

X

is to be used where it occurs during the use of the medicinal product but

its causal relationship is not yet established. Note that adverse events

without at least a suspected causal relationship should not be listed in

the SPC.

adverse events, adverse

reactions

aspirin X acetylsalicylic acid

breast-feeding X

childrenX

age 2 years to 11 years (Note for guidance on clinical investigation of

medicinal products in children, CPMP/EWP/462/97)

children, youngX

see Note for guidance on clinical investigation of medicinal products in

children, CPMP/EWP/462/97.

children, infants and toddlers

(depending on age)

clinical studiesX

correct term, if chosen must be used consistently throughout text

without alternating with "clinical trials".

clinical trialsX

correct term, if chosen must be used consistently throughout text

without alternating with "clinical studies".

dextrose X Not in Ph. Eur. glucose

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Term

approved

preferred

acceptabl

in

PL

notto

be

used

Comments Go to

dosage X to be used in package leaflets instead of "posology". posology

drugX

active substance; medicinal

product

drug substanceX

active substance; medicinal

product

excipients X to be used in SPC. In PL: "other ingredients" is accepted. other ingredients

expiration X expiry, expiry date

expiry X

expiry date X

formulation X medicinal product

glucose X Ph. Eur.

health experts

X

Reference to "health experts" generally means "best medical practice".

It is advised to use the wording "It is recommended that..."

HIV- X HIV negative

HIV associatedX

should not be hyphenised, as a hyphen at the end of a line can be

mistaken for a negative sign.HIV infected X HIV positive

HIV negative X

HIV positive X

HIV+ X HIV infected/HIV positive

HIV-infected X the hyphen at the end of a line can be mistaken for a negative sign. HIV infected

inactive ingredientX

"excipients" in SPC, "other

ingredients" in PL

inactive substanceX

"excipients" in SPC, "other

ingredients" in PL

infants and toddlersX

age 28 days to 23 months (Note for guidance on clinical investigation of

medicinal products in children, CPMP/EWP/462/97)

intramuscular route X intramuscular use

intramuscular use X "Standard Terms" published by the Council of Europe.

intravenous X

intravenous route X intravenous use

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Term

approve

preferred

acceptab

in

PL

notto

be

used

Comments Go to

intravenous use X "Standard Terms" published by the Council of Europe.

lactating mothers X nursing mothers

medication X medicinal product

medicinal product X

medicine X medicinal product

nursing mothers X

other ingredients X to be used in package leaflet. In SPC use "excipients". excipients

overdose X

overdosage X overdose

pack size X

posology X to be used in SPC. In package use "dosage".

presentation X ambiguous can mean "pack size" or "pharmaceutical form" pack size

pre-term new-born infantsX

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Term

approve

preferre

acceptab

in

PL

notto

b

used

Comments Go to

Keys

approved

preferred

acceptable

in

PL

notto

be

used

Definitions

ApprovedX

Terms used in legislation and templates, or originating from other

official sources

Preferred

X

Terms which cannot be traced to a specific source, but which the group

understands to constitute "good practice" and prefers to any other of the

same meaning

Acceptable in PL

X

Terms considered to be correctly used in Package Leaflet (which

requires "patient-friendly" terms). Such terms are accompanied by a

"Go to" reference to the approved term

Not to be used

X

Terms which the group deems unsuitable for use because misleading,

unclear, obsolete or for other reasons. The "Go to" reference always

leads to the approved term.

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Issues Connected problems QRD Suggestions

Units: degrees Degrees are expressed in different styles; No space between the symbol and the indicator of scale used; e.g. 10C, 10C

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g g y

e.g. 10C, 10 C, 10 Cp y ; g ,

(= non-breaking space)

Units: SI base units International Standard base units have been introduced in the

European Union with Council Directive 80/181/EEC of 20.12.79.(O.J. L 39 of 15.2.80). However this directive allows litre to be

written either l or L.

Litre must always be written as l, i.e. l, ml, dl, etc.

Units: microgram

( g)

Microgram in name of the medicinal product and in text

To be spelt out as micrograms in name of the product and in the

text of package leaflet? Can it appear as g in the text of the

SPC?

However in blisters or small immediate packs there might not be

enough space for the full name.

Issue addressed in the European Commissions Readability Guideline concerning the

labelling and PL:

3.3 ... micrograms should always be spelled out in full rather than abbreviated, for safety

reasons. However, in certain instances where this poses a practical problem which cannot be

solved by using a smaller point size (< 7 points Didot) then abbreviated forms may be used,

if they are justified and there are no safety concerns.

In the SPC, it is acceptable to use the abbreviated form (g) throughout the text of the

document. Except for the name of the medicinal product in section 1 of the SPC, where it

should be spelled out in full to ensure consistency with the name on the label and the

package leaflet.

The accepted abbreviation is g, although there may be some Member-States where this

abbreviation is not used.

Issues Connected problems QRD Suggestions

Unit dose pack The term unit dose is intended to differentiate a perforated On the outer carton, the pack size must be stated in section 4 as e.g. 28 x 1 tablets. In the SPC and Package leafletth k i t b t t d 28 1 t bl t i < t i l*> f t d it d bli t

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sizes blister, which is presented to facilitate single tablet administration,

from the standard tablet blister presentation.

the pack size must be stated as e.g. 28 x 1 tablets in perforated unit dose blisters.

Please find below the term perforated unit dose blisters translated in all official languages plus Icelandic and Norwegian.

BG :

CS: perforovan blistr jednodvkov

DA: perforeret enkeltdosisblister

DE: perforierter Blister zur Abgabe von Einzeldosen

EN: perforated unit dose blisters

ES: blister precortado unidosis

ET: heannuseline perforeeritud blisterpakend

FI: yksittispakattu lpipainopakkaus

FR: plaquette thermoforme pour dlivrance l'unit

EL: blister,

HU: adagonknt perforlt bliszter

IT: blister divisibile per dose unitaria

IS: rifgataar s takskammtaynnur

LT: perforuoti vienadoziai blisteriai (for veterinary products)

LT: perforuotos vienadozs lizdins ploktels (for human products)

LV: perforti blisteri ar vienu devu kontrligzd

NL: geperforeerde eenheidsblisterverpakking

NO: perforert endoseblister

PL: blister perforowany podzielny na dawki pojedyncze

PT: blisters destacveis para dose unitria

RO: blister perforat pentru eliberarea unei uniti dozate

SK: blister s perforciou, umoujci oddelenie jednotlivej dvky

SL: perforiranem pretisnem omotu za enkratni odmerek

SV: perforerat endosblister

*e.g. Aluminium/PVC

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APPENDIX IV

TERMS FOR BATCH NUMBER AND EXPIRY DATE TO BE USED ON

OUTER AND/OR INNER LABELLING

FULL TERM ABBREVIATION

Batch number

Batch

Lot

BN

Expiry date EXP

European Medicines Agency

V i 7 TABLES OF NON STANDARD ABBREVIATIONS 12/2005

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Page 1 of 3

Version 7 TABLES OF NON-STANDARD ABBREVIATIONS 12/2005

USE IN SUMMARY OF PRODUCT CHARACTERISTICS

FULL TERM EN BG CS DA DE EL ES ET FI FR HU IS

angiotensin converting enzyme ACE ECA AKE IEC

deoxyribonucleic acid DNA

DNA DNS orDNA

ADN DNS

monoamine oxidase inhibitors MAOI-

IMAO

MAO-

Hemmer

IMAO MAO-estj IMAO MAO-gtlk MAO-hemill

volume of distribution Vd

activated partial thromboplastintime

aPTT aPTT X X X TCA aPTI

half-life t

area under the curve AUC ASC

maximum serum concentration Cmax minimum serum concentration Cmin time to maximum concentration tmax

acquired immunodeficiencysyndrome AIDS SIDA SIDA ALNMI

cytomegalovirus CMV * X human immunodeficiency virus HIV VIH VIH

tumour necrosis factor alpha TNF X X FNT

electrocardiogram ECG

EKG EKG EKG EKG EKGhjartalnurit

(ECG)

magnetic resonance imaging MRI

MRTX

X

IRM

segulmun

(MRI)percutaneous transluminalcoronary angioplasty

PTCA

X PTKA ACPT

kransavkkun

international unit IU IU or

m.j. I.E. UI

R (IU canbe used)

UI NE a.e.

polyvinylchloride PVC

high density polyethylene HDPE X PEHD

low density polyethylene LDPE

X PEBD

FULL TERM IT LT LV NL NO PL PT RO SK SL SV

angiotensin converting enzyme AKF AKE IECA ECA deoxyribonucleic acid DNR DNS ADN ADN DNA

monoamine oxidase inhibitors

IMAOMAO

i hibit i iMAO-inhibitori MAO- MAO-

hIMAO IMAO IMAO IMAO zaviralci

MAOMAO-

h

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Page 2 of 3

inhibitoriai remmers hemmere MAO hmmare

volume of distribution Vd x activated partial thromboplastintime

DATL *

APTT

X *

half-life t t, t0,5 area under the curve AUC ASC maximum serum concentration Cmax minimum serum concentration Cmin time to maximum concentration tmax

acquired immunodeficiencysyndrome AIDS

SIDA SIDA

cytomegalovirus CMV human immunodeficiency virus IV VIH hivtumour necrosis factor alpha TNF FNT

electrocardiogram EKG EKG EKG EKG EKG EKG EKGmagnetic resonance imaging RMI BMR NMR X IRM NMR X

percutaneous transluminal coronary

angioplasty

PTKA

X

X

international unit UI TV SV IE IE j.m. UI UI i.e. IE

polyvinylchloride PVC PVH PCW high density polyethylene DTPE ABPE X PEID low density polyethylene MTPE ZBPE X PEJD

same abbreviation as in English X no abbreviation available in this language, use full term.

SMALL IMMEDIATE PACKAGING LABELLING ONLY

FULL TERM EN BG CS DA DE EL ES ET FI FR HU IS IT LT LV

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Page 3 of 3

FULL TERM EN BG CS DA DE EL ES ET FI FR HU IS IT LT LV

Intravenous IV i.v. i.v. i.v. i.v. i.v. iv. i.v. e.v. i.v. i.v.Subcutaneous SC s.c. s.c. s.c. s.c. X s.c. sc. s.c s.c. s.c. s.c.

Intramuscular IM i.m. i.m. i.m. i.m. i.m. im. i.m. i.m. i.m. i.m.

FULL TERM EN NL NO PL PT RO SK SL SV

Intravenous IV IV/I.V./i.v./iv

iv / IV iv. i.v.

i.v.i.v.

Subcutaneous SCSC/S.C./s.

c/scsc / SC sc.

s.c.s.c.

s.c.

Intramuscular IM IM/I.M./i.m./im

im / IMim.

i.m.

i.m.i.m.

same abbreviation as in English X no abbreviation available in this language, use full term. although not commonly used.