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CONSULTATION WITH TARGET PATIENT GROUPS -
MEETING THE REQUIREMENTS OF ARTICLE 59(3) WITHOUT
THE NEED FOR A FULL TEST -
RECOMMENDATIONS FOR BRIDGING
Revision 1, April 2009

1. INTRODUCTION

Guidance has already been issued from the CMD(h) which indicates that although all
package leaflets (PLs) for medicines must reflect the results of consultation with
target patient groups (user consultation) and include within the marketing
authorisation (MA), data in module m-1-3-4- of the application [eCTD], not every
leaflet needs to be subject to a separate test. Applicants and marketing authorisation
holders (MAH) may be able to rely on testing applied to PLs for similar products.
The guidance is available from http://www.hma.eu/116.html#irfaq_31_14bfd
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-
2/c/user_consultation_200605.pdf
Additional guidance is available from the European Commission in the guideline on
the readability of the labelling and on the package leaflet. A link to the draft guidance
is attached.
http://ec.europa.eu/enterprise/pharmaceuticals/pharmacos/docs/doc2006/09_2006/rea
dability_consultation_2006_09_25.pdf
This document provides guidance on when, in general, competent authorities will
consider that because they are sufficiently similar in both content and layout, an
applicant/MAH, may rely on the user consulation already carried out for one leaflet to
demonstrate that an other leaflet meets the requirements of article 59(3) of Council
Directive 2001/83/EC. It also provides guidance on the type of evidence which will
need to be provided in support of applications where data in line with the
requirements of article 59(3) of Council Directive 2001/83/EC are required. Even
though some examples are provided within this document this is not exhaustive and
each case will be judged on its merits.
2. SCOPE

The guidance will apply to applications for new MAs, significant variations to MAs,
renewal applications and applications where harmonisation of the PL is undertaken
and which must be accompanied by data demonstrating compliance with article 59(3).

3. DEFINITIONS

Minor changes to content or layout of a document can impact adversely on the
readability. These differences can affect whether or not the resultant PL is clear,
legible and easy to use as required by law. In this guidance the term bridging is used
to describe the situation where, because the leaflets are sufficiently similar in both
content and layout, a successful user consultation on one leaflet can be used to
demonstrate that another leaflet meets the requirements of article 59(3) of Council
Directive 2001/83/EC.
In bridging, a successful user test on one PL [the “parent” PL] can be used to support
a justification for not testing other similar leaflets [“daughter” PLs]. In some
circumstances it may be appropriate for some “daughter” PLs to rely on the results of
testing for more than one “parent” PL. For example it would be possible to refer to
the design and layout of one leaflet and to the content of the leaflet for an other
product.
Since the design and layout of the information is crucial to how the information is
used and understood, “daughter” PLs should be of the same design, layout and writing
style as the “parent” PL in order for bridging to be successful. A bridging proposal
is unlikely to be acceptable to the competent authority where this concept has not
been adhered to.

4.
KEY MESSAGES FOR SAFE USE

A successful user consultation will have identified up-front the key messages for safe
use with the particular medicine in question. For each medicine these messages will
be different although the leaflet will cover the same sort of information in the same
manner. The questionnaire within the protocol which has been submitted with the
application for the “parent” PL will have to address these key messages and provide
evidence that people who are likely to rely on the PL can find and understand these
messages and act appropriately so that the medicine can be used safely. Such a user
consultation could then be relied upon to support a PL drawn up in the same manner
for a closely related medicine. In a bridging report submitted for the “daughter” PL
the key messages for safe use for both the “parent” and “daughter” PLs need not be
identical.
5.
FORMAT, DESIGN AND LAYOUT AND WORDING OF THE PL
The design and layout of the information in the PL is crucial to the way in which patients access the key messages for safe use. Most marketing authorisation holders have a recognisable “house style” in this regard. In order for bridging to be successful both the “parent” and “daughter” PLs should have a common design, layout and style of writing. The following important aspects should be considered: • Headings and sub-headings including consistency of placement • PL dimensions including whether the document is laid out in portrait or • Layout of critical safety sections of the PL
Each different leaflet design (with particular sizes) or variations in format (such as a
booklet, or peelable leaflet) will need to have been the subject of a number of
successful user consultations in order for other leaflets to claim similarity to a
particular format in a bridging study. The number of consultations required for a
particular format will depend on the complexity of the information conveyed in each
case and will be judged on a case-by-case basis.
6.
APPLYING BRIDGING IN PRACTICE

Earlier guidance from CMD(h) (see above) indicated that there may be particular
circumstances where bridging could be used. Each of these is discussed in this
section and acceptance criteria are explored. In all cases the target patient population
for the particular medicines will be similar. However, the PLs of some medicines
may need to be the subject of a specific user consultation particularly where there is
evidence of risk.
(a) Line
Extensions

Bridging will normally be acceptable for PLs for medicines of the same active moiety
for different strengths or routes of administration. In these cases the “parent” PL
should be the one which contains the more/most complex information concerning safe
and effective use. For example the PL for diazepam oral solution could be designated
the “parent” PL for diazepam tablets (“daughter” PL). Where a medicine is
presented in a formulation not normally supplied to patients for self-medication the
relevant PL could be bridged to that for the same medicine which is self-administered.
For example the PL for diazepam injection (“daughter”) could be bridged to the PL
for diazepam oral solution (“parent”).
Where (as in the case of the diazepam example above) potentially similar products
require the patient to understand significantly different methods of administration
different criteria will apply. Examples include but are not restricted to an inhalation
device, an auto-injection pen and a patch. Here it will be important to ensure that the
information in relation to the posology has been the subject of a successful user
consultation. However, a “daughter” PL could rely on user tests carried out on the
PLs associated with more than one product. For example a “double bridge” could be
applied to the PL for a salbutamol inhaler (“daughter”) which could be bridged to a
successful user test for a PL for an oral salbutamol preparation (covers information
relating to the active moiety) and to the PL for a beclometasone product with an
identical inhaler device (covers information relating to delivery).
Where a product includes a new method or route of administration but is otherwise
identical to an existing presentation, the leaflet could be supported by reference to the
data for the existing product accompanied by a focus test concentrating on the new
method or route of administration.
Where a company portfolio includes a range of conventional topical dosage forms
(ointments; creams; eye, ear or nose drops or ointments/creams; scalp applications;
lotions), individual tests of the administration instructions will not normally be
required unless these contain untested pictograms (see below). However, the
requirement remains that the daughter PLs must be of the same design, layout and
writing style.

(b)
Medicines in the same “drug class”

Bridging will normally be acceptable for PLs for medicines in the same therapeutic
class where the key safety information set out in the summary of product
characteristics (and therefore the information in the PL) is similar. It would be
expected that such products would be authorised for similar indications. Importantly
the key messages for safe use with the related medicines should be similar. However,
the format and layout of the PLs to be bridged should also be identical for the reasons
set out above. This means that the “daughter” PL should be revised and drawn up in
a design, layout and linguistic style which conform to the “parent” PL which will
already have been the subject of a successful user consultation.
A therapeutically similar product is defined as a group of medicines which have similar modes of action. The following examples are included but this list is not exhaustive. Bridging across ATC codes is permitted as indicated by Q5 of Q&As on Product Information. For example, results from consultation with target patient groups for a simvastatin-containing medicine could apply to all products in the C10AA group. C10AA01 Another example would be the diuretic bendroflumethiazide: C03AA01 C03AB03 Hydrochlorothiazide and potassium 25mg C03AB04 C03AB06 Trichlormethiazide and potassium In these cases, the chosen “parent” PL will be that containing the widest range of information. As stated in the introduction each case will be judged on its merits. Particular consideration will be given to medicines which are considered to be a “group” simply in terms of the therapy area they cover but which actually contain many different medicines with differing modes of action and key messages for safe use. For example the following medicines will not normally be considered appropriate for successful bridging due to the differing clinical considerations: • Anti-arrythymics such as amiodarone and disopyramide • Anti-epileptics such as valproate, lamotrigine and phenytoin • Disease modifying anti-rheumatics such as gold and penicillamine In therapy areas where there are many different medicines with differing modes of action but the key issues around safe use are much less critical, bridging may be acceptable. The following are given as examples In most cases, the chosen parent PL will be that containing the widest range of information. Same Key Messages for Safe Use

Where the key messages for safe use which have been identified for a range of
medicines are similar and the PLs are designed, laid out and written in an identical
manner bridging here will be easiest to justify.
(d)
Same Patient Population

Medicines within the same therapeutic class are normally used within the same patient population. However, some medicines are used in more than one therapeutic area. An example of this would be glucocorticoids. In such examples “double” bridging can be applied making sure that the “parent” PLs to which the “daughter” PLs are
bridged covers all key messages for safe use.

(e) Combination
medicines

Generally, the PL for the combination medicine should be considered as the “parent”
PL for the purpose of bridging to the individual component “daughter” PLs.
Applicants/MAHs will need to make sure that any key messages for safe use relating
to the individual components have been addressed in the questionnaire submitted in
the protocol for the combination PL. Exceptionally, it may be possible to use the
individual component PLs as the “parent” PLs and bridge to the combination PL as
the “daughter” provided any differences in layout and length of the combination PL
have been the subject of a successful user consultation within the company portfolio.
(f)
Short PLs for medicines with minor therapeutic actions and very low risk
profile.

Short PLs for such products are unlikely to need to be the subject of a specific user
consultation. It will be sufficient to rely on the successful consultations carried out
for other products within the portfolio even though these may not be in the same
therapeutic class. Examples of such medicines are water for injection, aqueous
cream, hypromellose eye drops.

(g) Pictograms

Pictograms used within a company house style will need to be tested as part of a user
consultation. For bridging to encompass pictograms successfully the pictograms in
“daughter” PLs should have the same design, dimensions and colours as those in the
“parent” PL. NOTE In general, pictograms, if used, should be the subject of a
common understanding across all member states.
7.
DRAFTING AND SUBMITTING A SUCCESSFUL BRIDGING
REPORT

Each marketing authorisation will have to address the requirements of Article 59(3)
and include information which demonstrates that patients can find and understand the
information which is necessary for safe and effective use. A bridging report will not
include the original data submitted in respect of the “parent” PL. The user
consultation for the “parent” PL should have been submitted in another application in
and the leaflet approved prior to the approval of the “daughter” PL(s).
Simultaneously to the bridging report, a focused test may be submitted in addition to address 1 or 2 points differing from the parent PL. How much information is required will depend on the relationship between “parent” and “daughter” PLs and there will be a spectrum of complexity of information required. For example, where the leaflet for a 5mg tablet is relying on the user consultation information submitted for the10mg strength of the same product, the bridging report will by necessity be brief. However, where the leaflet for a medicine is relying on the user test submitted in support of a leaflet for a medicine in a different
therapeutic class, a more fulsome report will be required. The issues which will need
to be addressed in bridging report are set out below.
(a)
Identifying the Key Messages for Safe Use

The bridging report will need to discuss first of all the key messages for safe use
within the “daughter” PL and justify how these are covered within the test carried out
on the “parent” PL. Where the key messages are not identical (and this will apply to
many bridged PLs) the bridging report will need to critically appraise these
differences and address the relevance of the questionnaire to the “daughter” PL.
Synergies and similarities in the key messages should be discussed.
(b)
Design and Layout Issues

There will need to be a critical comparison of the design and layout of both
“daughter” and “parent” PLs and synergies and similarities drawn out in support of
the bridging exercise.
(c)
Complexity of Message and Language Used
A critical discussion of the complexity of the messages contained within the “parent” and “daughter” PLs should be presented. The language used in both PLs should be discussed and compared. Again similarities and synergies should be discussed. All reports should address any general issues raised by participants in the user test concerning aspects of the PL which they liked or disliked.

Source: http://www.impf-check.de/de/service/pdf/CMDh_Bridging-Guideline_2009.pdf