<Co->Rapporteur><Joint rapporteur><extension of
indication variation <group of variations including an
extension of indication> <updated> assessment report
<Invented Name>
<(Active substance)>
EMEA/H/C/<xxx>
<MAH> <Worksharing applicant (WSA)>:
Note : The initial Rapporteur AR should be used as the basis for the
subsequent rapporteur ARs (as appropriate)and will ultimately be the
basis for the CHMP AR. It is a “living” document which should be
updated during the whole procedure as appropriate after each RSI.
If an RSI is requested, the draft RSI questions are annexed to the
report (see Annex 1). The assessment of the responses to the RSI is
also included in a separate annex, (see Annex 2). In addition, the
relevant sections of the scientific assessment should be
updated(sections 2-5) accordingly (scientific discussion, B/R,
recommendations).
Rapporteur:
Co-rapporteur:
EMA PTL:
Start of the procedure:
<Date of this report>:
<This Assessment report is updated following assessment of the MAH
answer to the RSI adopted by CHMP on:
Deadline for comments:
<Timetable for responses to the CHMP>
The table below should be completed by the EMA PTL after check with MAH
and rapporteurs.
Date of this report:
Submission of written responses by:
Rapporteurs’ assessment report:
<DD Month YYYY>
Comments from CHMP members:
<DD Month YYYY>
CHMP opinion:
<DD Month YYYY>
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 2/33
Table of contents
Important: This Table of Contents should also be included in the EPAR
1. Background information on the procedure .............................................. 5
1.1. Type II < and group of> variation<s> .................................................................... 5
2. Scientific discussion ................................................................................ 7
2.1. Introduction......................................................................................................... 7
2.2. <Non-clinical aspects>.......................................................................................... 7
2.2.1. <Introduction> ................................................................................................. 8
2.2.2. <Pharmacology> ............................................................................................... 8
2.2.3. <Pharmacokinetics> .......................................................................................... 8
2.2.4. <Toxicology> .................................................................................................... 8
2.2.5. Ecotoxicity/environmental risk assessment ........................................................... 8
2.2.6. <Discussion on non-clinical aspects> ................................................................... 9
2.2.7. <Conclusion on the non-clinical aspects> ............................................................. 9
2.3. Clinical aspects .................................................................................................. 10
2.3.1. <Introduction> ............................................................................................... 10
2.3.2. <Pharmacokinetics> ........................................................................................ 10
2.3.3. <Pharmacodynamics> ..................................................................................... 11
2.3.4. < PK/PD Modelling>......................................................................................... 11
2.3.5. <Discussion on clinical pharmacology> .............................................................. 11
2.3.6. <Conclusions on clinical pharmacology> ............................................................ 11
2.4. Clinical efficacy .................................................................................................. 11
2.4.1. <Dose response study(ies)> ............................................................................. 12
2.4.2. <Main study(ies)> ........................................................................................... 12
2.4.3. <Discussion on clinical efficacy> ....................................................................... 15
2.4.4. <Conclusions on the clinical efficacy> ................................................................ 16
2.5. Clinical safety .................................................................................................... 16
2.5.1. <introduction> ................................................................................................ 16
2.5.2. Discussion on clinical safety .............................................................................. 17
2.5.3. <Conclusions on clinical safety> ........................................................................ 18
2.5.4. PSUR cycle ..................................................................................................... 18
2.6. <Risk management plan> ................................................................................... 19
2.7. Update of the product information ........................................................................ 21
2.8. <<Significance> <Non-Conformity> of paediatric studies> ..................................... 22
3. Benefit-risk balance .............................................................................. 23
4. Recommendations ................................................................................. 24
5. Annexes................................................................................................. 30
5.1. Questions raised by the <rapporteur><CHMP> ...................................................... 30
6. Appendix ............................................................................................... 33
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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List of abbreviations
<Text>
Please provide a comprehensive list for all abbreviations used
throughout the assessment report (quality, nonclinical, clinical).
Important: This List of Abbreviations should also be included in the
EPAR!
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 4/33
1. Background information on the procedure
1.1. Type II < and group of> variation<s>
Pursuant to <Article 16 for single><7.2 for grouped> variation<s> of Commission Regulation (EC) No
1234/2008, <MAH> submitted to the European Medicines Agency on <date> an application for a
variation <group of variation<s> including an extension of indication <, following a worksharing
procedure according to Article 20 of Commission Regulation (EC) No 1234/2008>.
This application concerns the following medicinal product<s>:
Extend table as needed in case of a WS procedure
<International non-proprietary name>
Medicinal product:
Presentations:
<Common name>:
Product Name1
See Annex A
<Product Name 2>
See Annex B
[in case of
MRP/DCP
products]
The following variation<s> <was> <were> requested <in the group>:
Variation(s) requested
C.1.6 a)
Type
Addition of a new therapeutic indication or modification of
II
an approved one
<Class num –
<Scope>
OpinionAll>.
[legislation clssification]
<var
type>
Include the precise REQUESTED scope of the respective variation(s) as
text following the table above, using the following formula:
The <MAH> <WSA> applied for a <new> <an extension of the> indication for <the treatment of
xxx>. Consequently, the MAH proposed the update of section<s> X, X, and X of the SmPC. <In
addition, the MAH proposed to <add a warning> <update the safety information> […]. <The Package
Leaflet <and Labelling> were proposed to be updated in accordance.>
<In addition, the <MAH> <WSA> applied for <a><X> variation to update …>
<In addition, the MAH took the opportunity to update the list of local representatives in the Package
Leaflet.>
<Furthermore, the <MAH> <WSA> proposed this opportunity to bring the PI in line with the latest
QRD template version Y.y. >
The <variation> <group of variations> proposed amendments to the <SmPC>, <Annex II><127a>,
<Labelling> and <Package Leaflet.>
For all submissions, information related to the type of application
(orphan, paediatric, scientific advice..) need to be filled in. Please
tick the box below when appropriate.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 5/33
This application concerns:
Information related to orphan status, similarity and orphan market
exclusivity :
An orphan medicinal product designated on <date> for the following indication <insert the
orphan indication if it relates to the indication in the MAA>.
The new indication, which is the subject of this application, falls within the above mentioned
orphan designation.>
The new indication, which is the subject of this application, falls within a separate orphan
designation EU/../../… granted on <date>.
A critical report assessing possible similarity with authorised orphan medicinal products has been
submitted by the MAH.
The MAH submitted a claim for derogation of market exclusivity (under Art 8.3) related to :
the holder of the marketing authorisation for the original orphan medicinal product has given his
consent to the applicant .
the holder of the marketing authorisation for the original orphan medicinal product is unable to
supply sufficient quantities of the medicinal product.
the applicant can establish in the application that the medicinal product, although similar to the
orphan medicinal product already authorised, is safer, more effective or otherwise clinically superior.
There is no claim for derogation of market exclusivity in the application.
Information on paediatric requirements
This application concerns a product with :
a PIP
a class waiver
a product specific waiver
not applicable
The PIP is
completed
not yet completed as some measures were deferred
The PDCO issued an opinion on compliance for the PIP <insert decision number for the PIP eligible
for the reward
Scientific advice/ protocol assistance
The applicant received:
CHMP Scientific Advice
Quality
non clinical
CHMP Protocol Assistance on <date> pertaining to
clinical aspects
paediatric development
The applicant did not seek scientific advice or Protocol assistance at the CHMP.
Additional data protection/marketing exclusivity
The applicant requested consideration of one year data protection (Article 14(11) of Regulation (EC)
726/2004).
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 6/33
The applicant requested consideration of marketing exclusivity (Article 10(5) of Directive
2001/83/EC).
The applicant requested consideration for a change in the legal status classification (Article 74a of
Directive 2001/83/EC).
In case any of the 3 above options apply, a separate CHMP AR should be
produced and included as an annex to this report.
2. Scientific discussion
The applicable section(s) and subheading(s) should be completed. For
further instruction on how to complete the non clinical and clinical
aspects, please refer to the CHMP initial MA guidance template.
Note : Occasionally, in case of extensive clinical data submitted
within the extension of indication variation application, a separate
clinical assessment report can be prepared in addition to this report
similarly to Initial Marketing authorisation procedures.
For claimed indications that are not planned to be approved by the CHMP
(even if a positive opinion is foreseen i.e. update of SmPC section
5.1. instead of section 4.1), sufficient details should be given so as
to allow an understanding of the reasons for not approving such
indications.
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
with the relevant information.
2.1. Introduction
A brief statement on the medicinal product and pharmacotherapeutic
action, problem statement and rationale for the proposed change
including aspects of developments (scientific advice, paediatric
investigation plan, orphan indication…) should be provided here.
2.2. <Non-clinical aspects>
If no non-clinical data is submitted in the application, the statement
below should be added:
No new clinical data have been submitted in this application, which was considered acceptable by the
CHMP.
If new non-clinical data is submitted in the application see below
recommendations:
In general, the applicable section(s) and subheading(s) of the initial
MA guidance template should be followed for the non-clinical aspects.
Note that headings are optional and should be used as applicable, (e.g.
carcinogenicity, juvenile animal studies, local tolerance..)
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 7/33
2.2.1. <Introduction>
Summarise briefly the non-clinical data (e.g. previously submitted and
assessed in previous applications)from the EPAR/SmPC as appropriate.
Only sections relevant to the data submitted should be detailed.
Mention should be given on how the updated information is reflected in
the SmPC.
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
with the relevant information.
2.2.2. <Pharmacology>
<Primary pharmacodynamic studies>
<Secondary pharmacodynamic studies>
<Safety pharmacology programme>
<Pharmacodynamic drug interactions>
2.2.3. <Pharmacokinetics>
2.2.4. <Toxicology>
<Single dose toxicity>
<Repeat dose toxicity>
<Genotoxicity>
<Carcinogenicity>
<Reproduction toxicity>
<Toxicokinetic data>
<Local tolerance>
<Other toxicity studies>
2.2.5. Ecotoxicity/environmental risk assessment
Where applicable, environmental risk studies should be included and
assessed with extensions of indication, unless justified according to
the current ERA guideline (CPMP/SWP/4447/00).
As a principle, the initial MA CHMP AR guidance should be followed to
complete this section.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 8/33
The assessment should provide an update on the risks of the product for
the environment focussing on the changes in the use of the product in
relation to this application.
In case of Request for Supplementary Information proposed, the
scientific discussion should be updated as appropriate with the
relevant information.
If updated/new tests are performed, the ERA summary table should be
provided here only for these data (refer to initial guidance template
for initial MAA).
2.2.6. <Discussion on non-clinical aspects>
The discussion should address primarily the non-clinical data submitted
in the application. Where relevant, reference to existing non clinical
data could be provided here.
E.g. Any difference of the existing non clinical data (ie new target
organ, new toxicity, different safety margin due to higher strength
should be highlighted for example) should be mentioned in the
discussion.
Ensure correspondence with amendment of SmPC where relevant
(particularly 5.3 Preclinical safety data but also other sections as
appropriate). In situations, where there is absence or lack of
information, this could be stated in the SmPC.
In case of Request for Supplementary Information proposed, the
scientific discussion should be updated as appropriate with the
relevant information (eg update of toxicity results, juvenile animal
study results…).
<Assessment of paediatric data on non-clinical aspects>
2.2.7. <Conclusion on the non-clinical aspects>
Please choose the appropriate proposal in relation to the ERA
assessment
The updated data submitted in this application <do not>lead to a significant increase in environmental
exposure further to the use of <active substance>.
Please choose one of the following options below:
- Considering the above data, <active substance> is not expected to pose a risk to the environment.
- Considering the above data, <active substance> should be used according to the precautions stated
in the SPC in order to minimize any potential risks to the environment.
In case some additional ERA studies are requested, please use the
following paragraphs.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 9/33
<In the context of the obligation of the MAH to take due account of technical and scientific progress,
the CHMP recommends the following points <for further investigation><to be addressed:>
Obligation to complete post-authorisation measures: In a limited number
of cases, non-clinical data that are considered as “key” to the benefit
risk balance in the new indication may be requested as a condition of
the MA. In case non-clinical issues have been identified for inclusion
in Annex II as conditions, use the following statement. Any measure
identified as a condition needs to be well motivated in the CHMP AR,
notably the need for a condition should be explained in the context of
a positive benefit/risk balance:
<The CHMP considers the following measures necessary to address the non clinical issues:>
2.3. Clinical aspects
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion (eg pharmacokinetics,
pharmacology, efficacy, safety...) should be updated as appropriate
with the relevant information.
2.3.1. <Introduction>
GCP
<The Clinical trials were performed in accordance with GCP as claimed by the applicant>
<The applicant has provided a statement to the effect that clinical trials conducted outside the
community were carried out in accordance with the ethical standards of Directive 2001/20/EC.>
•
Tabular overview of clinical studies
2.3.2. <Pharmacokinetics>
<Absorption>
<Distribution>
<Elimination>
<Dose proportionality and time dependencies>
<Special populations>
Age 65-74
(Older subjects number
/total number)
Age 75-84
(Older subjects number
/total number)
Age 85+
(Older subjects number
/total number)
PK Trials
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 10/33
<Pharmacokinetic interaction studies>
<Pharmacokinetics using human biomaterials>
2.3.3. <Pharmacodynamics>
<Mechanism of action>
<Primary and secondary pharmacology>
2.3.4. < PK/PD Modelling>
2.3.5. <Discussion on clinical pharmacology>
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
with the relevant information.
2.3.6. <Conclusions on clinical pharmacology>
Obligation to complete post-authorisation measures: In a limited number
of cases, pharmacology related data that are considered as “key” to the
benefit risk balance in the new indication may be requested as a
condition of the MA. In case pharmacology related issues have been
identified for inclusion in Annex II as conditions, use the following
statement. Any measure identified as a condition needs to be well
motivated in the CHMP AR, notably the need for a condition should be
explained in the context of a positive benefit/risk balance:
<The CHMP considers the following measures necessary to address the issues related to
pharmacology:>
2.4. Clinical efficacy
In case of Request for Supplementary Information proposed, the
scientific discussion should be updated as appropriate with the
relevant information.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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2.4.1. <Dose response study(ies)>
2.4.2. <Main study(ies)>
<Title of study>
Methods
Study participants
Treatments
Objectives
Outcomes/endpoints
Sample size
Randomisation
Blinding (masking)
Statistical methods
Results
Participant flow
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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Excluded (n=…)
Not meeting Inclusion
criteria
Refused to participate
(n=…)
Other reasons (n=…)
Analysis
Follow-up
Allocation
Enrolment
Assessed for
Eligibility (n=…)
Randomised
(n=…)
Allocated to intervention (n=…)
Received allocated intervention
(n=..)
Did not receive Allocated
intervention; give reasons (n=..)
Allocated to intervention
(n=…)
Received allocated intervention
(n=..)
Did not receive Allocated
intervention; give reasons
(n=..)
Lost to follow-up; give
reasons (n=..)
Discontinued
intervention; give
reasons (n=..)
Lost to follow-up; give
reasons (n=..)
Discontinued
intervention; give
reasons (n=..)
Analysed (n..)
Excluded from analysis;
give reasons (n=..)
Analysed (n..)
Excluded from analysis;
give reasons (n=..)
Recruitment
Conduct of the study
Baseline data
Numbers analysed
Outcomes and estimation
Ancillary analyses
Summary of main study(ies)
The following tables summarise the efficacy results from the main studies supporting the present
application. These summaries should be read in conjunction with the discussion on clinical efficacy as
well as the benefit risk assessment (see later sections).
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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Table 1. Summary of Efficacy for trial <trial>
Title: <title>
Study identifier
<code>
Design
<free text>
Duration of main phase:
<time>
Duration of run-in phase:
<time> <not applicable>
Duration of extension phase:
<time> <not applicable>
Hypothesis
<Superiority> <Equivalence> <Non-inferiority> <Exploratory: specify>
Treatment groups
<group descriptor>
<treatment>. <duration>, <number
randomised>
<group descriptor>
<treatment>. <duration>, <number
randomised>
<group descriptor>
<treatment>. <duration>, <number
randomised>
Endpoints and
<Co-
definitions
>Primary
<label>
<free text>
<label>
<free text>
<label>
<free text>
endpoint
<Secondary>
<other:
specify>
endpoint
<Secondary>
<other:
specify>
endpoint
Database lock
<date>
Results and analysis
Analysis
Primary analysis
description
Analysis population
<Intent to treat> <Per protocol> <other: specify>
and time point
<time point>
description
Descriptive statistics
Treatment group
<group
<group
<group
descriptor>
descriptor>
descriptor>
<n>
<n>
<n>
<endpoint>
<point
<point
<point
(<statistic>)
estimate>
estimate>
estimate>
<variability
<variability>
<variability>
<variability>
<endpoint>
<point
<point
<point
(<statistic>)
estimate>
estimate>
estimate>
and estimate
variability
Number of
subjects
statistic>
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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<variability
<variability>
<variability>
<variability>
<endpoint>
<point
<point
<point
(<statistic>)
estimate>
estimate>
estimate>
<variability
<variability>
<variability>
<variability>
statistic>
statistic>
Effect estimate per
<Co->Primary
Comparison groups
<group descriptors>
comparison
endpoint
<test statistic>
<point estimate>
<variability statistic>
<variability>
P-value
<P-value>
<<Co->Primary>
Comparison groups
<group descriptors>
<Secondary>
<test statistic>
<point estimate>
<other: specify>
<variability statistic>
<variability>
endpoint
P-value
<P-value>
<<Co->Primary >
Comparison groups
<group descriptors>
<Secondary>
<test statistic>
<point estimate>
<other: specify>
<variability statistic>
<variability>
endpoint
P-value
<P-value>
Notes
<free text>
Analysis
<Secondary analysis> <Co-primary analysis> <Other, specify: >
description
<Analysis performed across trials (pooled analyses and meta-analysis)>
<Clinical studies in special populations>
Age 65-74
(Older subjects number
/total number)
Age 75-84
(Older subjects number
/total number)
Age 85+
(Older subjects number
/total number)
Controlled Trials
Non Controlled trials
<Supportive study(ies)>
2.4.3. <Discussion on clinical efficacy>
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated here as
appropriate with the relevant information (e.g. updated methods,
results, additional statistical analysis, conclusions …) and reflected
also in the previous sections, 2.4.1, 2.4.2 as appropriate).
<Invented Name>
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variations including an extension of indication> <updated> assessment report
Rev.04.14
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<Design and conduct of clinical studies>
<Efficacy data and additional analyses>
<Additional expert consultation>
<Assessment of paediatric data on clinical efficacy>
2.4.4. <Conclusions on the clinical efficacy>
Obligation to complete post-authorisation measures: In a limited number
of cases, efficacy related data that are considered as “key” to the
benefit risk balance in the new indication may be requested as a
condition of the MA. In case efficacy issues have been identified for
inclusion in Annex II as conditions, use the following statement. Any
measure identified as a condition needs to be well motivated in the
CHMP AR, notably the need for a condition should be explained in the
context of a positive benefit/risk balance:
<The CHMP considers the following measures necessary to address issues related to efficacy:>
2.5. Clinical safety
2.5.1. <introduction>
A brief summary of the existing safety profile of the medicinal product
in the existing indication should be provided here.
The updated safety data should consider the experience available from
all patients exposed and therefore should be presented as an integrated
analysis pertaining to the updated claimed indication where applicable.
However specific study related features should be described and the
CHMP interpretation provided.
In case of Request for Supplementary Information proposed, the
scientific discussion should be updated as appropriate with the
relevant information (e.g. updated adverse event analysis…).
<Patient exposure>
<Adverse events>
<Serious adverse event/deaths/other significant events>
<Laboratory findings>
<Safety in special populations>
MedDRA Terms
Age <65
number
(percentage)
Age 65-74
number
(percentage)
Age 75-84
number
(percentage)
Age 85+
number
(percentage)
<Invented Name>
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variations including an extension of indication> <updated> assessment report
Rev.04.14
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Total AEs
Serious AEs – Total
- Fatal
- Hospitalization/prolong
existing hospitalization
- Life-threatening
- Disability/incapacity
- Other (medically significant)
AE leading to drop-out
Psychiatric disorders
Nervous system disorders
Accidents and injuries
Cardiac disorders
Vascular disorders
Cerebrovascular disorders
Infections and infestations
Anticholinergic syndrome
Quality of life decreased
Sum of postural hypotension,
falls, black outs, syncope,
dizziness, ataxia, fractures
<other AE appearing more
frequently in older patients>
<Safety related to drug-drug interactions and other interactions>
<Discontinuation due to adverse events>
<Post marketing experience>
2.5.2. Discussion on clinical safety
Any new safety concern arising from the new population should be
highlighted and discussed in this section. A summary of the full safety
profile for all indications could be envisaged highlighting differences
where appropriate. (eg, different safety profile in the paediatric
population).
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
with the relevant information.
The summary of the safety profile should be consistent with the
important identified risks mentioned in the Safety Specification of the
Risk management plan. Any new risk identified from the updated
application should be fist discussed in the safety section and also
mentioned in the RMP section. It should also be highlighted if the
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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medicinal product did not have an RMP previously and an RMP is firstly
introduced in this application.
Conclusion on what key finding should be reflected in the SPC, the RMP,
what key findings or uncertainties should be reflected in the benefitrisk assessment.
The need for additional post marketing studies to be considered as an
obligation should be discussed as appropriate. Justification as to why
these data are considered as post approval data not precluding granting
of an authorisation should be elaborated.
<Additional expert consultations>
<Assessment of paediatric data on clinical safety>
2.5.3. <Conclusions on clinical safety>
Any new safety concern arising from the new population, as appropriate
should be provided here in relation to the known safety profile of the
drug.
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
with the relevant information.
If need for additional post marketing studies to be considered as an
obligation. This should be summarised here with rationale as to why
these data are requested as post approval data not precluding granting
of an authorisation.
Obligation to complete post-authorisation measures: In a limited number
of cases, in the context of a standard MA safety related data that are
considered as “key” to the benefit risk balance in the new indication
may be requested as a condition of the MA. In case safety issues have
been identified for inclusion in Annex II , 127a, asconditions, use the
following statement. Any measure identified as a condition needs to be
well motivated in the CHMP AR, notably the need for a condition should
be explained in the context of a positive benefit/risk balance:
<The CHMP considers the following measures necessary to address issues related to safety:>
2.5.4. PSUR cycle
Mention here if the PSUR cycle needs to be amended or not based on the
data submitted in the application or the new population in which the
product is proposed to be used including a rationale.
The next PSUR cycle should also be stated here, by giving the new
frequency and the next data lock point as of when this is required to
be applied.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
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<The PSUR cycle remains unchanged.>
<The PSUR cycle for the medicinal product should follow a <half-yearly> <yearly> cycle until
otherwise agreed by the CHMP>.
The next data lock point will be < date>.
The annex II related to the PSUR, refers to the EURD list which <remains unchanged> < need to the
updated>.
2.6. <Risk management plan>
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
with the relevant information.
POSITIVE OPINION (POSITIVE B/R)
The CHMP received the following PRAC Advice on the submitted Risk Management Plan:
[Choose one of the following options, based on the latest “PRAC RMP
Advice and assessment overview” document, or ”PRAC endorsed PRAC
Rapporteur Assessment Report” (in case of adoption of the latest RMP
version without plenary discussion). The respective document should be
included in the CHMP Assessment Report as an attachment.]
[A)
If the RMP is acceptable:]
The PRAC considered that the risk management plan version <X> is acceptable. <In addition, minor
revisions were recommended to be taken into account with the next RMP update>. The <PRAC
advice><PRAC endorsed PRAC Rapporteur assessment report> is attached.
[B) If the RMP could be acceptable with revisions required before
opinion.]
The PRAC considered that the risk management plan version <X> could be acceptable if the applicant
implements the changes to the RMP as described in the <PRAC advice><PRAC endorsed PRAC
Rapporteur assessment report>.
[C) If the RMP is not acceptable.]
The PRAC considered that the risk management plan version <X> is not acceptable. Details are
provided in the <PRAC advice><PRAC endorsed PRAC Rapporteur assessment report>.
The <Co->Rapporteur endorsed this advice <with the following changes :><without changes.>
[In case the CHMP asked for changes to the RMP, please expand. Please
specify all elements where the CHMP deviated from the PRAC advice and
the scientific justification for the decision to deviate from the PRAC
advice.]
<The applicant implemented the changes in the RMP as requested by <PRAC> <and/or> <CHMP>.>
[Ensure that the changes requested by the PRAC and CHMP have been
implemented prior to the opinion]
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 19/33
The <Co->Rapporteur endorsed the Risk Management Plan version <X> with the following content:
Safety concerns
[Copy here the full text including tables from section 2.1 (PRAC
advice) or 5.8 (PRAC Rapp RMP AR) “Safety concerns”.
If the applicant provided a revised RMP after PRAC, please copy table
from final RMP Part II Module SVIII.]
Pharmacovigilance plan
[Copy here the full text including tables from section 2.2 (PRAC
advice) / 6.1 (PRAC Rapp RMP AR) “Pharmacovigilance plan”
If the applicant provided a revised RMP after PRAC, please copy final
RMP table III.5.1 (only studies of categories 1-3).]
Risk minimisation measures
[Copy here the full text including tables from section 2.3 (PRAC
advice) / 8 (PRAC Rapp RMP AR) “Risk minimisation measures for <product
name(s)>”
If the applicant provided a revised RMP after PRAC, please copy table
from final RMP section V.3.]
NEGATIVE OPINION (NEGATIVE B/R)
The CHMP received the following PRAC Advice on the submitted Risk Management Plan:
[Choose one of the following options, based on the latest “PRAC RMP
Advice and assessment overview” document, or ”PRAC endorsed PRAC
Rapporteur Assessment Report” (in case of adoption of the latest RMP
version without plenary discussion). Either document should be included
in the CHMP Assessment Report as an attachment.]
A) If the RMP was acceptable for the PRAC:
The PRAC considered that the risk management plan version <X> is acceptable. <In addition, minor
revisions were recommended to be taken into account with the next RMP update>. The <PRAC
advice><PRAC endorsed PRAC Rapporteur assessment report> is attached.>
B) If the RMP could be acceptable with revisions required before
opinion:
The PRAC considered that the risk management plan version <X> could be acceptable if the applicant
implements the changes to the RMP as described in the <PRAC advice><PRAC endorsed PRAC
Rapporteur assessment report>.
C) If the RMP is not acceptable.
The PRAC considered that the risk management plan version <X> is not acceptable. Details are
provided in the <PRAC advice><PRAC endorsed PRAC Rapporteur assessment report>.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 20/33
The <Co->Rapporteur, having considered the data submitted in the application was of the opinion that
due to the concerns identified with this application, the risk management plan cannot be agreed at this
stage.
2.7. Update of the product information
[Changes to the Product Information should be summarised here
(presented as new text underlined and deleted text marked as
strikethrough) particularly those related to sections 4.1, 4.2, 4.3,
4.4 as appropriate. However, if the changes are too extensive, they can
be cross refered to the full PI in attachment. (eg sections 4.8, 5.1…)
Following assessment of the responses to a Request for Supplementary
Information, the scientific discussion should be updated as appropriate
in line with the RSI assessment report provided in annex 2 of this
report.
As a consequence of this new indication, sections X, Y, Z of the SmPC have been updated.
<Particularly, a new warning with regard to XXX has been added to the product information.> The
Package Leaflet has been updated accordingly.
In case of grouped variations changes related to each variation should
be highlighted separately.
<In addition, changes related to sections X,Y … of the SmPC have been updated with regard to XXXX>.
<Changes were also made to the PI to bring it in line with the current Agency/QRD template, SmPC
guideline and other relevant guideline(s) [e.g. Excipients guideline, storage conditions, Braille, etc…],
which were reviewed <by QRD> and accepted by the CHMP.>
[If user consultation results were submitted within this procedure,
please discuss here as well.]
<The results of the user consultation with target patient groups on the package leaflet submitted by
the MAH show that the package leaflet meets the criteria for readability as set out in the Guideline on
the readability of the label and package leaflet of medicinal products for human use.>
<The results of the user consultation with target patient groups on the package leaflet submitted by
the MAH show that the package leaflet does not yet meet the criteria for readability as set out in the
Guideline on the readability of the label and package leaflet of medicinal products for human use. The
applicant will address the following minor issues concerning the user consultation with target patient
group population on the package leaflet.>
<No full user consultation with target patient groups on the package leaflet has been performed on the
basis of a bridging report making reference to <name(s) of product(s)>. The bridging report submitted
by the applicant has been found <acceptable> <unacceptable>.>
<In addition, the list of local representatives in the PL has been revised to amend contact details for
the representative(s) of <MS A, B, > >
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 21/33
2.8. <<Significance> <Non-Conformity> of paediatric studies>
[Attention, if a paediatric validation has occurred for this
application submission or if this submission includes a paediatric
study mentioned in the PIP, please use relevant section on Paediatric
in case CHMP Denied conformity]
The assessment of significance of paediatric studies is a transitional
measure and is only needed in situation (3) below. A completed PIP is a
prerequisite for the need of this assessment and conclusion.
1- PIP containing only studies completed before 26 January 2007 -> NOT
subject of assessment of significance of studies (and not entitled for
the reward); No need of this section in the CHMP AR.
2- PIP containing at least one study initiated after 26 January 2007->
by default this study is considered ‘significant’ and NO need for the
assessment of the significance of any other study(ies) included in the
PIP; No need of this section in the CHMP AR.
3- PIP containing only studies completed before 26 January 2007 AND/OR
studies initiated before this date but completed after -> only the
studies which were initiated before this date and completed after
should be considered for assessment of the significance of studies;
This section is needed in the CHMP AR.
The CHMP is of the opinion that <study(ies) identifier>, which <is><are> contained in the agreed
Paediatric Investigation Plan, which is <completed> <not yet completed>, and <has><have> been
completed after 26 January 2007, <is> <are> <not> considered as significant.
Where the significance of studies has to be assessed and there is a
positive outcome, provide a brief summary of the studies considered
significant and a concise justification according to the criteria of
the guideline
Where the significance of studies has to be assessed and there is a
negative outcome, this section should be extended to provide a more
detailed justification.
Only in case the CHMP denies conformity with the agreed PIP, whereas
the compliance check performed by the PDCO was positive, add the
following sentence (this may be due to unexpected aspects not obvious
at time of the compliance check performed by the PDCO (e.g. inspection
finding, discrepancy in the number of patients, etc)):
The CHMP concluded that <study(ies) identifier> <is><are> not in conformity with the agreed
Paediatric Investigation Plan as set out in Article 24 of Regulation (EC) No 1901/2006. The detailed
grounds for the non-conformity conclusion are as follows:
In case this section is needed, a detailed justification should be
provided.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 22/33
3. Benefit-risk balance
[Include here a critical review of the data underlining the proposed
extension of indication request and its impact on the benefit risk
balance of the product.]
Following assessment of the responses to a Request for Supplementary
Information, the Benefit Risk balance should be updated as appropriate
with the relevant information.
Benefits
Beneficial effects
Uncertainty in the knowledge about the beneficial effects
Risks
Unfavourable effects
Uncertainty in the knowledge about the unfavourable effects
Benefit-risk balance
Importance of favourable and unfavourable effects
Benefit-risk balance
Discussion on the benefit-risk balance
Note regarding Obligation to complete post-authorisation measures:
In a limited number of cases, data that are considered as “key” to the
benefit risk balance of the new indication may be requested as a
condition of the MA. It should be made clear why there is a need for a
condition(s) as a part of annex II in the context of this variation for
a new indication that does not preclude the recommendation of a
positive benefit risk balance.
In case issues have been identified for inclusion in Annex II as
conditions, use the following statement. Any measure identified as a
condition needs to be well motivated in the CHMP AR, notably the need
for a condition should be explained in the context of a positive
benefit/risk balance.
<The CHMP considers the following measures necessary <to address the nonclinical issues> <to
address the issues related to pharmacology> <to address issues related to efficacy> <to address
issues related to safety>:>
[In case of safety-related requests by the CHMP (i.e. cumulative safety
review to be submitted), please include the following sentence:]
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 23/33
<In addition, the CHMP considered that the applicant should submit the following safety data <within X
months> <the next PSUR>:>
4. Recommendations
Please choose one of the following options:
The application for < scope of the application > is not approvable since < major objection> and
<other concerns> <has><have> been identified, which preclude a recommendation at the present
time.
The application for <scope of the application> could be approvable since other concerns
<has><have> been identified, which preclude a recommendation at the present time.
The details of these <major objections>< other concerns> are provided in Annex <> (RSI 1) and
should be addressed in writing <and in an oral Explanation>.
The application for <scope of the application> is approvable <since other concerns <major
objections> <has><have> all been resolved>.
Following assessment of the responses to a Request for Supplementary
Information proposed, the Recommendation should be updated as
appropriate.
<Final > Outcome
Positive recommendation
<Based on the review of the submitted data, the CHMP considers the following <group of>
variation<s> acceptable and therefore recommends <, by a majority of {number} out of {number}
votes,> the variation(s) to the terms of the Marketing Authorisation, concerning the following
change(s):
Variation(s) accepted
<Classification>
Type
<Scope>
<var type>
[legislation classification]
<Classification>
<Scope>
<var type>
[legislation classification]
Add final precise scope accepted, using the following “formula”.
Extension of Indication to include <new indication/population> for <product>.
As a consequence, update of section<s> X, X, and X of the SmPC in order to <add a warning>
<update the safety information> […]. <The Package Leaflet <and Labelling> is/are updated in
accordance.>
<In addition, the MAH took the opportunity to update the list of local representatives in the Package
Leaflet.>
<Furthermore, the PI is being brought in line with the latest QRD template version Y.y. >
<This variation application was submitted following the finalisation of an urgent safety restriction
procedure.>
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 24/33
The requested <variation><group of variations><worksharing procedure><grouped worksharing
procedure> proposed amendments to the <SmPC>, <Annex II>, <Labelling> and <Package Leaflet.>
Negative recommendation
<Based on the review of the submitted data,> <In addition,>the CHMP considers the following <group
of> variation<s> not acceptable and therefore does not recommend <, by a majority of {number} out
of {number} votes,> the variation(s) to the terms of the Marketing Authorisation, concerning the
following change(s):
Variation(s) rejected
Type
<Class num – Opinion
<Scope>
Refused>.
[legislation classification]
<Class num – Opinion
<Scope>
Refused>.
[legislation classification]
<var type>
<var type>
Add final precise scope refused, using the above mentioned “formula”.
Grounds for refusal:
[Include grounds for non-acceptance in case of negative opinion, as
also reflected in Annex IV to this opinion]
In case of changes to the conditions in Annex II use the following
sentence and ONLY use the appropriate text where changes to the Annex
II are being introduced within this procedure:
<This CHMP recommendation is subject to the following <new> <amended> condition<s>: >
<The CHMP is of the opinion that the following obligation has been fulfilled, and therefore recommends
its deletion from the Annex II:>
<Conditions and requirements of the marketing authorisation >
<Risk management system> <and PSUR cycle>
<The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1 of the
marketing authorisation, is in place and functioning before and whilst the product is on the market.>
<The MAH shall perform the pharmacovigilance activities detailed in the Pharmacovigilance Plan, as
agreed in {insert version reference} of the Risk Management Plan (RMP) presented in Module 1.8.2 of
the marketing authorisation and any subsequent updates of the RMP agreed by the CHMP.>
<As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
In addition, an updated RMP should be submitted:
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
at the request of the EMA>
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 25/33
Use the below statement in case a substance is listed in the published
EURD list.
<The marketing authorisation holder shall submit periodic safety update reports for this product in
accordance with the requirements set out in the list of Union reference dates (EURD list) ) provided for
under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-portal.>
Conditions or restrictions with regard to the safe and effective use of the medicinal product
•
Risk management plan (RMP)
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreeed subsequent
updates of the RMP.
[The rapporteur should specify a time schedule for routine submission
of updates to the RMP. In the absence of a different CHMP specified
time schedule, the default is that RMPs should be submitted annually
until renewal and every three years once an indefinite licence is
granted]
An updated RMP should be submitted:

At the request of the European Medicines Agency;

Whenever the risk management system is modified, especially as the result of new information
being received that may lead to a significant change to the benefit/risk profile or as the result
of an important (pharmacovigilance or risk minimisation) milestone being reached.
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same time.
[When justified on a proportional risk-based approach, the CHMP
could specify the deadline for the submission of the next update to
the RMP. In that case, please include
<An updated RMP shall be submitted by {CHMP agreed deadline}>]
[For products submitted before 2nd of July without a risk management
plan:]
<Not applicable.>
•
<Additional risk minimisation measures>
All additional risk minimisation measures from the RMP (e.g. controlled
distribution, educational material, pregnancy prevention programmes) to
be listed/summarised here in collaboration with the RM PTM. Any
measures already described in Annex II should not be copied
automatically into the Annex related to Art. 127a. Use of an Annex 127a
should be exceptional and limited to activities that require specific
actions from the member states.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 26/33
•
<Obligation to conduct post-authorisation measures>
The MAH shall complete, within the stated timeframe, the below measures:
[All post-authorisation measures that are imposed as a condition to the
MA to be listed here.
If the preferred methodology of an imposed PASS is either
interventional or non-interventional, please state this clearly in the
study description.
Due date: please only include the projected time point of the final
study report. The exact milestones regarding protocol
submission/agreement and interim reports should be detailed in the CHMP
AR/RMP, as appropriate and included in Siamed for tracking/chasing.]
Description
Due date
Conditions or restrictions with regard to the safe and effective use of the medicinal product
to be implemented by the Member States.
<not applicable>
Actual risk minimisation activities to be implemented by the Member
States being NEWLY introduced based on this extension of indication
application should be listed here. These should mirror the information
under the section above, unless there are risk minimisation activities
specific to single Member States.
This annex should be provided for whenever there are ‘Conditions or
restrictions with regard to the safe and effective use of the medicinal
product’ specified in Annex IIB (e.g. controlled distribution,
educational material, pregnancy prevention programmes) that require
Member States to ensure their correct implementation. Any exception to
this rule (e.g. set up of surveillance programmes in only a few MS)
should be discussed and reflected in the CHMP AR but not mentioned
here.
<Additional data protection /market exclusivity>
For opinions including a new indication, for which the applicant
claimed an additional year of data/ market exclusivity in accordance
with Art 14(11) of Regulation (EC) No 726/2004 – new indication
submitted within the 8 first years of a MA or in accordance with Art
10(5) of Directive 2001/83/EC - new indication for a well established
substance
<Furthermore, the CHMP reviewed the data submitted by the <MAH>, taking into account the
provisions of <Article 14(11) of Regulation (EC) No 726/2004> <Article 10(5) of Directive
2001/83/EC>, and <considers> <does not consider> <, by a majority of {number} out of {number}
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 27/33
votes,> that <the new therapeutic indication brings significant clinical benefit in comparison with
existing therapies> [For Art 10(11)] OR that <the <pre-clinical tests> <and> <clinical
studies> carried out in relation to the new indication were significant>[For
Art 10(5)] (see
appendix X).>
[For opinions including a legal status switch, for which the applicant
claimed an additional year of data exclusivity:]
<Furthermore, the CHMP reviewed the data submitted by <the applicant>, taking into account the
provisions of Article 74(a) of Directive 2001/83/EC, and <considers> <does not consider> <, by a
majority of {number} out of {number} votes,> that the <pre-clinical tests> <and> <clinical trials>
submitted in support of the classification of {specify medicinal product name} as ‘medicinal product
not subject to medical prescription’ are significant (see appendix X).>
<Paediatric data>
The statements below regarding paediatric are only needed in case the
application contains paediatric data collected in accordance with a
PIP.
These statements indicate the status of the PIP and whether data is
included in the SmPC/PL and – if appropriate – a statement on
significance in accordance with the above assessment. This will form
the basis of the compliance status of the medicinal product with regard
to the paediatric requirements in order for the EC to issue a
“compliance statement” in view for the MAH to obtaining the reward.
IMPORTANT NOTE REGARDING THE COMPLIANCE STATUS ANNEXED TO THE EC
LETTER: This annex to the letter to the Commission is only needed in
case the application contains paediatric data collected in accordance
with a PIP, that the PIP is fully completed and compliance is confirmed
and that the results of the studies from the PIP have been reflected in
the SmPC through this procedure and/or any previous procedures. It must
not be included if the PIP is not yet fully completed or if the CHMP
denies conformity.
PIP fully or partly completed and paediatric data included in the
assessment:
<Furthermore, the CHMP reviewed the available paediatric data of studies subject to the agreed
Paediatric Investigation Plan <insert relevant PIP decision number(s)> and the results of these studies
are reflected in the Summary of Product Characteristics (SmPC) and, as appropriate, the Package
Leaflet.>
When a CHMP opinion on significant study(ies) is required - see above
related section 2.8
<In accordance with Article 45(3) of Regulation (EC) No 1901/2006, significant studies in the agreed
paediatric investigation plan <insert decision number for the PIP eligible to the reward> have been
completed after the entry into force of that Regulation.>
OR
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 28/33
<No significant studies in the agreed paediatric investigation plan <insert decision number for the PIP
eligible to the reward> have been completed, in accordance with Article 45(3) of Regulation (EC) No
1901/2006, after the entry into force of that Regulation.>
Only in case the CHMP denies conformity with the agreed PIP – see above
related section 2.8
<However, the CHMP is of the opinion that the studies are not in conformity with the agreed paediatric
investigation plan <insert relevant PIP decision number(s)> as set out in Article 24 of Regulation (EC)
No 1901/2006. >
For PIP (completed or not yet completed) including a waiver in a
condition for all subsets of the paediatric population and/or a
deferral, note that a statement is required to be included in section
5.1 of the SmPC according to the revised SmPC guideline.
IN CASE OF RE-EXAMINATION THE BELOW STATEMENTS SHOULD BE FILLED IN AS
APPROPRIATE
Re-examination of the CHMP opinion of <date>
Following the CHMP conclusion that <name of product> was not approvable <provide more details>,
the applicant submitted detailed grounds for the re examination of the grounds for refusal.
Detailed grounds for re-examination submitted by the applicant
Following a request from the applicant at the time of the re-examination, the CHMP convened a
<Scientific Advisory Group (SAG) or Ad Hoc expert Group> inviting the experts to provide their views
on the CHMP grounds for refusal, taking into account the applicant’s response. <…>
The applicant presented in writing <and at an oral explanation> <…>
Report from the SAG
<…>
Overall conclusion on grounds for re-examination
The CHMP assessed all the detailed grounds for re-examination and argumentations presented by the
applicant and considered the views of the Scientific Advisory Group. <…>
Recommendations following re-examination
For the final opinion after re-examination statement, please use the
following beginning of the outcome recommendation:
Based on the arguments of the applicant and all the supporting data on quality, safety and efficacy, the
CHMP re-examined its initial opinion and in its final opinion concluded <by consensus/majority
decision> that
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 29/33
<Include grounds for non-acceptance in case of negative opinion, as also reflected in Annex
IV to this opinion>.
5. Annexes
Annex 1 : <Rapporteur><CHMP><proposed><adopted>
Request for Supplementary Information discussed at <
month> <year> CHMP
5.1. Questions raised by the <rapporteur><CHMP>
1. Non clinical aspects
Major objections
Other concerns
2. Clinical Aspects
<2.1 Efficacy>
Major Objections
Other concerns
<2.2 Safety>
Major Objections
Other concerns
<2.3 RMP>
Major Objections
Other concerns
<3. Product information >
Note: In case of extensive comments on the PI, they can be provided as
a separate attachment of this report. (refer to the detailed assessment
of the RSI in annex).
The <Rapporteur><CHMP> comments to the Product information <is>< are> provided <below><as
an attachment to this report>.
<4. Others >
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 30/33
Annex 2: <Rapporteur><Co-rapporteur><joint
Rapporteur><preliminary><updated> assessment report of
the MAH answer to the Request for Supplementary
Information
Note: The report of the RSI(s) should be drafted by the rapporteurs and
updated following comments received from the CHMP members.
The scientific part of the rapporteur/CHMP AR (sections 2-4) should be
updated in parallel with the relevant information.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 31/33
1. Non clinical aspects
<Major objections>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<Other concerns>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
2. Clinical Aspects
<2.1 Efficacy>
<Major objections>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<Other concerns>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<2.2 Safety>
Major Objections
<Major objections>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<Other concerns>
CHMP question
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 32/33
Summary of MAH answer
Rapporteur <updated>Assessment
<2.3 RMP>
<Major objections>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<Other concerns>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<3. Product information >
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
<4. Others>
CHMP question
Summary of MAH answer
Rapporteur <updated>Assessment
6. Appendix
<<Co-> Rapporteur clinical critical Assessment report>
<Annotated product information>
In case of extensive clinical data submitted within the extension of
indication variation application, a separate clinical assessment report
can be prepared similarly to Initial Marketing authorisation
procedures.
<Invented Name>
<Co->Rapporteur><Joint rapporteur><extension of indication variation <group of
variations including an extension of indication> <updated> assessment report
Rev.04.14
Page 33/33