18/04/12
Submission of comments on 'GVP Module I –
Pharmacovigilance systems and their quality systems'
(EMA/541760/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
General comment
(To be completed by the
Outcome
(To be completed by the Agency)
Agency)
Clarify the difference between Quality System and PV
System throughout this document
2/7
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 5 – section
Comment: Change the order of importance – safety should be
I.B.4
before legal requirements
Proposed change (if any):

preventing harm from adverse reactions in humans arising
from the use of authorised medicinal products within or
outside the terms of marketing authorisation or from
occupational exposure;

complying with the legal requirements for pharmacovigilance
tasks and responsibilities;
Page 6 – line 155
Comment: For clarity change managerial staff to management
– throughout the document
Proposed change (if any): management should be responsible
for:
Page 8 – line 222
Comment: Insert “to” before patients
Proposed change (if any): all information on the risks of
medicinal products as regards to patients’ or public health,
including
3/7
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 10 – line
Comment: the term “quality objectives” appears 3 times in
293
one sentence
Proposed change (if any): rewrite
Page 10 – line
Comment: clarify what resource documentation is
326
Proposed change (if any):
Page 12 – line
Comment: For clarity change managerial staff to management
391
– throughout the document
Proposed change (if any):
Page 14 – line
Comment: Please provide a list of the countries that require a
463
local QP for PV to be appointed
Proposed change (if any): further information requested
Page 14 – line
Comment: For clarity change managerial staff to management
487
– throughout the document
Proposed change (if any):
Page 15 – line
Comment: For clarity change managerial staff to management
492
– throughout the document
Proposed change (if any):
4/7
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 15 – lines
Comment: for the following sentence - When a marketing
502 to 504
authorisation holder intends to expand its product portfolio,
for example, by acquisition of another company or by
purchasing individual products from another marketing
authorisation holder, the QPPV should be notified early in the
due diligence process in order – this is not always possible due
to confidentialities
Proposed change (if any): consider revising the text
Page 15 – line
Comment: - what is a natural person
528
Proposed change (if any): clarification
Page 17 – line
Comment: add “the before this sentence
585
Proposed change (if any): the monitoring of the use of
terminology, with data entry staff being instructed in the use
of terminology
587 - 589
Comment: This section provides guidance on the timelines for
retention of essential documents describing the PV system.
Proposed change (if any): It would be helpful if this document
provided guidance on what was considered an essential
document for this purpose.
5/7
Line number(s) of
the relevant text
(e.g. Lines 20-23)
589
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: This line and various others refer to the
Implementing Measures. It is confusing to have two
documents to describe the same processes, especially when
they appear to contradict each other – see comment below.
Proposed change (if any): Incorporate all relevant information
from the Implementing Measures into this and other GVP
guidelines, as applicable.
587 – 589
Comment: The timelines given in this section for the retention
590 - 592
of PV system and product related documents (5 & 10 years
respectively) do not agree with the timelines in the draft IM
article 15 (10 and 30 years respectively).
Proposed change (if any): Please clarify the required
timelines.
Page 18 – line
Comment: add “to ensure” to this sentence
618
Proposed change (if any): holder to another organisation, the
marketing authorisation holder shall retain responsibility to
ensure that an
Page 18 – line
Comment: add ”the”
625
Proposed change (if any): included in the pharmacovigilance
system master file (PSMF) [IM Art 4(1)(f)] and a list of the
6/7
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
contractual
Page 22 – line
Comment: remove “for” from the end of the sentence
800
Proposed change (if any): and the Agency shall put in place
the following additional specific quality system processes:
Please add more rows if needed.
7/7
18/04/12
Submission of comments on 'GVP Module II –
Pharmacovigilance system master file'
(EMA/816573/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
(To be completed by the
General comment
Outcome
(To be completed by the Agency)
Agency)
2/6
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
50
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: This line and various others refer to the
Implementing Measures. It is confusing to have two
documents to describe the same processes.
Proposed change (if any): Incorporate all relevant information
from the Implementing Measures into this and other GVP
guidelines, as applicable.
53 - 54
Comment: This section states that there is no requirement for
variations for changes in the content of the PSMF, yet lines
114 to 117 state that amendments to the particulars or
documents referred to in the PSMF shall be submitted via a
variation.
Proposed change (if any): Please could these seemingly
contradictory statements be clarified.
Page 3 line 68
Comment: Need a possessive ‘s after (QPPV)
Proposed change (if any): Add ‘s
Page 4 – line 113
Comment: Change “not longer applicable” to “no longer
applicable”
Proposed change (if any): change not to no
3/6
Line number(s) of
the relevant text
(e.g. Lines 20-23)
121 - 139
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: Since there are instructions regarding the location
of the PSMF, does this mean that if kept electronically, the
server where the file is held electronically must be located
within the EU?
Proposed change (if any): It would be helpful if the issue of
location was clarified as this has caused some considerable
discussion / confusion.
Page 7 – line 228
Comment:– add “it” before “is advised
Proposed change (if any): as above
Page 8 – line 250
Comment:– this should be a bullet point
Proposed change (if any): make this sentence a bullet point
Page 8 – line 255
Comment: can the Agency provide a list of countries in the EU
where it is required to have a local qualified person?
Proposed change (if any): EMA to provide a comprehensive list
of EU countries where it is a legal requirement to have a local
qualified person for PV
Page 9 – line 297
Comment: it is not practical or value added to include actual
copies of signed agreements within the Master File – a list
detailing where agreements are in place should be provided
and the actual agreements available on request
Proposed change (if any): remove the need to include signed
4/6
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
copies of the contracts in the PMF
Page 11 – line
Comment: “to” missing
376
Proposed change (if any): insert “to” before “competent
authorities
384
Comment: This section refers to the Annex of the PSMF.
Proposed change (if any): Since this is the first time the
Annex has been mentioned a cross reference to section
II.B.4.8 should be made.
417 - 426
Comment: Once post-audit CAPA have been implemented, the
note regarding audit findings can be removed from the PSMF.
Proposed change (if any): Clarification is required as to what
is required in the file regarding the audit, after this note is
removed.
Page 12 – line
Comment: how similar do the products in the non-EU
443
countries have to be to the EU authorised products to be
included in the Annex?
Proposed change (if any): - clarification requested
Page 14 –
Comment:– do we have 7 days or can immediate access to
paragraph starting
the PMF be requested
at line 514
Proposed change (if any): – please clarify as this is confusing
5/6
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Please add more rows if needed.
6/6
18/04/12
Submission of comments on 'GVP Module V – Risk
management systems' (EMA/838713/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
General comment
(To be completed by the
Outcome
(To be completed by the Agency)
Agency)
Can we have consistency with the use of the phrase
benefit-risk? It switches between benefit-risk and riskbenefit.
Can we use MAH or Companies or Pharmaceutical
Companies, but not switch between these names in the
document?
Can we use Competent Authorities or Regulatory
Authorities or Regulatory Agencies consistently
2/8
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 4 – line 136
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: In the section “risk minimisation will be tailored to
regional specifics.” What does the term “regional” refer to
Proposed change (if any): Please clarify
Page 6 – line 183
Comment: Safety concern in defined on row 195 and could be
included in the definition here
Proposed change (if any): Important identified risk, important
potential risk or important missing information (also known as
safety concern against important identified risk, potential risk
or important missing information)
Page 6 – line 211
Comment: Where this sentence mentions RMP it appears it
should actually refer to system rather than plan
Proposed change (if any): Although the primary aim and focus
of the RMS remains that of risk 211 management,
Page 7 – lines
Comment: This section appears to refer only to prescription
226-240
medicines – what about OTC medicines?
Proposed change (if any): Include reference to OTC medicines
3/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 8 – line 258
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: The two sentences have different tenses
Proposed change (if any): ICH-E2E defines two basic parts of
a RMP: the safety specification and the pharmacovigilance
plan. It does not include risk minimisation.
Page 8 – line 270
Comment: the word risk before risk management plan is
superfluous - this is not a known phrase
Proposed change (if any): Since a risk management plan is
primarily a pharmacovigilance document,
Page 8 – line 283
Comment: Change this bullet for consistency in the wording
Proposed change (if any): ensuring the implementation of risk
minimisation activities at a national level;
Page 8 – lies 287
- 289
Comment: the following wording is confusing and poorly
written - ensuring marketing authorisation holders of generic
and/or similar biological medicinal products 287 make similar
changes when changes are made to the reference medicinal
product risk minimisation 288 measures;
Proposed change (if any): clarify the wording
Page 9 – line 302
Comment: not well written, can not identify the safety profile
but it can be characterised, remove identify or
4/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Proposed change (if any): characterise the safety profile of the
medicinal product(s) concerned;
Page 9 – line 303
Comment: change the order of the words further and
characterise for clearer meaning
Proposed change (if any): indicate how to further characterise
the safety profile of the medicinal product(s) concerned;
Page 10 – line
Comment: would it make more sense to say plan rather than
334
system?
Proposed change (if any): The risk management plan shall be
proportionate to the identified risks and the potential risks of
the
Page 14 – line
Comment: it may not be appropriate to use patient years or
470
moths for short duration studies
Proposed change (if any): patient time (patient-years, patientmonths) exposed to the medicinal product, as appropriate.
Page 15 – lines
Comment: The following sentence is too long and difficult to
527 - 531
understand - The effects of particular impairments, e.g. renal,
hepatic, or of concomitant disease or medication will be
discussed mainly in the appropriate sections below, but
discussion in this section should reflect the fact that in the
5/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
elderly population many of these factors may co-exist so the
cumulative effect of multiple impairments and multiple
medications should be evaluated.
Proposed change (if any): rewrite sentence or split it
Page 20 – line
Comment: is this the correct referenced section or should it be
727
SVI? V.B.8.6.6. RMP module SV section “Projected postauthorisation use”
Proposed change (if any): check it is the correct section
Page 21 – line
Comment: what does the most important refer to in the
750
following sentence - This RMP section should provide more
information on the most important identified and potential
risks. 750
Proposed change (if any): clarify most important
Page 21 – whole
Comment: do labelled events have to be included as identified
section
risks or not – unclear from this section
Proposed change (if any): clarify
Page 21 –
Comment: what if there is no clinical data available?
paragraph starting
line 777
Proposed change (if any): provide clarity
6/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 21 –
Comment: this section is geared towards Rx medicines, what
paragraph starting
about OTC medicines?
785
Proposed change (if any): provide information about OTC
medicines
Page 26 – line
Comment: For the section entitled - Routine
961
pharmacovigilance (safety) activities – what should go in
this section – would it be more appropriate to remove
“routine” from the title?
Proposed change (if any): please clarify
Page 27 – line
Comment: The sentence - If, when reviewing a study protocol,
1017
a 1017 study is thought to be primarily promotional, the
applicant/marketing authorisation holder will be 1018 required
to modify it or remove it from the pharmacovigilance plan and
resubmit the RMP. – is unnecessary – it has already been
stated that studies should not be promotional
Proposed change (if any): delete this sentence
Page 27 – lines
Comment: These sections are in the PASS module, remove
1043 to 1076
and just cross reference to that module
Proposed change (if any): see above
7/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 32
Comment: This whole section does not provide guidance delete
Proposed change (if any): see above
Page 38 – line
Comment: Move full stop to after the bracket
1415
Proposed change (if any): medicinal product (and a much
wider range of (suspected) adverse reactions).
Page 39 – line
Comment: Is the dossier referred to here the submission
1439
dossier?
Proposed change (if any): clarify
Please add more rows if needed.
8/8
18/04/12
Submission of comments on 'GVP Module VI –
Management and reporting of adverse reactions to
medicinal products' (EMA/873138/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
(To be completed by the
General comment
Outcome
(To be completed by the Agency)
Agency)
2/8
2. Specific comments on text – P&G
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 5 line 158
Comment: Page 5 line 158 – this refers to events being
and page 12 line
unrelated to the medicinal product while on page 12 line 366
366
it refers to events being excluded – is this consistent?
Proposed change (if any): Ensure consistency
Page 6 line 189
Comment: Use of “Since” is confusing at the start of the
sentence
Proposed change (if any): or trade names of the medicinal
product. A medicinal product is authorised with a defined
287 – 290
Comment: ICRS are to be identified from the literatures, but it
is not clear if this means all ADRs, whether or not
serious/non-serious or unexpected/expected.
Proposed change (if any): Please clarify if all ADRs including
non-serious expected ADRs should be recorded in the MAH’s
database.
291 – 295
Comment: The statement regarding reports in the literature
from a country where the MAH has never commercialised the
product is unclear.
Proposed change (if any): Please clarify here that the MAH can
3/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
ignore such reports as far as expediting cases is required, as
indicated in lines 835 to 838.
Page 10 line 293
Comment: “This also applies..” use of these words is confusing
Proposed change (if any): Reword
384 - 387
Comment: If an HCP cannot downgrade a consumer report to
Not-related, there does not seem to be any point in asking for
medical confirmation of a case in future (lines 412-416), since
the case will be expedited regardless, based on assumed
causality as per lines 155 & 156.
Proposed change (if any): Please clarify why medical
confirmation is still required.
Page 22 line 740
Comment: could you clarify the word “concluded in this
sentence?
Proposed change (if any)
822 - 830
Comment: The MAH’s role regarding publications monitored
by the agency is unclear. Is the MAH still expected to review
the same journals and add any case reports included in them
to their database? Will the Agency inform them of any case
reports identified during their monitoring?
Proposed change (if any): Clarification on the MAHs role
4/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
regarding such publications is required.
Page 25
Comment: does this mean if there is a literature report with a
paragraph starting
table that contains enough detail to qualify as a valid report, if
at 843
it is serious it does not need reporting within 15 days?
Proposed change (if any)
Page 25 line 845
Comment: surplus “s” after “article”
Proposed change (if any): literature article describes adverse
reactions, which occur in a group of patients with a designated
921 - 928
Comment: This section states that Emerging Safety Issues are
to be reported forthwith / immediately. Since these include
safety issues from Signal detection activity and urgent safety
restrictions the reporting timelines are unclear.
Proposed change (if any): It would be helpful if the timelines
for reporting such issues were specified more clearly.
1044 - 1050
Comment: The Agency will report ADRs to WHO, but will WHO
report cases to the Agency?
Proposed change (if any):
1226 - 1227
Comment: Discretion is allowed for MedDRA coding of either
the diagnosis alone, or the diagnosis plus its associated signs
5/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
and symptoms.
Proposed change (if any): This guidance should not allow for
alternatives, but state which option should be followed, in
order to ensure consistency of reporting between companies.
1289 - 1290
Comment: New information should be clearly identifiable in
the case narrative.
Proposed change (if any): Guidance should be provided as to
how this should be achieved (e.g. leaving the original
narrative as previously submitted and adding new information
at the end).
1308 – 1310
Comment: 1308-1310 says the correction of typos does not
1318 - 1321
require expedited reporting. However, 1318 – 1321 suggests
that this can be done but without changing the date of receipt
of the most recent information.
Proposed change (if any): Please clarify this apparent
contraindication.
1336 - 1345
Comment: Pseudonymisation may be used for names and
addresses.
Proposed change (if any): Please clarify exactly what is
expected in these fields.
1407
Comment: This line and others in the guideline refer to the
6/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Implementing Measures. It is confusing to have two
documents to describe the same processes.
Proposed change (if any): Incorporate all relevant information
from the Implementing Measures into this and other GVP
guidelines, as applicable.
1442 – 1444
Comment: This section refers to expediting Non-serious cases
of lack of efficacy. Should cases of lack of efficacy which are
subject to 15 day reporting (e.g. for vaccines and
contraceptives), not all be considered as medically important
and thus serious cases?
Proposed change (if any): Please clarify why these cases
should not automatically be considered serious.
Page 26 section
Comment: why has the transmission of an infectious agent
C.2.25
been removed from the definition of serious but requires 15
day reporting?
Proposed change (if any): clarification of the change
Page 40 – section
Comment: Why are the EMA dictating the LLTs that should be
6.2.3.5
used for quality defects or falsified medicinal products
Proposed change (if any): Allow MAHs to determine the most
appropriate coding
Appendix 3
Comment: Appendices 3.1 and 3.2 are self-explanatory, but it
is not clear when Appendix 3.3 should be followed.
7/8
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Proposed change (if any): Please clarify when the process in
Appendix 3.3 is to be followed.
Please add more rows if needed.
8/8
18/04/12
Submission of comments on 'GVP Module VII – Periodic
safety update report' (EMA/816292/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
General comment
(To be completed by the
Outcome
(To be completed by the Agency)
Agency)
Consistently use either benefit-risk or risk-benefit, not a
mixture of both throughout the document
Clarify the differences between annexes and appendices
and exactly what information should be found in each
What implications does this guidance have concerning
the need for PSURs at renewal?
2/14
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 5 – line 149
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: add “be” into the sentence
Proposed change (if any):
normally be specified in the request,
Page 5 – line 156
Comment: Remove extra s from PSUR
Proposed change (if any): PSUR reporting should therefore be
Page 6 – line 166
Comment: add “the” before basis
Proposed change (if any): State on the basis of concerns
relating to pharmacovigilance data or due to the lack of PSURs
for an active
Page 6 – line 166
Comment: What are the circumstances that are referred to
concerning lack of PSURs. Why would there be a lack of
PSURs?
Proposed change (if any): Clarification of the above
Page 7 – line 220
Comment: In the phrase - Critically summarising relevant new
safety, efficacy and effectiveness information that could have
– please clarify what effectiveness means in this context.
3/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Proposed change (if any): clarification
Page 7 –line 222
Comment: The following sentence does not make sense Conducting an integrated benefit-risk analysis for authorised
indications based on the cumulative information available
since the international birth date (IBD), the date of the first
marketing authorisation in any country in the world /
development international birth date (DIBD), the date of first
authorisation for the conduct of an interventional clinical trial
in any country.
Proposed change (if any): The addition of an “and” or and “or”
make improve the sense.
Page 7 – section
Comment: This section only discusses products with one
VII B.3.
active substance.
Proposed change (if any): Include medicines with multiple
actives
Page 7 – line 235
Comment: Add the word “safety” before information and
change “on” to “covering” before all
Proposed change (if any): containing the same active
substance with safety information covering all the authorised
indications, route of
Page 8 – line 253
Comment: Remove the comma after “both” not required
4/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Proposed change (if any): should be used as the reference for
both, the benefit and the risk sections of the PSUR. The core
safety
Page 11 – line
Comment: Specify who should be the signatory
356
Proposed change (if any): clarification
Page 11 – line
Comment: What about countries where an authorisation
366
system is not in place e.g. US monograph system
Proposed change (if any): further information
Page 12 – line
Comment: Add “for safety reasons” to the end of the sentence
406
Proposed change (if any):
marketing authorisation application for safety reasons;
Page 12 – lines
Comment: Add “for safety reasons” to the end of the
418 and 419
sentences
Proposed change (if any):
failure to obtain a marketing authorisation renewal for safety
reasons;
withdrawal or suspension of a marketing authorisation for
safety reasons ;
5/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 12 – line
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: Add consumers to this bullet point
424
Proposed change (if any): communications to health care
professionals and consumers; and
Page 15 – line
Comment: include post-marketing data in the scope for this
516
section, as it is discussed later in the section
Proposed change (if any): The objective of this PSUR section
is to present clinical and post-marketing safety data through
summary tabulations of
Page 18 – line
Comment: Progress or final study reports generated during
630
the reporting interval for post-authorisation safety 630 studies
should also be included in the regional appendix of the PSUR
(see VII.B.5.20.) –this sentence refer to PASS, but the title to
this section refers only to non-interventional studies
Proposed change (if any): clarify
Page 18 – line
Comment: Change “is” to “are”, as the sentence discusses the
634
plural “sources”
Proposed change (if any): medicinal product from other
clinical trial/study sources that are accessible11 by the
marketing
6/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Page 18 – line
Comment: Change the order of this sentence slightly
644
Proposed change (if any): This PSUR section should include a
summary of new and significant safety findings, either
published in the peer-reviewed scientific literature or made
available as unpublished manuscripts, that the marketing
authorisation holder became aware of during the reporting
interval, when relevant to the medicinal product.
Page 18 – line
Comment: add “of” after “aware”
646
Proposed change (if any): the medicinal product that the
marketing authorisation holder became aware of during the
reporting
Page 20 – line
Comment: Delete “important” as important safety concerns
709
have not been referred to previously
Proposed change (if any): The purpose of this PSUR subsection is to provide a baseline summary of safety concerns
Page 20 – lines
3
Comment: Change “safety specification” to “RMP”
721-723
Proposed change (if any): For products with a RMP (see
Module V), the information included in this sub-section should
be equal to the summaries provided in the version of the RMP
current at the beginning of the PSUR reporting interval.
7/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 20 – lines
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: Add important to the bullet points
728 to 732
Proposed change (if any):
Important interactions with other medicinal products;
•important identified medication error where no adverse
events occurred, or near misses of medication errors
Important interactions with foods and other substances;
• important occupational exposure;
• important pharmacological class effects.
Page 22 – line
Comment: Define the “sentinel” adverse reaction
791
Proposed change (if any): clarification
Page 23 – line
Comment: Change “has” to “have”
815
Proposed change (if any): important identified risks that have
become available during the reporting interval should be
Page 26 – line
Comment: Add as applicable
939
Proposed change (if any): In addition, as applicable, the
conclusions should include preliminary proposal(s) to optimise
8/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
or further evaluate the
Page 26 – line
Comment: Does this refer to the Reference Safety
946
Information?
Proposed change (if any):
1. Reference Safety Information
Page 27 – line
991
Comment: - what does this sentence mean? “and
inappropriate dismissal of cases with no reported risk factors
in cumulative reviews;”
Proposed change (if any): clarification required
Page 27 – line
Comment: Should have a small “p” after a colon
988
Proposed change (if any): poor quality reports: poor
documentation or insufficient information or evaluation
provided to
Page 27 – line
Comment: This documentation should be available at all
996-997
times. – available to whom, where and in what context
Proposed change (if any): clarification required
Page 28 – line
Comment: State that this is the responsibility of the QPPV
Proposed change (if any): It is the responsibility of the person
responsible for the pharmacovigilance system (the QPPV) to
9/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
ensure that the
Page 30 – line
Comment: Remove extra s from PSURs
1048
Proposed change (if any): Optimisation of the management of
PSURs and PSUR assessments within the EU:
Page 31 – line
Comment: addition of “is”
1087
Proposed change (if any): Where specificity is deemed
necessary, the list should include the scope of the PSUR and
related EU
Page 31 – line
Comment: What are the circumstances that are referred to
1093
concerning lack of PSURs? Why would there be a lack of
PSURs?
Proposed change (if any): Clarification of the above
Page 32 -
Comment: Explain that the diagram does not apply to all
products – i.e. some products will not be included in the list
Proposed change (if any):
Page 35 – line
Comment: Doesn’t immediately usually mean within 90 days?
1162
Proposed change (if any): Marketing authorisation holders
10/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
shall submit PSURs immediately upon request (usually 90
days) from a competent
Page 38 – line
Comment: Add an “s” to PSUR
1230
Proposed change (if any): Any changes to the dates and
frequencies of submission of PSURs specified in the list take
effect six
Page 39 – line
Comment: Change to “an EU”
1247
Proposed change (if any): list of EU reference dates, an EU
single assessment of all PSURs is conducted with
recommendation from
Page 42 – line
Comment: change “hold” to held”
1334
Proposed change (if any): whether or not held by the same
marketing authorisation holder and for which the frequency
and dates
Page 44 – line
Comment: Change “has” to “have”
1344
Proposed change (if any): have been granted in accordance
with the centralised procedure;
Page 44 – line
Comment: Change “from” to “of”
11/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
1376
Proposed change (if any): and to the Member States
concerned [DIR Art 107e(2)], within 60 days of the start of
the
Page 45 – line
Comment: Change “from” to “of”
1409
Proposed change (if any): meeting following the PRAC
adoption. Within 30 days of receipt, the CHMP shall consider
the PRAC
Page 50 – line
Comment: VII.C.5.3. PSUR EU regional appendix, sub-section
1577
“Company core safety 1577 information and summary of
product characteristics” – is this country specific?
Proposed change (if any): clarification
Page 50 line 1591
Comment: This section assumes that you have a RMP in place
– what happens if there is not a requirement for a RMP?
Proposed change (if any): clarification
Page 51 – line
Comment: How often will the EU reference list of dates and
1634
frequencies be updated?
Proposed change (if any): further information
12/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 52 - line
1645
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: Add an “s” to the first risk
Proposed change (if any): authorisation holder should
maintain on file a specification of important identified risks,
important
Page 53 – line
Comment: Remove “s” from program
1696
Proposed change (if any): consistent, sustainable and efficient
records management program and it has been developed in
Page 53 – line
Comment: Change “on” to “of”
1714
Proposed change (if any): information in cases of noncompliance and take appropriate regulatory actions as
required.
Page 53 – line
Comment: Change to “an “ EU
1716
Proposed change (if any): only one Member State and
containing an active substance for which an EU reference date
and
Page 54 – line
Comment: Remove the “s” from communication
1724
Proposed change (if any): communication across the EU
regulatory network and the actions to be taken regarding the
13/14
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
variation,
Page 54 – line
Comment: Add a full stop at the end of the sentence
1735
Proposed change (if any): EudraVigilance database or other
data used to support the PSUR assessment.
Please add more rows if needed.
14/14
18/04/12
Submission of comments on 'GVP Module VIII – Postauthorisation safety studies' (EMA/813938/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
(To be completed by the
General comment
Outcome
(To be completed by the Agency)
Agency)
2/4
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 3 – line 54
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: also include medicines that are non-prescription
Proposed change (if any):
Page 11 – line
Comment: swap the order of the two sentences in this
364
paragraph – it would read more clearly.
Proposed change (if any): The marketing authorisation holder
shall submit the final study report to competent authorities of
the Member States in which the study was conducted [DIR Art
107m(6)]. The study report should be submitted to the
competent authority(ies) as soon as possible after its
finalisation and within 12 months of the end of data collection.
Page 13 – section
Comment: Is not a summary of the AEs received during the
10.6
study also required – it appears that all that is required is the
management and reporting of AEs – yet this is the results
section
Proposed change (if any): clarification
Page 16 –
Comment: What about nationally authorised products not
Paragraph starting
done through DCP or MRP? For points a-c need to say that
at line 564
nationally authorised products will not go to PRAC
3/4
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Proposed change (if any):
Please add more rows if needed.
4/4
14/08/12
Submission of comments on 'GVP Module IX – Signal
management' (EMA/827661/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
(To be completed by the
General comment
Outcome
(To be completed by the Agency)
Agency)
2/6
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Page 4 – line 95
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment: Change “of” to “on” before “periodic monitoring”
Proposed change (if any): based on periodic monitoring of
large databases such as the EudraVigilance database
Page 4 – line 100
Comment: What is “adverse reaction databases” referring to?
Proposed change (if any): Clarify examples of such databases
Page 4 – line 120
Comment: Remove the semi-colon
Proposed change (if any): as possible after the acceptance of
the manuscript of the results of post-authorisation
Page 5 – line 132
Comment: Change “that” to “than”
Proposed change (if any): require other methodological
strategies than other medicinal products.
Page 5 – line 133
Comment: Clarification or removal of the word structured
Proposed change (if any): In order to determine the evidence
supporting a signal, a recognised methodology shall……..
136
Comment: This line and others in the guideline refer to the
Implementing Measures. It is confusing to have two
documents to describe the same processes.
Proposed change (if any): Incorporate all relevant information
3/6
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
from the Implementing Measures into this and other GVP
guidelines, as applicable.
Page 5 – line 139
Comment: Severity of the event should also be considered
Proposed change (if any): Different factors may be taken into
account for the prioritisation of signals, namely the fact
whether the association or medicinal product is new, factors
related to the strength of the association, factors related to
the seriousness or severity of the reaction involved and
factors related to the documentation of the reports in the
EudraVigilance database
Page 6 –
Comment: Why do non-valid (inadequately documented) AEs
IX.B.3.2.1
have to be collected for signal detection, but then this text
says to remove them from the signal detection process
Proposed change (if any): clarifiation
185
Comment: Module VI makes it clear that literature reports
relating to other brands, formulations and routes of
administration or from countries where the MAH has never
marketed the product do not need to be expedited. However
it is not clear if these should be used for signal detection.
Proposed change (if any): Clarification is required on exactly
what literature cases should be considered for signal detection
purposes.
Page 7 – line 224
Comment: Correct used to uses
4/6
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Proposed change (if any): Where signal detection uses an
automated screening of a database
Page 8 – line 250
Comment: Refer to the two bullets
Proposed change (if any): In principle only signals not falling
under the above two categories should be validated
Page 8 – line 261
Comment: Add an A at the start of the sentence
Proposed change (if any): A signal becomes a validated signal
if the verification process of all relevant documentation
Page 9 – line 283
Comment: Why are only valid cases being considered? There
may be circumstances where a non-valid case e.g. nonidentifiable reporter, may be an indicator of a potential signal
Proposed change (if any): …a high number of cases reported
in a short period of time,
Page 9 – line 312
Comment: Do not understand the meaning in the first
sentence of this paragraph
Proposed change (if any): Clarify the wording
Page 10 –
Comment: This sections includes recommendations for other
IX.B.3.6
parties than just the CAs. Remove CA from the title of this
section
Proposed change (if any): IX.B.3.6. Recommendation for
action
Page 14 – line
Comment: Change “to” to “with”
5/6
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
495
Proposed change (if any): should collaborate with the signal
validation performed by a national competent authority
556 - 560
Comment: This section states that the MAH shall monitor the
EV database at least monthly proportionate to the identified
and potential risk. For a product with few ICSRs and with
small risk, monthly monitoring seems rather excessive.
Proposed change (if any): Clarification is required as to how
the MAH will monitor the EV database. Also the timelines for
monitoring the database should allow for more flexibility
depending on the product and its identified and potential risks.
564 - 565
Comment: The MAH is supposed to inform the CA of any
signal in line with a list published by the Agency. This list is
said to be referred to in lines 463 and 464, but this is not the
case.
Proposed change (if any): Please provide the correct reference
and further clarification regarding this list (what is it and
where will be found?).
Page 16 – line
Comment: should “emergency” be “emerging”?
566
Proposed change (if any): Clarification
Please add more rows if needed.
6/6
18/04/12
Submission of comments on 'GVP Annex I – Definitions'
(EMA/876333/2011)
Comments from:
Name of organisation or individual
Faculty of Pharmaceutical Medicine
Please note that these comments and the identity of the sender will be published unless a specific
justified objection is received (please see privacy statements:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000516.jsp&mid and
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123144.pdf).
When completed, this form should be sent to the European Medicines Agency electronically, in Word
format (not PDF) (see Introductory cover note for the public consultation of GVP under Practical advice
for the public consultation:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/02/WC500123145.pdf).
7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom
Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416
E-mail [email protected] Website www.ema.europa.eu
An agency of the European Union
1. General comments
Stakeholder number
General comment
(To be completed by the
Outcome
(To be completed by the Agency)
Agency)
Include a definition of expedited
Include a definition of a stimulated report
Include a definition of off-label use
Include a definition of interventional study
2/3
2. Specific comments on text
Line number(s) of
the relevant text
(e.g. Lines 20-23)
Stakeholder number
Comment and rationale; proposed changes
Outcome
(To be completed by
(If changes to the wording are suggested, they should be
(To be completed by the Agency)
the Agency)
highlighted using 'track changes')
Comment:
Proposed change (if any):
Comment:
Proposed change (if any):
Comment:
Proposed change (if any):
Please add more rows if needed.
3/3