06 PSUR PBRER Thomas Munz

Good
G d Pharmacovigilance
Ph i il P
Practice
ti (GVP):
(GVP)
The New EU Pharmacovigilance Modules and Switzerland
y, 9th September
Monday, p 2013,, Hotel Allegro/Kursaal
g Bern
The new PBRER

Th
Recommendations from Swissmedic
Thomas Munz
Clinical Reviewer,
Reviewer
Department Safety of Medicines, Unit Risk Management
Swissmedic Schweizerisches Heilmittelinstitut Hallerstrasse 7 CH-3000 Bern www.swissmedic.ch

Some drugs with negative risk-benefit ratios
Inscription Burgerspital Bern:
Lets do good work and never get tired
Questions from Industry
How to implement the new PV regulations in Switzerland ?
Lead questions compiled by scienceindustries working groups
pharmacovigilance (AG PV) and regulatory affairs (AG RA)
Q & A (1)
Time interval between DLP and submission to
Swissmedic unchanged?
YES, same interval

Q & A (2):
Duration of obligation to submit periodic reports?
Unchanged: 5 years, beginning with date of market

authorization (Verfgung Gutheissung)
Unchanged: new indication - restart 5 y period
Q & A (3)
PBRER frequency ?
Yearly, as a rule
On request: adapation to EU birthdate / frequency

Granting request is a product-specific decision, not setting
a precedent
Q & A (4)
Are two -y PBRERs submitted together accepted ?
YES.
12 mo PBRER clearly preferred
C t i information
Certain i f ti (exposition
( iti CH,
CH internationally)
i t ti ll )
per year on PSUR Formular
No bridging report
report accepted
Q & A (5)
Significance of EUDR list for Swissmedic ?
List of European Union reference dates and frequency of submission of
Periodic Safety Update Reports
Reports. Last update August 6
6, 2013
www.ema.europa.eu/Regulatory/Human medicines/ Pharmacovigilance/ EU reference
dates and PSUR submission
No direct relevance: First: Swissmedic regulations,

Second: Request
q by
y MAH
Swissmedic = EMA: This approach is without prejudice to the
right of a National Competent Authority to request the
submission of PSURs at any time.
time
Q & A (5)
Q & A (5)
Q and A (6)
Significance of List of substances under PSUR Work Sharing
scheme and other substances contained in Nationally Authorised
Products
oducts witht DLP sysynchronised
c o sed ?
Last update: June 30, 2013
www.hma.eu/Human Medicines/CMDh/Pharmacovigilance/PSURs/PSUR Work Sharing
and Synchronisation Project
Q & A (7)
No direct relevance:
Fi t Swissmedic
First: S i di regulations,
l ti
Second: Request by MAH
Swissmedic = EMA: This approach is without
prejudice to the right of a National Competent Authority
to request the submission of PSURs at any time.
Q and A (8)
PSURs / PBRERs for new generic ?
Due to some legal reasons the term generic will be no longer

used in CH.
Art 16 (1) HMG / LPTH
Art.
Das Institut verfgt die Zulassung, wenn die Voraussetzungen erfllt sind. Es kann die Zulassung mit
Auflagen und Bedingungen verknpfen.
Linstitut
L institut autorise la mise d
dun
un mdicament sur le march si les conditions sont remplies. Il peut lier
lautorisation des charges et des conditions.
No condition, no PBRER.
Your PBRER: its content leads the
way for the product
products
s life cycle
Recent PBRER experiences
Up to now only a minority, majority still PSURs
Variable volume
Variable annexes
Tables yes, figures lacking with exeption
References: (un)representative selection ?

Good example to follow:
Summary of benefit / risk of no treatment
Summaryy of benefit / risk of alternatives
Strengths, limitations, uncertainties of the
evidence of benefit
Sources screened for Signals:
Corporate Safety Database
Global literature search
Non-clinical data (as applicable)
Within these sources,, the following
g information was reviewed..
PBRER: absolute no go
No summary tabulation including total
figures of fatal cases, serious cases, SAEs
neither in core document, nor in appendices

Unchanged Swiss requirement:
Comparison: EU-SmPC versus CH
Fachinformation / information professionelle
With approved dates

O ti l fform: three
Optimal th rows: EU / CH / commentt
Colors for differences
Generally good presentation by companies
Cross No in box in PSUR Formular has legal implication
Requests from Swissmedic for the time
being:
g
Format:
S i
Swissmedic
di accepts
t the
th new EU format
f t
During the transition period defined by the EU, Swissmedic also

accepts
t the
th old
ld format
f t = PSUR
CH legal basis remains unchanged: Art. 34 VAM, Art. 16 HMG
Swissmedic requirements for national accompanying documents

remain unchanged = to do as previously
Requests from Swissmedic at present:
Period type:
Basically unchanged: YEARLY
To overcome certain difficulties:
ON DEMAND: Swissmedic may grant other periodicity
ams-rm@swissmedic.ch
@
Requests from Swissmedic for the time
being:
g
Risk Managemant Plans:
Unchanged: RMP updates (without new application) to be

submitted together with PSUR or PBRER
Current Swissmedic requests:
ICH - Guideline:
E2C (R2)
Periodic benefit-risk evaluation report (PBRER)
Actually at ICH@ema.europa.eu: Step 3
Swissmedic will follow the final E2C guideline

Transport of information
Implementation Working Group
Clustered sample question
Postmarketing exposition:
Often only US-data available.
To get worldwide exposition data is
difficult and expensive
PSURs in the past almost exclusively had data on
worldwide exposition, often with subdivided for
USA/Europe/ROW.
p With some effort MAH can do it and
WILL do it.
Appendix B: Examples of summary tabulations: Cumulative
exposure from marketing experience
Appendix B: Examples of summary tabulations: Numbers of
ADRs by Term from Post-marketing sources
Here: additionally necessary:

medically confirmed, not medically confirmed
clustered sample questions:
What is the range of benefit information? Only blinded
controlled studies , blinded dose-finding studies in
humans? Or also observational studies and non-clinical
non clinical
studies?
3.17, 3.17.3
Broad information on newly analysed - succinct for each
new study:
A new diagnostic
di ti method
th d may help
h l reduce
d a known
k risk
i k
An intervention method with less complications may extenuate
a specific
p SAE
New therapeutic procedure (surgery, radiotherapy) may reduce
the medical need
New
N non-clinical
li i l study
t d may be
b relevant
l t for
f the
th whole
h l ATC-
ATC
group (own drug and comparators)
Largeg PASS / observational study y in several countries mayy
show differences
If relevant: HTA-study, QoL
Summary of Safety Concerns lists factors to be considered
when determining whether or not a risk is important. More
specifical explanation would be useful.
useful
3.16.1
baseline vs new information
pre- and post-approval experience
important identified risks
important potential risks
important missing information
EMA New PV legislation Key concepts
A safety concern is an important identified risk, an important
information By
potential risk or important missing information.
important we understand a risk or side effect

which could have significant clincial
consequences for a patient and could affect the
decision made by a doctor to prescribe the
drug.
Interactions with other medicinal products: not: antidepressants,
but: eg fluoxetin due to CYP
Effects of occupational exposure: anaesthetics; HIV prevention after
accidental needle stick; malaria prophylaxis for travellers
Medication errors: depending on name confusion in certain
countries?
Impact on individual patient: irreversable brain damage after
thromboembolic event; tardive dyskinesia; transplant rejection
due to interaction;
MAH having benefits and risks in mind
The authority having risks and benefits in mind .
The PBRER has to present both

06 PSUR PBRER Thomas Munz

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What are some of the questions discussed regarding implementing new PV regulations in Switzerland?

What are some of the questions discussed regarding implementing new PV regulations in Switzerland?

What information is included in a PBRER?

What information is included in a PBRER?

Good

The new PBRER

Swissmedic Schweizerisches Heilmittelinstitut Hallerstrasse 7 CH-3000 Bern www.swissmedic.ch

YES, same interval

Unchanged: 5 years, beginning with date of market

On request: adapation to EU birthdate / frequency

No direct relevance: First: Swissmedic regulations,

Due to some legal reasons the term generic will be no longer

Up to now only a minority, majority still PSURs

Tables yes, figures lacking with exeption

References: (un)representative selection ?

neither in core document, nor in appendices

With approved dates

During the transition period defined by the EU, Swissmedic also

CH legal basis remains unchanged: Art. 34 VAM, Art. 16 HMG

Swissmedic requirements for national accompanying documents

Basically unchanged: YEARLY

To overcome certain difficulties:

ON DEMAND: Swissmedic may grant other periodicity

Unchanged: RMP updates (without new application) to be

Periodic benefit-risk evaluation report (PBRER)

Actually at ICH@ema.europa.eu: Step 3

Swissmedic will follow the final E2C guideline

Here: additionally necessary:

A safety concern is an important identified risk, an important

important we understand a risk or side effect

The authority having risks and benefits in mind .

The PBRER has to present both

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