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
Implementation Working Group
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
Implementation Working Group
clustered sample questions:
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
Implementation Working Group
clustered sample questions:
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.
Implementation Working Group
clustered sample questions:
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