Transcript Pharmacovigilance during clinical development SAE reporting

Pharmacovigilance during clinical development
SAE reporting, ASUR and PSUR
IFF Seminar, 21. February 2007
H. Lundbeck A/S
5-Apr-16
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Recording of ADRs
EU Directive 2001/83/EC:
The Marketing Autorisation Holder (MAH) shall
be required to maintain detailed records of all
suspected adverse reactions occuring either in
the Community or in a third country.
MAH shall have a global ADR system
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Agenda
1. Reporting of SAEs
2. Annual Update Reports
3. Periodic Safety Update Reports
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Directive 2001/20/EC and
Guidance
EU Clinical Trial Directive 2001/20/EC (4 April 2001):
• This Directive came into force 1 May 2004
• Safety articles:
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Article
Article
Article
Article
2: Definitions
16: Notification of Adverse Events
17: Notification of Serious Adverse Reactions
18: Guidance concerning reports
• Detailed guidance on:
– The European clinical trials database (EUDRACT database)
– The European database of SUSARs
– Collection, verification and presentation of adverse
reactions reports arising from clinical trials.
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Adverse Events vs. Adverse Drug
Reaction
AEs
ADRs
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Assessment
Sponsor has to perform evaluation of:
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Seriousness
Expectedness/listedness
Causality
Reportable
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Serious Adverse Reaction
Definition
A serious adverse reaction is any untoward
medical occurrence or effect that at any dose:
– results in death,
– is life-threatening,
– requires hospitalisation or prolongation of
existing hospitalisation,
– is a congenital anomaly or birth defect,
– is medial important
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Expectedness/Listedness
Company Core Safety Information (CCSI)
Listedness
Summary of Product Characteristics
(SPC)
Expectedness
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Causality
An assessment of the relationship
between the drug and the ADR
Probably
Possibly
Not related
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Definition of SUSAR
• Suspected
Evaluated by sponsor and/or investigator as
possible/probable related to IMP
• Unexpected
Evaluated by sponsor as unexpected according to the
reference document
• Serious
(death, life-threatening, hospitalisation, ect.)
• Adverse Reaction
Any untoward and unintended response to an IMP
related too any dose administered
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Whom to report to?
MAH must report all relevant safety
information to:
– the concerned competent authorities
– the Ethics Committees concerned
– all investigators concerned
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Competent Authorities
What and when to report?
Clinical trials:
– Fatal and life-threatening SUSARs:
• no later than 7 calendar days
– Other SUSARs
• no later than 15 calendar days
Post-marketing:
• no later than 15 calendar days
The clock starts (day 0) on the date when any
personnel of the MAH first receive a case report that fulfill the
minimum criteria
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Ethics Committees (ECs)
Only receive individual reports of SUSARs that
occurred in that Member State, provided that:
– All SUSARs from Member States and third
countries are reported at least quarterly as
a line listing and a brief report.
– Other changes increasing the risk to
subjects should be provided as soon as
possible within 15 days
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Investigators
Line listings of SUSARs in periods as warranted
by the nature of the clinical development
project and the volume of SUSARs generated.
Accompanied by a concise summary of the
evolving safety profile of the IMP
The blind should be maintained when possible
and appropriate
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Annual Safety Report - content
ADRs from clinical trials produced on one drug
substance.
– Report on subjects’ safety
– Line listing of all SARs (unblinded)
– Aggregated summary tabulation of SARs (unblinded)
May trigger amendments to study protocol,
changes and updates to the IB
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Annual Safety Report - reporting
To concerned competent authorities and Ethics
Committees
Reporting responsibility starts with the first
authorisation in any Member State – the date is
used for cut-off date for data to be included
MAH should submit the report within 60 days of
data lock point
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Directive 2004/27/EC and
Guidance
Directive 2004/27/EC of the European Parliament and of the
Council of 31 March 2004 amending Directive 2001/83/EC on
the Community code relating to medicinal products for human
use
• Article 101 to 108
• Into force 20 November 2005
Guidance documents:
• Volume 9A of The Rules Govering Medicinal Products in
the European Union of January 2007
– Pharmacovigilance for Medicinal Products for Human Use
• ICH E2C incl. Addendum, latest of Febuary 2003
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Periodic Safety Update Report
(PSUR)
Definition
– An update of the world-wide safety experience with a
medicinal product
– A condition for marketing authorisation
– Prepared for Regulatory Authorities
Objective
– Safety of the product is in accordance with previous
knowledge.
– To indicate whether changes should be made to the
product information.
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PSUR - Source of information
Adverse drug reactions (ADRs) from:
• spontaneous notifications
• marketing authorisation holder sponsored clinical
studies or named patient (compassionate) use
• literature
• reports on ADRs exchanged between contractual
partners (e.g. licensors-licensees)
• data in special registries
• epidemiological databases
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PSUR - Reporting
PSURs should be submitted at the following
times from the International Birth Date:
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immediately upon request
6-monthly for the first 2 years after authorisation
annually for the subsequent 2 years
at the first renewal
thereafter 5-yearly at renewal.
MAH should submit the report within 60 days of
data lock point
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Questions
Questions
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