Pharmacovigilance during clinical development SAE reporting

Download Report

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
1
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
H. Lundbeck A/S
5-Apr-16
2
Agenda
1. Reporting of SAEs
2. Annual Update Reports
3. Periodic Safety Update Reports
H. Lundbeck A/S
5-Apr-16
3
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:
–
–
–
–
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.
H. Lundbeck A/S
5-Apr-16
4
Adverse Events vs. Adverse Drug
Reaction
AEs
ADRs
H. Lundbeck A/S
5-Apr-16
5
Assessment
Sponsor has to perform evaluation of:
•
•
•
•
Seriousness
Expectedness/listedness
Causality
Reportable
H. Lundbeck A/S
5-Apr-16
6
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
H. Lundbeck A/S
5-Apr-16
7
Expectedness/Listedness
Company Core Safety Information (CCSI)
Listedness
Summary of Product Characteristics
(SPC)
Expectedness
H. Lundbeck A/S
5-Apr-16
8
Causality
An assessment of the relationship
between the drug and the ADR
Probably
Possibly
Not related
H. Lundbeck A/S
5-Apr-16
9
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
H. Lundbeck A/S
5-Apr-16
10
Whom to report to?
MAH must report all relevant safety
information to:
– the concerned competent authorities
– the Ethics Committees concerned
– all investigators concerned
H. Lundbeck A/S
5-Apr-16
11
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
H. Lundbeck A/S
5-Apr-16
12
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
H. Lundbeck A/S
5-Apr-16
13
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
H. Lundbeck A/S
5-Apr-16
14
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
H. Lundbeck A/S
5-Apr-16
15
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
H. Lundbeck A/S
5-Apr-16
16
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
H. Lundbeck A/S
5-Apr-16
17
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.
H. Lundbeck A/S
5-Apr-16
18
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
H. Lundbeck A/S
5-Apr-16
19
PSUR - Reporting
PSURs should be submitted at the following
times from the International Birth Date:
–
–
–
–
–
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
H. Lundbeck A/S
5-Apr-16
20
Questions
Questions
H. Lundbeck A/S
5-Apr-16
21