H. Lundbeck A/S21-Sep-151 Pharmacovigilance during clinical development SAE reporting, ASUR and PSUR...
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Transcript of H. Lundbeck A/S21-Sep-151 Pharmacovigilance during clinical development SAE reporting, ASUR and PSUR...
H. Lundbeck A/S Apr 21, 2023 1
Pharmacovigilance during clinical developmentSAE reporting, ASUR and PSUR IFF Seminar, 21. February 2007
H. Lundbeck A/S Apr 21, 2023 2
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 Apr 21, 2023 3
Agenda
1. Reporting of SAEs2. Annual Update Reports3. Periodic Safety Update Reports
H. Lundbeck A/S Apr 21, 2023 4
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 2: Definitions– Article 16: Notification of Adverse Events– Article 17: Notification of Serious Adverse Reactions– Article 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 Apr 21, 2023 5
Adverse Events vs. Adverse Drug Reaction
AEs
ADRs
H. Lundbeck A/S Apr 21, 2023 6
Assessment
Sponsor has to perform evaluation of:
• Seriousness• Expectedness/listedness• Causality• Reportable
H. Lundbeck A/S Apr 21, 2023 7
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 Apr 21, 2023 8
Expectedness/Listedness
Company Core Safety Information (CCSI) Listedness
Summary of Product Characteristics (SPC) Expectedness
H. Lundbeck A/S Apr 21, 2023 9
Causality
An assessment of the relationship between the drug and the ADR
Probably
Possibly
Not related
H. Lundbeck A/S Apr 21, 2023 10
Definition of SUSAR
• SuspectedEvaluated by sponsor and/or investigator as
possible/probable related to IMP
• UnexpectedEvaluated by sponsor as unexpected according to the
reference document
• Serious(death, life-threatening, hospitalisation, ect.)
• Adverse ReactionAny untoward and unintended response to an IMP
related too any dose administered
H. Lundbeck A/S Apr 21, 2023 11
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 Apr 21, 2023 12
Competent AuthoritiesWhat 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 Apr 21, 2023 13
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 Apr 21, 2023 14
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 Apr 21, 2023 15
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 Apr 21, 2023 16
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 Apr 21, 2023 17
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 Apr 21, 2023 18
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 Apr 21, 2023 19
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 Apr 21, 2023 20
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 Apr 21, 2023 21
Questions
Questions