Template zur Erstellung eines:
Periodic Safety Update Reports
(PSUR)
für
ATMPs
Advanced Therapy Medicinal Products
Version: 001 26.06.2015
Product name
Company:
Street:
City:
Country:
Date: xx.xx.2015
Paul Ehrlich Institut
Paul-Ehrlich-Str. 51-59
63225 Langen
Germany
Periodic safety update report
(PSUR)
For Advanced Therapy Medicinal Products (ATMP)
(Genehmigungsverfahren nach §4b AMG)
Product:
Active Substance:
MAH:
Authorisation status:
Authorisation number:
national
PEI.A.XXXXX.01.1
Date of authorisation in
Germany
International Birthdate
XX.XX.XXXX
XX.XX.XXXX
Reporting period:
XX-XXX-201X to XX-XXX-201X
Date of report:
XX-XXX-201X
Contact person for the procedure:
Name:
Contact details:
Signature:
______________________________________
Product name
Please read before starting!!!
This template is intended to provide guidance for preparation of the PSUR document.
It needs to be tailored to the specific product that is subject of the specific PSUR.
For example: If the tabular form does not suit your needs just fill in the chapter in an
appropriate, suitable form or modify the tables according to your requirements.
Most likely some of the questions may not concern your product or in certain settings
data required are still missing due to ongoing studies.
Please state that these data are missing / lacking or write “not applicable” but do not
delete the concerned section.
Grey marked sections give you further advice or examples regarding the topics that
should be discussed in the respective sections.
Please Note: The template only covers the requirements for a PSUR in general.
It thus should only be used for PSURs which concern nationally authorized ATMPs in
Germany.
Product name
Table of contents
List of Abbreviations: ...................................................................................................................................... 5
1. Introduction ............................................................................................................................................... 6
Product details ................................................................................................................................................... 6
2. Worldwide marketing authorisation Status.................................................................................... 6
3. Actions taken in the reporting interval for safety reasons ...................................................... 6
3.1. Actions related to investigational uses ....................................................................................... 6
3.2. Actions related to marketing experience ................................................................................... 6
3.3. Regulatory actions taken for safety reasons by Authorities ............................................... 6
4. Changes to Reference Safety Information ..................................................................................... 6
5.1. Exposure in Clinical Studies ............................................................................................................ 7
5.2. Cumulative and interval patient exposure from marketing experience ......................... 7
6. Data in Summary Tabulations ............................................................................................................ 8
6.1. Reference information ....................................................................................................................... 8
6.2. Cumulative summary tabulations of serious adverse events from clinical studies .... 8
6.3. Cumulative and interval summary tabulations from post-marketing data sources... 8
7. Summary of significant findings in the reporting period .......................................................... 8
7.1. Findings from completed clinical trials ........................................................................................ 8
7.2. Findings from ongoing clinical trials ............................................................................................. 8
7.3. Findings from non-interventional studies .................................................................................. 9
7.4. Findings from long-term follow-up ............................................................................................... 9
7.5. Findings from literature or independent studies ..................................................................... 9
7.6. Findings from non-clinical studies................................................................................................. 9
9. Literature .................................................................................................................................................... 9
10.
Lack of efficacy in controlled clinical trials................................................................................. 9
11.
Late-Breaking Information ............................................................................................................... 9
11.1.
Risk minimisation measures/other actions ........................................................................... 9
11.2.
Ongoing risk minimisation measures ...................................................................................... 9
11.3.
Newly initiated risk minimisation measures (reporting period) .................................... 9
11.4.
Planned risk minimisation measures ..................................................................................... 10
12.
Other Information ............................................................................................................................. 10
13.
Signal evaluation and detection .................................................................................................. 10
13.1.
Signal detection ............................................................................................................................. 10
13.2.
Closed signals ................................................................................................................................. 10
13.3.
Ongoing signals ............................................................................................................................. 10
13.4.
New signals ..................................................................................................................................... 10
14.
Risk evaluation ................................................................................................................................... 10
14.1.
Summary of Safety Concerns .................................................................................................. 10
14.2.
Characterisation and evaluation of risks .............................................................................. 10
14.3.
Characterisation of important potential problems with the treatment and with
certain populations ........................................................................................................................................ 11
15.
Benefit/Risk Assessment ................................................................................................................ 11
16.
Overall Conclusions .......................................................................................................................... 11
RMS
Product name
List of Abbreviations:
AEs
Adverse Events
Product name
1. Introduction
This Periodic Safety Update Report (PSUR) No. X for XXXXX covers the period from 01XXX-201X to 31-XXX-201X. It is based on all available cumulative data since the
international birth date (XX.XX.XXXX) and is focused on new information which has
emerged since 01-XX-201X.
Product details
Invented name of the medicinal product
(product short name)
Active substance(s) (INN or common
name)
Pharmaco-therapeutic group (ATC Code):
Brief description of product (chemical
class, origin, production/modification,
mode of action etc.)
Indication/s (target population)
Dosage
Pharmaceutical form and strength
(concentration)
Rout of administration
(See also SmPC product information).
2. Worldwide marketing authorisation Status
Please state in which countries your product has a marketing authorisation and since when
3. Actions taken in the reporting interval for
safety reasons
3.1. Actions related to investigational uses
Please give an overview of planned and ongoing studies
3.2. Actions related to marketing experience
Please provide an overview on actions performed in the reporting period e.g. quarantine
measures because of contaminations…
3.3. Regulatory actions taken for safety reasons by
Authorities
4. Changes to Reference Safety Information
e.g.: In the beginning of the reporting interval the applicable reference safety information was the
Company Core Data Sheet (CCDS) version no. X, dated XX-XXX-20XX. This version was updated
on XX-XXX-20XX (version no. X) and the CCDS version no. X is now considered the reference
safety information during the reporting period according to its date of effectiveness.
The following changes were made in detail:
• XXXXX
• XXXXX
Product name
5. Estimated exposure and use patterns
In the interval XXX post-authorisation studies were ongoing and XXX were completed.
5.1. Exposure in Clinical Studies
Cumulatively, XXX individual patients were exposed to “Product” in clinical trials.
Study
Number
[Ref.]
Country
Indication Objectives
No. of
Exposure
patients
(no. of
treated treatments)
Status
(ongoing,
finished)
Interventional
Non-interventional
If placebo treated or comparator patients were also studied in the trials please also present their
relevant data and numbers.
5.2. Cumulative and interval patient exposure from marketing
experience
Country
Number of
treatments
period
cumulative
period
cumulative
Describe the method(s) used to estimate the patient exposure?
If feasible/possible also calculate patient-years of treatment.
Patients treated
Product name
6. Data in Summary Tabulations
6.1. Reference information
Please state which MedDRA version was used for coding of adverse events/reactions
6.2. Cumulative summary tabulations of serious adverse
events from clinical studies
e.g.: Appendix XXX provides a cumulative summary tabulation of related and unrelated
SAEs presented per SOC and Preferred term (PT).
Please add the mentioned table in the Annex
6.3. Cumulative and interval summary tabulations from
post-marketing data sources
e.g.: Cumulatively, the MAH received XXX spontaneous ICSRs with “Product” from
worldwide source which included XXX ADRs, thereof XXX ADRs were serious.
During the reporting interval the MAH received XXX spontaneous ICSRs with “Product”
from worldwide source which included XXX ADRs, thereof XXX ADRs were serious.
Table X: Reports of adverse drug reactions
SOC
PT
e.g. Immune
system
disorders
Urticaria
No of serious
events in
interval
No of nonserious
events in
interval
No of serious
events
cumulatively
No of nonserious
events
cumulatively
Total number
of ADRs
Fatal cases:
Please provide a short description of all fatal cases and provide company causality assessment for
each case.
7. Summary of significant findings in the
reporting period
7.1. Findings from completed clinical trials
7.2. Findings from ongoing clinical trials
Product name
7.3. Findings from non-interventional studies
7.4. Findings from long-term follow-up
7.5. Findings from literature or independent studies
7.6. Findings from non-clinical studies
8. Non-clinical data
9. Literature
The MAH should perform a search using his internal literature database. The report should include
results of regular literature searches for defined active substances of the “product”.
Please state who performs the literature searches, which literature databases are regularly
searched (e.g. Medline, EMBASE) and discuss major publications.
XXXX et al. Journal page year, short description of content
XXXX et al. Journal page year, short description of content
XXXX et al. Journal page year, short description of content
10. Lack of efficacy in controlled clinical trials
Give a short overview of cases with treatment failure related to the IMP.
11. Late-Breaking Information
Provide information on the safety or efficacy of “product” which was received after the
data lock point of the report.
11.1. Risk minimisation measures/other actions
11.2. Ongoing risk minimisation measures
11.3. Newly initiated risk minimisation measures
(reporting period)
The following risk minimisation measures / actions were taken during the period covered
by this safety report:
Product name
11.4. Planned risk minimisation measures
Please give a short overview on relevant measures for risk minimisation.
E.g. ongoing / planned studies that can detect new risks, long term follow up measures
…..
12. Other Information
e.g.: There has been no new information about abuse, misuse, or overdose of the
product during the period covered by the PSUR.
During the period of this report no case with medication error has been reported.
13. Signal evaluation and detection
13.1. Signal detection
Please describe shortly the procedures in place for signal detection.
13.2. Closed signals
Please add table(s) with signals that were closed during the reporting period. Give a
short description of the signal and outline the reason for closing it.
13.3. Ongoing signals
Please add table(s) with ongoing signals and describe nature of the signal.
13.4. New signals
Please add table(s) with signals newly detected in the period and give a short
description of the signal.
14. Risk evaluation
14.1. Summary of Safety Concerns
Important Identified Risks
Important Potential Risks
Important identified interactions
Missing Information
14.2. Characterisation and evaluation of risks
Give a short description of all identified risks and evaluate risk associated cases. Give a
short overview and state if the risk-benefit ratio has changed.
Product name
14.3. Characterisation of important potential problems
with the treatment and with certain populations
Overview of current status
Lack of effect
Elderly patients
Patients with renal and/or
hepatic impairment
Pregnant and lactating
women
Pediatric patients
(<16yr/ <6yr/ <2yr)
15. Benefit/Risk Assessment
16. Overall Conclusions
e.g.: The data provided in this PSUR describe sufficiently the safety profile of “product” in the
interval and cumulatively.
or
The following new areas of concern related to the use of “product” in its licensed indications were
identified:
The benefit-risk evaluation remains positive because ……