Periodic Safety Report for

Marketed Drugs (PSUR)

 ICH (International Conference on Harmonization)

Before going to PSUR we should know about ICH (International Conference on

Harmonization) : The International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH) is a unique project that brings together the regulatory authorities of
Europe, Japan and the United States and experts from the pharmaceutical
industry in the three regions to discuss scientific and technical aspects of
product registration.
 Purpose of the PSUR

•A stand alone GLOBAL-STANDARDIZED DOCUMENT that can be used

“worldwide" for:
–Identification of new safety signals
–Identification of changes to benefit-risk profile of medical product
Establish whether information recorded during the reporting period is
in accord with previous knowledge on the drug’s safety
•Change in product label
•Change in product name/package/promotional material
•Need for risk management initiatives
•Withdrawal from the market
–Monitoring effectiveness of risk management initiatives
 Why PSUR is required?

To harmonise technical requirements for marketing authorization &

avoid duplication of effort and to ensure that important data is
submitted with consistency to regulatory authorities.
 Types of PSUR

FDA: Post marketing Periodic Adverse Drug

Experience Report
Japan: Anzenteikihoukoku
ICH: PSUR
FDA: Post marketing Periodic Adverse Drug
Experience Report

Described in
21 CFR 314.80 (c) (2)
21 CFR 600.80 (c) (2)
Submit quarterly for first 3 years then yearly forever
30 days to prepare quarterly report, 60 days to prepare annual
report
FDA: Post marketing Periodic Adverse Drug
Experience Report

Contains
An analysis of safety issues
A history of actions taken (PI changes)
Scientific literature
Med Watch forms: all individual AE reports which were received
during that period and have not already been submitted to FDA as
15 day reports
No line listings
No cumulative tabulations
FDA: Post marketing Periodic Adverse Drug
Experience Report

Proposal to change to the ICH PSUR format in the “tome”

Proposed Rule of March 14, 2003
Unclear when or if this Rule will be implemented
 Japan: Anzenteikihoukoku

Periodic report focused on local safety experience

The PSUR is to be included as an appendix to this report
Only produced in Japanese
Limited/No use outside of Japan
 PSUR Principles

One PSUR for one active substance

Multiple indications, doses and even formulations
will usually be covered in one PSUR
Interval data for the period covered
Except for cumulative tabulations and table of
worldwide regulatory status
Create as a “stand alone” report
Interval covered changes as product matures
Every 6 months for first 2 years
Every 1 year for next 3 years
Every 5 years subsequently (changing to every 3
years)
 Table of Contents of PSUR
•Introduction
•Worldwide market authorization
•Update of regulatory authority or MAH actions taken for
safety reasons
•Changes in reference safety information
•Patient exposure
•Presentation of individual case histories
•Studies
•Other information
•Overall safety evaluation
•Conclusion
•Appendix
–Company Core Data Sheet
–Consumer Reports (US)
Introduction

–Brief summary of the drug’s characteristics

–When the data lock date was, and what period of time the report
covers
–What number the report represents, e.g., this is the first periodic
report, this is the 6thperiodic report
Worldwide market authorization

–Typically a table summarizing:

•Countries where the drug has been approved
•Countries where there was a lack of approval, etc.

Update of regulatory authority or MAH actions taken for safety

reasons -for example:

•Failure to obtain marketing re-authorization

•Withdrawal from the market
•Suspension of clinical trials, etc.
Changes in reference safety information
–Summarizes what changes to CCSI have or will be made from
current one

Patient exposure
–Estimate of exposure and methodology used:
•Number of tablets sold
•Number of bottles of medication distributed
•Number of prescriptions written
Presentation of individual case histories

–Listings –“Capsule view" of all the AEs reported by a patient with the most serious
listed first
•All serious reactions, and non-serious unlisted reactions, from spontaneous
notifications;
•All serious reactions (attributable to drug by either investigator or sponsor), available
from studies or named-patient (“compassionate”) use;
•All serious reactions, and non-serious unlisted reactions, from the literature;
•All serious reactions from regulatory authorities
–Tabulation of AEs including a tabulation for non-serious, listed reactions
–Analysis of individual case histories
Studies
–Completed studies with new safety information

Other information
–New relevant efficacy information
–Late breaking news
Overall safety evaluation -A concise analysis of the data presented, taking
into account any late-breaking information, and followed by the MAH’s
assessment of the significance indicating a change in the benefit-risk profile of
the drug

–In addition:
•Specifically looks at certain populations, e.g., elderly, pediatric, pregnancy
•Drug interactions
•Overdose
•Long-term effects
•Etc
Conclusion

–Should indicate the safety findings that are different than that found in the
current reference safety information
–Indicate what actions were or will be taken
•Change in CCSI
•Risk management initiatives, etc.

Appendix
–Company Core Data Sheet
–Consumer Reports (US)
 SAMPLE TITLE PAGE

*PERIODIC SAFETY UPDATE REPORT FOR: (PRODUCT)

*MAH’s NAME AND ADDRESS

(Corporate headquarters or other company entity responsible for
report preparation)

*PERIOD COVERED BY THIS REPORT: (dates)

*INTERNATIONAL BIRTH DATE: Date (Country of IBD)

*DATE OF REPORT
(Other identifying information at the option of MAH, such as
report number)
 TEMPLATE FOR PSUR SUBMISSION
<Serial number> PERIODIC SAFETY UPDATE REPORT
for
ACTIVE SUBSTANCE(S): <Name(s)>
ATC CODE(S): <Code(s)>
MEDICINAL PRODUCTS COVERED:
Marketing Authorization Date of Authorisation Marketing Authorization
Name of the Medicinal Number (Underline EU Birth Date) Holder
Product

<> <> <> <>

AUTHORISATION PROCEDURE in the EU:

<Centralized/Mutual Recognition/National>
INTERNATIONAL BIRTH DATE (IBD): <Date>
PERIOD COVERED BY THIS REPORT:
from <Date> to <Date> (Data lock point)
DATE OF THIS REPORT:<Date>
VOLUME: <Number>/ <Total number of volumes>
OTHER INFORMATION:
<Other identifying or clarifying information at the option of MAH>
DATA LOCK POINT OF NEXT REPORT:
<Date>
MARKETING AUTHORISATION HOLDER'S NAME AND ADDRESS:
<Name>
<Address>
NAME AND CONTACT DETAILS OF THE QUALIFIED PERSON RESPONSIBLE FOR PHARMACOVIGILANCE:
<Name>
<Address>
<Telephone number>
<Fax number>
<E-mail address>
SIGNATURE: <Signature>
LIST OF SERIAL NUMBERS

<Serial number> <Period covered>

DISTRIBUTION LIST 9
<Number of copies>
<Competent authority in the EU>

9For medicinal products authorised through mutual recognition the Reference Member State and the
Concerned Member States should be indicated.
 Key PSUR Definitions

Company Core Data Sheet (CCDS) - A document prepared by the MAH

containing, in addition to safety information, material relating to indications,
dosing, pharmacology and other information concerning the product.

Company Core Safety Information (CCSI) - All relevant safety

information contained in the Company Core Data Sheet prepared by the
MAH and which the MAH requires to be listed in all countries where the
company markets the drug, except when the local regulatory authority
specifically requires a modification. It is the reference information by which
listed and unlisted are determined for the purpose of periodic reporting for
marketed products, but not by which expected and unexpected are
determined for expedited reporting.
Data Lock-Point (Data Cut-off Date) - The date designated as the cut-off
date for data to be included in a PSUR. It is based on the International Birth
Date (IBD) and should usually be in six monthly increments.

International Birth Date (IBD) - The date of the first marketing

authorization for a new medicinal product granted to any company in any
country in the world.

Listed Adverse Drug Reaction - An ADR whose nature, severity,

specificity, and outcome are consistent with the information in the CCSI.

Spontaneous Report or Spontaneous Notification - An unsolicited

communication to a company, regulatory authority or other organization
that describes an adverse drug reaction in a patient given one or more
medicinal products and which does not derive from a study or any
organized data collection scheme.

Unlisted Adverse Drug Reaction - An ADR whose nature, severity,

specificity or outcome are not consistent with the information included in
the CCSI.
 Thanks!!
Sukhwinder. K
Assistant Manager
ADI Back office Professional Pvt. Ltd | www.adibackoffice.com
E-mail: Sukhwinder@adibackoffice.com