Safety Reports: PBRER / PSUR

The aim of Safety reports is describe the safety during the lifecycle of the medicinal product. These reports are necessary during development as well as during the authorization process or renewal. In addition, several of these reports may be required by Health Authorities in case of safety concerns.
This presentation contains a full overview about periodic safety update reports and all the information related with it.

1. Safety Reports:
PSUR/PBRER

2. Index
1.What is a Periodic Safety Update Report (PSUR)?
2.Objective of the PSUR
3.Periodicity, EU Reference Dates and Data lockPoints
4.
Exemption from submitting PSURS
5.EU single assessmentof PSUR (PSUSA)
6.
Summaryof GVP Module VII
7.
Howto reviewa PSUR/PBRER
Safety Reports: PSUR/PBRER

3. 1. WHAT IS A PERIODIC SAFETY REPORT (PSUR)?
Periodicsafetyupdatereports(PSURs)arepharmacovigilancedocuments
intendedtoprovideanevaluationoftherisk-benefitbalanceofamedicinal
productforsubmissionbymarketingauthorisationholdersatdefinedtime
pointsduringthepost-authorisationphase.
PBRER(Periodic Benefit Risk Evaluation Report) are referred to as PSUR
since implementation in Europe via GVP module VII.

4. 2. OBJECTIVE OF THE PSUR (1)
To present a comprehensive and critical analysis of new or emerging
information on the risksand, where pertinent, new evidence of benefit to
enable an appraisal of overall benefit risk.
To contain an evaluation of new relevant informationthat became available to
the MAH during the reporting interval, in the context of cumulative
information:
•Examine whether new information is in accord with previous knowledge of
the benefit risk profile
•
Summarises relevant new safety information that may impact the benefit
risk profile
•
Summarises any important new efficacy and effectiveness information
•Conduct an integrated Benefit/Risk evaluation (where new important safety
information has emerged)

5. 2. OBJECTIVE OF THE PSUR (2)
This evaluation of risk-benefit assessment should be undertaken in the
context of ongoing pharmacovigilance and risk management:
Module VII: Post-authorization safety studies
Module V: Risk management systems

6. 3. PERIODICITY (1)
PSUR must be prepared at the following intervals:
•
Immediatelyupon request
•
Every six monthsfrom authorisation until product placed on the market
•
Every six months for first two yearson the market
•
Annuallyfor the next two years
•
Thereafter
every 3 years
Exception–frequencyanddatesofsubmissionarelaiddownasaconditionoftheMA
ordeterminedotherwiseinthelistofUnionReferenceDates(EURDList).
Submit: •
By day 70 for intervals up to 12 months
•By day 90 for intervals in excess of 12 months

7. 3. INTERNATIONAL BIRTH DATE AND DATA LOCK POINT (2)
The date of the first marketing approval for the medicinal product in
any country in the world is the International Birth Date (IBD). Data
lock point is the date designated as the cut-off for data to be included,
based on IBD.

8. TheEUReferenceDatesListisacomprehensivelistofactive
substancesandcombinationsofactivesubstancesforwhichPSURs
shallbesubmitted:
•
Legally binding
•Periodicity defined on a risk-based approach
TheEUReferenceDatesListwasputinplaceinordertofacilitatethe
harmonisationofDataLockPoints(DLPs)andfrequencyof
submissionofPSURsformedicinalproductscontainingthesame
activesubstanceorthesamecombinationofactivesubstances
subjecttodifferentmarketingauthorisations,authorisedinmorethan
oneMemberState.
EMAhaspublishedthelistofUnionreferencedatesandfrequencyof
submissioninformationwhichwillbelegallybindingwhenModuleVII
becomeseffective2July2012.
3. EU REFERENCE DATES LIST (3)

9. EUreferencedateslist
3. EU REFERENCE DATES LIST (4)

10. TheEURDlistisalivingdocumentwhichwillbeamendedwhenever
considerednecessarybythePRAC,theCHMPorCMDhinresponseto
theemergenceofrelevantnewsafetyinformation,newlyauthorised
substancesandrequestsreceivedfromMAHs.Substancescanbe
addedorremovedasappropriate.TheEURDlistisupdatedona
monthlybasis; MAHsshouldthereforemaintainanawarenessofthe
currentstatusofthelist.PSURsshallalsobesubmittedatanytime
immediatelyuponrequestbytheregulatoryauthorities.
3. EU REFERENCE DATES LIST (EURD List) (5)

11. 3. EU REFERENCE DATES LIST (EURD List)
REGULATORY NETWORK (6)
11
TheCo-ordinationGroupforMutualRecognitionand
DecentralisedProcedures–Human,examineanyquestion
relatingtomarketingauthorisationofamedicinalproductin
twoormoreMemberStatesinaccordancewiththemutual
recognitionprocedureorthedecentralisedprocedure.
ExecutivebodyoftheEuropean
Unionresponsibleforproposing
legislation, implementing
decisions,upholdingtheUnion's
treatiesandday-to-dayrunningof
theEU.
Helps protect and promote health in Europe by evaluating
medicines for both human and veterinary use.
HeatlhAuthorities of each Member State
TheCommitteeforMedicinalProductsforHumanUseisthe
committeeattheEMAthatisresponsibleforpreparing
opinionsonquestionsconcerningmedicinesforhumanuse.
CHMP
ThecommitteeattheEMAthatisresponsibleforassessing
andmonitoringsafetyissuesforhumanmedicines.
EMA
PRAC
National Competent Authorities (NCA)

12. 4. EXEMPTION FROM SUBMITTING PSURS
Generics,well-establisheduse,andtraditionalherbalmedicinal
productsareexemptedfromsubmittingPSURsexceptinthe
followingcircumstances:
Themarketingauthorisationprovidesforthesubmissionof
PSURsasacondition.

PSURsis(are)requestedduetoconcernsrelatingtoPVdataor
duetothelackofPSURsrelatingtoanactivesubstanceafter
theMAhasbeengranted(e.g.whenthe“reference”medicinal
productisnolongermarketed).
FortheproductswherePSURsarenolongerrequiredtobe
submittedroutinely,itisexpectedthatmarketingauthorisation
holderswillcontinueto:
•
Evaluate the safety of their products on a regular basis and
Report any new safety information that impacts on the benefit-
risk profile or the product information.

13. 5. EU SINGLE ASSESSMENT OF PSUR (PSUSA) (1)
PSUSAisaPSURsingleassessmentofsubstancescontainedin
centrallyauthorisedproduct(s)ANDnationallyauthorised
products.Thisassessmentleadtolegallybindingoutcomes:
maintenance,variation,suspension,revocationofthemarketing
authorisation.
Objectives:harmoniseandstrengthenthesafetyandbenefit-risk
reviewofmedicinesacrosstheEU;increasetheshareduseof
resourcesbetweencompetentauthorities;Assessmentbythe
PRACwithCHMPinvolvement(forCAPandCAP/NAP)orCMDh
(forNAP)incaseofregulatoryaction.

14. 5. EU SINGLE ASSESSMENT OF PSUR (PSUSA) (2)

15. 5. EU SINGLE ASSESSMENT OF PSUR (PSUSA) (3)
TheEMApublishesalistofoutcomesforNAPsontheirwebsite
whileoutcomesforCAPsarepublishedaspartofeachmedicine’s
Europeanpublicassessmentreport(EPAR).Anychangestothe
productinformationasaresultofthePSURassessmentare
implementedwithoutsubsequentvariationforCAPsandthrough
theappropriatevariationatnationallevelforNAPs.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/g
eneral/general_content_000620.jsp&mid=WC0b01ac0580902b8d

16. 6. SUMMARY OF GVP MODULE VII
ModuleVIIincludesguidanceontheobjectives,formatandcontentsofthe
PSUR,aswellasrecommendationsforqualitysystemsforPSURsandtraining
ofstaffmembersonthePSURprocess.
OverallContent
PSURsshouldprovidegreateremphasisonanalysisofcasereports;to
include:

scientific evaluationof the benefit-risk profile

summaries of relevant scientific/clinical data including literature searches
available sales/prescription data to calculate patient exposure
ThereactiontermsusedinthePSURshouldbeinaccordancewiththe
MedDRAterminology.

17. 7. HOW TO REVIEW A PSUR/PBRER
Reviewbyanexperiencedpersonwhoknowsthedrugandwhoknows
drugsafety.
HIGHQUALITY/AUDITS/INSPECTIONS
•AllpromisesandcommitmentsmadetotheHealthAgencies(HAs),whetherin
thePSURitselforinaccompanyingemailsorcommunicationsshouldbenoted.
ResponsestoHAs.
•Makesureyouhaveinhandtheappropriatelabels(CCSI,nationallabelingetc.).
•Thereviewershouldbeawareofanycurrentconcerns(safetysignals,special
populations,neworremovedindications,anyactionstakenforsafetyreasonsby
thecompanyoranotherhealthagency,anylabelchangesforsafetyreasons
anywhereintheworld….)
•CarefulreviewoftheSAEs/ADRs:
•InwhichSOCshavemostSAEs/ADRsoccurred?
•AnysurprisesorsignalsinthelistedSAEs/ADRs?
•AnysurprisesorsignalsintheunlistedSAEs/ADRs?
•AnysurprisesorissuesinthefatalSAEs/ADRs?
•Arethereanyfindingsinspecificpatientpopulationsasdefinedbydisease,age,
vulnerablegroupsetc?

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