ICH Guidelines for Pharmacovigilance

Organization and objectives of ICH, expedited reporting, ICSR, PSURs, post approval expedited reporting, pharmacovigilance Planning, good clinical practices

1. ICH Guidelines for
Pharmacovigilance
Dr. Ramesh Bhandari
Asst. Professor,
Department of Pharmacy Practice,
KLE College of Pharmacy, Belagavi

2. Organization and
Objectives of ICH
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3. Organization and objectives of ICH
INTERNATIONAL CONFERENCE ON HARMONISATION (ICH) of Technical
Requirements for Pharmaceuticals for Human Use
◉EstablishedinApril1990
◉Initiativeforregulatorsandpharmaceuticalindustries
◉Reformedasanon-profitlegalentityunderSwissLawon23October
2015
◉Formedtoassuresafety,qualityandefficacyofmedicines,themembers
ofICHwhoincludemembersfromdrugregulatoryauthoritiesand
researchbasedindustriesofEuropeanUnion,USandJapanwilldiscuss
onthetechnicalproceduresanddocumentsrequired.
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4. Need for harmonization
◉Thedifferenceinthetechnicalrequirementsandthe
proceduresfollowedbydifferentcountriesmadetheglobal
marketingofdrugsastimeconsumingandexpensive
◉Toreducethecostandtimerequiredfortheglobal
marketingofdrugs
◉Harmonizationoftechnicalrequirementshastobepromoted
◉Specialguidelinestobeframedtoensurethequality,safety
andtheefficacyofthedrugs

5. Purpose or Objectives of ICH
◉Harmonizedinterpretationandapplicationoftechnical
guidelinesandrequirementsformarketingauthorizationto:
Reduceduplicationoftestingofthedrugsunder
investigation
Increaseeconomicaluseofresources
Eliminateunnecessarydelayinavailabilityofnew
medicines
◉Safeguardingquality,safetyandefficacy
◉AccomplishedthroughTechnicalGuidelinesthatare
implementedbytheregulatoryauthorities.

6. Categories agreed for Harmonization
◉Newtypesofmedicinalproducts
◉Lackofharmonizationofcurrenttechnical
requirements
◉Transitionstotechnicallyimprovedtesting
procedures
◉ReviewofexistingICHguidelinesresultingin
majorchanges&
◉MaintenanceofexistingICHguidelines
requirementminorchanges

7. ICHMembers
ICH covers 3 regions:
◉European Union
◉United Statesof America
◉Japan
“Six Parties”
1.The European commission, (representing 28 members states of EU)
2.The European federation of pharmaceutical industries and associations (IFPMA)
3.The Ministry of Health, Labourand Welfare of Japan
4.The Japanese Pharmaceutical Manufactures Association (JPMA)
5.The US Food and drug Administration (FDA)
6.The Pharmaceutical Research and Manufacture of America (PhRMA)

8. ICHMembers
18 Members:
Founding Regulatory Members
◉European Union
◉FDA, United Statesof America
◉MHLW/PMDA, Japan
Founding Industry Members
◉EFPIA
◉JPMA
◉PhRMA
Standing Regulatory Members
◉Health Canada, Canada
◉Swissmedic, Switzerland
Regulatory Members
◉ANVISA, Brazil
◉HSA, Singapore
◉MFDS, Republic of Korea
◉NMPA, China
◉SFDA, Saudi Arabia
◉TFDA, Chinese Taipei
◉TITCK, Turkey
Industry Members
◉BIO
◉Global Self-Care Federation
◉IGBA

9. ICH Guidelines for
Pharmacovigilance -Introduction

10. ICH Guidelines for Pharmacovigilance
◉TheICHhaspublishedanumberofdocumentssetting
standardsforsafety,bothclinicalandpre-clinical.
◉Pre-clinicalguidelineshavean“S”designatione.g.S1,S2
etc.Itshouldbenotedthattheclinicalsafetyguidelinesare
designatedas“E”
◉Thesedocumentsprovideahighdegreeofdetailaboutthe
expectedmanner,method,timing,frequencyand
circumstancesinwhichpharmaceuticalcompaniesandother
relevantpartiesneedtoreportsuspectedadversereactions
andothervitalclinicaldatatotheregulatoryauthorities.

11. ICH Guidelines for Pharmacovigilance
◉Eachofthefollowingclinicalsafetyguidelinehasanidentifyingcode,and
duringthelifetimeoftheICHthecodeshavealreadybeenrevisedtoreflectthe
developmentandevolutionofthosestandardsdocuments:
E1ClinicalSafetyforDrugsIntendedforLong-TermTreatmentofNon-Life
ThreateningConditions
E2AClinicalSafetyDataManagement:DefinitionsandStandardsfor
ExpeditedReporting
E2B(R2)MaintenanceoftheClinicalSafetyDataManagementincluding
DataElementsforTransmissionofIndividualCaseSafetyReports
E2B(R3)ClinicalSafetyDataManagement:DataElementsforTransmission
ofIndividualCaseSafetyReports

12. ICH Guidelines for Pharmacovigilance
E2C(R1)ClinicalSafetyDataManagement:PeriodicSafetyUpdateReportsfor
MarketedDrugs
E2C(R2)PeriodicBenefit-RiskEvaluationReport
E2DPost-ApprovalSafetyDataManagement:DefinitionsandStandardsfor
ExpeditedReporting
E2EPharmacovigilancePlanning
E2FDevelopmentSafetyUpdateReport

13. EXPEDITED
REPORTING
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14. EXPEDITED REPORTING
CLINICAL SAFETY DATA MANAGEMENT: DEFINITIONS AND
STANDARDS FOR EXPEDITED REPORTING (E2A)
Itisimportanttoharmonisethewaytogatherand,ifnecessary,totake
actiononimportantclinicalsafetyinformationarisingduringclinical
development.Thus,agreeddefinitionsandterminology,aswellas
procedures,willensureuniformGoodClinicalPracticestandardsinthis
area.
Thisguidelineaddressesthefollowing:
1.thedevelopmentofstandarddefinitionsandterminologyforkey
aspectsofclinicalsafetyreporting,and
2.theappropriatemechanismforhandlingexpedited(rapid)reporting,in
theinvestigational(i.e.,pre-approval)phase.

15. EXPEDITED REPORTING
◉Expedited Report:SAEs which are unexpected (not labelled), be
reported in 15 Calendar days from the first notification of anyone
in the company including its agent, business partners, contractors,
distributors, and vendors. Also known as alert report, 15-day
report.
◉7-day report:Patient in question has died or had life threatening
SAE which is also unexpected and possibly related. This report
should be sent to the health authorities within 7 calendar days.
Note:All 7-day reports are also 15-day report. It must also be followed
up as a 15 day report

16. EXPEDITED REPORTING
STANARDSFOREXPEDITEDREPORTING
WhatShouldbeReported?
1.SingleCasesofSerious,UnexpectedADRs:
◉Alladversedrugreactions(ADRs)thatarebothseriousandunexpectedare
subjecttoexpeditedreporting.
◉Thisappliestoreportsfromspontaneoussourcesandfromanytypeof
clinicalorepidemiologicalinvestigation,independentofdesignorpurpose.
◉Informationobtainedbyasponsorormanufactureronserious,unexpected
reportsfromanysourceshouldbesubmittedonanexpeditedbasisto
appropriateregulatoryauthoritiesiftheminimumcriteriaforexpedited
reportingcanbemet.
◉Causalityassessmentisrequiredforclinicalinvestigationcases.

17. EXPEDITED REPORTING
2.OtherObservations:
◉Therearesituationsinadditiontosinglecasereportsof"serious"
adverseeventsorreactionsthatmaynecessitaterapid
communicationtoregulatoryauthorities
Examplesinclude:
◉Foran"expected,"seriousADR,anincreaseintherateof
occurrencewhichisjudgedtobeclinicallyimportant.
◉Asignificanthazardtothepatientpopulation,suchaslackof
efficacywithamedicinalproductusedintreatinglife-threatening
disease.

18. EXPEDITED REPORTING
STANARDSFOREXPEDITEDREPORTING
WhomShouldbeReported?
Determination Sponsor Investigator
Serious/Life-Threatening Yes Yes
Causality(Responsible Possibility) Yes Yes
Expectedness (Labeled/Unlabeled) Yes Yes

19. EXPEDITED REPORTING
1.FatalorLife-ThreateningUnexpectedADRs
◉Fatalorlife-threatening,unexpectedADRsoccurringin
clinicalinvestigationsqualifyforveryrapidreporting.
Regulatoryagenciesshouldbenotified(e.g.,bytelephone,
facsimiletransmission,orinwriting)assoonaspossiblebut
nolaterthan7calendardaysafterfirstknowledgebythe
sponsorthatacasequalifies,followedbyascompletea
reportaspossiblewithin8additionalcalendardays.
ReportingTimeFrames:

20. EXPEDITED REPORTING
2.AllOtherSerious,UnexpectedADRs
◉Serious,unexpectedreactions(ADRs)thatarenotfatalorlife-
threateningmustbefiledassoonaspossiblebutnolaterthan15
calendardaysafterfirstknowledgebythesponsor
3.Minimumcriteriaforreporting
◉Anidentifiablepatient;asuspectmedicinalproduct;anidentifiable
reportingsource;andaneventoroutcomethatcanbeidentifiedas
seriousandunexpected,andforwhich,inclinicalinvestigation
cases,thereisareasonablesuspectedcausalrelationship.
ReportingTimeFrames:

21. EXPEDITED REPORTING
HowtoReport:
◉TheCIOMS-Iformhasbeenawidelyacceptedstandardfor
expeditedadverseeventreporting.However,nomatterwhatthe
formorformatused,itisimportantthatcertainbasic
information/dataelements,whenavailable,beincludedwithany
expeditedreport,whetherinatabularornarrativepresentation.
◉Allreportsmustbesenttothoseregulatorsorotherofficialparties
requiringthemincountrieswherethedrugisunderdevelopment.

22. EXPEDITED REPORTING
KEYDATAELEMENTSFORINCLUSIONINEXPEDITEDREPORTSOF
SERIOUSADVERSEDRUGREACTIONS

23. EXPEDITED REPORTING

24. EXPEDITED REPORTING

25. EXPEDITED REPORTING

26. EXPEDITED REPORTING

27. Individual Case Safety
Reports (ICSR)

28. Individual Case Safety Reports (ICSR)
◉Itisadocumentprovidingthemostcomplete
informationrelatedtoanindividualcaseatacertain
pointoftime.
◉AnIndividualCaseStudyReport(ICSR)isasafetyservice
documentwhichincludesinformationrequiredforreporting
theadverseeventsandproblemsrelatedtoproductsand
complaintsfiledbyconsumerswithrespecttoanyproduct.
◉Itisanimportantfacetofadverseeventreportingwhichisa
sourceofdatainPV(pharmacovigilance).

29. Individual Case Safety Reports (ICSR)
Sourcesofindividualcasesafetyreports
1.UnsolicitedSources
■Spontaneousreports
■Literature
■Internet
■Othersources-suchaslaypressandothermedia
2.Solicitedsources
3.ContractualAgreements
4.RegulatoryAuthoritySources

30. Individual Case Safety Reports (ICSR)
◉Becauseofnationalandinternationalagreements,rules,and
regulations,individualcasesafetyreportsofadversedrugreactions
andadverseeventsneedtobetransmitted
fromidentifiedreportingsourcestoregulatoryauthoritiesand
pharmaceuticalcompanies;
betweenregulatoryauthorities;
betweenpharmaceuticalcompaniesandregulatory
authorities;
withinauthoritiesorpharmaceuticalcompanies;
fromclinicalinvestigators,viathesponsor,toethics
committees;
fromauthoritiestotheWorldHealthOrganization(WHO)
CollaboratingCenterforInternationalDrugMonitoring.

31. Individual Case Safety Reports (ICSR)
◉Thetransmissionofsuchindividualcasesafetyreports
currentlyreliesonpaper-basedformats(e.g.,Yellowcards,
CIOMSforms,MedWatch)orelectronicmedia.
◉Consideringthelargenumberofpotentialparticipantsina
world-wideexchangeofinformation,thereisaneedforan
electronicformatcapableofaccommodatingdirectdatabase
todatabasetransmission

32. Individual Case Safety Reports (ICSR)
◉Successfulelectronictransmissionofinformationrelieson
thedefinitionofcommondataelementsandstandard
transmissionprocedures
◉Theformatforindividualcasesafetyreportsincludes
provisionsfortransmittingalltherelevantdataelements
usefultoassessanindividualadversedrugreactionor
adverseeventreport.Structureddataarestrongly
recommendedinelectronictransmission.

33. Individual Case Safety Reports (ICSR)
Minimuminformation:
◉Theminimuminformationforthetransmissionofareport
shouldincludeatleastoneidentifiablepatient(sectionB.1),
oneidentifiablereporter(sectionA.2),onereaction/event
(sectionB.2),andonesuspectdrug(sectionB.4).
◉Becauseitisoftendifficulttoobtainalltheinformation,any
oneofseveraldataelementsisconsideredsufficientto
defineanidentifiablepatientoranidentifiablereporter.

34. Individual Case Safety Reports (ICSR)
◉Itisalsorecognizedthatthepatientandthereportercanbe
thesameindividualandstillfulfilltheminimumreporting
criteria.
◉Inaddition,toproperlyprocessthereport,thefollowing
administrativeinformationshouldbeprovided:thesender’s
(case)safetyreportuniqueidentifier(A.1.0.1),thedateof
receiptofthemostrecentinformation(A.1.7),the
worldwideuniquecaseidentificationnumber(A.1.10)and
thesenderidentifier(A.3.1.2).

35. GUIDELINE: CONTENT OF THE DATA ELEMENTS

36. Elements of the specifications in the ICSR
◉Pre-Clinical:
Toxicity
General Pharmacology
Drug Interactions
Other toxicity related information
◉Clinical:
Limitations of the Human Safety Database
Populations not studied in the pre-approval phase
Adverse events/adverse drug reactions
Identified risks that require further evaluation
Potential risks that require further evaluation
Identified and potential interactions

37. PERIODIC SAFETY
UPDATE REPORTS (PSUR)

38. PERIODIC SAFETY UPDATE REPORTS
◉Theperiodicsafetyupdatereport(PSUR)isadocumentthat
allowsaperiodic,comprehensiveassessmentoftheworldwide
safetydataofamarketeddrugorbiologicalproduct.
◉TheconceptevolvedfromtheCouncilforInternational
OrganizationsofMedicalSciences(CIOMS)WorkingGroupII
report(CIOMS,1992).
◉ThePSURcreatestheopportunityforaperiodicoverallsafety
evaluationtoshowwhetheraproduct’ssafetyprofilehasremained
thesameorhasundergonechangesinceitwasauthorizedandto
indicatewhetherchangesshouldbemadetoproductinformation
tooptimizetheuseofaproduct.

39. PERIODIC SAFETY UPDATE REPORTS
PurposeofthePSUR:
◉Thereasonsuchareviewisneededperiodicallyisbecauseclinical
trialstendtobeofshortdurationandtoincludealimitednumberof
patients.
◉Moreover,clinicaltrialshaveinclusionandexclusioncriteria.Aftera
productislaunched,itmaybeusedbypatientsnotstudiedinclinical
trials,forexamplechildren,theelderly,pregnantorbreastfeeding
womenorpatientswithcomorbiditiessuchashepaticorrenaldisease.
◉Afterapproval,adrugbecomessoavailableforimmediateuseinlarge
populations,sorareadversedrugreactions(ADRs)canbemoreeasily
identified.Thedrugsalsobecomeavailableforindefiniteuse(unless
prescribinginformationindicatesotherwise),anddelayedonsetADRs
becomeeasiertoidentify.

40. PSUR –GENERAL PRINCIPLES
ONE REPORT FOR PRODUCTS CONTAINING ONE ACTIVE SUBSTANCE
AUTHORISED TO ONE MARKETING AUTHORISATION HOLDER
◉Ordinarily,alldosageformsandformulationsaswellas
indicationsforagivenpharmacologicallyactivesubstance
authorizedtoonemarketingauthorizationholder(MAH)maybe
coveredinonePSUR.
◉WithinthesinglePSUR,separatepresentationsofdatafor
differentdosageforms,indicationsorpopulations(e.g.children
versusadults)maybeappropriate.

41. PSUR –GENERAL PRINCIPLES
PRODUCTSAUTHORISEDTOMORETHANONEMAH
◉EachMAHisresponsibleforsubmittingPSURs,evenifdifferent
companiesmarketthesameproductinthesamecountry.
COMBINATION PRODUCTS
◉Safetyinformationforthefixedcombinationmaybereported
eitherinaseparatePSURorincludedasseparatepresentationsin
thereportforoneoftheseparatecomponents,dependingonthe
circumstances.

42. PERIODIC SAFETY UPDATE REPORTS
GENERAL SCOPE OF INFORMATION
◉Allrelevantclinicalandnon-clinicalsafetydatashouldcoveronly
theperiodofthereport(intervaldata).
Exception-Regulatorystatusinformationonauthorization
applicationanddataonseriousunlistedADRs-canbeprovided
withcumulativesummarytabulations.
◉ThesafetyinformationcontainedwithinthePSURcomesfroma
varietyofdifferentsources.Theseincludespontaneousreportsof
adverseeventsfromdifferentcountries,theliterature,clinical
trials,registries,regulatoryADRdatabasesandimportantanimal
findings.

43. PERIODIC SAFETY UPDATE REPORTS
◉Reportsoflackofefficacyspecificallyfordrugsusedinthe
treatmentoflife-threateningconditionsandforcertainother
medicinalproducts,suchascontraceptivesandvaccines,may
representasignificanthazard,andinthatsensemaybeasafety
issue.ThesetypesofcasesshouldbediscussedinthePSUR.
Frequencyofreporting
◉EachPSURshouldcovertheperiodsincethelastupdatereport.
Theneedforareportandthefrequencyofreportsubmissionto
authoritiesaresubjecttolocalregulatoryrequirements.Theageof
amedicinalproductonthemarketmayinfluencethisprocess.

44. PERIODIC SAFETY UPDATE REPORTS
◉IntheEU,reportsbesubmittedevery6monthsforthefirst2years
afterauthorization,annuallyforthethreefollowingyearsandthen
fiveyearly
◉IntheUnitedStates,theFDArequiresquarterlyreportsduringthe
first3years,thenannualreports;and
◉InJapan,theauthoritiesrequireannualsurveyreportonacohortof
afewthousandpatientsestablishedbyacertainnumberof
identifiedinstitutionsduringthe6yearsfollowingauthorization.
◉Regardingothermarketingexperience,adversereactionswhichare
non-serious,butbothmildinseverityandunlabeled,mustbe
reportedevery6monthsfor3yearsandannuallythereafter.

45. PSUR Content

46. PSUR Content
TITLE
◉PSURscontainproprietaryinformation,sothetitlepageshouldcontainastatement
ontheconfidentialityofthedataandconclusionsincludedinthereport.
EXECUTIVESUMMARY
◉Theexecutivesummaryshouldconsistofabriefoverviewprovidingthereaderwitha
descriptionofthemostimportantinformation.
INTRODUCTION
◉Theintroductionputsthereportincontext,describingthoseproducts/formulations
thatareincludedandexcluded,outliningthepharmacologyoftheproduct,its
indications(bothmarketedandinclinicaltrials)
WORLDWIDE MARKETINGAUTHORISATIONSTATUS
◉ThePSURshouldincludeashortsummaryoftheworldwidemarketingauthorisation
status

47. PSUR Content
UPDATEONREGULATORY AUTHORITYORMAHACTIONSTAKENFOR
SAFETYREASONS
◉TheupdateonregulatoryauthorityorMAHactionstakenforsafetyreasons
referstomarketingauthorization,withdrawalorsuspension;failuretoobtaina
marketingauthorizationrenewal;restrictionsondistribution;clinicaltrial
suspension;dosagemodification/formulationchangesandchangesintarget
populationorindications.
CHANGES IN REFERENCE SAFETY INFORMATION
◉The changes in reference safety information section refers to changes in the
CCSI (company core safety information). The CCDS (company core data sheet),
which incorporates the CCSI, should be included as an appendix.

48. PSUR Content
PATIENTEXPOSURE
◉Patientexposurereferstobothmarketexposureandclinicaltrials(ifrelevant).
Estimatesofpatientexposureformarketeddrugsoftenrelyongross
approximationsofin-houseorpurchasedsalesdataorvolume.
PRESENTATIONOFINDIVIDUALCASEHISTORIES
◉ThereisnospecificguidanceinE2Conthepresentationofindividualcase
histories,butbecauseitisimpracticaltopresentallcasereportsforthereporting
period,abriefdescriptionofthecriteriausedtoselectcasesforpresentation
shouldbegiven.
◉ThissectionofthePSURshouldcontainadescriptionandanalysisofselected
cases,includingfatalities,presentingnewandrelevantsafetyinformationand
groupedbymedicallyrelevantheadings

49. PSUR Content
STUDIES
◉Studiesrefertoonlythosecompany-sponsoredstudiesandpublishedsafety
studies,includingepidemiologystudies,thatproducefindingswithpotential
impactonproductsafetyinformation.
OTHERINFORMATION
◉OtherinformationmayincluderiskmanagementprogrammestheMAHhasput
inplaceand/orabenefit–riskanalysisreport.
◉Ifsuchananalysishasbeenconductedseparately,asummaryoftheanalysis
shouldbeincludedinthissection.
◉ThissectioncanalsoincludeimportantinformationreceivedaftertheDLP(data
lockpoint).

50. PSUR Content
OVERALLSAFETYEVALUATION
◉Theoverallsafetyevaluationshouldhighlightnewinformationonseriousand
non-seriousunlistedADRs.Iftherearenonewsafetyissues,thisshouldbe
statedwithanotethattheinformationisinkeepingwiththeestablishedsafety
profile.Thissectionshouldalsoreviewreportsof
○druginteractions;
○overdose:deliberateoraccidentalandtreatment;
○abuseormisuse;
○pregnancyorlactation:positiveandnegativeexperiences;
○specialpatientgroups(e.g.children,elderly,organ
○impaired)and
○effectsoflong-termtreatment.

51. PSUR Content
CONCLUSION
◉Theconclusionshouldindicatesafetydatawhicharenotinaccordancewith
previousexperienceand/orwiththeCCSIandspecifyandjustifyanyaction
recommendedorinitiated.

52. PSUR process
A.Intake of ADR information
B.Case processing
C.Data retrieval
D.Data analysis and
E.Medical review and risk assessment
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53. POST APPROVAL
EXPEDITED REPORTING

54. Post approval safety management guideline
Postapprovalsafetymanagement(E2D)guidelinewas
finalizedin2003andprovidesastandardizedprocedurefor
postapprovalsafetydatamanagement,includingpost
approvalexpeditedreportingtotheconcernedauthority.
ItparallelsandaddstotheE2Adocument,whichcovered
preapproval(clinicaltrial)safetydatamanagement,by
coveringpostmarketingsafetydatamanagement.
Thisdocumentstandardizesdatamanagementofcasesfrom
consumers,literature,internet,andothertypesof
postmarketingcases.

55. DEFINITIONS
i.Adverse Event
ii.ADR
iii.Serious AE/ADR
iv.Unexpected ADR
v.Healthcareprofessional:Anymedically-qualifiedperson
suchasaphysician,dentist,pharmacist,nurse,coroner,oras
otherwisespecifiedbylocalregulations.
vi.Consumer:Apersonwhoisnotahealthcareprofessional,
suchaspatient,lawyer,friendorrelativeofthepatient.

56. SOURCES
1. Unsolicited Sources
Spontaneous reports
Literature
Internet
Other sources-such as lay press and other media
2. Solicited sources
3. Contractual Agreements
4. Regulatory Authority Sources

57. STANDARDS FOR EXPEDITED REPORTING
◉Serious ADRs:
Serious and unexpected cases of ADRs are subject to
expedited reporting.
For reports from studies and other solicited sources, all
cases judged by either the reporting health care
professionals or the MAH for causal relationship to the
medicinal product qualifying as ADRs.
Spontaneous reports associated with approved drugs
imply a possible causality

58. STANDARDS FOR EXPEDITED REPORTING
◉Other observations:
Any significant unanticipated safety findings, including in
vitro, animal, epidemiologic, or clinical studies, that
suggest a significant human risk and could change the
benefit–risk evaluation should be communicated to the
regulatory authorities as soon as possible.
Lack of efficacy observations should not be expedited but
should be discussed in PSURs unless local requirements
oblige their being expedited.

59. STANDARDS FOR EXPEDITED REPORTING
Overdoseswithnoassociatedadverseoutcomeshouldnotbe
reportedasadversereactions.
Minimumcriteriaforreportingincludeanidentifiablereporter,an
identifiablepatient,anadversereaction,andasuspectproduct.
Reportingtimeframesforexpeditedreportsarenormally15
calendardaysfrominitialreceiptoftheminimalinformationby
anypersonneloftheMAH.Thisisday0.Additionalmedically
relevantinformationforapreviouslysubmittedreportrestartsthe
clock.
Non-seriousADRsarenotnormallyexpeditablewhetherexpected
ornot

60. PHARMACOVIGILANCE
PLANNING (E2E)

61. PHARMACOVIGILANCE PLANNING
Thisguidelinewasfinalizedin2004andis
intendedtoaidinplanningpharmacovigilance
activities,especiallyinpreparationfortheearly
postmarketingperiodofanewdrug.
ThemainfocusofthisguidelineisonaSafety
SpecificationandPharmacovigilancePlanthat
mightbesubmittedatthetimeoftheapplication
formarketing.

62. PHARMACOVIGILANCE PLANNING
AllthreeregionsoftheICH(UnitedStates,
EuropeanUnion,andJapan)havebeenturning
theirattentiontoriskmanagementand
pharmacovigilanceplanningthroughoutthelife
cycleofadrug.
ThisdocumentreflectsICH’sviews.

63. Principles of Pharmacovigilance Planning
guidelines
i.Planning of pharmacovigilance activities
throughout the product life cycle
ii.Science-based approach to risk documentation
iii.Effective collaboration between regulators and
industry
iv.Applicability of the pharmacovigilance plan across
the three ICH region

64. Sections of Pharmacovigilance Plan
1.Safety Specification
2.Pharmacovigilance plan
3.Annex-Pharmacovigilance methods

65. Sections of Pharmacovigilance Plan
1.Safety Specification:
Thesafetyspecificationisasummaryofthe
importantidentifiedrisksofadrug,important
potentialrisks,andimportantmissinginformation.
It should refer to the three safety sections in the
Common Technical Document:
Non-clinical
Clinical
Epidemiology

66. Sections of Pharmacovigilance Plan
2.Pharmacovigilance Plan:
The pharmacovigilance plan should be based on the safety
specification and developed by the sponsor.
This includes:
•Summary of ongoing safety issues, including the important
identified risks, potential risks, and missing information.
•Routine pharmacovigilance practice
•Summary of actions to be completed, including milestones

67. Sections of Pharmacovigilance Plan
3.Pharmacovigilance Methods:
The best method to address a specific situation may vary
depending on the product, indication, population treated.
Sponsors should choose the most appropriate design.
Design and conduct of observational studies
Annexure -A detailed discussion of pharmacovigilance
methods is appended to the document.

68. GOOD CLINICAL PRACTICES
IN PHARMACOVIGILANCE
STUDIES
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69. GOOD CLINICAL PRACTICES (GCP)
◉GCPs are stand alone document and its guidelines are given
in ICH E6.
◉Good Clinical Practice (GCP) is an international ethical and
scientific quality standard for designing, conducting,
recording and reporting trials that involve the participation
of human subjects.
◉Compliance with this standard provides public assurance
that the rights, safety, and well-being of trial subjects are
protected, consistent with the principles that have their
origin in the Declaration of Helsinki, and that the clinical
trial data are credible.
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70. GOOD CLINICAL PRACTICES (GCP)
1)Clinical trials should be conducted in accordance with the ethical principles
that have their origin in the Declaration of Helsinki, and that are consistent
with GCP and the applicable regulatory requirement(s).
2)Before a trial is initiated, foreseeable risks and inconveniences should be
weighed against the anticipated benefit for the individual trial subject and
society. A trial should be initiated and continued only if the anticipated
benefits justify the risks.
3)The rights, safety, and well-being of the trial subjects are the most
important considerations and should prevail over interests of science and
society.
4)The available nonclinical and clinical information on an investigational
product should be adequate to support the proposed clinical trial.
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71. GOOD CLINICAL PRACTICES (GCP)
5)Clinical trials should be scientifically sound, and described in a clear,
detailed protocol.
6)A trial should be conducted in compliance with the protocol that has
received prior institutional review board (IRB)/independent ethics
committee (IEC) approval/favourable opinion.
7)The medical care given to, and medical decisions made on behalf of,
subjects should always be the responsibility of a qualified physician or,
when appropriate, of a qualified dentist.
8)Each individual involved in conducting a trial should be qualified by
education, training, and experience to perform his or her respective
task(s).
9)Freely given informed consent should be obtained from every subject
prior to clinical trial participation.
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72. GOOD CLINICAL PRACTICES (GCP)
10)All clinical trial information should be recorded, handled, and
stored in a way that allows its accurate reporting, interpretation and
verification.
11)The confidentiality of records that could identify subjects should
be protected, respecting the privacy and confidentiality rules in
accordance with the applicable regulatory requirement(s).
12)Investigational products should be manufactured, handled, and
stored in accordance with applicable good manufacturing practice
(GMP). They should be used in accordance with the approved
protocol.
13)Systems with procedures that assure the quality of every aspect of
the trial should be implemented.
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73. GOOD CLINICAL PRACTICES (GCP)
INVESTIGATOR’S RESPONSIBILITIES:
All SAEs should be reported immediately by the investigator to the
sponsor except for those SAEs which the protocol or other document
identifies not needing immediate reporting.
Identify the subject by trial code number rather than by subject name,
personal information and/or address
Investigator should comply with the applicable regulatory requirement
while reporting unexpected SAEs to the regulatory authorities
Adverse events or laboratory abnormalities should be reported to the
Sponsor within the time periods specified by sponsor.
For reported death, the investigator should provide additional information
if requested by sponsor or IRB/IEC.
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74. GOOD CLINICAL PRACTICES (GCP)
INVESTIGATOR’S RESPONSIBILITIES:
If the investigator terminates or suspended trial without prior agreement of
the sponsor, the investigator should promptly inform the institute and
where applicable (such as Institutions, IRB/IEC) by providing detailed
information.
If the sponsor terminates or suspended trial, the investigator should
promptly inform the institutes and where applicable (such as Institutions,
IRB/IEC) by providing detailed information.
If IRB/IEC terminates or suspends its approval/favourable opinion of a
trial, the investigator should inform the institution where applicable.
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75. GOOD CLINICAL PRACTICES (GCP)
SPONSOR’S RESPONSIBILITIES:
Sponsor is responsible for the ongoing safety
evaluation of the investigational product(s).
Should notify all concerned
investigator(s)/institution(s) and the regulatory
authorities of findings that could adverse affect
the safety of subjects, impact the conduct of trial.
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76. GOOD CLINICAL PRACTICES (GCP)
ADR Reporting guidelines:
Sponsor should expedite the reporting to all concerned
investigator(s)/Institution(s) to the IRB/IEC, where required
to the regulatory authority of all ADRs that are both serious
and unexpected.
Expedited reports should comply with the applicable
regulatory requirement and with the ICH guidelines for
clinical safety data management.
Sponsor should submit to the regulatory authority(ies) all
safety updates and periodic reports as required by applicable
regulatory requirement(s).
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77. REFERENCES
1.BortonCobert.Cobert’sManualofDrugSafetyand
Pharmacovigilance.2
nd
Edition.JonesandBartlett
Learning.2012.
2.Dr.S.B.Bhise,Mrs.M.S.Bhise.Pharmacovigilance.
NiraliPrakashan.1
st
Edition.February2021.
3.Dr.D.K.Tripathi,Dr.ShivShankarShukla,Dr.Ravindra
KumarPandey.Pharmacovigilance.NiraliPrakashan.2
nd
Edition.February2021.
4.ElizabethB.Andrews,NicholasMoore.Mann’s
Pharmacovigilance.3
rd
Edition.WileyBlackwell.2014.
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78. Thanks!
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