Pharmacovigilance Planning

Pharmacovigilance planning refers to the systematic and proactive approach taken by pharmaceutical companies, regulatory agencies, and other stakeholders to establish strategies and procedures for monitoring the safety of drugs throughout their lifecycle. It involves creating a comprehensive framework to detect, assess, understand, and prevent adverse effects or any other drug-related problems. Here are some key aspects to consider in pharmacovigilance planning

1. PHARMCOVIGILANC E
PLANNING
Presentedby-MounikaMaduri
(Pharm-D)
shahzadMustaqeem(BPharm)
PoojaLaxmanPatil(BPharm)
ClinosolresearchPvt.Ltd
EducationandResearchCenter

2. Content:
1.Definition
2.Pharmacovigilanceplan
3.Why Pharmacovigilance
Planning
4.Scope
5.SafetySpecification
6.Elementsofsafetyspecification
7.PharmacovigilancePlan
8.StructureofthePharmacovigilancePlan
9.Summaryof ongoingsafetyissues
10.Routine Pharmacovigilance Practices
11.Summary of actions to be
completed,including milestones
12.References

3. Pharmacovigilanceisthescienceand
activitesrelatingtothe
detection,assessment,andpreventionof
adverseeffectsoranyother
medicine/vaccinerelatedproblem.
Definition
Pharmacovigilance:

4. PHARMACOVIGILANCE
PLANNING
Theconceptofpharmacovigilance
planningwasinitatedintheyear2004
byInternationalCouncilfor
Harmonisation(ICH)followedbythe
publicationofICHE2E
ThemainfocusofthisguidelineisonaSafety
SpecificationandPharmacovigilancePlanthatmight
besubmittedatthetimeoflicenseapplication.

5. Carefullyplannedandeffectivepharmacovigilance
activites,particularlyfornewdrugs,canreducethe
riskofdrugtoxicityandincreasethebenefitto
publichealth.
Robustsafetydatacanhelpavoidwithdrawalof
effectivedrugsfromthemarket.
WhyPharmacovigilance
planning:

6. SCOPE:
The purpose of this guidelineis to propose a structure for a
Pharmacovigilance Plan, and Safety Specification that
summarises theidentified andpotential risksofthe product
to be addressed in the plan. The guideline is divided into the
followingsections.
Safety Specification;
PharmacovigilancePlan
During the course ofimplememting the various components
of the plan ,any important emerging bebefit or risk
information should be discussed and used to revise the plan.

7. The
following
principles
underpin
this
guidelines:
Planning pharmacovigilance activities
throughout the Product life-cycle:
Science-based approach to risk
documentation;
Effective collaboration between
regulators and industry:
Applicability of the
Pharmacovigilance plan across the
threeICHregions.

8. Safety
Specific
ation
The Safety Specificationshould be a summary of;
The important identified risks of a drug
Importantpotentialrisks
Importantmissinginformation
Itshouldalsoaddressthepopulationspotentiallyat
risk (where the productislikelytobe used)
Outstanding safety questions which warrant further
investigation to refine understanding of the benefit-risk
profileduring thepost-approval period.
ThisSafetySpecificationisintendedtohelindustryand
regulatorsidenitfyanyneedforspecificdatacollectionandalso
tofacilitatetheconstructionofthePharmacovigilancePlan.

9. ElementsofSafetySpecification:-
ThefocusoftheSafetySpecification
shouldbeontheidentifiedrisks,
important potential risks, and
importantmissinginformation.The
following elements should be
considered
1.Non-Clinical
2.Clinical

10. Non-Clinical:-
1.Toxicity (including repeat-dose
toxicity,reproductive/developmental
toxicity,nephrotoxicity,hepatotoxicity,
genotoxicity,carcinogenicityetc.
2.General pharmacology
(cardiovascular,includingQTinterval
prolongation;nervoussystem;etc.);
3.Druginteractions;
4.Othertoxicity-relatedinformation
or data.

11. Clinical:-
A.LimitationsoftheHumanSafety
Database
Theworld-wideexperienceshouldbe
brieflydiscussed,including:
Theextentoftheworld-wideexposure;
Anynewordifferentsafetyissues
identified;
Anyregulatoryactionsrelatedtosafety.

12. B.PopulationsnotStudiedinthePre-ApprovalPhase
Populationshavenotbeenstudiedorhaveonlybeen
studiedtoalimiteddegreeinthepre-approvalphase
Children;
The elderly;
Pregnantorlactatingwomen;
Patientswithrelevantco-morbiditysuchashepatic
orrenaldisorders;
Patientswithdiseaseseveritydifferentfromthat
studiedinclinicaltrials;
Sub-populationscarryingknownandrelevant
geneticpolymorphism;
Patientsofdifferentracialand/orethnicorigins.

13. C.AdverseEvents(AEs)/AdverseDrug
Reactions(ADRs)
Moredetailedinformationshouldbeincluded
onthemostimportantidentifiedAEs/ADRs,
whichwouldincludethosethatareseriousor
frequentandthatalsomighthaveanimpact
onthebalanceofbenefitsandrisksofthe
product.Thisinformationshouldinclude
evidencebearingonacausalrelationship,
severity,seriousness,frequency,reversibility
andat-riskgroups,ifavailable.

14. AttheendoftheSafetySpecificationa
summaryshouldbeprovidedofthe:
Importantidentifiedrisks;
Importantpotentialrisks;
Importantmissinginformation.

15. PharmacovigilancePlan:-
ThePharmacovigilancePlanwouldnormallybe
developedbythesponsorandcanbediscussedwith
regulatorsduringproductdevelopment,priorto
approval(i.e.,whenthemarketingapplicationis
submitted)ofanewproduct,orwhenasafety
concernarisespost-marketing.
ThePharmacovigilancePlanshouldbebasedonthe
SafetySpecification.
Itcanbeastand-alonedocumentbutelements
couldalsobeincorporatedintotheCTD.

16. StructureofthePharmacovigilancePlan:-
Thestructurecanbevarieddependingonthe
productinquestionandtheissuesidentifiedinthe
SafetySpecification.Theplanshouldbeupdatedas
soonasimportantinformationonsafetybecomes
available.
SuggestedstructureforPVplanare:-
1.Summaryofongoingsafetyissues
2.RoutinePVpractices
3.Actionplanforsafetyissues
4.SummaryofActionstobecompleted,including
milestones

17. SummaryofOngoingsafetyissues:-
Atthebeginningofthe
PharmacovigilancePlanasummary
shouldbeprovidedofthe:
Importantidentifiedrisks;
Importantpotentialrisks;
Importantmissinginformation.
Thisisimportantifthe
PharmacovigilancePlanisaseparate
documentfromtheSafetySpecification.

18. RoutinePharmacovigilancePractices:-
Routinepharmacovigilanceshouldbeconductedforall
medicinalproducts,regardlessofwhetherornot
additionalactionsareappropriateaspartofa
PharmacovigilancePlan.Thisroutine
pharmacovigilanceshouldincludethefollowing:
•Systemsandprocessesthatensurethatinformation
aboutallsuspectedadversereactionsthatarereported
tothepersonnelofthecompanyarecollectedand
collatedinanaccessiblemanner;

19. •Thepreparationofreportsforregulatory
authorities:
Expeditedadversedrugreaction(ADR)
reports;
PeriodicSafetyUpdateReports(PSURs).
•Continuousmonitoringofthesafetyprofileof
approvedproductsincludingsignaldetection,
issueevaluation,updatingoflabeling,and
liaisonwithregulatoryauthorities;
•Otherrequirements,asdefinedbylocal
regulations.

20. ActionPlanforSafetyissues:-
ThePlanforeachimportantsafetyissueshould
bepresentedandjustifiedaccordingtothe
followingstructure:
Safetyissue;
Objectiveofproposedaction(s);
Action(s)proposed;
Rationaleforproposedaction(s);
Monitoringbythesponsorforsafetyissue
andproposedaction(s);
Milestonesforevaluationandreporting.

21. Summaryofactionstobecompleted,
includingmilestones:
ThePharmacovigilancePlanfortheproduct
shouldbeorganisedintermsoftheactionstobe
undertakenandtheirmilestones.
Thereasonforthisisthatoneproposedaction
(e.g.,aprospectivesafetycohortstudy)could
addressmorethanoneoftheidentifiedissues.

22. Itisrecommendedthatmilestonesforcompletionof
studiesandotherevaluations,andforsubmissionof
safety results, beincluded in thePharmacovigilance
Plan. In developing thesemilestones oneshould
considerwhen:
•Exposuretotheproductwillhavereachedalevel
sufficient toallow potential
identification/characterisation of theAEs/ADRs of
concernorresolutionofaparticularconcern;and/or
•Theresultsofongoingorproposedsafetystudiesare
expectedtobeavailable.

23. Thesemilestonesmightbe
alignedwithregulatory
milestones(e.g.,PSURs,annual
reassessmentandlicense
renewals)andusedtorevisethe
PharmacovigilancePlan.

24. References:-
1.https:/www.ich.org/efficacy-
guidelines/e2eguidelines