PDA‘s Post Approval Change Innovation For Availability Of .
FDANews WebinarPDA‘s Post Approval Change Innovation for Availabilityof Medicines Program (PAC iAMsm)February 8th, 2017Anders Vinther, Emma Ramnarine, Melissa Seymour, Denyse BakerConnecting People, Science and Regulation Copyright 2017 by PDA
Globaliza(onvs.Na(onaliza(onCompanies are globalizedIdeally: one productfor one worldRegulatory approvals are nationalized*Reality: one productwith 100 approvals*Note: or regionalized (e.g. EU)Connecting People, Science and Regulation Copyright 2017 by PDA2
PostApprovalChange,explained1ChangeONE ProductONE IndicationONE Process2Change3Change4ONE ProductONE IndicationMANY POST APPROVAL CHANGE PERIOD47 80 1 2 35 6INVENTORYConsequenceLogistics challenge à less ability to act on changein demand for one versionà shortage risk of errors llproductporMolio.Connecting People, Science and Regulation Copyright 2017 by PDA3
PAC- ‐arealexampleOnepentavalentvaccine- ‐oneyear83 batches : 55 variations of the same process MULTIVALENTFINISHEDBATCHESLotLOT 1LOT 2LOT 3LOT 4LOT 5LOT 6LOT 7LOT 8LOT 9LOT 10LOT 11LOT 12LOT 13LOT 14LOT 15LOT 16LOT 17LOT 18LOT 19LOT 20LOT 21LOT 22LOT 23LOT 24LOT 25LOT 26LOT 27LOT 28LOT 29LOT 30LOT 31LOT 32LOT 33LOT 34LOT 35LOT 36LOT 37LOT 38LOT 39LOT 40LOT 41LOT 42LOT 43LOT 44LOT 45LOT 46LOT 47LOT 48LOT 49LOT 50LOT 51LOT 52LOT 53LOT 54LOT 55LOT 56LOT 57LOT 58LOT 59LOT 60LOT 61LOT 62LOT 63LOT 64LOT 65LOT 66LOT 67LOT 68LOT 69LOT 70LOT 71LOT 72LOT 73LOT 74LOT 75LOT 76LOT 77LOT 78LOT 79LOT 80LOT 81LOT 82LOT 83H2221- ‐1H4131- ‐1H4131- ‐2H4132- ‐1J2035- ‐1J2209- ‐1J2210- ‐1J2214- ‐1J2215- ‐1J2216- ‐1J2251- ‐1J4001- ‐1J4002- ‐1J4032- ‐1J4033- ‐1J4034- ‐1J4035- ‐1J4087- ‐1J4090- ‐1J4098- ‐1J4104- ‐1J4109- ‐1J4118- ‐1J4122- ‐1J4133- ‐1J4156- ‐1K2038- ‐1K2039- ‐1K2042- ‐1K2043- ‐1K2044- ‐1K2045- ‐1K2086- ‐1K2108- ‐1K2113- ‐2K2121- ‐1K2122- ‐1K2124- ‐1K2125- ‐1K2146- ‐1K2148- ‐1K2152- ‐1K2155- ‐1K2160- ‐1K2160- ‐1K2161- ‐1K2162- ‐1K2163- ‐1K2164- ‐1K2165- ‐1K2166- ‐1K2167- ‐1K2168- ‐1K2169- ‐1K2170- ‐1K2172- ‐1K2172- ‐1K4006- ‐1.K4007- ‐1.K4007- ‐1.K4039- ‐1K4047- ‐1K4073- ‐1K4093- ‐1K4098- ‐1K4106- ‐1K4122- ‐1K4153- ‐1K4157- ‐1K4158- ‐1K4159- ‐1K4163- ‐1K4164- ‐1K4165- ‐1K4170- ‐1K4174- ‐1K4175- ‐1K4176- ‐1K4177- ‐1K4178- ‐1K4179- ‐1K4180- ‐1K4181- ‐1Connecting People, Science and Regulation C C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C RC C 062002062002042 102012062032032 102092092092072032042062002 10 119 32080063084607462463952 1586558534933916 93577583029032534 168783 1626830439793337248387509868520237615 911176254037897736183705323438540390787638 Copyright 2017 by PDA4
PDA’sContribu(onPDAPACiAMsmDeliverablesAboutPDA Globalorganiza(onwith regula(onsomemberscanbeUerservepa(ents.ü CallForAc(onü rg/PAC Connecting People, Science and Regulation ü LifecycleManagementü Effec(vePQSforManagementofPACs– QRMandKnowledgeManagementforPACs lesWorkshops,Trainings,Tools&Templates Copyright 2017 by PDA5
haracterisDcs Difficult to clearly define Many interdependencies and often multi-causal Attempts to address the problem often leads tounforeseen consequences Often not stable Usually no clear solution Socially complex Rarely is the responsibility of one stakeholderonly Solutions involve changing behaviors Some characterized by chronic policy failureSource: Vinther, A., Drug Shortage is a “Wicked Problem “, PDA Letter May 2016Connecting People, Science and Regulation Copyright 2017 by PDA6
EWERapprovalsDSDSDrugShortageRELIANCEConnecting People, Science and Regulation Copyright 2017 by PDA7
EstablishedCondi(ons,explained fromPDA oduct implicitbasedonexis(ngregula(onandguidance. siontotheregulatoryauthorityConnecting People, Science and Regulation ll&do”to“do&tell” Copyright 2017 by PDA8
Repor(ngCategoriza(onofChanges Prior- atoryauthorityreviewandapproval. llywithinadefined(meperiodaierimplementa(on. onnecting People, Science and Regulation Focus&ContribuDonfromPDA HowtoapplyQRMforeffec(vechangecategoriza(on nd/orpa(entsafety GlobalalignmentonPACcategoriza(on berofpriorapprovalchanges Csresultinlowerrisk Copyright 2017 by PDA9
Established Conditions & Reporting Categories explainedIf .POST PACRiskPRE PACThen .Implement change as ‘Do & Tell’even for Established ConditionsThe company must have an effective PQS (includingrisk and knowledge management) for managing PACsConnecting People, Science and Regulation Copyright 2017 by PDA10
ChangestoEstablishedCondi(ons,ExampleChange in a starting raw material(can impact a CQA)COMPANY ACOMPANY kAssessmentRiskAssessmentHigh riskModerate/low riskPrior Approval“Tell and Do”Notification“Do and Tell”COMPANY dimpacttoCQANoRiskAssessmentPrior Approval“Tell and ting People, Science and Regulation Copyright 2017 by PDA11
PostApprovalChanges ica(onofpa(ent- ‐centric,risk- anallowmorepost- ity.Focus&ContribuDonfromPDA Strongeradop(onofICHQ10Annex1- dpost- nnova(onandcon(nualimprovement” ec(onassessingthestateofthePQS ssen(alforbeforethefirmcanusethepost- orPAC radedno(fica(ontoregulatoryauthori(es.Connecting People, Science and Regulation Copyright 2017 by PDA12
agingPost- ‐ApprovalChanges ateofcontrol,andfacilitatecon(nualimprovement dprovidecompaniestheopportunitytomanagepost- ght ThePointstoConsiderpaperisastep- ‐by- gPACs–andisadirectcon(nua(onofICHQ10 ntageofICHQ10,Annex1 ledgeManagement–QualityCultureConnecting People, Science and Regulation Copyright 2017 by PDA13
cting People, Science and Regulation Copyright 2017 by PDA14
Objec(vesofLCMElementsofLifecycleManagement Achieveproductrealiza(on Establishandmaintainastateofcontrol Facilitatecon(nualimprovement ySummary PlannedPost- ‐ApprovalChanges �� lLifecycle Product&ProcessMonitoring AnnualProductReview(APR) Post- ‐marke)ngSurveillanceandPharmacovigilance– ControlSystemManagement– ManagingPACsinthePQSFocus&ContribuDonfromPDA dgeManagementNote: Additional elements to considerSupply strategyDrug shortage prevention planConnecting People, Science and Regulation Copyright 2017 by PDA15
Role of Knowledge Management in LCM and PAC Management é knowledge should enable risk reduction, continualimprovement & possible reduction in filing categoryCan enable faster PAC implementationCountry-specific filings continue to add complexity andimpact implementation timelinesKNOWLEDGEStructured framework inPQS essential to capture/manage growing knowledgeCTDCTD updates areless Connecting People, Science and Regulation CommercialManufacturing Copyright 2017 by PDAProductDiscon(nua(on16
MovingtoScience&Risk- ‐BasedPACManagementTodayBased on different regional regulatory guidelinesType IA/AnnualNotificationOnly in PQSType IB/CBE/Minor variationType II/ PAS/MajorvariationFutureOurambi(onAll changes documented in the PQSOnly in PQSLowest RiskNotification(Do and Tell)Moderate/Low RiskPrior Approval(Tell and Do)High RiskScience & risk-based approachConnecting People, Science and Regulation Copyright 2017 by PDA17
PDA Deliverables and PAC iAM WebsiteMission: Identify, assess and address current barriers to implementation of PACs that areintended to ensure continued operations, drive innovation and continual improvementü WebsiteforPACiAMsmpda.org/PACü CallForAc(onPDALeUerJanuary2016ü PointstoConsiderPDAJournalü LifecycleManagementü Effec(vePQSforManagementofPACs– QRMandKnowledgeManagementforPACsü PDA PAC iAM Survey Open until Feb 16th BiologicsandPharmaceu(calDrugs fExamples Workshops,Trainings,Tools&Templates PDAEUAnnualMee(ngJune13- ‐14,Berlin PACWorkshopSept13- ‐14,WashD.C. esul(ngfromPACcomplexitypda.org/drugshortage giesandfacilityupgradesConnecting People, Science and Regulation Copyright 2017 by PDA18
PDAPACiAMsmTaskForce AndersVinther,SanofiPasteur(co- ‐lead)EmmaRamnarine,Roche/Genentech(co- BarbaraJengtes,PhACTGmBHConnecting People, Science and Regulation MaikJornitz,G- ,PDA Copyright 2017 by PDA19
PDAPACiAMsmTaskForce AddiDonalcontactinformaDon– DenyseBaker,baker@pda.org WebsiteforPACiAMsmpda.org/PACConnecting People, Science and Regulation Copyright 2017 by PDA20
lot 13 j4002 1 lot 14 j4032 1 lot 15 j4033 1 lot 16 j4034 1 lot 17 j4035 1 lot 18 j4087 1 lot 19 j4090 1 lot 20 j4098 1 lot 21 j4104 1 lot 22 j4109 1 lot 23 j4118 1 lot 24 j4122 1 lot 25 j4133 1 lot 26 j4156 1 lot 27 k2038 1 lot 28 k2039 1 lot 29 k2042 1 lot 30 k2043 1 lot 31 k2044 1 lot 32 k2045 1
4. From a CFG to an equivalent PDA ¾ Given a CFG G , we can construct a PDA P such that N( P ) L( G ). ¾ The PDA will simulate leftmost derivations of G. ¾ Algorithm to construct a PDA for a CFG o Input: a CFG G (V, T, P, S). o Output: a PDA P such that N( P )
PDA Estimating Guidelines Introduction to PDA Facility Considerations The PDA Facility Considerations document is intended to complement the Preliminary Damage Assessment (PDA) and for use in collecting sufficient information to estimate the type, quantity, and cost of eligible damage
English In N structions for Use it‐Occlud PDA Product Description Nit w Nit‐Occlud PDA ‐Occlud PDA is a system for transcatheter occlusion of Patent Ductus Arteriosus (PDA) ith
PDA balance is insufficient to fully fund a future annual premium, the remaining balance will be applied to the policy as a partial premium payment. The PDA is designed to help agents capture incremental life insurance sales. Therefore, the PDA
Genesis Packaging Technologies Peter Pratt Bioscience International, Inc. Jason Willett Veltek Associates, Inc. Alison Caballero PDA David Hall PDA This Buyer’s Guide is designed to help you maximize your virtual 15th Annual PDA Global Conference on Pharmaceutical
Genesis Packaging Technologies Peter Pratt Bioscience International, Inc. Jason Willett Veltek Associates, Inc. Alison Caballero PDA David Hall PDA This Buyer’s Guide is designed to help you maximize your virtual 2020 PDA Universe of Pre-Filled Syringes and
2014 PDA Visual Inspection Survey — PDA Task Force John Shabushnig, Ph.D., Insight Pharma Consulting, LLC Acknowledgments Jahanvi (Janie) Miller, Senior Project Manager, Science and Regulatory (PDA Staff) Morgan Holland, Coordinator, Science and Regulatory (PDA Staff) Th
Regular Expressions (RE) Context free langauges o Context free grammars o Pushdown automata q Definition of PDA q Computation PDA q Design of PDA q PDA and CFG q DPDA vs NPDA o Non-context free languages q Limitations of CFLs q Pumping lemma for CFL q Closure properties for CFL Ø Goals:
