paent safety: importance of data integrity in ensuring ...paent safety: importance of data integrity...

Pa#entSafety:ImportanceofDataIntegrityinensuringqualityofmedicineDineshSThakurExecu#veChairman

Context&Agenda

•  Data Integrity – why does it matter?

•  Real cost of breach of data integrity

•  Why does it take so long to fix this problem?

•  Closing thoughts

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Streptokinaseac#vity

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Hermintin et al, European Heart Journal (2005) 26, 933-940

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100%ofErgometrinetabletsfailassay

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GenericClopidogrel

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Analysis of Purity in 19 drug product tablets containing Clopidogrel: 18 copies vs the original brand Gomez et al., Journal of Pharmaceutical and Biomedical analysis, 34 (2004) 341-348

R-isomer Hydrolysis Product

Total Impurities

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Clinical implications of substandard, non-proprietary medicines in multiple sclerosis : focus on fingolimod, J. Correale et al. Drug Design, Development & Therapy, V10, 2109-2117, 2016

Impactofexcipients

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BreachofDIinwarningleSers

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DataIntegrityCon#nuum

Ignorance Sloppiness Intentional Falsification

Outright lies

cGMPregula#onsdonotrequiredeterminingintentwhileassessingDataIntegrity.Therefore,USFDAobserva#onsonForm-483donotmakeadis#nc#on

betweenignorance,sloppinessandmalfeasance.

WithoutaunderstandingoftheTRUEunderstandingoftheroot-causeforhumanmisbehavior,companiesaretakingwidespreadac#onswhichmaynot

helpaddresstheproblemintheleast.

Unintended Error Deliberate Falsification

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Dowehavetherightdiagnosis?

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Hereisoneperspec#ve

Source: Deloitte, Managing growth though better compliance management, June 2015

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Letslookatitfromadifferentperspec#ve

Regulatory Approach to Ensure Quality of Products - An Indian Perspective of Missing Linkage – Kumar N & Jha A, Pharmaceutical Regulatory Affairs

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USPVSCountrySpecificStandards(India)USP IP

>4200ReferenceStandards ~700ReferenceStandards

99.7%availability 0.5%availability

For Uncoated, Plain Coated Tablets & Capsules

For Extended Release & Enteric Coated

Dissolu#onApparatus

USP IP

Type1:PaddleTypeType2:BasketType

TypeI:BasketTypeTypeII:PaddleType

TypeIII:Reciproca#ngCylinder

TypeIV:FlowThroughCellType

TypeV:PaddleOverDiscTypeVI:CylinderTypeTypeVII:Reciproca#ng

Holder

For Transdermal Patches

INDIAN PHARMACOPOEIA -2007, P.NO.:179 to182 UNITED STATES PHARMACOPOEIA (USP XXVI), P.NO.:2155 to 2165

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Howeffec#vearethecorrec#veac#ons?

Incen)ve/Pressure•OOSarefrowneduponandalwaysblamedontheanalyst•Wedon’thaveenoughlicensesforthesoiwarebecausetheyareexpensive•Wedon’thaveenoughinstruments/columns•Columnsareexpensivesowedonotreplacein#me

Opportunity•Nosystemormethodaudittrail•Noindividualuserlogonandprofiles–allhaveadministratorrights•Archivalofdataisminimal•Methodsarenotlockeddown•Supervisoronlyreviewspaperprintouts

A6tude/Ra)onaliza)on•Mysourcedataismypaperrecord;noonewillknow•Re-integra#onisrou#ne;Idon’tneedauthoriza#on•Itsonlyjustoutofspecifica#on–itwillnotaffectthepa#ent•OOSrootcauseanalysistakestoolongtoperformanditsonlyfortheFDA•WeareallunderpressureandImustcompletemyalloca#on;otherwiseIwontlookgoodamongmypeersandbepenalized•Themethodhasbeenvalidated;soitmustbeme•Myfamilydependsonme•Thewholeindustryworksthisway!

Culture

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Areallifeexample

•  TevaPharmaceu#calIndustriesLtd.VsFERNANDOESPINOSAABDALÁ;LEOPOLDODEJESÚSESPINOSAABDALÁ;andPPTMINTERNATIONALS.à.r.l.,filedSeptember26,2016intheSupremeCourtofNY:CommercialDivision

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CulturaldeterminantsofQuality

Leadership Environment Message Credibility

Empowerment

Quality by Design

Reuters, Jul 24, 2014

The Hindu, July 25, 2014

Indian Express, August 11, 2016

Indian Express, August 11, 2016

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CulturaldeterminantsofQuality

Leadership Environment Message Credibility

Empowerment

Quality by Design

• How do you make the message credible? • How do you create an environment where

employees speak up for what is right? • How do you empower employees to do the

right thing?

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GewngtotheREALrootcause

•  FromRickFriedman’spresenta#onattheFDLIWorkshopinWashington,DC–July14-15,2014:–  Alargenumberofrecentmanufacturingfailurescanbetracedto

failuresinthefirm’sQualitySystem–  Insomecases,thequalitysystemignoredorfailedtofollowupon

customercomplaints–  Inothercases,mul#plerepeateddevia#onsweretreatedasseparate

incidents,ratherthananobvioustrend–  Anotherrecurringthemehasbeeninves#ga#ons“tonowhere…”

Theseendwithnoaddi#onalunderstadningorinsightintowhytheproblemmayhaveoccuredandthusnohopeforpreven#on

–  Allofthesefailuressuggestaqualitymanagementsystemthatisinsufficientlyempoweredorresourcedtoadequatelycarryoutitsessen#alfunc#ons

Wheredoesthebuckstop?

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Thankyou

dinesh.thakur@medassurecompliance.com