hans van bruggen | semantic interoperability to manage medicinal data and exchange idmp messages...

Managing and exchange of medicinal data within and

across companies and regions

Hans van Bruggenwww.ectdconsultancy.com

http://www.ectdconsultancy.com/

©eCTDconsultancy 2

Agenda• Objective of pharmaceutical medicine• Why manage medicinal data?

• Within industry• Within agencies• Between industry and agencies

• Examples of what can go wrong• What are the challenges?• Summary

September 2016

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Objective of pharmaceutical medicine

Concerns the development and maintenance of:• consistently produced• high-quality drugs with a• favorable efficacy-safety profile• to clearly defined patient population• when used according to the Product Information

September 2016

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Why manage medicinal data within industry?• Marketing sees a market for a therapy in target patient population• Pharmaceutical development produces the high-quality product• Clinical development tests therapy in target patient population• Production produces the high-quality product in a consistent manner• Regulatory Affairs registers that product in the patient population

tested, by proving a favourable efficacy-safety profile• Global supply chain ensures continued supply to the markets• Pharmacovigilance monitors adverse events in relation to a product,

considering its quality and usage by patients

September 2016

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Why manage medicinal data within agencies?• Ensure healthy volunteers are not at risk when exposed to new

medicines• Ensure patients receive the best therapy (efficacy-safety)• Ensure manufactures consistently produce high-quality drugs• Ensure clinical trials are predictive for the marketed situation (patient

and product information)• Ensure adverse events are collected, analysed and evaluated

adequately (efficacy-safety) CAPAs

September 2016

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Why manage medicinal data between industry and agencies?

• Shared responsibility to safeguard the patient

September 2016

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Examples• Vioxx• Thyrax• Mediator• Heparin• Drug shortages

• http://www.accessdata.fda.gov/scripts/drugshortages/default.cfm

Uiterlijk twee maanden voor de (tijdelijke) onderbreking van levering van het geneesmiddel, moeten handelsvergunninghouders dit melden aan het CBG. Zij moeten deze melding doen via het e-mailadres: [email protected].

September 2016

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Vioxx Adverse events not adequately evaluated• Used by >80 Milion people resulting 88,000 - 140,000 cases of

serious heart disease adverse events• 4-fold increase in heart attacks compared to naproxen (0.4% vs 0.1%)

• Product withdrawn by Merck&Co./MSD in 2004• No further risks• But also no further benefits!!!!!!!!

• What if patients with risk factors would have been excluded????• Advisory boards in US and Canada voted for return in 2005• Merck has not returned Vioxx on the market (yet)

September 2016

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Thyrax Different dissolution rate per package• Increase in adverse event rates for blister (new)

September 2016

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Heparin major recalls due to contamination of active substance

• Heparin active substance is derived from pig intestines• In 2008 FDA investigated >80 deaths related to heparin use

• Heparin products from multiple companies• FDA found serious deficiencies at Baxter’s Chinese heparin supplier• Could be traced back to contamination of active substance from SPL batches

processed in China

September 2016


Mediator • In 33 years used by about 5M French patients

• Intended use: diabetics• Off-label use: losing weight

• About 2000 people died and many more hospitalised• Withdrawn from the market in 2009

September 2016


Drug shortages

September 2016

How to solve the challenges?


What are the challenges?• What product?

• e.g. product in bottles or blisters; what bottles, what blisters• e.g. product from different sources; which manufacturer site; which batch

• What patient population?• e.g. with or without risk factors (disease status, comorbidity or comedication)• e.g. for the intended indication or for off-label use

• How dependent are users from a single producer/supplier?• e.g. drug shortages 4-fold increase of the past few years

• Ability to take corrective- or preventive actions when needed?• Within a company• Across companies by agencies

September 2016


How to solve the challenges?• Integrate systems between

• Industry• Agencies

• Regulatory bodies• Inspectorates

• Health care professionals• Move from unstructured data to structured data• Define a single source of truth• Apply semantic interoperability

• ISO-IDMP (IDentification of Medicinal Products)

September 2016

IDMP



Medicinal Product (Per registered product)MPIDCombined pharmaceutical dosage formIMPID cross referenceAdditional monitoring indicatorOrphan Designation Authorisation StatusName medicinal productInvented name partScientific Name PartStrength Name PartPharmaceutical Dose Form PartFormulation partIntended use partTarget Population PartContainer or pack partDevice partTrademark or Company Name PartTime / Period PartFlavour partDelimiter part

Country where MP name is applicableLanguage where the IMP is applicableClassification System ATCClassification System Value ATCClassification System Legal basis of approvalClassification System Value Legal basis of approvalClassification System Medicinal product typeClassification System Value Medicinal product typeClassification System Peadiatric useClassification System Value Peadiatric useClassification System Authorised dose formClassification System Value Authorised dose formClassification System Falsified medicine flagClassification System Value Falsified medicine flagMPID Version DateMPID Version IdentifierDocument typeDocument identifierRegulated document attachmentDocument effective date

September 2016


Authorization and OrganizationMarketing Authorisation NumberCountry where marketing authorization number is applicableLegal Status of SupplyMarketing Authorisation StatusMarketing Authorisation Status DateMA Procedure Identifier / NumberMA Procedure TypeCountry where MP is marketedJurisdiction marketing statusMarketing Date StartMarketing Date StopRisk of shortage supplyRisk of shortage supply comment

Name MAHMAH addressLocation address for MAHLocation role for MAHIdentifier for other MAH location

September 2016


Packaging and devices

PCIDPackage DescriptionPackage Item (Container) TypePackage Item (Container) QuantityPackage item (container) materialPackage component MaterialPackage component typeDevice TypeDevice Trade NameManufactured Dose FormManufactured item unit of presentationManufactured Item Quantity

To be repeated for every container,

material and device

September 2016


Ingredient Role APIIngredient Role ExcipientSubstanceSubstance Strength Range (Concentration)Substance Strength Range (Presentation)Specified Substance Reference SubstanceSpecified Substance Reference Specified SubstanceSpecified Substance Reference Strength Range

Ingredients

To be repeated for every ingredient in the product

September 2016


Clinical particulars and administration items

Indication textIndication as disease/symptom/procedureCo-morbidity for Indication

Administrable Dose FormUnit of PresentationRoute of AdministrationPhPID Identifier Sets

To be repeated for every indication

To be repeated for every dose form and

route of administration

September 2016


Other iterations• Another 300 attributes!

September 2016


Reducing health care costs and improving health?

September 2016

Connecting• batch number register• ePrescription• eHealth record

Improves impact analyses

Improves signal detection

Expedites corrective actions• Safety• Efficacy• Drug availability

IDMP

Falsified medicine

MD UDI

ePre-scription

eHealth Records

ICSRs

eSubmissions


Content vs Context - carrot and potato recipes

September 2016

Manufacturers

CompetentauthoritiesDrug

products

Productionprocess

(active)substances

Clinical studies

http://images.cookingwithmykid.com.s3.amazonaws.com/2010/07/dished-out.jpg


Standalone documents capturing content

September 2016

Manufacturers


products

Productionprocess

(active)substances



Content in Context of …………

September 2016

Manufacturers


products

Productionproces

(active)substances

If you are not the intended recipient of this disk, you are hereby notified that any disclosure, copying,

distribution or reliance upon the contents of this disk is strictly prohibited

eCTD on<INN>

Sequence <…..>

Disk <x> of <n>

<Application Number>

<Type of submission>

Marketing Authorisation Number(s):

<Company logo>

Applicant:Product Name:Date Sent:

For technical issues contact <………@................................>


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Different levels of interoperability

©eCTDconsultancy

Organizational Interoperability

SemanticInteroperability

TechnicalInteroperability

Standards Terminology

Meaning Languages

Laws Policies

Cooperation agreements Workflows

Transport protocols Data security

Data accessibility

Services and messages

Data accessibilityData integrity

Too often forgotten

September 2016


Semantic Hub

Industry content and context management toolsContent(as data or in documents)Intrinsic metadata• Applied upon entry or sharing• Regenerate by reading the content

ContextExtrinsic metadata• Applied upon planning, submission, agency feedback• Regenerate by checking “where used” and other

relationships

September 2016

eDMS eSubmission tool

RIM / MDM

eCTD US

eCTD EU

IDMP US

IDMP EU

ERPQMS

Status reports

Search results


Summary• Integrate systems and exchange standards between

• Industry• Technical interoperability• Semantic interoperability• Define a single source of truth

• Agencies• Regulatory bodies during the various stages of a product lifecycle• Inspectorates

• Health care professionals• eHealth records• ePrescription

• Move from unstructured data to structured data• Apply attributes at the right level (separate content from context)

September 2016

Thank you!

Hans van Bruggenhbruggen(at)ectdconsultancy.com

hans van bruggen | semantic interoperability to manage medicinal data and exchange idmp messages...

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