This document discusses the importance of managing medicinal data within and between the pharmaceutical industry and regulatory agencies. It outlines challenges such as ensuring consistent high-quality drug production, evaluating drug safety and efficacy, and exchanging information accurately. Examples are given where failures in data management led to health issues or drug shortages. The document argues that integrating systems using technical and semantic interoperability standards, and defining a single source of truth for medicinal product data, can help address these challenges by improving information sharing, signal detection, and corrective actions.

1. Managing and exchange of
medicinal data within and
across companies and regions
Hans van Bruggen
www.ectdconsultancy.com

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
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3. 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
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4. 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
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5. 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
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6. Why manage medicinal data between industry and
agencies?
• Shared responsibility to safeguard the patient
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7. 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: GMP-GCP@cbg-
meb.nl.
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8. 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)
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9. Thyrax Different dissolution rate per package
• Increase in adverse event rates for blister (new)
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10. 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
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11. 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
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12. Drug shortages
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13. How to solve the challenges?

14. 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
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15. 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)
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16. IDMP
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17. Medicinal Product (Per registered product)
MPID
Combined pharmaceutical dosage form
IMPID cross reference
Additional monitoring indicator
Orphan Designation Authorisation Status
Name medicinal product
Invented name part
Scientific Name Part
Strength Name Part
Pharmaceutical Dose Form Part
Formulation part
Intended use part
Target Population Part
Container or pack part
Device part
Trademark or Company Name Part
Time / Period Part
Flavour part
Delimiter part
Country where MP name is applicable
Language where the IMP is applicable
Classification System ATC
Classification System Value ATC
Classification System Legal basis of approval
Classification System Value Legal basis of approval
Classification System Medicinal product type
Classification System Value Medicinal product type
Classification System Peadiatric use
Classification System Value Peadiatric use
Classification System Authorised dose form
Classification System Value Authorised dose form
Classification System Falsified medicine flag
Classification System Value Falsified medicine flag
MPID Version Date
MPID Version Identifier
Document type
Document identifier
Regulated document attachment
Document effective dateSeptember 2016 ©eCTDconsultancy 17

18. Authorization and Organization
Marketing Authorisation Number
Country where marketing authorization number is applicable
Legal Status of Supply
Marketing Authorisation Status
Marketing Authorisation Status Date
MA Procedure Identifier / Number
MA Procedure Type
Country where MP is marketed
Jurisdiction marketing status
Marketing Date Start
Marketing Date Stop
Risk of shortage supply
Risk of shortage supply comment
Name MAH
MAH address
Location address for MAH
Location role for MAH
Identifier for other MAH location
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19. Packaging and devices
PCID
Package Description
Package Item (Container) Type
Package Item (Container) Quantity
Package item (container) material
Package component Material
Package component type
Device Type
Device Trade Name
Manufactured Dose Form
Manufactured item unit of presentation
Manufactured Item Quantity
To be repeated for
every container,
material and device
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20. Ingredient Role API
Ingredient Role Excipient
Substance
Substance Strength Range (Concentration)
Substance Strength Range (Presentation)
Specified Substance Reference Substance
Specified Substance Reference Specified
Substance
Specified Substance Reference Strength Range
Ingredients
To be repeated for every
ingredient in the product
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21. Clinical particulars and administration items
Indication text
Indication as disease/symptom/procedure
Co-morbidity for Indication
Administrable Dose Form
Unit of Presentation
Route of Administration
PhPID Identifier Sets
To be repeated for every
indication
To be repeated for
every dose form and
route of administration
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22. Other iterations
• Another 300 attributes!
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23. Reducing health care costs and improving health?
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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
eSubmis
sions

24. Content vs Context - carrot and potato recipes
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Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances
Clinical studies

25. Standalone documents capturing content
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Manufacturers
Competent
authoritiesDrug
products
Production
process
(active)
substances

26. Content in Context of …………
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Manufacturers
Competent
authoritiesDrug
products
Production
proces
(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
<………@................................>

27. Different levels of interoperability
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Organizational
Interoperability
Semantic
Interoperability
Technical
Interoperability
Standards Terminology
Meaning
Languages
Laws Policies
Cooperation agreements Workflows
Transport protocols Data security
Data accessibility
Services and messages
Data accessibility
Data integrity
Too often forgotten
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28. Semantic Hub
Industry content and context management tools
Content
(as data or in documents)
Intrinsic metadata
• Applied upon entry or sharing
• Regenerate by reading the content
Context
Extrinsic metadata
• Applied upon planning, submission, agency feedback
• Regenerate by checking “where used” and other
relationships
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eDMS
eSubmission
tool
RIM / MDM
eCTD US
eCTD EU
IDMP US
IDMP EU
ERPQMS
Status reports
Search results

29. 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)
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30. Thank you!
Hans van Bruggen
hbruggen(at)ectdconsultancy.com