building a link between ectd and xevmpd

Building a link between eCTD and XEVMPD

Samarind Webinar – 21st June 2013

Michiel Stam

Qdossier B.V.

21-JUN-2013 Building a link between eCTD and XEVMPD - Qdossier B.V.

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Agenda

Why new pharmacovigilance regulation?• Improve signal detection by more specifically attribute adverse

events to medicines• XEVMPD is just one of the tools for pharmacovigilance

Other (Pharmacovigilance) documentation needs to be considered in this context• Overview of all kind of structured information requested in the EU

What to learn • Conclusions

Need to improve public health

Medicines save lives and relieve suffering, but….• Can also cause side effects

• 5% of all hospital admissions• Nearly 200,000 deaths per year in the EU

Promote and protect public health by• Reducing burden of side effects• Optimizing the use of medicines


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Considering

Data collection and management

Benefit-Risk assessment

Signal detection

Safety Issue evaluation

Regulatory action

Communication

Audit

Impacts

Actors• EMA (PRAC)• NCAs• Pharmaceutical companies• Patients and Health Care

Professionals

Entire product lifecycle

Estimated to save between 500 and 5000 lives per year• savings to society of €250-

2,500 million/year


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How?

All MSs introduce direct consumer reporting

Establishment of PhVg Risk Assessment Committee (PRAC)

Robust EU decision making

Engaging patients and health care professionals

Science based

Risk proportionate

Greater proactivity

Reduced duplication and greater efficiency

Increased transparency and better information


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Direct consumer reporting


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Direct consumer reporting


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Tasks

Industry:• Maintain PhVg System Master File• Regulatory documents in eCTD (incl. cover letter, application form)

• PSURs evaluate benefit-risk; not only focus on safety• Modular RMP• Summary of PhVg System master file

PRAC to provide expert advice on safety and benefit-risk

Transparency and communication• Coordination of PhVg inspections• Routine PhVg audits • Better funding for public health protection

Better definition of intervening medicinal products• XEVMPD (To be submitted by XEVPRMs)


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SFDA campaign food additives


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11 Marketing License through CTD

PSUR

ICSRsby

E2B

Clinical

studiesNo link yet between ICSRs

and quality of the product

RMP

Literature

XEVMPD / IDMP

Educa-tional program

PhVgSystemMasterFile byGVP

ICSRs

Summary of PSMF

Quality

docu-

ments

Product

infor-

mation

Manu-facturing License through GMP

WW MA

status

RMP Interface

Cover

letter

Appli-cation form

Enve-lope Portal

Patient benefit/risk ratio

EU Envelope


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Cover letter Initial MAA + Variations


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Cover letter Post-authorisation commitments


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Application form 1


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Application form – 2, etc


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RMP Part I “Product overview”

Active substance information: • active substance(s); ATC code; name MAH or applicant; date and

country of first authorisation; date and country of first launch worldwide; number of medicinal product(s) to which this RMP refers.

Administrative information on the RMP: • DLP RMP; date submitted and version No.; list of RMP modules

(incl. date and version No.)• for each medicinal product included in the RMP:

• authorisation procedure; invented name(s) in EEA; • brief description of the product (incl. chemical class)• indications: • dosage: • pharmaceutical forms and strengths:


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RMP part II “Safety specification”

Module SI Epidemiology of the indication(s) and target population(s)

Module SII Non-clinical part of the safety specification

Module SIII Clinical trial exposure

Module SIV Populations not studied in clinical trials

Module SV Post-authorisation experience

Module SVI Additional EU requirements for the safety specification

Module SVII Identified and potential risks

Module SVIII Summary of the safety concerns


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RMP Interface ToC


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RMP interface – Administrative


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RMP interface – Product


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RMP interface – Indications


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RMP interface – Risks


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RMP interface – Interactions


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RMP interface – Missing information


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New PSUR - mandated since 10 Jan 2013

Part of a regulatory submission (e)CTD Module 5.3.6

Benefit-risk (not only safety) and cumulative• Based on AEs instead of ADRs• More structured evaluation based on cumulative data• No summary bridging reports or addendum reports• No acceptance of multiple 6 monthly reports

Assessment leads to automatic regulatory action• variation, suspension, revocation

Submission frequency will be variable (based on risks)

EMA list of substances with submission dates• Union Reference Dates and periodicity of submissions (EURD) list


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(EURD) European Union reference date


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PhVg System Master File (on file only, replacing DDPS in dossiers)

General details • EV code or local code (XEVMPD)• Name of MAH, the MAH of the

QPPV (if different), relevant QPPV 3rd party (if applicable)

• Name of concerned MAH(s)• List of PhVg system master files

with different PhVg system• Date of preparation/last update

MAH organization

Sources of safety data

Computerized systems and databases

QPPV particulars

PhVg processes

PhVg system performance

Quality system

Related documents• List of products covered by this

PhVg MF, incl.• MA #, Rapporteur or RMS, market

presence• Other (non-EU) territories• Specific safety monitoring

requirements

• Roles and Responsibilities if 3rd parties are involved


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Upon request, a Change control logbook, versions and archiving details may be requested

Summary of PSMF (mandated >July 2015)

Replacing the DDPS in dossiers

Proof that Company has a QPPV at its disposal

Statement of pharmacovigilance competence

Member states in which QPPV resides and carries out his tasks

QPPV contact details

PSMF location (Code as in XEVMPD)


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XEVMPD database filled by industry, owned by EMA (mandated >2 July 2012)

Organization (MAH and QPPV details)

ATC code (as in SmPC)

Pharmaceutical Form (EMA vocabulary)

Route of administration (EMA vocabulary)

Substance (EMA vocabulary)• Structured substance information not mandated yet

• Would have much more data

Product details• Next slide

Attachment • corresponding SmPC for verification

QPPV details


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Example of Product details


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Conclusion

What to learn from all these formats and forms requesting structured information?


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Conclusion CMC its relation to XEVMPD

Regulatory information should be reused at various eCTD documents, RMP interface and XEVMPD/IDMP

How? • Develop internal standards

• Leverage (do not copy!) from existing standards• Inherit values across disciplines, documents and tools• Define mapping and automate correlation to other standards

• Envelope, cover letter, application form, XEVMPD, IDMP, Module 3, etc.

Manage properly the regional aliases and translations, to support beyond the EU too


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Thank you !

Questions?

building a link between ectd and xevmpd

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