XEVMPD Guide for Pharmacovigilance Professionals

Introduction

The eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD) is one of the least visible yet most important components of the European pharmacovigilance ecosystem.

While pharmacovigilance professionals often focus on adverse event reporting, signal detection and risk management activities, those processes depend heavily upon accurate medicinal product information.

XEVMPD provides the structured product information that supports many regulatory and pharmacovigilance activities within Europe.

Although many QPPVs may never directly enter data into XEVMPD, they are expected to understand how medicinal product information is governed and how data quality issues can affect pharmacovigilance compliance.

What is XEVMPD?

XEVMPD stands for eXtended EudraVigilance Medicinal Product Dictionary.

It is the European database containing structured information relating to medicinal products authorised within the European Economic Area.

The database supports:

• Product identification
• Regulatory reporting
• Pharmacovigilance activities
• Signal detection
• Safety surveillance
• Data consistency

In simple terms:

Together these systems support the wider European pharmacovigilance framework.

Why XEVMPD Exists

Before structured product dictionaries became available, product information was often inconsistent across different systems and organisations.

This created challenges including:

• Duplicate product records
• Inconsistent product naming
• Difficulties linking reports to products
• Reduced analytical capability
• Data quality concerns

A central medicinal product dictionary helps ensure that safety reports can be associated with the correct products and analysed consistently.

What Information is Stored in XEVMPD?

XEVMPD contains structured information relating to medicinal products.

Examples include:

• Product names (proprietary and trade names)
• Active substances and substance roles
• Pharmaceutical forms
• Strengths and strength presentation
• Routes of administration
• Marketing authorisation details (MA number, MA holder, authorisation dates)
• Marketing status (authorised, withdrawn, suspended)
• Product identifiers (internal IDs, translations)
• Pack and manufacturer details
• ATC classification (where applicable)

The XEVMPD data model is extensive and includes relationships (e.g., product-to-authorisation, product-to-substance), attributes that are required versus optional depending on the record type, and controlled vocabularies for many fields.

Relationship Between XEVMPD and EudraVigilance

XEVMPD and EudraVigilance are closely connected. Product information from XEVMPD is used to populate and standardise medicinal product references when adverse reaction reports are submitted into EudraVigilance and EVDAS.

Accurate product information supports:

• Case processing (correct product association)
• Signal detection (aggregate case counts by product)
• Aggregate reporting (PSUR/RMP data consistency)
• Safety surveillance and regulatory analysis

Poor product data quality may affect downstream pharmacovigilance activities, leading to incorrect case grouping, missed signals, or regulator queries.

Why Product Data Quality Matters

Pharmacovigilance systems depend on accurate data.

Errors in medicinal product information may contribute to:

• Reporting inconsistencies
• Duplicate records
• Analytical limitations
• Signal detection challenges
• Regulatory concerns

Data quality issues often become visible only after they have already affected other processes.

Consequently, proactive governance is important.

Marketing Authorisation Holder Responsibilities

Marketing Authorisation Holders (MAHs) are responsible for maintaining accurate product information within applicable regulatory systems.

Responsibilities include:

• Initial submissions for newly authorised products
• Timely updates reflecting variations, withdrawals, or status changes
• Maintaining consistent master data that map to XEVMPD fields
• Managing change control and version history
• Coordinating with regulatory affairs and PV teams for authorisations in multiple Member States
• Ensuring evidence trail for changes and submissions

Organisations should have documented procedures describing how product information is governed and maintained, with clear accountabilities.

Product Lifecycle Management

Product information changes throughout the lifecycle of a medicinal product.

Examples include:

• New authorisations
• Variations
• Withdrawals
• Name changes
• Manufacturing changes
• Administrative updates

Effective lifecycle management helps ensure that regulatory systems remain accurate and up to date. XEVMPD submissions should be treated as regulated deliverables subject to change control, auditability, and reconciliation.

Common Data Quality Challenges

Maintaining high-quality product information can be difficult.

Common challenges include:

• Incomplete records (missing required fields)
• Inconsistent naming conventions across markets
• Delayed updates following regulatory decisions
• Duplicate entries due to different MA numbers or trade names
• Governance gaps and unclear ownership of master data
• Lack of reconciliation between internal ERP/regulatory systems and XEVMPD

These issues may increase regulatory risk and reduce confidence in downstream analyses.

XEVMPD and Signal Detection

Although signal detection activities are generally associated with EVDAS, product information quality remains important.

Signal detection relies upon accurate product identification.

Poor product data may affect:

• Case grouping
• Trend analysis
• Signal evaluation
• Data interpretation

Consequently, product data quality indirectly supports signal management activities and should be included in PV quality programs.

QPPV Oversight

The QPPV is not usually responsible for maintaining XEVMPD records personally.

However, regulators generally expect the QPPV to understand:

• How product data are maintained
• Governance arrangements
• Data quality controls
• Compliance risks
• Escalation pathways

The QPPV should have confidence that medicinal product information is appropriately governed and subject to periodic review, with escalation routes for data issues that impact safety reporting or regulatory outputs.

Inspection Perspective

Inspectors may review product data governance as part of broader pharmacovigilance system assessments.

Inspection activities may include review of:

• Governance structures and role descriptions
• Procedures for XEVMPD submissions and updates
• Change control and version management processes
• Data quality and reconciliation procedures
• Records of validation checks and submission receipts
• Training records for staff responsible for submissions

Inspectors are generally interested in whether organisations can demonstrate effective control over product information and can provide documentary evidence of timely updates following regulatory events.

Common Inspection Findings

Observed deficiencies may include:

• Incomplete product records in XEVMPD
• Delayed updates following a variation or withdrawal
• Poor governance controls and unclear responsibilities
• Inadequate documentation of changes and approvals
• Lack of reconciliation between XEVMPD and internal systems
• No evidence of validation checks performed prior to submission

Many findings arise because product data management is viewed as an administrative activity rather than a pharmacovigilance enabler. Effective oversight requires treating XEVMPD data as regulated content.

XEVMPD and the Future of IDMP

The future of medicinal product data management within Europe is closely linked to the Identification of Medicinal Products (IDMP) standards.

IDMP aims to improve:

• Data standardisation
• Product identification
• Regulatory interoperability
• Data quality

As regulatory systems evolve, organisations will increasingly need to understand the relationship between existing XEVMPD processes and future IDMP requirements, including the need to reconcile current product dictionaries with IDMP-compliant master data repositories.

Practical Considerations for Organisations

Effective product data governance commonly includes:

• Defined ownership and role matrices (Regulatory Affairs, PV, Quality, Commercial)
• Change control procedures requiring documented approval before submission
• Data quality reviews with defined acceptance criteria
• Periodic reconciliations between XEVMPD, internal master data, and EudraVigilance
• Compliance monitoring and KPIs for timeliness and completeness
• Training programmes and competency records for staff responsible for data entry and submissions

These controls help maintain confidence in medicinal product information and support wider pharmacovigilance activities.

Procedural Checklist for XEVMPD Submissions

This checklist is designed to be used as a controlled annex to SOPs covering XEVMPD submissions. Each step should be evidenced and retained in the submission record.

1. Initiation and Ownership
2. Identify the initiating event (new MA, variation, withdrawal, pack change).

3. Assign submission owner (Regulatory or PV data owner) and approver (Regulatory head / QPPV signatory where required).

4. Data Collection

5. Pull authoritative source documents: MA dossier, national MA decision, product specification, summary of product characteristics (SmPC), labelling and leaflet, GMP manufacturer confirmation, packaging artwork.

6. Extract internal master data (ERP/PLM): product code, trade name(s), marketing status, MA number, MA holder, ATC code.

7. Field Mapping (internal to XEVMPD)

8. Complete a field-level mapping spreadsheet mapping each internal field to the XEVMPD element (see Worked Example below).

9. Identify controlled vocabularies needed (pharmaceutical form, route, country codes).

10. Prepare Submission Package

11. Construct XEVMPD XML or use EMA submission tools (XEVMPD browser / gateway client) per current EMA schema.

12. Validate against the XEVMPD XML schema locally, producing validation report.

13. Internal Validation and QA

14. Perform internal validation checks: required fields present, controlled vocabulary values, consistent strengths and units, valid MA numbers and dates.

15. Run business rule checks: uniqueness, no duplicate trade names in same market, consistent MA holder names.

16. Change Control and Approval

17. Record proposed change in change control system with reason and impact assessment (safety, regulatory).
18. Obtain sign-off per procedure (Regulatory, PV, Quality as required).

19. Archive approval documentation into the submission record.

20. Submit to EMA

21. Submit via EV gateway or central submission channel per EMA instructions.

22. Retain submission receipt and acknowledge message.

23. Post-Submission Monitoring

24. Monitor for validation or processing errors returned by EMA; correct and resubmit promptly.

25. Reconcile final XEVMPD record with internal master data after processing into EMA systems.

26. Evidence Retention

27. Retain all artefacts in a submission file: mapping spreadsheet, source documents, change control record, validation reports, submission receipts, QA approvals, correspondence with EMA.

28. Periodic Review

29. Include the record in periodic XEVMPD reconciliation cycles (e.g., quarterly).
30. Raise any discrepancies for corrective action.

Minimum evidence checklist for an inspection file: - Field-level mapping spreadsheet - Source documents (MA decision, SmPC, labelling) - XEVMPD XML file submitted - Validation reports (pre-submission and EMA response) - Change control form and approvals - Submission receipt and acknowledgement - Reconciliation logs and post-submission verification - Training records for submitters

Worked Example: Complete XEVMPD Submission

This worked example demonstrates a full submission for a hypothetical product, including field-level mapping, validation errors encountered during local validation, the fixes applied, and the evidence inspectors commonly expect. The product used is fictional: "Cardiostop 50 mg Tablets" containing active substance "atenolol".

Note: The worked example uses representative XEVMPD field names and simplified values for illustration. Organisations must refer to the current XEVMPD schema and EMA guidance for exact element names and constraints.

Case summary (submission trigger)

• Event: Initial XEVMPD submission for a new national MA in Germany and Spain.
• Product: Cardiostop 50 mg Tablets (proprietary name)
• Active substance: Atenolol (INN)
• Pharmaceutical form: Tablet
• Strength: 50 mg
• Route: Oral
• MA numbers: DE/H/1234/001 and ES/H/7890/001
• MA holder: PharmaGlobal GmbH (Germany), PharmaGlobal S.A. (Spain)
• Manufacturer: ABC Manufacturing Ltd (site EU-PL-100)

Field-level mapping (internal system to XEVMPD)

Preparing the XML

• Use a validated XML editor or the EMA XEVMPD template.
• Populate entity relationships: product -> substance -> marketingAuthorisation -> productPresentation -> manufacturer.
• Ensure controlled vocabularies for pharmaceutical form and route are used.
• Include language-specific trade names if needed (e.g., "Cardiostop" in German & Spanish as same proprietary name).

Local validation run (pre-submission)

Run a local XML schema validation and business rule check. Typical local validation checks:

• Required fields presence
• Date formats
• Unit consistency
• Controlled vocabulary usage
• Cross-field consistency (e.g., strength unit compatible with pharmaceutical form)

Pre-submission validation report (representative):

• INFO: XML well-formed — PASS
• ERROR XEV-REQ-001: Missing required element: marketingAuthorisation.endDate for MA with status Withdrawn — (Not applicable) — pass
• ERROR XEV-CV-003: Pharmaceutical form 'Tablet' not using controlled vocabulary code — FAIL
• ERROR XEV-FORM-010: Strength unit 'mg' not mapped to unitCode attribute — FAIL
• ERROR XEV-DUP-001: Duplicate proprietaryName detected across country records — WARN
• ERROR XEV-AUTH-005: MA number format invalid for Spain record — FAIL

Resolving validation errors (actions taken)

1. Pharmaceutical form CV issue
2. Fix: Replace free-text "Tablet" with controlled vocabulary code per XEVMPD list (e.g., "TAB; tablet").

3. Evidence: Mapping spreadsheet annotated to show controlled vocabulary code source and version.

4. Strength unit attribute

5. Fix: Add unitCode attribute to strength element with code "MG" per XEVMPD unit list.

6. Evidence: XML fragment with unitCode and internal change log entry.

7. Duplicate proprietaryName warning

8. Analysis: Patent-protected name used in both countries is valid; confirm no duplicate internal product IDs.
9. Fix: Document justification in change control record. No data change required.

10. Evidence: Change control entry, product master record extract.

11. MA number format invalid (Spain)

12. Cause: Internal MA number recorded as "ES-7890/001" instead of "ES/H/7890/001".
13. Fix: Correct MA number formatting to match national MA.
14. Evidence: Copy of national MA decision; updated mapping spreadsheet.

Resubmit after fixes

• Re-run local validation: all errors resolved; warnings documented.
• Obtain QA approval per change control SOP.
• Submit XML via EV gateway.

EMA response

• Submission receipt: submission ID returned by EMA.
• EMA validation: minimal processing checks passed; EMA returns "processed" with medicinal product identifier (medicinalProductID) assigned.
• If EMA returns errors, they will be specific (see Validation Errors - Examples below). Correct and resubmit.

Final reconciliation

• Receive final XEVMPD ID and capture in internal master data (store medicinalProductID).
• Reconcile fields between internal system and the live XEVMPD record (screenshot or export).
• File all artefacts in the controlled submission archive.

Validation Errors — Examples and Resolutions

Understanding typical validation errors helps prepare submissions and respond quickly. Below are common categories with example error messages, likely causes and practical resolutions.

1. Missing required elements
2. Example: "ERROR XEV-REQ-014: marketingAuthorisation.startDate is missing"
3. Cause: Start date field omitted in MA block

4. Fix: Populate MA start date in YYYY-MM-DD format, attach MA decision as source document

5. Invalid controlled vocabulary term

6. Example: "ERROR XEV-CV-003: pharmaceuticalForm 'Capule' not recognised"
7. Cause: Typo or free-text entry

8. Fix: Map to exact XEVMPD code and description; validate CV list version and update mapping spreadsheet

9. Strength formatting error

10. Example: "ERROR XEV-FORM-010: strength.amount must be numeric"
11. Cause: Unit included in amount field (e.g., '50 mg' rather than '50')

12. Fix: Split into numeric amount and unitCode attributes; ensure unit in permitted list

13. MA number format incorrect

14. Example: "ERROR XEV-AUTH-005: MA number format invalid for given country"
15. Cause: Incorrect segmentation or missing country code

16. Fix: Correct to the official MA number as shown on the national decision

17. Duplicate product / trade name conflict

18. Example: "ERROR XEV-DUP-001: proprietaryName duplicates existing entry for same country"
19. Cause: Same trade name previously submitted for another MA

20. Fix: Confirm whether duplicate is legitimate (same product in different QPPV scope) or requires differentiation; provide justification and regulatory documentation

21. Missing substance identifiers

22. Example: "WARNING XEV-SUB-002: substance CAS/BDM code missing"
23. Cause: Not all submissions require CAS; however inspectors prefer robust identification

24. Fix: Where available include INN and CAS or other identifiers; document source

25. Invalid date consistency

26. Example: "ERROR XEV-DATE-002: marketingAuthorisation.endDate earlier than startDate"
27. Cause: Data entry error

28. Fix: Correct dates and include supporting regulatory document

29. Reference integrity

30. Example: "ERROR XEV-REF-001: productPresentation references unknown manufacturer ID"
31. Cause: Manufacturer entry missing or mismatched ID
32. Fix: Ensure manufacturer element is present and consistent; include GMP site ID if available

For each error, maintain a corrective action log including who performed the fix, timestamps, and cross-reference to the change control record. This log is critical evidence for inspections.

Evidence Inspectors Expect

Inspectors will typically request to see both procedural documentation and concrete evidence for individual submissions. They are interested in reproducibility, traceability and governance. Common document and evidence items include:

• SOPs and work instructions for XEVMPD submissions and maintenance.
• Field-level mapping spreadsheet linking internal master data to XEVMPD elements, including versioning of controlled vocabularies used.
• Source regulatory documents for each data element: MA decision, national authorisation letters, SmPC, labelling, certificates of GMP for manufacturers.
• The exact XML file(s) that were submitted to EMA and timestamps/receipts confirming submission.
• Validation reports from pre-submission checks and EMA validation/processing responses.
• Change control records demonstrating authorization for the submission (impact assessment, approvers with signatures).
• QA review and approval evidence (checklists, sign-off stamps).
• Reconciliation records showing XEVMPD live record versus internal master data after processing.
• Training records for staff who prepare XEVMPD submissions.
• Any correspondence with EMA regarding rejections, questions, or clarifications.
• Audit trails from systems used to generate or store XEVMPD files showing who changed what and when.
• Periodic monitoring reports (KPI dashboards, reconciliation metrics, open items lists).

Inspectioners often sample a recent submission and may trace from the regulatory decision to the XEVMPD record. Be prepared to demonstrate how the content of each XEVMPD field was derived from the authoritative document, and to present rationale when controlled vocabulary choices were made.

Governance and Quality Controls

Treat XEVMPD data as regulated content with appropriate governance controls. Key governance elements:

• Roles and responsibilities: define owners for product master data, the submitter role, QA approver, and the person authorised to sign regulatory submissions.
• Change control: all XEVMPD-relevant changes should be managed via change control, with impact assessments addressing PV and MA implications.
• Version control and archival: store each submitted XML and supporting documents in a controlled repository with retention consistent with regulatory requirements.
• Reconciliation schedule: perform scheduled reconciliations between XEVMPD and internal master data (recommended quarterly) and after major changes (e.g., national variations).
• KPIs and monitoring: track timeliness (time from MA decision to XEVMPD update), completeness (percentage of required fields populated), and error rates (validation rejections per submission).
• Training and competency: ensure personnel creating or reviewing XEVMPD submissions are trained on XEVMPD data model, EMA tools, and controlled vocabularies.
• Audit readiness: include XEVMPD processes in internal audit plans and remediate findings promptly.

From a governance perspective it is essential that QPPV oversight is documented — not necessarily performing submissions, but approving policies and confirming adequacy of control measures.

Inspection Relevance and Practicalities

During inspections auditors commonly expect to see that an organisation:

• Has a documented and implemented process for preparing and submitting XEVMPD changes.
• Can demonstrate traceability from source regulatory documents to the XEVMPD field values.
• Retains pre- and post-submission validation reports and EMA acknowledgements.
• Performs and documents routine reconciliations and monitors open discrepancies.
• Applies change control for product data changes with appropriate scientific/regulatory justification.

Practical tips that relate to inspection readiness:

• Keep a submission binder (electronic) for each MA that includes mapping, XML, validation reports, approvals and reconciliation evidence.
• Maintain a registry of XEVMPD medicinalProductIDs linked to internal product codes for rapid cross-reference during inspections.
• During inspections, present a worked-through example (as above) to show end-to-end controls rather than only theoretical descriptions.
• Ensure that the QPPV and responsible heads can demonstrate understanding of how XEVMPD issues could affect safety reporting.

Key Takeaways

• XEVMPD is the European medicinal product dictionary and is essential to accurate pharmacovigilance.
• Submissions should be performed against the current XEVMPD schema and controlled vocabularies with rigorous pre-submission validation.
• The QPPV should ensure appropriate governance, oversight and evidence retention for all XEVMPD activities.
• Inspections focus on traceability, governance, and evidence — keep complete submission packages and reconciliation records.
• Prepare for transition to IDMP standards by building robust master data governance and mapping current XEVMPD fields to future IDMP entities.

References

1. Regulation (EC) No 726/2004.
2. Directive 2001/83/EC.
3. Commission Implementing Regulation (EU) No 520/2012.
4. EMA XEVMPD Guidance Documents.
5. EMA EudraVigilance Documentation.
6. GVP Module I – Pharmacovigilance Systems and Their Quality Systems.
7. GVP Module II – Pharmacovigilance System Master File.
8. ISO Identification of Medicinal Products (IDMP) Standards.