Commission Implementing Regulation (EU) No 520/2012Dangos y teitl llawn

1. Introductory Text

2. CHAPTER I Pharmacovigilance system master file

   1. Article 1. Structure of the pharmacovigilance system master file

   2. Article 2. Content of the pharmacovigilance system master file

   3. Article 3. Content of the Annex to the pharmacovigilance system master file

   4. Article 4. Maintenance

   5. Article 5. Form of the documents contained in the pharmacovigilance system master file

   6. Article 6. Subcontracting

   7. Article 7. Availability and location of the pharmacovigilance system master file

3. CHAPTER II Minimum requirements for the quality systems for the performance of pharmacovigilance activities

   1. Section 1 General provisions

      1. Article 8. Quality system

      2. Article 9. Performance indicators

   2. Section 2 Minimum requirements for the quality systems for the performance of pharmacovigilance activities by marketing authorisation holders

      1. Article 10. Management of human resources

      2. Article 11. Compliance management

      3. Article 12. Record management and data retention

      4. Article 13. Audit

   3. Section 3 Minimum requirements for the quality systems for the performance of pharmacovigilance activities by national competent authorities and the Agency

      1. Article 14. Management of human resources

      2. Article 15. Compliance management

      3. Article 16. Record management and data retention

      4. Article 17. Audit

4. CHAPTER III Minimum requirements for the monitoring of data in the Eudravigilance database

   1. Article 18. General requirements

   2. Article 19. Identification of changed risks and new risks

   3. Article 20. Methodology for determining the evidentiary value of a signal

   4. Article 21. Signal management process

   5. Article 22. Worksharing for signal management

   6. Article 23. Signal detection support

   7. Article 24. Signal detection audit trail

5. CHAPTER IV Use of terminology, formats and standards

   1. Article 25. Use of internationally agreed terminology

   2. Article 26. Use of internationally agreed formats and standards

6. CHAPTER V Transmission of reports of suspected adverse reactions

   1. Article 27. Individual case safety reports

   2. Article 28. Content of the individual case safety report

   3. Article 29. Format of electronic transmission of suspected adverse reactions

7. CHAPTER VI Risk management plans

   1. Article 30. Content of the risk management plan

   2. Article 31. Summary of the risk management plan

   3. Article 32. Updates of the risk management plan

   4. Article 33. Format of the risk management plan

8. CHAPTER VII Periodic safety update reports

   1. Article 34. Content of periodic safety update reports

   2. Article 35. Format of periodic safety update reports

9. CHAPTER VIII Post-authorisation safety studies

   1. Article 36. Scope

   2. Article 37. Definitions

   3. Article 38. Format of post-authorisation safety studies

10. CHAPTER IX Final provisions

    1. Article 39. Data protection

    2. Article 40. Transitional provisions

    3. Article 41. Entry into force and application

11. Signature

12. 1. ANNEX I

       1. Risk management plans Format of the risk management plan

    2. ANNEX II

       Format of the electronic periodic safety update reports

       1. The periodic safety update report shall consist of the following...

    3. ANNEX III

       Protocols, abstracts and final study reports for post-authorisation safety studies

       1. 1. Format of the study protocol

          1. 1. Title: informative title including a commonly used term indicating the...

          2. 2. Marketing authorisation holder.

          3. 3. Responsible parties including a list of all collaborating institutions and...

          4. 4. Abstract: stand-alone summary of the study protocol, including the following...

          5. 5. Amendments and updates: any substantial amendment and update to the...

          6. 6. Milestones: table with planned dates for the following milestones:

          7. 7. Rationale and background: description of the safety hazard(s), the safety...

          8. 8. Research question and objectives in accordance with the decision of...

          9. 9. Research methods: description of the research methods, including:

          10. 10. Protection of human subjects: safeguards in order to comply with...

          11. 11. Management and reporting of adverse events/adverse reactions and other medically...

          12. 12. Plans for disseminating and communicating study results.

          13. 13. References.

       2. 2. Format of the abstract of the final study report

          1. 1. Title, with subtitles including date of the abstract and name...

          2. 2. Keywords (not more than five keywords indicating the main study...

          3. 3. Rationale and background.

          4. 4. Research question and objectives.

          5. 5. Study design.

          6. 6. Setting.

          7. 7. Subjects and study size, including dropouts.

          8. 8. Variables and data sources.

          9. 9. Results.

          10. 10. Discussion (including, where relevant, an evaluation of the impact of...

          11. 11. Marketing authorisation holder.

          12. 12. Names and affiliations of principal investigators.

       3. 3. Format of the final study report

          1. 1. Title: title including a commonly used term indicating the study...

          2. 2. Abstract: stand-alone summary referred to in Section 2 of this...

          3. 3. Marketing authorisation holder: name and address of the marketing authorisation...

          4. 4. Investigators: names, titles, degrees, addresses and affiliations of the principal...

          5. 5. Milestones: dates for the following milestones:

          6. 6. Rationale and background: description of the safety concerns that led...

          7. 7. Research question and objectives.

          8. 8. Amendments and updates to the protocol: list of any substantial...

          9. 9. Research methods

             1. 9.1. Study design: key elements of the study design and rationale...

             2. 9.2. Setting: setting, locations, and relevant dates for the study, including...

             3. 9.3. Subjects: any source population and eligibility criteria for study subjects....

             4. 9.4. Variables: all outcomes, exposures, predictors, potential confounders, and effect modifiers,...

             5. 9.5. Data sources and measurement: for each variable of interest, sources...

             6. 9.6. Bias.

             7. 9.7. Study size: study size, rationale for any study size calculation...

             8. 9.8. Data transformation: transformations, calculations or operations on the data, including...

             9. 9.9. Statistical methods: description of the following items:

             10. 9.10. Quality control: mechanisms to ensure data quality and integrity.

          10. 10. Results: comprising the following subsections:

          11. 11. Discussion

              1. 11.1. Key results: key results with reference to the study objectives,...

              2. 11.2. Limitations: limitations of the study taking into account circumstances that...

              3. 11.3. Interpretation: interpretation of results, considering objectives, limitations, multiplicity of analyses,...

              4. 11.4. Generalisability.

          12. 12. References.