Proposed Module VI Updates, Implications and How to Prepare

Sanyogita Rane

Approximately a year ago the EMA released draft revision 2 of GVP module VI “Management and reporting of adverse reactions to medicinal products” for public consultation. In May this year, the new EudraVigilance system was approved for release and will be implemented on 22 November, 2017. It is anticipated that within 6 months after the new EudraVigilance system is accessible, the latest version of Module VI will come into effect.

It is therefore timely for organizations to revisit the key changes, their potential impact, and evaluate whether they are prepared.

Key changes to Module VI include –

  • Updates on:
    • Electronic reporting modalities of ICSRs under the new ICH-E2B(R3) format
    • ICSR reporting, performing follow-up, duplicate detection, data quality management, in line with the provisions in Art. 24 of Reg. (EC) No 726/2004, Art 107 and 107a of Dir. 2001/83/EC
    • Validation of ICSRs based on patient and reporter identifiability: Identifiable reporter is characterised by qualification (e.g. physician, pharmacist, other healthcare professional, lawyer, consumer or other non-healthcare professional) and at least one of the following parameters: name, address or phone number. An ICSR should not be considered valid for reporting unless this information is available for at least one reporter. One single identifiable patient is characterized by at least one of the following qualifying descriptors: initials, identification number, date of birth, age, age group or gender.
    • Management of ICSRs described in scientific literature: The exclusion criteria for the reporting of ICSRs published in the scientific literature are elaborated with examples.Collection of information on patient’s age: information related to patient’s age is important to identify safety issues occurring specifically in the pediatric or elderly population. All possible efforts should be made to follow-up on an individual case to obtain age information of the patient, where it is initially not reported by the primary source.
  • Guidance on the management of:
    • Suspected adverse reactions reported through medical enquiry and product information services
    • Reports from post-authorisation efficacy studies: Reports of suspected adverse reactions originating from non-interventional post authorization studies and for which the protocol does not require a systematic collection should also be considered as spontaneous reports.
  • Transfer of the guidance on Emerging Safety Issues to GVP Module IX
  • Editorial amendments to align the format with other GVP Modules

What do these changes mean to organizations?

  • Providing access to the EudraVigilance database will ease the submission process. Furthermore, separate submissions to Competent Authorities (CA) of Member States (MS) by Marketing Authorization Holders (MAH) will not be required.
  • A detailed duplicate identification process is proposed and accompanying guidance for identifying and processing of duplicates will be released. Nullflavors have been introduced; these are a collection of codes specifying why a valid value is not present in an ICSR, which is in line with the R3.
  • Processes are mapped to match R3 guidelines and additional drug codes (E.g.: counterfeit, drug taken by father, etc.) have been introduced.
  • Enhanced data sharing between the EudraVigilance and WHO databases (in practice the Uppsala Monitoring Centre (UMC)).
  • Updates to existing guidance on the validation of ICSRs based on patient and reporter identifiers.
  • The follow-up process by MAH, MS and between MAH and MS has been streamlined. MS shall involve patients and healthcare professionals, as appropriate, in the follow-up of any reports they receive. Furthermore, for reports submitted by a MAH, MS on whose territory the suspected adverse reaction occurred may involve the MAH in the follow-up of the reports. In support of the operation of the follow-up procedures, a business process map and a process description are provided.
  • Emphasis is given on importance of quality assurance as a part of quality management and indications that it will be a focus of future regulatory inspections.
  • Additional fields have been incorporated at event level (e.g. medical confirmation, action taken, de-challenge, re-challenge, country of occurrence) to align with R3 guidelines.

What is the Impact on Organizations?

These updates will have a significant impact on technology and processes. At an organizational level, the process changes will require updates to procedural documents. Access to the EudraVigilance database will require significant changes to signal detection processes and impact aggregate report activities. Harmonization of reporting of cases to agencies outside of the EU may be impacted by the changes in validation criteria. Though improvements in the identification of duplicates will reduce the excess noise and the submission process within the EU will be greatly streamlined.

Overall the changes should allow streamlining of several processes and ultimately lead to improvements in the quality of safety data. The EMA has taken a well-planned, iterative approach with a series of updates and improvements since the new legislation in 2012. The release of the new EudraVigilance database has paved the way for E2B R3 implementation, linked with the updates in Module VI along with an updated Module IX (Signal Management).

MAHs should be looking out for the associated guidance documents that will be released by the EMA, e.g. for duplicate checks, perform gap assessments and initiate the necessary procedural changes. There will be a significant impact in terms of training staff on the process changes these updates will entail, as well as for the new database. Robust internal training plan will be required which can be based on the EudraVigilance auditable requirement project (EudraVigilance training plan). MAHs should start planning now and allocate resources to assess the impact of these changes within their organization and put implementation plans in place.

Sciformix has experience and expertise to help MAHs be ready ahead of time. You can reach us at You may also watch our webinar on An Industry Perspective on the Future Changes in Pharmacovigilance and Safety Assessment for IND Reporting.