VI.App.2.10. Electronic submission of copies of articles on suspected adverse reactions published in the medical literature

Location:
VI. Appendix 2

In accordance with Article 28(3) of the Commission Implementing Regulation (EU) No 520/2012, upon request of the Agency, the marketing authorisation holder that transmitted the initial report shall provide a copy of the relevant article taking into account copyright restrictions, and a full translation of that article into English.

Table VI.4. Electronic submission of copies of literature articles/translations in line with ICH-E2B

Reference E2B(R2)/(R3) requirements
ICH-E2B(R2) 1. Mailing address and format of literature articles:
Literature articles reportable to the Agency should be provided in PDF format and sent via e-mail to the following e-mail address: EVLIT@ema.europa.eu. In relation to copies of articles from the published medical literature, marketing authorisation holders are recommended to consider potential copyright issues specifically as regards the electronic submission and handling of electronic copies in the frame of regulatory activities.2. File name of literature articles sent in electronic format to the Agency: The file name of a literature article sent in PDF format should match exactly the data element A.1.10.1 or A.1.10.2 ‘World-Wide Unique Case Identification Number’ assigned to the individual case, which is described in the article and which is provided in the E2B(R2) ICSR format.If there is a follow-up article to the individual case published in the literature, the file name with the World-Wide Unique Case Identification Number must be maintained but should include a sequence number separated with a dash.Examples:

  • Initial ICSR published in the literature: FR-ORGABC-23232321 data element A.1.10.1 ‘World-Wide Unique Case Identification Number’;
    • File name of the literature article: FR-ORGABC-23232321.pdf.
  • Follow-up information published in the literature in a separate article:
    • ICSR: FR-ORGABC-23232321 data element A.1.10.1’’World-Wide Unique Case Identification Number’ remains unchanged;
    • File name: FR-ORGABC-23232321-1.pdf.

3. Submission of cases described in the medical literature referring to more than one patient:

When the literature article refers to the description of more than one patient, the copy of the literature article should be sent only once.

The file name of a literature article sent in PDF format should match exactly data element A.1.10.1 or A.1.10.2 as applicable ‘World-Wide Unique Case Identification Number’ assigned to the first submitted individual case described in the article.

In addition, all ICSRs which relate to the same literature article should be cross referenced in data element A.1.12 ‘Identification number of the report which is linked to this report’. The data element should be repeated as necessary to cross refer all related cases.
ICH-E2B(R3) Information on document attachments:

  • Information on how to attach documents to an ICSR is provided in section 3.5 ‘Document Attachments’ of the ICH-E2B(R3) Implementation Guide for Electronic Transmission of Individual Case Safety Reports (ICSRs) – Data Elements and Message Specification63.
  • When a literature article is sent as an attachment, the literature citation in Vancouver style is captured in data element C.4.r.1 ‘Literature Reference(s)’. The Digital Object Identifier (DOI) for the article should be included where available. The example reference hereafter highlights how this should be done:

“International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals. N Engl J Med 1997; 336:309-15. doi:10.1056/NEJM199701233360422.”

  • The electronic version of the document (i.e. the journal article and a copy of the translation where applicable) should be attached to the ICSR in data element C.4.r.2. ‘Included Documents’.
  • If the article and/or translation are not provided at the time of ICSR submission, attachments can be submitted separately. When the sender transmits an attachment later, the original ICSR along with all the same medical information captured in E2B(R3) data elements is retransmitted as an ‘amendment’ (see VI.C.6.2.2.8. for guidance on amendment reports). If new information has been received and the data elements in E2B(R3) have been updated, then the ICSR with attachment is transmitted as a follow-up.
  • In addition, all ICSRs which relate to the same literature article should be cross referenced in data element C.1.10.r ‘Identification Number of the Report Linked to this Report (repeat as necessary)’.