How marketing authorisation holders should inform MHRA of an ADR to a medicine, using the E2B messaging system.

Overview

MHRA uses the E2B messaging standard to send and receive information on adverse drug reactions (ADRs) reported by patients and healthcare professionals.

E2B is the mandatory messaging standard that enables us and marketing authorisation (MA) holders to receive information in a single format known as an individual case safety report (ICSR). You will need to carry out training by the European Medicines Agency beforehand using your current database systems to ensure that you meet the requirements and that your systems are compatible. You will also need to carry out some test scenarios.

If you are waiting for E2B to be set up we will send safety information in an anonymised single patient report (ASPR) format as a PDF via:

  • the MHRA portal
  • email to the qualified person in your pharmacovigilance team in Europe and another designated person (if you are not signed up to the portal)

If you are not signed up to the portal you need to email information on ADRs to pharmacovigilanceservice@mhra.gsi.gov.uk in the meantime.

There is no need to send us ADRs that are already on the literature report list.

Register to use the E2B reporting system

You need to follow this process to start using the E2B reporting system:

  1. Register with the European Medicines Agency (EMA) for training details and your ‘Eudravigilance IDs’ for testing and production
  2. Install one of the software packages offered by the EMA to support the E2B standard when you register for your ID if your current database isn’t compatible
  3. Familiarise yourself with the formatting standards by the International Conference on Harmonisation (ICH) when reporting ICSRs electronically as well as the validation rules below specifically for reporting to MHRA. You should also follow the coding standards](http://www.meddra.org/electronic-communication) on the Medical Dictionary for Regulatory Activities website
  4. Complete the E2B registration form (MS Word Document, 638KB) and email it to [ICSRtesting@mhra.gsi.gov.uk](mailto: ICSRtesting@mhra.gsi.gov.uk] along with:
    • your company name and address
    • the marketing authorisation number(s) starting ‘PL’ and the stem number of any clinical trial licences or centralised licences
    • a point of contact (name, position, phone, fax, email)
    • a technical contact (name, position, phone, fax, email)
    • your Eudravigilance IDs (testing and production)
    • the name of your database system and version
    • the earliest and preferred dates for testing
  5. Carry out the Test scenarios for market authorisation holders to register for the E2B messaging standard (PDF, 240KB, 5 pages) when you receive your test date and details. You will need to sign in to the testing platform with your ID and use the validation rules by MHRA below and on the ICH website to carry out the tests.

You must continue to send ICSR reports using the Council for International Organisations of Medical Sciences (CIOMS) format to pharmacovigilanceservice@mhra.gsi.gov.uk while your E2B account is being set up.

When you are set up to use the E2B standard you should receive an acknowledgement email. Email E2B.support@mhra.gsi.gov.uk if you haven’t and we will investigate the issue.

Validation rules

Follow these rules when sending ICSRs to MHRA as well as those on the ICH website.

E2B element E2B Validation
A1.1 primarysourcecountry Mandatory field for each case
A.2.1.4 qualification At least one required for each case
B1.2.2a patientonsetage Age cannot be greater than 120 years
B.1.3 patientweight Not to be greater than 500kg
B.1.4 patientheight Not to be greater than 300 cm
B.1.7.1c patientmedicalstartdate Date is not greater than the transmission date
B.1.7.1f patientmedicalstartdate Date is not greater than the transmission date
B.1.8c patientdrugstartdate Date is not greater than the transmission date
B.1.8e patientdrugstartdate Date is not greater than the transmission date
B.2.i.8 reactionoutcome All outcomes should be populated. If the outcome is unknown this field should be populated with ‘unknown’ and not left blank
B.3.1b testdate Date is not greater than the transmission date
N/A all dates All dates must be less than today’s date – future dates will be rejected
B.2.i.4b reactionstartdate The reaction start date must be greater than the suspect drug start dates
B.4.k.7 drugdosageform The pharmaceutical form can be reported using both the text and code format*
B.4.k.18.1b drugreactionassess the MeDRA code used should match the ‘reactionmeddrallt’ field
All numerical fields - The unit field must be completed for every numerical field. For eg both dosage fields must be completed.

*The terms / codes will need to be selected from the drug dosage form (PDF, 46.7KB, 9 pages)

Anonymised single patient report (ASPRs)

These reports include ADRs, which MHRA receives on a case by case basis by healthcare professionals and patients. They are presented in an anonymous PDF format, which we deliver to you via the MHRA Portal or email. ASPRs remain on the portal for 14 days.

We only send ASPRs this way while your E2B system is being set up or if you’re waiting for access to the MHRA portal. You can register for the portal if you haven’t already by emailing portal.manager@mhra.gsi.gov.uk.

When to report ADRs

You are legally required to report the safety information of your product according to the timeframes listed in module VI of guideline on good pharmacovigilance practices on the EMA’s website.

Literature report list

The literature report lists scientific literature relating to ADRs and is updated weekly. Rows may be repeated if there is more than one suspect drug related to the ADR or the reports have not been passed through the duplication detection process yet.

When you identify a literature article, you need to:

  1. Enter the literature article into your pharmacovigilance system for collection of ADR reports.
  2. Check to see if the literature is on the literature report list (MS Excel Spreadsheet, 3.16MB) if it is, there is no need to send it to us.
  3. If this is not already listed, submit it to MHRA via E2B the usual way.

You can see MHRA’s guidance for tips (PDF, 310KB, 2 pages) for help with searching through the list.

Email pharmacovigilanceservice@mhra.gsi.gov.uk if you have any queries on reporting new literature for ADRs.

Contact

Email E2B.support@mhra.gsi.gov.uk with technical queries or to escalate an E2B issue you can speak to a member of the E2B team:

If your query specifically relates to ASPRs email pharmacovigilanceservice@mhra.gsi.gov.uk

Or if you’re unhappy with how your query is dealt with contact the pharmacovigilance service coordinator, Rory Littlebury, 0203 080 6918.