How marketing authorisation holders should inform MHRA of an ADR to a medicine, using the E2B messaging system.
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 email@example.com 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:
- Register with the European Medicines Agency (EMA) for training details and your ‘Eudravigilance IDs’ for testing and production
- 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
- 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
- Complete the
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
- Carry out the the ICH website to carry out the tests. 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
You must continue to send ICSR reports using the Council for International Organisations of Medical Sciences (CIOMS) format to firstname.lastname@example.org 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.email@example.com if you haven’t and we will investigate the issue.
Follow these rules when sending ICSRs to MHRA as well as those on the ICH website.
|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
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 firstname.lastname@example.org.
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.
EMA are currently developing a reporting database but this is not yet ready. While this database is being developed, reports should be made to MHRA.
Mandatory reporting requirements which should be reported within 15 days:
- serious UK ADR reports
- serious third country (NON-EU) HCP ADR reports
Optional reporting requirements in addition to the mandatory requirements:
- serious non-UK EU ADR reports for products on the additional monitoring list, or where the UK is the Rapp or RMS
- serious third-country consumer ADR reports
These optional requirements will allow MHRA to carry out signal detection activities within our own database while the EMA database is being developed.
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:
- Enter the literature article into your pharmacovigilance system for collection of ADR reports.
- Check to see if the literature is on the if it is, there is no need to send it to us.
- If this is not already listed, submit it to MHRA via E2B the usual way.
You can see MHRA’sfor help with searching through the list.
Email email@example.com if you have any queries on reporting new literature for ADRs.
Email E2B.firstname.lastname@example.org with technical queries or to escalate an E2B issue you can speak to a member of the E2B team:
- Rebecca Owen, 020 3080 6022, email@example.com
- Tahira Jan, 020 3080 6191, firstname.lastname@example.org
If your query specifically relates to ASPRs email email@example.com
Or if you’re unhappy with how your query is dealt with contact the pharmacovigilance service coordinator, Rory Littlebury, 0203 080 6918.