On the 22nd of November 2017, the European Medicines Agency (EMA) launched a new version of EudraVigilance. The improvements and changes affected users of the EudraVigilance system, such as National Competent Authorities, Marketing Authorisation Holders and Sponsors of clinical trials. You can read more about the updated EudraVigilance system here.
Currently, ICSRs are accepted in the ICH E2B(R2) ICSR format and are converted to the ISO ICSR format upon receipt in EudraVigilance. However, this conversion is causing a number of challenges:
- Important information was often not available in dedicated data fields and may only be found in case narratives
- Data quality was reduced
- Search and data analysis capabilities for National Competent Authorities and the European Medicines Agency were lower
- Marketing authorisation holders and the WHO Uppsala Monitoring Centre had only restricted access to case narratives due to data protection
For these reasons, at its December 2019 meeting, EMA’s Management Board agreed to the mandatory use of the ISO ICSR format for reporting individual cases of suspected side effects. The use of the new international standard will become mandatory as of 30 June 2022 (1).
What’s new with the E2B(R3)?
The use of the following standards becomes mandatory (2):
- ISO Individual Case Safety Report standard as referred to in Article 26(2)(a) of the Commission Implementing Regulation (EU) No 520/2012 and the modalities on how to use this ISO ICSR standard defined in the ICH E2B(R3) documentation
- ISO terminology on pharmaceutical dose forms and routes of administration referred to in Article 25(1)(f) of Commission Implementing Regulation (EU) No 520/2012
This will result in the following changes:
- Message format: data structure, data elements, sender comments and diagnosis, free text for additional information available, event severity criteria and evaluation of the correlation between drug and reaction / event;
- Introduction of standard terminologies: ISO (country codes, gender codes and language codes), MedDRA (used for example in indication and reaction / event), UCUM (unit of measurement) and ISO IDMP (identification of medicines);
- New HL7 format for patient and consumer data;
- Introduction of null flavor;
- Introduction of seriousness criteria at the event level.
Who has to use the new format?
All organizations and entities in the Life Sciences sector like pharmaceutical companies, CROs or sponsors of clinical trials and medicines regulatory authorities must use the new standard format.
The change applies to the following reporting obligations (2):
- Article 28 of Regulation (EC) No 726/2004: obligations of marketing authorisation holders and Member States as regards the recording and reporting of suspected adverse reactions to medicinal products for human use authorised in accordance with this Regulation.
- Articles 107 and 107a of Directive 2001/83/EC: obligations of marketing authorisation holders and Member States as regards the recording and reporting of suspected adverse reactions to medicinal products for human use authorised in accordance with Regulation (EC) No 726/2004 and Directive 2001/83/EC/2001.
- Article 17(1) of Directive 2001/20/EC: obligations of sponsors of clinical trials and Member States as regards the recording and reporting of suspected unexpected serious adverse reactions to investigational medicinal products.
- Article 42 of Regulation (EU) No 536/2014obligations of sponsors of clinical trials and Member States as regards the reporting of suspected unexpected serious adverse reactions by the sponsor to the Agency.
What does it mean for pharmacovigilance professionals?
The mandatory use of international standard for the reporting of side effects allows pharmacovigilance professionals to minimise time for electronic reporting of ICSRs to EudraVigilance, and number of typing errors and optimises the work process.
The format ensures
- The transmission of accurate and verifiable data on suspected adverse reactions in the pre- and post-authorisation phase to the EudraVigilance database [IR Art 11 (1) (c)];
- The quality, integrity and completeness of the information transmitted on safety issues of medicinal products, including processes to avoid duplicate reporting [IR Art 11 (1) (d)];
- More effective protection of patient and consumer data and greater respect for privacy;
- Improved quality of data collected and increases the ability to search and analyse.
More details on the mandatory format are available in this guide that defines the electronic transmission process of ICSRs, the format and content of the ICSR, the business rules for report validation, and classification and data quality principles.
- Mandatory use of international standard for the reporting of side effects to improve safety of medicines
- Announcement of the EMA Management Board: Confirmation of the mandatory use of the ISO Individual Case Report
standard based on ICH E2B(R3) modalities and related ISO standard terminology
- EU Individual Case Safety Report (ICSR) Implementation Guide