Change ahead: New E2B(R3) guideline for case safety reports

Latest revision of ICH guideline updates required data elements for transmission of Individual Case Safety Reports (ICSRs)

Biopharma companies will need to begin transitioning their pharmacovigilance systems to comply with the latest ICH E2B(R3) guideline for adverse event reporting. Regulatory agencies around the globe have adopted the revised guideline, which implements ISO IDMP data standards to improve patient safety and create more efficient and compliant submissions.

Who:  ICH – International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

  • Influences regulatory agencies around the globe, which adopt ICH guidelines

What:  E2B(R3) is the newest version of a critical guideline for electronic submission of individual case safety reports (ICSRs).

Working with Standards Development Organizations (SDOs) around the globe, the latest revision outlines requirements for the data included in an individual case safety report (ICSR). The E2B guideline, titled “Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports”, ensures consistent data standards across entities.

When:  Transitioning now / varying compliance timelines for regulatory agencies around the globe

The EMA, FDA, and PMDA have already adopted the E2B(R3) guideline. Companies should begin their transitions to meet the new requirements, which will be a complex process.

The worldwide regulatory and pharmacovigilance environment continues to evolve to facilitate more efficient exchange of data and safety information across regions and between health authorities on one hand, and between healthcare professionals and pharmaceutical companies on the other.

One component of this evolution is the improvement of electronic adverse event reporting with the transition from the older, ICH E2B(R2) guideline to E2B(R3). R3 brings the addition of new and updated data elements:

  • Causality Assessment – Better control of the causality assessment according to the ISO individual case safety report (ICSR), which requires the use of controlled vocabularies for source, method and result of assessment (E2B(R2) relied on free text fields instead).
  • Amendment Reports – Added capability to submit Amendment Reports if case information has changed (e.g., change in evaluation but no new information has been received). Amendments can be used for sending Data Corrections or providing literature articles. The EMA will monitor the submission of Amendment Reports to prevent misuse by companies.
  • Attachments – Added capability to embed files such as literature articles or other documentation to the E2B message.
  • Case vs. Event Level Tracking– Moving information tracking from case level to event level to allow for variations from case to case depending on the severity of the adverse events, medical requirements and the occurrence.
  • ISO IDMP Standards – Additional date fields and codes for the identification of medicinal products by implementing the new international standards for the Identification of Medicinal Products (IDMP) (use of controlled vocabularies).

HighPoint strongly believes that ISO IDMP will have a key role in these improvements. ISO IDMP will enable better identification of medicinal products and pharmacovigilance reporting for ICSR, PSUR and pharmacovigilance (PV) databases.

The synergies between EudraVigilance and ISO IDMP become essential for the implementation of these new safety systems requirements. Because ICSR was approved prior to IDMP completion, ICSR was implemented without requiring an IDMP identifier in their messages. Once IDMP is implemented, ICSR submissions will likely change to use the Medicinal Product Identifiers: Medicinal Product Identifier, Pharmaceutical Product Identifier, Product Name Parts, and the Substance / Specified Substance Identifier.

IDMP is critical to ensuring unique and clear identification of an active substance, units of measurement, ingredients, dosage form, units of presentation and route of administration (Table 1, below). This detailed identification enables a specific, individual case safety report to be specified.

Element ID

Element Name Object ID Reference
D.8.r.2b Medicinal Product ISO11615 MPID
D.8.r.3b Pharmaceutical Product ISO11616 PhPID
D.10.8.r.2b Medicinal Product ISO11615 MPID
D.10.8.r.3b Pharmaceutical Product ISO11616 PhPID
G.k.2.1.1b Medicinal Product ISO11615 MPID
G.k.2.1.2b Pharmaceutical Product ISO11616 PhPID
G.k.2.3.r.2b Substance/Specified Substance ISO11238 IDMP Substance
G.k.4.r.9.2b Pharmaceutical Dose Form ISO11239 IDMP Dosage Forms & Routes of Administration
G.k.4.r.10.2b Route of Administration ISO11239 IDMP Dosage Forms & Routes of Administration
G.k.4.r.11.2b Parent Route of Administration ISO11239 IDMP Dosage Forms & Routes of Administration

Table 1: E2B(R3) data elements and IDMP Object IDs (Source:  https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm275638.pdf )

 

The leveraging of ISO IDMP standards will improve the quality, accuracy and value of adverse event reports by allowing clear identification of products and facilitating clear and accurate communication of product information between various stakeholders (e.g., pharmaceutical companies and regulators) and across jurisdictions.

The future use of the ISO IDMP and its different identifiers in the context of the new E2B(R3) format clearly shows the importance and the crucial role of the ISO IDMP initiative in pharmacovigilance systems. This will lead to better signal detection downstream in the process and ultimately lead to the improvement of drug safety globally.

Additional links / resources:

Read more about E2B(R3):  Enhancing Patient Safety: IDMP & ICH E2B(R3) Synergy


Don’t get left behind – get ahead of the transition curve with ISO IDMP and E2B(R3)

Learn more about how to leverage ISO IDMP for a successful E2B(R3) implementation. Contact HighPoint’s ISO IDMP and pharmacovigilance experts for support during your journey to E2B(R3) compliance – Jens-Olaf Vanggaard, Director R&D Europe