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The latest ICH E2B (R3) standards will have a major impact on biopharmaceutical companies’ pharmacovigilance systems and processes, particularly on adverse event reporting and collection of data on drugs. Companies will be required to overhaul several key individual case safety report (ICSR) processes and procedures to prepare for the rapidly-approaching deadline for implementing these new standards. Biopharma companies need to start working on transition plans as the integration process will require time, training and a shift in culture.

In November 2012, the updated E2B (R3) standard reached step 4 at the International Conference on Harmonization (ICH). This was an update to its standard for electronic transmission of ICSRs. The original standard, E2B (R2), was implemented in 2001, and there have been many changes in regulatory reporting requirements and pharmacovigilance practices since that time. The new R3 update features many adaptations intended to simplify the exchange of information across regions and stakeholders, while improving accuracy and the level of detail in the information collected.

How R2 and R3 differ

At a broad level, there are more data elements in the new version than the old. The R2 format had 271 unique data elements with the average file using 120-150 of them. In R3, there are 333 unique data elements -- 38 of which are new, and 33 of which have been altered. The increase in data elements may potentially impact the time it takes to process an ICSR in a safety database and additional time may be required to verify that data in source documents have been transferred to the safety database.

Along with more data elements, there are changes in the way information is shared and coded, and the extent to which explanations can be included. Some most significant changes include:

  • Null values: The R3 update features a new method for transmitting unknown data, giving companies the ability to add codes when information is missing. These additions will help companies close gaps related to missing information in their submissions. Companies will need to consider revamping processes to ensure that null values can be populated in ICSRs prior to reporting to business partners. 

  • Seriousness criteria: The new standard allows for seriousness criteria to be captured at the event level rather than the case level. This means that older systems may need to be adapted or upgraded to meet this new criteria. As such, biopharma companies should review the capabilities of their current systems as part of their implementation plan. Biopharmaceutical companies will need to revamp how they collect safety data to ensure that seriousness criteria can be captured at an event level. 
     
  • Changes to the drug section: The drug section in the R3 submissions will integrate with the new standards for the Identification of Medicinal Products (IDMP) from the International Organization for Standardization (ISO). IDMP addresses the demand for global identification of medicines through the use of more consistent documentation, coding and exchange of information across regions. However IDMP and E2B (R3) will not go live at the same time. As a result, companies will still be able to still submit E2 codes in this section until IDMP is mandatory.The drug section of the R3 standard will also allow for scalability of characterization to show things like whether the study drug was administered, investigational product status, submission of blinded information, and submission of data related to multiple indications and/or dosing regimens. These changes are expected to drive greater clarity around drug information in these reports.  

  • Backwards – Forwards Compatibility (BFC). BFC means that all receivers will need to be able to accept R2 and R3 files and have processes in place to update and accommodate remediation of imported E2B files to avoid data losses. Companies with products approved in the EU will need to have a BFC tool by November 2017 in order to handle cases that are received in the R3 format.

Start planning now

To adapt, pharmacovigilance business leaders should assemble a transition team that includes subject matter experts from all impacted areas who can put together an integration plan and communicate the necessary changes to key stakeholders. That plan should include technology upgrades, form revisions, governance strategies, and training for all affected employees to ensure their people have the tools and knowledge they will need to adapt to the new standard. These transition plans shouldn’t be limited to internal stakeholders. To be effective, companies also need to work with vendors and partners to develop an updated model for information exchange that is clearly written into a contract, and establish standard operating procedures for data collection and reporting to ensure every aspect of the clinical research environment is compliant with the new R3 standard.

Timing for compliance to the new E2B (R3) standard varies across regions.

  • The European Medicines Agency (EMA) will begin accepting R3 formatted reports in November, 2017, however the standard likely won’t become mandatory until sometime in 2020, contingent on EMA’s implementation of IDMP.  

  • The U.S. Food and Drug Administration (FDA) has published implementation specifications for R3 reporting, but has not yet set a firm deadline. We expect it to occur sometime in 2017 or 2018.  

  • The Japanese authority made R3 submissions optional as of April 1, and set a deadline for all submissions to conform to R3 by April 1, 2019.

While there is still time for companies to adapt their current safety reporting strategies to accommodate the new standard, time is quickly running out. In a recent webinar on this topic hosted by QuintilesIMS, almost half (46 percent) of participants said their companies had not yet considered the need to develop an E2B (R3) implementation plan. We recommend companies start as soon as possible, as integration of this new standard to safety reporting submission practices will require a substantial culture change, along with training and system assessments across multiple teams.

This transformation will take time and effort, and biopharma companies need to start now. Companies that are concerned about implementing this transition process, should reach out to their partners and vendors who understand the intricacies of the new standard to help them develop a plan to meet looming deadlines for compliance.