The European Medicines Agency (EMA) recently issued a crucial update in March 2024. This update explicitly targets Marketing Authorization Holders (MAHs) to provide clarity on the concept of “Day Zero (Day 0)” concerning Individual Case Safety Reports (ICSRs) sourced from electronic and hard copy journals.

Before this revision, interpretations varied, complicating matters for pharmacovigilance professionals:

• Local literature sourced via reference databases had Day 0 tied to the search date. 
• Online literature followed a similar trajectory, pegged to the search date.
• Hard copy journals received different treatment, with Day 0 linked to the physical arrival date of the journal.

In 2023, when this definition of Day 0 first came up, our blog post advised staying calm rather than panicking prematurely. Now, with the updated explanations from 2024, it’s evident there’s still no reason to panic. After all, the March 2024 update did bring about significant changes:

Defining Day 0 in Local Literature Sources:

For ICSRs described in local literature monitored through literature reference databases, Day 0 is set as the date of the conducted search.

Identifying Day 0 in Online/Electronic Literature Sources:

For ICSRs described in online/electronic literature sources, Day 0 is determined when MAH identifies sufficient information to meet the minimum criteria for a valid ICSR report.

Prompt Review and Regulatory Reporting

MAHs must promptly review published journals to identify and manage potential adverse drug reaction cases within a week of receipt. Consequently, Day 0 for regulatory reporting of valid ICSRs should be at most seven calendar days from the date of receipt.

Establishing Day 0 in Hard Copy Literature Sources:

For ICSRs described in hard copy literature sources, Day 0 is recognized when MAH identifies adequate information to meet the minimum criteria for a valid ICSR report.

Consistent Regulatory Oversight

Like online literature, MAHs must swiftly review hard copy journals to identify and manage potential adverse drug reactions within a week of receipt, ensuring Day 0 aligns with regulatory reporting standards.

Determining Day 0 in Local Literature Indexed in Weekly Databases:

For ICSRs described in local literature sources indexed in weekly literature reference databases, the date of first receipt establishes Day 0.

Publication Reception and Review

If the publication is first received through medical journals, MAHs must promptly review it, ensuring Day 0 stays within the seven-day threshold from the date of receipt. Alternatively, if MAHs identify the publication through systematic literature reviews from monitored reference databases, Day Zero aligns with the search date.

Conclusion

The updated interpretation aligns closely with the Good Pharmacovigilance Practices (GVP) guidelines. This alignment marks Day 0 with the recognition of a publication containing the minimum criteria for an ICSR. However, it’s essential to underscore that receiving local literature doesn’t automatically signify awareness of the ICSR’s minimum criteria. Digging deeper, the September 2023 guidance overlooked practical realities. These include delays between hard copy receipt and review and the intricate screening process required. In pharmacovigilance, EMA’s recalibration of Day 0 offers a more precise roadmap for MAHs. Therefore, this ensures expedited and informed responses to safeguard public health.

Key Takeaways:

• The March 2024 revision reshapes Day 0. It pivots on MAHs’ identification of enough information to meet the minimum criteria for a valid report.
• Day 0 for hard copy and online/electronic local literature transcends mere receipt dates.
• MAHs must promptly review these sources within a week to identify potential ICSRs. 
• They define Day Zero by gathering sufficient information for a valid report within seven days of receipt.