🔎 Common Queries from EU Authorities (EMA / CHMP) on Module 2.4 & 2.5 for Generic Applications

A comprehensive list of all queries raised by EU health authorities on Module 2.4 (Non-Clinical Overview) and Module 2.5 (Clinical Overview) is not publicly available, as most assessment reports remain confidential.

However, based on EMA procedural guidance, the Day 80 Generic Assessment Report template, and publicly available EPARs (European Public Assessment Reports), several recurring trends and queries can be identified.

Common Queries from EU Authorities (EMA / CHMP)

1. Justification for Using Bibliographic (Literature) Data

For generic applications, non-clinical studies are often not conducted, and the overview relies on literature.

Authorities may ask:

- Is the literature search strategy robust and comprehensive?

- How do you justify that published data are sufficient to replace new studies?

- Are there gaps in data, and what is the scientific rationale for not performing studies?

2. Impurity / Degradation Product Profile

Even for generics, assessors evaluate impurities:

- Are impurities summarized in Module 2?

- If the salt/ester/isomer differs from the reference, is comparability justified?

3. Bioequivalence / Biopharmaceutics

Common questions in Module 2.5:

- Do BE data support dose, formulation, and population?

- Why was BE study not conducted (biowaiver justification)?

- Is EMA product-specific guidance followed?

4. Consistency with SmPC / Label Claims

- Are claims aligned with the reference product?

- Are deviations supported by literature or data?

5. Risk–Benefit from Literature

- Are known risks adequately evaluated?

- Are safety signals addressed for the generic product?

6. Well-Established Use / Historical Data

- Is literature sufficient and relevant?

- Are differences from the reference product justified?

7. Environmental Risk Assessment (ERA)

- Is ERA required?

- If omitted, is justification scientifically sound?

8. Template and Format Issues

- Is the overview aligned with EMA Day-80 templates?

- Is the scientific discussion clearly structured?

Strategic Tips to Address These Queries

- Prepare a well-documented literature search strategy

- Clearly justify absence of studies

- Align content with EMA templates

- Highlight impurity comparability

- Provide critical evaluation (not just summary)

- Include risk management strategies

- Justify ERA approach

Examples from EMA / EPAR Reports

1. Mevlyq (Eribulin) – Generic

- No additional non-clinical data submitted

- Literature-based overview accepted

2.Ibuprofen Gen.Orph (IV Generic)

- No new non-clinical or clinical studies submitted

- Literature-based approach accepted

3.Ertapenem SUN (Generic)

- No additional studies conducted

- Reliance on innovator data

Key Takeaways

- Justification for absence of studies is critical

- Literature must be relevant, recent, and robust

- Strong BE waiver justification is essential

- Clear bridging strategy is required

- Balanced benefit–risk evaluation is expected

Detailed Queries – Module 2.4 (Non-Clinical Overview)

- Literature adequacy: Provide search strategy

- Missing tox data: Include pivotal endpoints

- Impurity qualification: Address via ICH guidelines

- Excipient justification: Provide safety data

- ERA: Provide justification

- Local tolerance: Justify scientifically

- Pharmacology gaps: Include mechanism data

- Species relevance: Provide rationale

Detailed Queries – Module 2.5 (Clinical Overview)

- BE justification: Compare with reference

- Literature quality: Provide structured summary

- Bridging: Provide justification

- Clinical pharmacology: Discuss excipients

- Lack of clinical data: Justify approach

- Safety update: Include PSUR

- SmPC consistency: Cross-check sections

- PV considerations: Link to RMP

- BE clarity: Provide concise tables

- Strength bridging: Use EMA guideline

Best Practices

- Maintain a scientific and critical tone

- Avoid copying SmPC text verbatim

- Focus on justification and interpretation

- Use tables and summaries for clarity

- Ensure alignment across modules

- Reference EMA guidelines clearly

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