Regulatory Questionnaire Response

Response to EMA List of Questions – Type II Variation (ID001)

Procedure: EMEA/H/C/005432/II/0023 | Submitted: 2025-11-18

This document presents the official response to the regulatory questions issued by the health authority. It provides detailed evidence, justifications, and technical data in a structured format that maintains full traceability to the original request and the CTD structure.

Participants & Contacts

SENDER (MAH)

SynthPharma AG
Global Regulatory Strategy
Basel, Switzerland
john.doe@synthpharma.example

RECIPIENT (REGULATOR)

European Medicines Agency
Scientific and Regulatory Management
Human Medicines Evaluation Division
jane.doe@ema.europa.eu

1.0 Administrative Information

CTD Ref: 1.1 Application Form ID: 1

Is the fee for the Type II variation fully paid and documented?

Response

Yes, the fee was paid on June 25, 2025. Payment confirmation and receipt are included in the application form (see Section 1.1).

CTD Ref: 1.1 Application Form ID: 2

Are all required metadata fields in the application form complete?

Response

Yes, all required metadata fields are complete:

MAH: SynthPharma AG
Product: ExampleDrug 10 mg Tablets
Procedure: EMEA/H/C/005432/II/0023
Submission Date: 2025-06-25

1.3 Product Information

CTD Ref: 1.3.1 SmPC, Labelling and Package Leaflet ID: 3

Do the updated storage conditions require additional patient guidance?

Response

No additional patient guidance is required. The ePI clearly states: "Store in a refrigerator (2°C – 8°C). Do not freeze." The 36-month shelf life is supported by stability data.

CTD Ref: 1.3.1 SmPC, Labelling and Package Leaflet ID: 4

Is the patient leaflet revised to clarify the extended shelf life?

Response

Yes, the patient leaflet has been updated to state: "Shelf life after first opening: 36 months when stored at 2–8°C". The revised leaflet is included in the submission.

3.2.P.5 Control of Drug Product

CTD Ref: 3.2.P.5.2 Analytical Procedures ID: 5

Are the test methods used consistent with previous submissions?

Response

Yes, all test methods are consistent with the previously approved dossier. No changes have been made to the analytical procedures. Full validation data per ICH Q2(R1) is available on request.

CTD Ref: 3.2.P.5.4 Impurities ID: 6

Are there any new degradation products identified?

Response

No new degradation products have been identified. All impurities remain below the 0.10% reporting threshold per ICH Q3B(R2). Batch analysis data is included in Section 3.2.P.5.4.

3.2.P.7 Container Closure System

CTD Ref: 3.2.P.7 Container Closure ID: 7

Any changes in the packaging configuration during stability?

Response

Yes, the packaging was changed from PVC/PVDC to Alu/Alu. New stability studies were initiated and stored under standard conditions.

Cross-section diagram of Alu/Alu blister pack showing aluminum forming foil, lid foil, tablet cavity, and heat-sealed edges

Figure 1: Cross-section of new Alu/Alu blister showing foil thickness and lidding layers

Parameter	Original	New
Material	PVC/PVDC	Alu/Alu
Storage	25°C/60% RH	Unchanged

3.2.P.8 Stability

CTD Ref: 3.2.P.8.1 Stability Summary and Conclusion ID: 8

Are there any new stability studies conducted?

Response

The submission includes both extended long-term data (36 months) for primary batches and new studies for pilot-scale batches in Alu/Alu packaging. No protocol deviations occurred.

Attachments

📄

Stability_Summary_Report_ID001.pdf

PDF • 2.4 MB • Section 3.2.P.8.1

⬇ Download

📊

Stability_Data_Tables_Batch_A-C.xlsx

XLSX • 480 KB • Section 3.2.P.8.3

⬇ Download

CTD Ref: 3.2.P.8.1 Stability Summary and Conclusion ID: 9

Does the data support all intended climatic zones?

Response

Yes, all batches remain within specification across all ICH climatic zones, including Zone IVb (30°C/75% RH). Full tabulated data is provided in Section 3.2.P.8.3.