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
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
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
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.

ID: 4
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.8 Stability
CTD Ref: 3.2.P.8.1 Stability Summary and Conclusion ID: 6
6
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.

CTD Ref: 3.2.P.8.1 Stability Summary and Conclusion ID: 7
7
Does the data support all intended climatic zones?
Response

Yes, the data supports all ICH climatic zones, including Zone IVb (30°C/75% RH). All batches remain within specification.

3.2.P.7 Container Closure System
CTD Ref: 3.2.P.7 Container Closure ID: 10
10
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.

Lidding Foil (Aluminium) Dispersion Adhesive Coldform Foil (Alu/PVC/OPA) Cross-section: Forming Cavity for 10mg Tablet

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