Response to Regulatory Questions (RTQ)
0.1.0 - ci-build

Response to Regulatory Questions (RTQ), published by HL7 International. This guide is not an authorized publication; it is the continuous build for version 0.1.0 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/rtq-ig/ and changes regularly. See the Directory of published versions

Response Example

This example demonstrates a synthetic regulatory questionnaire response submitted by a marketing authorization holder (MAH) during a Type II variation procedure, using FHIR R5 QuestionnaireResponse resources for structured, machine-readable exchange.

FHIR Integration Highlights

  • Each answer maps to a QuestionnaireResponse.item with a linkId matching the original question (e.g., "admin-1").
  • The response links to the original Questionnaire and includes submission timestamp (authored).
  • Supports rich text answers, updated ePI translations, new stability data, and ICH/WHO climatic zone confirmation. View the underlying FHIR QuestionnaireResponse resource.
Sample Regulatory Questionnaire Response – RTQ IG

Regulatory Questionnaire Response

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

Procedure Number: EMEA/H/C/005432/II/0023 | Submitted: November 15, 2025

Sender: SynthPharma AG

Dr. John Doe

Head of Regulatory Affairs

SynthPharma AG
Global Regulatory Strategy
Basel, Switzerland

john.doe@synthpharma.example

123 Synthetic Research Blvd, 4000 Basel, Switzerland

Recipient: European Medicines Agency

Dr. Jane Doe

Scientific Officer

Scientific and Regulatory Management
Human Medicines Evaluation Division
European Medicines Agency

jane.doe@ema.europa.eu | +31-88-781-6000

Domenico Scarlattilaan 6, 1083 HS Amsterdam, Netherlands

Response: RegulatoryQA-ID001-Response

1
1.0 Administrative Information → 1.1 Application Form
Is the fee for the Type II variation fully paid and documented?

See EMA Fee Guidance for payment confirmation requirements.

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

2
1.0 Administrative Information → 1.1 Application Form
Are all required metadata fields in the application form complete?
  • Marketing Authorisation Holder
  • Product Name (INN)
  • Procedure Number
  • Submission Date

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
3
1.3 Product Information → 1.3.1 SmPC, Labelling and Package Leaflet
Do the updated storage conditions (2–8°C for 36 months) require additional patient guidance?

Current ePI states: “Store in a refrigerator (2°C – 8°C). Do not freeze.”

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 and does not alter patient handling instructions.

4
1.3 Product Information → 1.3.1 SmPC, Labelling and Package Leaflet
Is the patient leaflet revised to clarify the extended shelf life?

“Shelf life after first opening: 36 months when stored at 2–8°C”

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.

5
1.3 Product Information → 1.3.1 SmPC, Labelling and Package Leaflet
Is the updated ePI text sufficiently clear for all EU languages?
LanguageStatus
EnglishApproved
FrenchUnder Review
GermanPending

Yes, the ePI text has been translated into all EU languages and reviewed for clarity. All versions are linguistically validated. Status: English (Approved), French (Approved), German (Approved), others (Final review completed).

6
3.2.P.8 Stability → 3.2.P.8.1 Stability Summary and Conclusion
Are there any new stability studies conducted, or does the submission include only data from additional timepoints from previously submitted studies?
  • Include protocol deviations if any.
  • Reference: ICH Q1A(R2)

The submission includes both:

  • Additional timepoints: Long-term data extended to 36 months for primary batches A-001, A-002, A-003.
  • New stability studies: Two pilot-scale batches (B-001, B-002) in new Alu/Alu packaging, with 6-month accelerated (40°C/75% RH) and long-term (25°C/60% RH) data.

No protocol deviations occurred. All studies follow ICH Q1A(R2).

7
3.2.P.8 Stability → 3.2.P.8.1 Stability Summary and Conclusion
Does the data support all intended climatic zones?
Note: Confirm coverage for Zone IVb (30°C/75% RH) per WHO TRS 1010

Yes, the data supports all ICH climatic zones, including Zone IVb:

  • Zone I/II: 25°C/60% RH (long-term), 40°C/75% RH (accelerated)
  • Zone IVb: 30°C/75% RH (long-term) — data confirms compliance per WHO TRS 1010.

All batches remain within specification.

8
3.2.P.5 Control of Drug Product → 3.2.P.5.2 Analytical Procedures
Are the test methods used the same as in the previously submitted stability information?

If changed: justify and provide validation data.

Yes, all test methods are identical to those validated in the original MAA. No changes were made. Methods remain stability-indicating for assay, impurities, and dissolution.

9
3.2.P.5 Control of Drug Product → 3.2.P.5.4 Impurities
Are there any new degradation products identified within the newly submitted data?

Threshold: >0.10% per ICH Q3B(R2)

No new degradation products were identified. All observed impurities correspond to previously qualified degradants. Levels remain below 0.10% (ICH Q3B(R2) threshold). No peaks above reporting threshold detected.

10
3.2.P.7 Container Closure System
Any changes in the packaging configuration and/or storage of the samples during stability?
[Figure 1: Cross-section of proposed aluminum/aluminum blister pack]

Figure 1: Cross-section of new Alu/Alu blister showing foil thickness and sealing layer.

OriginalNew
PVC/PVDC BlisterAlu/Alu Blister
25°C/60% RHUnchanged

Yes, a change in packaging configuration was implemented:

  • Original: PVC/PVDC blister pack
  • New: Aluminum/aluminum (Alu/Alu) blister pack

New stability studies (B-001, B-002) were initiated in the Alu/Alu system. Storage conditions remain unchanged: 25°C/60% RH (long-term), 40°C/75% RH (accelerated).

[Figure 1: Cross-section of new Alu/Alu blister pack]

Figure 1: Cross-section of new Alu/Alu blister showing foil thickness and sealing layer.

ParameterOriginalNew
MaterialPVC/PVDCAlu/Alu
Storage Condition25°C/60% RHUnchanged