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
@prefix fhir: <http://hl7.org/fhir/> .
@prefix owl: <http://www.w3.org/2002/07/owl#> .
@prefix rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
# - resource -------------------------------------------------------------------
a fhir:QuestionnaireResponse ;
fhir:nodeRole fhir:treeRoot ;
fhir:id [ fhir:v "RegulatoryQA-ID001-Response"] ; #
fhir:meta [
fhir:versionId [ fhir:v "1" ] ;
fhir:lastUpdated [ fhir:v "2025-11-15T14:59:00-05:00"^^xsd:dateTime ] ;
( fhir:profile [
fhir:v "http://hl7.org/fhir/uv/brr/StructureDefinition/RegulatoryQuestionnaireResponse"^^xsd:anyURI ;
fhir:l <http://hl7.org/fhir/uv/brr/StructureDefinition/RegulatoryQuestionnaireResponse> ] )
] ; #
fhir:text [
fhir:status [ fhir:v "generated" ] ;
fhir:div [ fhir:v "<div xmlns=\"http://www.w3.org/1999/xhtml\">\n <h2>Response to Regulatory Questionnaire ID001</h2>\n <p><b>Procedure:</b> EMEA/H/C/005432/II/0023</p>\n <p><b>Product:</b> ExampleDrug 10 mg Tablets</p>\n <p><b>Submitted by:</b> SynthPharma AG</p>\n <p><b>Submitted to:</b> European Medicines Agency (EMA)</p>\n <p><b>Date:</b> November 15, 2025</p>\n <hr/>\n <p>This response addresses all administrative, labeling, and CMC stability questions for the Type II Variation.</p>\n </div>"^^rdf:XMLLiteral ]
] ; # Narrative
fhir:identifier ( [
fhir:system [
fhir:v "http://hl7.org/fhir/uv/brr/identifier/qa-request"^^xsd:anyURI ;
fhir:l <http://hl7.org/fhir/uv/brr/identifier/qa-request> ] ;
fhir:value [ fhir:v "ID001" ]
] [
fhir:system [
fhir:v "https://ema.europa.eu/procedure-number"^^xsd:anyURI ;
fhir:l <https://ema.europa.eu/procedure-number> ] ;
fhir:value [ fhir:v "EMEA/H/C/005432/II/0023" ]
] ) ; # Identifiers
fhir:questionnaire [
fhir:v "http://hl7.org/fhir/uv/brr/Questionnaire/brr-regulatory-qa-questionnaire"^^xsd:anyURI ;
fhir:l <http://hl7.org/fhir/uv/brr/Questionnaire/brr-regulatory-qa-questionnaire>
] ; # Reference to original Questionnaire
fhir:status [ fhir:v "completed"] ; #
fhir:subject [
fhir:l fhir:MedicinalProductDefinition/example-drug-10mg ;
fhir:reference [ fhir:v "MedicinalProductDefinition/example-drug-10mg" ] ;
fhir:display [ fhir:v "ExampleDrug 10 mg Tablets" ]
] ; #
fhir:authored [ fhir:v "2025-11-15T14:59:00-05:00"^^xsd:dateTime] ; #
fhir:item ( [
fhir:linkId [ fhir:v "admin-1" ] ;
fhir:text [ fhir:v "Is the fee for the Type II variation fully paid and documented?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "Yes, the fee was paid on June 25, 2025. Payment confirmation and receipt are included in the application form (see Section 1.1)." ] ] )
] [
fhir:linkId [ fhir:v "admin-2" ] ;
fhir:text [ fhir:v "Are all required metadata fields in the application form complete?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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" ] ] )
] [
fhir:linkId [ fhir:v "labeling-1" ] ;
fhir:text [ fhir:v "Do the updated storage conditions (2–8°C for 36 months) require additional patient guidance?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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." ] ] )
] [
fhir:linkId [ fhir:v "labeling-2" ] ;
fhir:text [ fhir:v "Is the patient leaflet revised to clarify the extended shelf life?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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." ] ] )
] [
fhir:linkId [ fhir:v "labeling-3" ] ;
fhir:text [ fhir:v "Is the updated ePI text sufficiently clear for all EU languages?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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)." ] ] )
] [
fhir:linkId [ fhir:v "cmc-1-DP-Stability" ] ;
fhir:text [ fhir:v "Are there any new stability studies conducted, or does the submission include only data from additional timepoints from previously submitted studies?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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)." ] ] )
] [
fhir:linkId [ fhir:v "cmc-2-DP-Stability" ] ;
fhir:text [ fhir:v "Does the data support all intended climatic zones?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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." ] ] )
] [
fhir:linkId [ fhir:v "cmc-3-DP-Analytical Methods" ] ;
fhir:text [ fhir:v "Are the test methods used the same as in the previously submitted stability information?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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." ] ] )
] [
fhir:linkId [ fhir:v "cmc-4-DP-Impurities" ] ;
fhir:text [ fhir:v "Are there any new degradation products identified within the newly submitted data?" ] ;
( fhir:answer [
fhir:value [
a fhir:String ;
fhir:v "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." ] ] )
] [
fhir:linkId [ fhir:v "cmc-5-DP-Container Closure System" ] ;
fhir:text [ fhir:v "Any changes in the packaging configuration and/or storage of the samples during stability?" ] ;
( fhir:answer [
( fhir:extension [
fhir:url [
fhir:v "http://hl7.org/fhir/uv/brr/StructureDefinition/questionnaire-itemRichText"^^xsd:anyURI ;
fhir:l <http://hl7.org/fhir/uv/brr/StructureDefinition/questionnaire-itemRichText> ] ;
fhir:value [ a fhir:Xhtml ] ] ) ;
fhir:value [
a fhir:String ;
fhir:v "Yes, packaging changed from PVC/PVDC to Alu/Alu. New stability studies initiated. See rich text for diagram and details." ] ] )
] ) . # ====================== ANSWERS (exact match with Questionnaire) ====================== , admin-1
IG © 2025+ HL7 International. Package hl7.fhir.uv.rtq-ig#0.1.0 based on FHIR 5.0.0. Generated 2025-11-15
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QA Report