{
    "resourceType": "Questionnaire",
    "id": "questionnaire-ID001",
    "meta": {
        "versionId": "1",
        "lastUpdated": "2025-11-11T22:30:00Z",
        "profile": [
            "http://hl7.org/fhir/uv/rtq/StructureDefinition/rtq-questionnaire"
        ]
    },
    "identifier": [
        {
            "system": "http://hl7.org/fhir/uv/brr/identifier/qa-request",
            "value": "ID001",
            "type": {
                "coding": [
                    {
                        "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/rtq-identifier-type",
                        "code": "regulator-id",
                        "display": "Regulator-issued Identifier"
                    }
                ]
            }
        },
        {
            "system": "https://ema.europa.eu/procedure-number",
            "value": "EMEA/H/C/005432/II/0023",
            "type": {
                "coding": [
                    {
                        "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/rtq-identifier-type",
                        "code": "regulator-id",
                        "display": "Regulator-issued Identifier"
                    }
                ]
            }
        }
    ],
    "version": "1.1.5",
    "name": "BRRRegulatoryQAQuestionnaire",
    "title": "Question Set ID001",
    "status": "active",
    "subjectType": [
        "MedicinalProductDefinition"
    ],
    "date": "2025-11-11",
    "contact": [
        {
            "purpose": {
                "coding": [
                    {
                        "system": "http://hl7.org/fhir/uv/brr/CodeSystem/contact-purpose",
                        "code": "SENDER",
                        "display": "Sender (Health Authority)"
                    }
                ]
            },
            "organization": {
                "reference": "Organization/ema",
                "identifier": {
                    "system": "https://ema.europa.eu/organization-id",
                    "value": "EMA-ORG-001"
                },
                "display": "European Medicines Agency",
                "name": "European Medicines Agency",
                "address": {
                    "line": [
                        "Domenico Scarlattilaan 6"
                    ],
                    "city": "Amsterdam",
                    "postalCode": "1083 HS",
                    "country": "NL"
                },
                "contact": [
                    {
                        "telecom": [
                            {
                                "system": "email",
                                "value": "jane.doe@ema.europa.eu"
                            },
                            {
                                "system": "phone",
                                "value": "+31-88-781-6000"
                            }
                        ]
                    }
                ]
            }
        },
        {
            "purpose": {
                "coding": [
                    {
                        "system": "http://hl7.org/fhir/uv/brr/CodeSystem/contact-purpose",
                        "code": "RECIPIENT",
                        "display": "Recipient (Marketing Authorization Holder)"
                    }
                ]
            },
            "organization": {
                "reference": "Organization/synthpharma",
                "identifier": {
                    "system": "urn:oid:1.3.6.1.4.1.519.1",
                    "value": "DUNS-123456789"
                },
                "display": "SynthPharma AG",
                "name": "SynthPharma AG",
                "address": {
                    "line": [
                        "123 Synthetic Research Blvd"
                    ],
                    "city": "Basel",
                    "postalCode": "4000",
                    "country": "CH"
                },
                "contact": [
                    {
                        "telecom": [
                            {
                                "system": "email",
                                "value": "john.doe@synthpharma.example"
                            },
                            {
                                "system": "phone",
                                "value": "+41-61-123-4567"
                            }
                        ]
                    }
                ]
            }
        }
    ],
    "item": [
        {
            "linkId": "admin-1",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.0",
                    "display": "1.0 Administrative Information"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.1",
                    "display": "1.1 Application Form"
                }
            ],
            "type": "question",
            "text": "Is the fee for the Type II variation fully paid and documented?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Is the fee for the Type II variation fully paid and documented?</p><p style=\"font-size:0.9em; color:#555;\">See <a href=\"https://www.ema.europa.eu/en/documents/regulatory-procedural-guidance/fees-payable-european-medicines-agency_en.pdf\">EMA Fee Guidance</a> for payment confirmation requirements.</p></div>"
                }
            ]
        },
        {
            "linkId": "admin-2",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.0",
                    "display": "Administrative Information"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.1",
                    "display": "Application Form"
                }
            ],
            "type": "group",
            "text": "Are all required metadata fields in the application form complete?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Are all required metadata fields in the application form complete?</p><ul><li>Marketing Authorisation Holder</li><li>Product Name (INN)</li><li>Procedure Number</li><li>Submission Date</li></ul></div>"
                }
            ]
        },
        {
            "linkId": "product-1",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.3",
                    "display": "1.3 Product Information"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.3.1",
                    "display": "SmPC, Labelling and Package Leaflet"
                }
            ],
            "type": "question",
            "text": "Do the updated storage conditions (2–8°C for 36 months) require additional patient guidance?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Do the updated storage conditions (2–8°C for 36 months) require additional patient guidance?</p><p>Current ePI states: “Store in a refrigerator (2°C – 8°C). Do not freeze.”</p></div>"
                }
            ]
        },
        {
            "linkId": "product-2",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.3",
                    "display": "Product Information"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.3.1",
                    "display": "SmPC, Labelling and Package Leaflet"
                }
            ],
            "type": "question",
            "text": "Is the patient leaflet revised to clarify the extended shelf life?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Is the patient leaflet revised to clarify the extended shelf life?</p><p style=\"font-style:italic\">“Shelf life after first opening: 36 months when stored at 2–8°C”</p></div>"
                }
            ]
        },
        {
            "linkId": "product-3",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.3",
                    "display": "Product Information"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "1.3.1",
                    "display": "SmPC, Labelling and Package Leaflet"
                }
            ],
            "type": "question",
            "text": "Is the updated ePI text sufficiently clear for all EU languages?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Is the updated ePI text sufficiently clear for all EU languages?</p><table><tr><th>Language</th><th>Status</th></tr><tr><td>English</td><td>Approved</td></tr><tr><td>French</td><td>Under Review</td></tr><tr><td>German</td><td>Pending</td></tr></table></div>"
                }
            ]
        },
        {
            "linkId": "quality-1",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.8",
                    "display": "Stability"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.8.1",
                    "display": "Stability Summary and Conclusion"
                }
            ],
            "type": "question",
            "text": "Are there any new stability studies conducted, or does the submission include only data from additional timepoints from previously submitted studies?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Are there any new stability studies conducted, or does the submission include only data from additional timepoints from previously submitted studies?</p><ul><li>Include protocol deviations if any.</li><li>Reference: <a href=\"https://www.ich.org/page/ich-guidelines\">ICH Q1A(R2)</a></li></ul></div>"
                }
            ]
        },
        {
            "linkId": "quality-2",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.8",
                    "display": "Stability"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.8.1",
                    "display": "Stability Summary and Conclusion"
                }
            ],
            "type": "question",
            "text": "Does the data support all intended climatic zones?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Does the data support all intended climatic zones?</p><div class=\"rtq-note\"><b>Note:</b> Confirm coverage for Zone IVb (30°C/75% RH) per <a href=\"https://www.who.int/publications/i/item/9789240011922\">WHO TRS 1010</a></div></div>"
                }
            ]
        },
        {
            "linkId": "quality-3",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.5",
                    "display": "Control of Drug Product"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.5.2",
                    "display": "Analytical Procedures"
                }
            ],
            "type": "question",
            "text": "Are the test methods used the same as in the previously submitted stability information?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Are the test methods used the same as in the previously submitted stability information?</p><p style=\"color:#d32f2f\">If changed: justify and provide validation data.</p></div>"
                }
            ]
        },
        {
            "linkId": "quality-4",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.5",
                    "display": "Control of Drug Product"
                },
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.5.4",
                    "display": "Impurities"
                }
            ],
            "type": "question",
            "text": "Are there any new degradation products identified within the newly submitted data?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Are there any new degradation products identified within the newly submitted data?</p><p style=\"font-size:0.9em\">Threshold: <b>&gt;0.10%</b> per <a href=\"https://www.ich.org/page/quality-guidelines\">ICH Q3B(R2)</a></p></div>"
                }
            ]
        },
        {
            "linkId": "quality-5",
            "code": [
                {
                    "system": "http://hl7.org/fhir/uv/rtq/CodeSystem/ctd-categories-full",
                    "code": "3.2.P.7",
                    "display": "Container Closure System"
                }
            ],
            "type": "question",
            "text": "Any changes in the packaging configuration and/or storage of the samples during stability?",
            "extension": [
                {
                    "url": "http://hl7.org/fhir/StructureDefinition/rendering-xhtml",
                    "valueXhtml": "<div xmlns=\"http://www.w3.org/1999/xhtml\"><p>Any changes in the packaging configuration and/or storage of the samples during stability?</p><p style=\"font-size:0.9em;color:#555\"><b>Figure 1:</b> Cross-section of new Alu/Alu blister showing foil thickness and sealing layer.</p><table><tr><th>Original</th><th>New</th></tr><tr><td>PVC/PVDC Blister</td><td>Alu/Alu Blister</td></tr><tr><td>25°C/60% RH</td><td>Unchanged</td></tr></table></div>"
                }
            ]
        }
    ]
}