提交藥品標籤及患者資訊傳單變更

1. 背景

英國法規依人類藥品法規2012第267條要求英國行銷授權及第126a條授權的行銷授權持有人（MAHs）通知主管機關所有與產品特性摘要（SmPC）變更無關的標籤及患者資訊傳單（PILs）變更。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 包裝及PILs資訊責任僅在MAH。MHRA依更好法規原則擴大此類變更通知方案，自2012年7月起為快速有效處理預設。第3節定義變更僅適用產品資訊品質單位（PIQU）全評估。本指南適用所有藥品包裝組件變更，除平行進口產品、傳統草藥註冊及順勢療法藥品。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

2. 提交一般指導

大多與SmPC變更無關的標籤及/或PILs變更受MAH自證後通知MHRA，第3節例外。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 這些變更無法正式評估，資料保障品質團隊（DAQ）不接受為全申請。通知為「告知並執行」，收訖後14日內接受，MHRA接受函後可引入變更。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 任何適用費用依相關法定文書定義。通知須附擬議最終包裝組件全彩模擬，合併藝術檔包括變更及未變更元素。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 接受依MAH支持文件聲明；MHRA透過隨機及針對抽樣審計，結果報告發布網站。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 需全PIQU申請或變更（依第3節）無法使用通知，須全申請。審計識別無效通知可撤銷，需進一步申請，若公衛風險存在潛在庫存移除。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

3. MHRA全評估申請

標籤及PILs全彩模擬首次批准通常於行銷授權授予（但文字版可能於行銷授權申請（MAA）早批准）。SmPC相關變更新藝術於變更申請評估。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 後續需全PIQU評估變更包括：

• P1：行銷授權授予後模擬首次批准，僅文字版於MAA提交及批准；上市前要求。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• P2：PILs變更有顯著內容、設計或布局變更，支持使用者測試資料、橋接資料（證明患者理解）或額外法定資訊資料；使用者測試或橋接需求全細節於傳單最佳實務指導。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• P3/P3EX：包裝設計及布局變更，包括布局、內容或圖形；總需申請。第三方預批准允許加速審查，有效申請後30日內評估。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• P4：MHRA通知徵求變更，需全申請；或若變更後果則透過變更處理（例如，新自有品牌供應商藝術、產品名稱變更、專家委員會後顯著新安全資訊，或患者安全投訴後修正）。變更申請可於PIQU處理。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

4. 如何提交正式評估申請

MAHs須於申請表格（Word: 標籤及患者資訊傳單變更申請；或入口表格Adobe PDF: [行銷授權變更]）註明提交為無SmPC修正包裝變更，指定類別P1、P2、P3及/或P4。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 求職信描述變更，包括支持資料細節。包裝組件參考變更；若正確參考允許多變更。申請可包括自證變更。非P1–P4變更被拒，須重新作為通知提交。提交須附擬議最終組件全彩模擬。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

5. 自證（通知）提交

MAHs須於通知表格（Word: 標籤及患者資訊傳單自證變更通知；或入口表格Adobe PDF作為一般產品許可資訊更新）註明通知修正無SmPC變更包裝，詳述精確變更並確認無其他變更引入。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets 包裝參考變更；若正確參考允許多變更。未通知變更或需正式申請（依第3節）使通知無效。通知須附全彩模擬。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

6. 模擬

模擬為平面藝術設計全彩副本，呈現復製外及即時包裝（包括必要切割及折疊）三維形式，清晰顯示標籤文字。通常為紙本，非必要銷售呈現材料。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

7. 時間表及程序

• 通知：收訖後14日內接受；接受函後可引入變更。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• P3/P3EX申請：若第三方預批准及有效，30日內加速審查。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• 審計：MHRA進行隨機/針對審計；報告發布。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• 一般：第3節外變更僅自證通知；第3節變更需全申請。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

8. 變更及自證

• 自證適用大多非SmPC變更（自2012年7月預設）；「告知並執行」程序。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• 變更若後果可納入藝術（例如，供應商變更、名稱變更、安全更新）。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• 無效自證（例如，包括第3節變更）導致撤銷及需重新申請。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

9. 費用

通知費用依相關法定文書定義；申請無特定費用詳述。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

10. 更新

更新2023年12月22日。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets

11. 相關指導

• 傳單最佳實務指導（P2使用者測試/橋接資料）。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• MHRA網站發布審計結果報告。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets
• 提交表格及入口連結。 https://www.gov.uk/government/publications/submitting-changes-to-labelling-and-patient-information-leaflets/submitting-changes-to-labelling-and-patient-information-leaflets