【正文】 R) ? Will have a very positive impact ?New resources developed ? Dissolution Database ? Individual Product Bioequivalence Information ?Encouraged the use of telephone in review process ? Increased the number of 1st cycle approvals ? Decreased the total number of review cycles ? Total time to approval did not increase in spite of increased workload ben This guidance contains an Inter link to a listing of drug products, each linked in turn to a corresponding bioequivalence remendation. Clicking on a product name in that list will bring up the bioequivalence remendations for that specific product. Remendations have been developed for several drugs that are not yet eligible for generic petition (., newly approved products) and some older products for which information has previously been provided. As additional remendations are developed, those will be posted on the Web site. When this guidance is finalized, the listing will be available through the Agency’s Web page. OFFICE OF GENERIC DRUGS TABLE OF BIOEQUIVALENCE RECOMMENDATIONS Active Ingredient Potency Dosage Form Route of Administration Date Finalized Almotriptan Malate mg Tablet Oral 5/16/2023 Alosetron 1 mg Tablet Oral 5/31/2023 Atazanavir 200 mg Capsule Oral 3/18/2023 Atomoxetine 60 mg Capsule Oral 6/13/2023 Cefditoren Pivoxil 200 mg Tablet Oral 3/18/2023 Dutasteride mg Capsule Oral 7/5/2023 Eplerenone 50 mg Tablet Oral 3/18/2023 Fosamprenavir Calcium 700 mg Tablet Oral 3/18/2023 Memantine 10 mg Tablet Oral 7/8/2023 Rosuvastatin 40 mg Tablet Oral 3/18/2023 Tadalafil 20 mg Tablet Oral 3/18/2023 Vardenafil HCl 20 mg Tablet Oral 4/11/2023 QbR: 從提出到完善 ? 1/2023 – 2/2023: Questionbased Review Drafted ? 3/2023 – 4/2023: Division Directors Discussion ? 5/2023 – 6/2023: Team Leaders Discussion ? 7/2023 – 8/2023: Reviewers Discussion ? 9/2023 – 1/2023: Model Pharmaceutical Development Report and Quality Overall Summary ? 2/2023 – 12/2023: Discussions with Stakeholders and Upper Management ? 1/2023 – 12/2023: Gradual Implementation ? 1/2023: Full Implementation QbR的內(nèi)涵 ?Questionbased Review is a general framework for a science and riskbased assessment of product quality ?Questionbased Review contains the important scientific and regulatory review questions to ? 關(guān) 鍵 制 備 工 藝 及其 質(zhì) 控 ? 產(chǎn) 品的工 藝 、處 方是否有 設(shè)計(jì) 缺陷 ? 強(qiáng)調(diào) QbD ANDAs Under QbR (Continued) ? Future Generic Applications ? generic sponsors submit generic applications based on the format of ICH CTD, preferably, electronically ? Module 1: Administrative Information ? Module 2: Quality Overall Summary and Clinical Summary ? Module 3: Quality –Pharmaceutical Development。在美國應(yīng)包括以下信息：①申請(qǐng)書 3674；②專利認(rèn)證信息；③原研藥信息，包括 NDA號(hào)、藥名和生產(chǎn)商；④仿制藥和原研藥的對(duì)比，包括使用條件、有效成分、非有效成分、給藥途徑、劑型和劑量；⑤環(huán)境影響分析；⑥藥品說明書（草稿）。它包括藥理作用分類，作用模式以及臨床適應(yīng)證。 FDA仿制藥部（ OGD）鼓勵(lì)申請(qǐng)人根據(jù) ICH對(duì)于人用藥物的注冊(cè)技術(shù)要求，即通用技術(shù)文件（ CTD）的格式，提交 ADNA。所以，仿制藥申請(qǐng)一般不包含模塊 4。對(duì)于 ADNA，生物等效性信息應(yīng)該在這個(gè)部分體現(xiàn)，包括：①生物等效性研究；②體外－體內(nèi)相關(guān)性研究；③生物分析方法開發(fā)。 OGD QBR The question based review (QBR) serves as a general framework for the CMC assessment of ANDAs that focuses on critical pharmaceutical attributes of product quality. With justification, deviations or alternate approaches to this framework can be utilize, as necessary, to ensure the adequacy of the assessment of product quality For ease of discussion, a simple dosage form is defined as a solution or an immediate release (IR) solid oral dosage form. QBR: Drug Substance ?Description and Characterization ? What are the nomenclature, molecular structure, molecular formula, and molecular weight? ? What are the pKa, aqueous solubility (as function of pH), partition coefficient, polymorphism, hygroscopicity, and melting points? ?Control of Drug Substance ? Appearance and Identification ? Are the specifications for appearance and identification appropriate? ? Assay ? Is the proposed drug substance assay limit acceptable? ? Is the analytical method validated and st