【導(dǎo)讀】告，其復(fù)印件要轉(zhuǎn)發(fā)一份呈交到HFD-300，作為規(guī)范行為建議的一部分。門，個(gè)案管理和指導(dǎo)部門。專門建立了一個(gè)e-mail賬戶接收警告信。該帳戶e-mail地址是CDERCGMPWL.本綱要闡述了評(píng)估CGMP遵守情況的方法指南。當(dāng)前FACTS程序提呈報(bào)告，包括整理OAI通知和撤銷該通知。的條款一致，并在工廠檢查報(bào)告內(nèi)有獨(dú)立的標(biāo)題進(jìn)行說(shuō)明。采用實(shí)用的單獨(dú)PAC，把這些檢查行動(dòng)以數(shù)據(jù)系統(tǒng)信息的方式進(jìn)行報(bào)告。要求檢查官以該修訂的需遵守條例為準(zhǔn)，進(jìn)行一切GMP檢查。確保這些產(chǎn)品達(dá)到法案501的要求。FDA制定了兩個(gè)基本策略：

　　

【正文】 systems because a determination must be made 美國(guó)食品藥品管理局 GMP 檢查程序 指導(dǎo)手冊(cè)綱 要 公布日期： 2/1/2020 由 FDA 2438(7/92)提供 18 on the overall pliance status of the firm after the corrective actions are taken. The firm is expected to address all of its operations in its corrective action plan after a previously violative inspection, not just the deficiencies noted in the FDA483. The Full Inspection Option should be used for a pliance inspection, especially if the Abbreviated Inspection Option was used during the violative inspection. 法規(guī)遵守檢查 用 于 在對(duì) 某公司 采取法定 行 動(dòng) 后，對(duì) 公司 相應(yīng) 的整改行動(dòng) 進(jìn)行評(píng)估或 確認(rèn) 。首先，法規(guī)遵守檢查 包含 的內(nèi)容必須與 經(jīng) 發(fā)現(xiàn) 存在 缺陷的領(lǐng) 域有關(guān) ， 并在整改行動(dòng)后進(jìn)行 。另外， 檢查時(shí) 要 以 體系 /系統(tǒng) 為單位 ,因?yàn)?整改 后 一定要對(duì)公司總的 CGMP狀 況 進(jìn)行判斷。 檢查時(shí)發(fā)現(xiàn)違規(guī)后， 被檢查的 公司要在 整改方案 中 的所有操作進(jìn)行 詳細(xì) 說(shuō)明，而不僅僅是 FDA483中注明的缺陷。法規(guī)遵守檢查 應(yīng)采用 全面檢查選項(xiàng)， 尤其 在 簡(jiǎn)化檢查中發(fā)現(xiàn)違反 GMP后更應(yīng)如此 。 Compliance Inspections include For Cause Inspections. For Cause Inspections are pliance inspections which are done to investigate a specific problem that has e to the attention of some level of the agency. The problems may be indicated in Field Alert Reports (FARs), industry plaints, recalls, indicators of defective products, etc. Coverage of these areas may be assigned under other pliance programs, however, expansion of the coverage to a GMP inspection is to be reported under this program. For Cause Inspections may be assigned under this program as the need arises. 法規(guī)遵守檢查包括 專項(xiàng)檢查 。專項(xiàng)檢查指 對(duì)已經(jīng)引起 FDA某種程度 注意的某個(gè)具體問題進(jìn)行調(diào)查的法規(guī)遵守檢查。這些問題在現(xiàn)場(chǎng)警告報(bào)告（ FARs）、行業(yè)投訴、召回、缺陷產(chǎn)品指示 等內(nèi)容中有 表述 。 其它法規(guī)遵守 程序 可能也會(huì)指定檢查這些領(lǐng)域， 但是，在這個(gè)程序中 ，如果要擴(kuò)大 為 一次 GMP檢 查 則需要提供 報(bào)告。在這個(gè)程序中 ，必要時(shí) 可能要進(jìn)行專項(xiàng)檢查。 3. State of Control/控制 狀態(tài) A drug firm is considered to be operating in a state of control when it employs conditions and practices that assure pliance with the intent of Sections 501(a)(2)(B) of the Act and portions of the CGMP regulations that pertain to their systems. A firm in a state of control produces finished drug products for which there is an adequate level of assurance of quality, strength, identity and purity. 如果一家公司 采用的條件和實(shí)踐活動(dòng)能夠保證符合法案第 501(a)(2)(B)部分的要求以及 GMP與其系統(tǒng) /體系有關(guān)的部分法規(guī)要求，則認(rèn)為該公司的運(yùn)作處于控制狀態(tài)。 處于控制狀態(tài)的公司可以保證 其生產(chǎn)的藥品在質(zhì)量、效力、均 一性和純度方面有足夠的水平 。 美國(guó)食品藥品管理局 GMP 檢查程序 指導(dǎo)手冊(cè)綱 要 公布日期： 2/1/2020 由 FDA 2438(7/92)提供 19 A firm is out of control if any one system is out of control. A system is out of control if the quality, identity, strength and purity of the products resulting from that/those system(s) cannot be adequately assured. Documented CGMP deficiencies provide the evidence for concluding that a system is not operating in a state of control. See Part V. Regulatory/Administrative Strategy for a discussion of pliance actions based on inspection findings demonstrating out of control systems/firm. 任何一個(gè)體系 /系統(tǒng)失控則表明該公司處于失控狀態(tài)。如果由于這個(gè) /這些體系 /系統(tǒng)的原因?qū)е庐a(chǎn)品的質(zhì)量、均一、有效 和純度 等性質(zhì) 不能充分保證，則認(rèn)為該體系 /系統(tǒng)失控。 已登記備案的 CGMP缺陷 文件 證明某個(gè)體系 /系統(tǒng) 運(yùn)行 失控 。參見第 V部分 法規(guī) /管理 策略 針對(duì)檢查發(fā)現(xiàn)體系 /系統(tǒng) /公司失控時(shí)對(duì)應(yīng)采取行動(dòng)的 討論 。 藥工藝 Drug Process A drug process is a related series of operations which result in the preparation of a drug or drug product. Major operations or steps in a drug process may include mixing, granulation, encapsulation, tableting, chemical synthesis, fermentation, aseptic filling, sterilization, packing, labeling, testing, etc. 制藥工藝 指制備 一種藥物或藥品的一系列相關(guān)操作。制藥工藝的主要 操作 或 步 驟可包 括混合、制粒、 膠囊填充 、壓片、化學(xué)合成、發(fā)酵、無(wú)菌灌裝、滅菌、包裝、貼 簽、檢驗(yàn)等。 5. Drug Manufacturing Inspection/藥品 生產(chǎn)檢查 A drug manufacturing inspection is a factory inspection in which evaluation of two or more systems, including the Quality System, is done to determine if manufacturing is occurring in a state of control. 藥品生產(chǎn)檢查是指對(duì)工廠 進(jìn)行的檢查， 包括 對(duì) 質(zhì)量體系在內(nèi)的兩個(gè) 或兩個(gè) 以上的體系 /系統(tǒng)進(jìn)行評(píng)估， 檢查的目的是為了判定藥品生產(chǎn)是否處于 受 控狀態(tài)。 B. Inspection Planning/檢查方案 The Field will conduct drug manufacturing inspections and maintain profiles or other monitoring systems which will ensure that each drug firm receives biennial inspectional coverage, as provided for in the strategy. 美國(guó)食品藥品管理局 GMP 檢查程序 指導(dǎo)手冊(cè)綱 要 公布日期： 2/1/2020 由 FDA 2438(7/92)提供 20 現(xiàn)場(chǎng) 進(jìn)行 藥品生產(chǎn)檢查 ，保留外形類別及其它監(jiān)控 系統(tǒng)，并按照 策略 中所述，確保對(duì)每家制藥公司 兩年 檢查 一次。 The District Office is responsible for determining the depth of coverage given to each drug firm. CGMP inspectional coverage shall be sufficient to assess the state of pliance for each firm. 區(qū) 域 辦公室 決定對(duì)每家制藥公司進(jìn)行檢查的深度。 制定的 CGMP檢查范圍應(yīng) 足以 評(píng)定每家公司 的 CGMP狀況。 The frequency and depth of inspection should be determined by the statutory obligation, the firm39。s pliance history, the technology employed, and the characteristics of the products. When a system is inspected, the inspection of that system may be considered applicable to all products which use it. 檢查的頻率和深度 根據(jù)法規(guī)規(guī)定的義務(wù) 、公司 的 CGMP歷史記 錄 、采用的技術(shù)以及產(chǎn)品特性而定。對(duì)一個(gè)體系 /系統(tǒng)進(jìn)行檢查時(shí)，要考慮到在其應(yīng)用于所有產(chǎn)品中的實(shí)際情況 。 Investigators should select an adequate number and type of products to acplish coverage of the system. Selection of products should be made so that coverage is representative of the firm’s overall abilities in manufacturing within CGMP requirements. 調(diào) 查員為了全面檢查該體系 /系統(tǒng)，應(yīng)選擇足夠數(shù)量和類型的產(chǎn)品。產(chǎn)品的選擇應(yīng)能代表公司在 CGMP要求下的總生產(chǎn)能力。 Review of NDA/ANDA files may assist in selecting significant drug processes for coverage in the various systems. Significant drug processes are those which utilize all the systems in the firm very broadly and/or which contain steps with unique or difficult manipulation in the performance of a step. Products posing special manufacturing features, ., low dose products, narrow therapeutic range drugs, bination drugs, modified release products, etc., and new products made under an approved drug application, should be considered first in selecting products for coverage. 可通過(guò)審核 NDA/ANDA文件 來(lái)幫助選擇重要的藥品 工藝 ，并涉及不同的體系 /系統(tǒng) 。重要的 藥品工藝是指充分 運(yùn)用公司所有體系 /系統(tǒng) 和 /或包括特殊步驟或某一步驟 操作 有難度 的工藝。 選擇產(chǎn)品時(shí)優(yōu)先考慮 含特殊生產(chǎn)特征的產(chǎn)品，如，低劑量產(chǎn)品、治療范圍較窄的藥品、復(fù)方抗菌藥、緩釋產(chǎn)品等， 以及