Refuse to Receive for Lack of Justification of Impurity Limits
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
August 2016
Generics
Refuse to Receive for Lack of Justification of Impurity Limits
Guidance for Industry
Additional copies are available from:
Office of Communications
Division of Drug Information, WO51, Room 2201
Center for Drug Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave., Silver Spring, MD 20993-0002
Phone: 301-796-3400; Fax: 301-847-8714
druginfo@https://www.doczj.com/doc/0b12878257.html,
https://www.doczj.com/doc/0b12878257.html,/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
August 2016
Generics
TABLE OF CONTENTS
I.INTRODUCTION (1)
II.BACKGROUND (2)
III.JUSTIFYING IMPURITY LIMITS IN DRUG SUBSTANCES AND PRODUCTS . 3
A.Refusal to Receive for Lack of Impurities Information (3)
B.Providing Justification for Impurity Limits (4)
ANDA Submissions – Refuse to Receive for Lack of Justification of
Impurity Limits
Guidance for Industry1
I. INTRODUCTION
This guidance is intended to assist applicants preparing to submit to the Food and Drug Administration (FDA) original abbreviated new drug applications (ANDAs) and prior approval supplements (PASs) to ANDAs for which the applicant is seeking approval of a new strength of the drug product.2 The guidance highlights deficiencies in relation to information about impurities that may cause FDA to refuse to receive (RTR) an ANDA.3,4 An RTR decision indicates that FDA determined that an ANDA is not sufficiently complete to permit a substantive review.5
Typical deficiencies leading to an RTR decision include: (1) failing to provide justification for proposed limits in drug substances and drug products for specified identified impurities that are above qualification thresholds; (2) failing to provide justification for proposed limits for specified unidentified impurities that are above identification thresholds; and (3) proposing limits for unspecified impurities (e.g., any unknown impurity) that are above identification thresholds.
This guidance is not meant to be a comprehensive list of deficiencies in relation to impurity information that may or will lead FDA to make an RTR determination. Rather, this guidance clarifies that a failure to provide justification for proposed impurity limits may lead FDA to RTR 1 This guidance has been prepared by the Office of Generic Drugs in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration.
2 For purposes of this guidance, the use of the term ANDA will mean ANDAs and new-strength PAS submissions.
3 This should not be confused with a refuse-to-approve determination.
4 The following types of products are currently excluded from this guidance: (1) biological/biotechnologicals; (2) peptides; (3) oligonucleotides; (4) radiopharmaceuticals; (5) fermentation products; (6) semisynthetic products derived from fermentation products; (7) herbal products; (8) crude products of animal or plant origin; and (9) enantiomeric impurities. For additional information on the applicability to ANDAs, see guidances for industry ANDAs: Impurities in Drug Substances; ANDAs: Impurities in Drug Products; See also, guidances for industry
Q3A(R) Impurities in New Drug Substances (Q3A(R)); and Q3B(R2) Impurities in New Drug Products (Q3B(R2)).
5 21 CFR 314.101(b)(1).
an ANDA. It also makes recommendations to ensure that applicants include appropriate justification for impurities in their ANDA submissions.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe FDA’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.6
II. BACKGROUND
Pursuant to the enactment of the Generic Drug User Fee Amendments of 2012 (GDUFA),7 the Office of Generic Drugs (OGD) is tasked with a number of activities, including the development of “enhanced refusal to receive standards for ANDAs and other related submissions by the end of year 1 of the program….”8 Enhanced RTR standards are important because the practice of submitting an ANDA that is not sufficiently complete to permit a substantive review, which then is “repaired” via several cycles of applicant resubmission and FDA response, is inherently inefficient and wasteful of resources.
FDA evaluates each submitted ANDA individually to determine whether it can be received for Agency review. FDA’s receipt of an ANDA means the Agency has made a threshold determination that the ANDA is sufficiently complete to permit a substantive review.9FDA’s regulations at 21 CFR 314.101 provide the regulatory authority by which FDA may in certain cases, and will in others, RTR an ANDA.10
Generally, FDA will not receive an ANDA for substantive review unless it contains the information required under Section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and in 21 CFR 314.101 and other regulations, for example:11
?21 CFR 314.50
?21 CFR 314.94
?21 CFR 320.21
6 At various points this guidance notes that when FDA sees a particular type of deficiency in an ANDA it will RTR the ANDA. It is important to understand that such statements do not impose legal obligations on applicants or on FDA, but are included for purposes of transparency. This means that FDA, in the normal course, will RTR an ANDA on the grounds described in this guidance. This guidance does not preclude the possibility that an ANDA applicant may be able to demonstrate, in particular circumstances, that the regulatory requirements for receiving an ANDA have been met even when, as described in this guidance, FDA would in the normal course find the application not sufficiently complete and RTR it.
7 Generic Drug User Fee Amendments of 2012 (GDUFA), Public Law 112-144, Title III.
8 See Generic Drug User Fee Act Program Performance Goals and Procedures (the Commitment Letter):
https://www.doczj.com/doc/0b12878257.html,/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM282505.pdf.
9 See 21 CFR 314.101(b)(1).
10 See 21 CFR 314.101(d) -(e).
11 In certain cases, other statutes or regulations may apply.
21 CFR 320.22
This guidance focuses on when FDA expects to RTR an ANDA because it lacks justification for proposed impurity limits.12
III. JUSTIFYING IMPURITY LIMITS IN DRUG SUBSTANCES AND PRODUCTS All ANDAs must contain a description of the composition, manufacture, and specifications of the drug substance and the drug product (see 21 CFR 314.94(a)(9) and 314.50(d)(1)). Applicants are required to submit a full description of the drug substance including, but not limited to: its method of synthesis (or isolation) and purification of the drug substance; the process controls used during manufacture and packaging; and the specifications necessary to ensure the identity, strength, quality, and purity of the drug substance (§314.50(d)(1)(i)). Applicants are also required to submit a list of all components used in the manufacture of the drug product13 (regardless of whether they appear in the drug product) and a statement of the specifications for each component and the specifications necessary to ensure the identity, strength, quality, purity, potency, and bioavailability of the drug product (§314.50(d)(1)(ii)(a)). To ensure purity, applicants should propose and justify appropriate limits on the impurities in their drug substances and drug product.
A. Refusal to Receive for Lack of Impurities Information
FDA may RTR an ANDA that is not sufficiently complete because it does not on its face contain information required under §314.94, which includes a demonstration of the purity of the drug substance and drug product and information on impurities and residues (§§314.101(d)(3), 314.94(a)(9) (requiring ANDA to contain the information required under § 314.50(d)(1)) (see also Final Rule on Abbreviated New Drug Applications, 57 FR 17950 at 17959 (Apr. 28, 1992)).14
Accordingly, FDA may RTR an ANDA for: (1) failing to provide justification for proposed limits in drug substances and drug products for specified identified impurities that are above qualification thresholds; (2) failing to provide justification for proposed limits for specified unidentified impurities that are above identification thresholds; and (3) proposing limits for
12 At the time of filing, FDA reviews the content of an ANDA to determine, among other things, whether the ANDA applicant has provided a complete justification for proposed impurity limits. FDA does not conduct a thorough review of the justification of the proposed impurity limits until after filing, during technical review of the ANDA. To help applicants ensure the appropriate purity of their drug substance (§314.50(d)(1)(i)) and drug product
(§314.50(d)(1)(ii)(a)), FDA has published the following guidances for industry: ANDAs: Impurities in Drug Substances; ANDAs: Impurities in Drug Products; and M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk .
13 Impurities that are monitored in the drug product are classified as degradation products. Process impurities from the drug substance synthesis are normally controlled during drug substance testing, and therefore are not generally included in drug product specifications, unless they are also degradation products.
14“As for possible impurities or residues in the ANDA product, ANDA applicants would be required to provide information on the drug substance and the drug product as part of the chemistry, manufacturing, and controls section of t he application. This would include information on impurities and residues.” 57 FR 17950 at 17959.
unspecified impurities (e.g., any unknown impurity) above identification thresholds. FDA expects applicants to develop and use appropriate analytical methods to detect all observed impurities. Applicants are encouraged to review the draft guidance for industry ANDA Submissions – Content and Format of Abbreviated New Drug Applications for more information on the characterization of impurities for drug substances and drug products.
B. Providing Justification for Impurity Limits
As stated in Section II, to help applicants ensure the appropriate purity of their drug substance (§314.50(d)(1)(i)) and drug product (§314.50(d)(1)(ii)(a)), FDA has published two guidances for industry: ANDAs: Impurities in Drug Substances and ANDAs: Impurities in Drug Products. These guidances provide recommendations on what CMC information applicants should include regarding the reporting, identification, and qualification of impurities in drug substances and impurities that are classified as degradation products in drug products. These guidances provide recommendations for justifying appropriate impurity limits15 in a drug substance or drug product.16
If a generic product contains specified identified impurities that exceed the qualification thresholds17 or specified unidentified impurities18 that exceed identification thresholds,19,20,21 the ANDA should propose impurity limits and include supporting data to demonstrate that:
15The terms “impurity limit” as used in this guidance and “acceptance criterion” as used in the FDA guidances referenced above in this paragraph and in note 4 are synonymous.
16 The referenced guidances apply to drug substances and drug products, generally. However, if FDA has issued a product-specific guidance, the most stringent impurity identification or qualification threshold would apply. For example, the guidance for industry Nasal Spray and Inhalation Solution Suspension, and Spray Drug Products –Chemistry, Manufacturing, and Controls Documentation states that unspecified impurities (degradation products) at levels of 0.1% or greater should be specified. Therefore, for these specific products, the limits for unspecified impurities (degradation products) should not exceed 0.1%.
17 See guidances for industry Q3A(R) and Q3B(R2). Identification and qualification thresholds should be based on the maximum daily dose (MDD) of the drug and total daily intake of impurities, which refers to the publicly available drug product dosage labeling. These thresholds should be reported as a percentage, and percentages should be based on lowest total daily intake (TDI) of impurities per ICH guidance tables for all impurities.
18 See supra, note 16. When specified unidentified impurities are listed in the specification, FDA recommends that applicants describe the identification efforts attempted and clearly identify the procedure used and assumptions made in establishing the level of the impurity. It is important that specified unidentified impurities are referred to by an appropriate qualitative analytical descriptive label (e.g., unidentified A, unidentified with relative retention of 0.9).
19 See supra, note 16. In some cases, it may be appropriate to decrease the threshold for qualifying impurities. For example, if there is evidence that an impurity in certain drug classes or therapeutic classes has previously been associated with adverse reactions in patients, it may be important to establish a lower qualification threshold. When such circumstances arise, and when these circumstances have not already been contemplated in a product-specific guidance, these changes will not be evaluated during the filing review but will be addressed during the technical review of the ANDA.
20 See guidances for industry Q3A(R) and Q3B(R2)for definitions of an identified impurity, identification threshold, qualification, and qualification threshold.
21 Acceptance criteria for unspecified impurities should not exceed the identification threshold in the guidances for industry Q3A(R) and Q3B(R2), even in the case when higher acceptance criteria for unspecified (other) impurities are listed in the U.S. Pharmacopeia (USP) monograph. If the acceptance criteria for unspecified (other) impurities
(1)the observed impurity levels and proposed impurity limits do not exceed the level
observed in the reference listed drug (RLD) product;22
(2)the impurity is a significant metabolite of the drug substance;23
(3)the observed impurity levels and proposed impurity limits are adequately justified by
the scientific literature;24
or
(4)the observed impurity levels and proposed impurity limits do not exceed the level that
has been adequately evaluated in toxicity studies.25
FDA will RTR an ANDA under §314.101(d)(3) if the ANDA lacks supporting data or information to justify the proposed limits for specified identified and/or specified unidentified impurities that exceed qualification thresholds and/or identification thresholds, respectively, as described above. Also, FDA will RTR an ANDA under §314.101(d)(3) with proposed limits for unspecified impurities that exceed identification thresholds.
in the USP monograph are lower than the identification threshold in Q3A(R) and Q3B(R2), the acceptance criteria for unspecified impurities should be set to the USP level.
22 In the event that the RLD is no longer marketed, thereby preventing the ANDA applicant from obtaining samples to conduct a comparative analysis, an applicant is required to provide a justification of the proposed impurity limits based on other criteria delineated in this guidance (e.g., metabolite, scientific literature, or toxicity studies) in order for that ANDA to be received. An applicant that wishes to use an alternative approach is encouraged to submit a controlled correspondence to determine the acceptability of the approach prior to ANDA submission.
23 The guidances for industry ANDAs: Impurities in Drug Substances and ANDAs: Impurities in Drug Products state that a significant metabolite of the drug substance is considered qualified. However, if the level of the significant metabolite impurity is too high, other quality attributes, such as potency, could be significantly affected. In this case, FDA recommends that the acceptance criterion be set lower than the qualified level.
24 If the applicant relies on published literature, complete and legible copies of each publication should be included in the ANDA submission.
25The toxicity assessment should also include an evaluation of potentially genotoxic impurities (PGI) that may include in silico, in vitro and/or in vivo analyses.
德信诚培训网 更多免费资料下载请进：https://www.doczj.com/doc/0b12878257.html, 好好学习社区 Document Control Procedure 文件管理程序 1.0 Purpose 目的 Define the requirements and responsibilities for Document control. 定义出文件控制的要求和权责。 2.0 Scope 范围 This procedure applies to all QMS documentation, including: quality manual, procedure, WI, external document and form. 适用于与质量管理体系有关的所有文件。包括:手册、程序文件、操作指导书、外来文件及表单。 3.0 Definitions 定义 3.1 Quality Manual: According to the requirements of International and national standard (such as ISO9001), describe quality management system documentation in Co-active. 3.1质量手册：根据相关国际或国家标准(如ISO9001)要求，阐述本公司质量管理体系的文件。 3.2 Procedure: Define the function of QMS requirement allocation by department. Such as document control, management review, internal audit procedure. 3.2程序文件：描述为实施质量管理体系要求所涉及的各职能部门的活动的文件。如文件控制程序、 管理评审控制程序、内部审核控制程序。 3.3 Working Instruction: Operation procedures, inspection standards, design drawing and etc. 3.3操作指导书：操作规程、检验标准、加工图纸等。 3.4 Form: Records of operation results. 3.4表单：用于记录作业结果所用的文件。 4.0 Procedure 程序 4.1 Responsible for the formulation of documents to file the proper approval, and timely send the electronic document and the paper version to DCC, ensure that the relevant departments to understand the change. Once the document released, the relevant departments must follow procedures. When the file changes do not affect the contents of the file (such as correcting typos,
一、File<文件> 1.New<新建> 2.Open<打开> 3.Open As<打开为> 4.Open Recent<最近打开文件> 5.Close<关闭> 6.Save<存储> 7.Save As<存储为> 8.Save for Web<存储为Web所用格式> 9.Revert<恢复> 10.Place<置入> 11.Import<输入> <1>PDF Image <2>Annotations<注释> 页脚内容1
12.Export<输出> 13.Manage Workflow<管理工作流程> <1>Check In<登记> <2>Undo Check Out<还原注销> <3>Upload To Server<上载到服务器> <4>Add To Workflow<添加到工作流程> <5>Open From Workflow<从工作流程打开> 14.Automate<自动> <1>Batch<批处理> <2>Create Droplet<创建快捷批处理> <3>Conditional Mode Change<条件模式更改> <4>Contact Sheet<联系表> <5>Fix Image<限制图像> <6>Multi <多页面pdf到psd> <7>Picture package<图片包> 页脚内容2
<8>Web Photo Gallery 15.File Info<文件简介> 16.Print Options<打印选项> 17.Page Setup<页面设置> 18.Print<打印> 19.Jump to<跳转到> 20.Exit<退出> 二、Edit<编辑> 1.Undo<还原> 2.Step Forward<向前> 3.Step Backward<返回> 4.Fade<消退> 5.Cut<剪切> 6.Copy<拷贝> 页脚内容3
一、File 文件 1.New 新建 2.Open 打开 3.Open As 打开为 4.Open Recent 最近打开文件 5.Close 关闭 6.Save 存储 7.Save As 存储为 8.Save for Web存储为Web所用格式 9.Revert 恢复 10.Place 置入 11.Import 输入 1 PDF Image PDF图象导入 2 Annotations 注释 12.Export 输出 13.Manage Workflow 管理工作流程 1 Check In 登记 2 Undo Check Out 还原注销 3 Upload To Server 上载到服务器 4 Add To Workflow 添加到工作流程 5 Open From Workflow 从工作流程打开 14.Automate 自动 1 Batch 批处理 2 Create Droplet 创建快捷批处理 3 Conditional Mode Change 条件模式更改 4 Contact Sheet 联系表 5 Fix Image 限制图像 6 Multi Page PDF to PSD 多页面PDF文件到PSD文件 7 Picture package 图片包 8 Web Photo GalleryWeb照片画廊 15.File Info 文件简介 16.Print Options 打印选项 17.Page Setup 页面设置 18.Print 打印 19.Jump to 跳转到 20.Exit 退出 二、Edit 编辑 1.Undo 还原 2.Step Forward 向前 3.Step Backward 返回 4.Fade 消退 5.Cut 剪切 6.Copy 拷贝 7.Copy Merged 合并拷贝 8.Paste 粘贴 9.Paste Into 粘贴入 10.Clear 清除 11.Fill 填充 12.Stroke 描边 13.Free Transform 自由变形 14.Transform 变换 1 Again 再次 2 Sacle 缩放 3 Rotate 旋转 4 Skew 斜切 5 Distort 扭曲 6 Prespective 透视 7 Rotate 180°旋转180度 8 Rotate 90°CW 顺时针旋转90 9 Rotate 90°CCW 逆时旋转90 10 Flip Hpeizontal 水平翻转 11 Flip Vertical 垂直翻转 15.Define Brush 定义画笔 16.Define Pattern 设置图案 17.Define Custom Shape 定义自定形 状 18.Purge 清除内存数据 1 Undo 还原 2 Clipboard 剪贴板 3 Histories 历史纪录 4 All 全部 19.Color Settings 颜色设置 20.Preset Manager 预置管理器 21.Preferences 预设 1 General 常规 2 Saving Files 存储文件 3 Display ＆Cursors 显示与光标 4 Transparency ＆Gamut 透明区 域与色域 5 Units ＆Rulers 单位与标尺 6 Guides ＆Grid 参考线与网格 7 Plug Ins ＆Scratch Disks 增效工 具与暂存盘 8 Memory ＆Image Cache 内存和 图像高速缓存 9 Adobe Online Adobe在线 10 Workflows Options 工作流程选 项 三、Image 图像 1.Mode 模式 1 Bitmap 位图 2 Grayscale 灰度 3 Duotone 双色调 4 Indexed Color 索引色 5 RGB Color RGB色 6 CMYK Color CMYK色 7 Lab Color Lab色 8 Multichannel 多通道 9 8 Bits/Channel 8位通道 10 16 Bits/Channel 16位通道 11 Color Table 颜色表 12 AssingProfile 制定配置文件 13 Convert to Profile 转换为配置文 件 2.Adjust 调整 1 Levels 色阶 2 Auto Laves 自动色阶 3 Auto Contrast 自动对比度 4 Curves 曲线 5 Color Balance 色彩平衡 6 Brightness/Contrast亮度/对比度 7 Hue/Saturation 色相/饱和度 8 Desaturate 去色 9 Replace Color 替换颜色 10 Selective Color 可选颜色 11 Channel Mixer 通道混合器 12 Gradient Map 渐变映射 13 Invert 反相 14 Equalize 色彩均化 15 Threshold 阈值 16 Posterize 色调分离 17 Variations 变化
CONFIDENT IAL IT Y PROCEDURE 10 DECEMBER 2010
SYNOPSIS
CONTENTS CONTENTS (3) 1.PURPOSE 目的 (4) 2.RESPONSIBILITYS 职责 (5) 3.CONFIDENTIAL INFORMATION SCOPE (6) 4.STORAGE，COPY, DISTRIBUTION, BORROW AND DISPOSAL (7) 4.1Storage and Copy (7) 4.2Distribution (7) 4.3Disposal (8) APPENDIX 1– CONFIDENTIAL DOCUMENT DISTRIBUTION REGISTER APPENDIX 2– CONFIDENTIAL DOCUMENT CHECKLIST
1. PURPOSE 目的 This procedure provides the necessary requirements and guidelines for controlling confidential documents to assure XX COMPANY personnel are aware of storage, copy, distribution, and disposal confidential documentation. 本程序旨在提供了一些必要的要求和准则，用于控制保密级别的文件以确保XX公司员工明确保密文件的存储，复印，发布和销毁的程序。
2. RESPONSIB IL IT YS职责 XX Manager is responsible for the implementation of this procedure in order to protect the company and client intellectual property information. 为了更好的对公司和业主的知识产权进行保护XX经理负责实施本程序。 Document Control has the administrative responsibility for implementing the procedure from the electronic file, hard copy distribution, and record keeping standpoint. 文档控制工程师根据本程序的要求负责管理电子档文件，硬拷贝文件的发布，以及记录和追踪。 XX company member should be required to comply Confidentiality Procedure. XX公司所有员工要求遵守本程序。
1.Sales Agreement The agreement, (is) made in Beijing this eighth day of August 1993 by ABC Trading Co., Ltd., a Chinese Corporation having its registered office at Beijing, the People’ Repubic of China (hereinafter called “Seller”) and International Tradi ng Co., Ltd., a New York Corporation having its registered office at New York, N.Y., U.S.A. (hereinafter called “Buyer”). 2.WITNESSETH WHEREAS, Seller is engaged in dealing of (product) and desires to sell (product)to Buyer, and WHEREAS, Buyer desires to purchase(product) from Sellers, Now, THEREFORE, it is agreed as follows: 3.Export Contract This Contract is entered into this 5th day of August 1993 between ABC and Trading Co., Ltd. (hereinafter called “Seller”) who agrees to sell, and XYZ Trading Co., Ltd. (hereinafter called “Buyer”) who agrees to buy the following goods on the following terms and condition. 4.Non-Governmental Trading Agreement No. ＿＿This Agreement was made on the＿day of＿19＿, BETWEEN ＿ (hereinafter referred to as the Seller) as the one Side and ＿ (hereinafter referred to as the Buyer) as the one other Side. WHEREAS, the Seller has agreed to sell and the buyer has agreed to buy ＿ (hereinafter referred to as the Goods ) the quantity, specification, and price of which are provided in Schedule A. IT IS HEREBY AGREED AS FOLLOWS: 5.Contract For Joint-Operation Enterprise ＿＿ COMPANY LTD., a company duly organized under the Law of ＿＿ and having its registered office at (hereinafter called “Party A”) AND ＿＿ COMPANY LTD., a company duly organized under the Law of ＿＿ and having its registered office at (hereinafter called “Party B”) Party A and Party B (hereinafter referred to as the “Parties”) agree to jointly form a Co-operation Venture Company (hereinafter referred to as the “CVC”) in accordance with “the Laws of the People’s Republic of China on Joint Ventures Using Chinese and Foreign Investment” and the “Regulations for the Implementation of the Laws of the People’s Republic of China on Joint Ventures Using Chinese and Foreign Investment” and other applicable laws and regulations. 6.MODEL CONTRACT Contract No. Date: Seller: Signed at: Address: Cable Address: Buyer: Address: Cable Address: The Seller and the Buyer have agreed to conclude the following transactions according to the terms and conditions stipulated below: https://www.doczj.com/doc/0b12878257.html, of Commodity: 2.Specifications: 3.Quantity: 4.Unit Price: 5.Total Price: U.S.$: 6.Packing: 7.Time of Shipment: days after receipt of L/C. 8.Loading Port & Destination Port: From via to . 9.Insurance:
5S : 5S 管理 ABC : 作业制成本制度(Activity-Based Costing) ABB : 实施作业制预算制度(Activity-Based Budgeting) ABM : 作业制成本管理(Activity-Base Management) APS : 先进规画与排程系统(Advanced Planning and Scheduling) ASP : 应用程序服务供货商（Application Service Provider） ATP : 可承诺量(Available To Promise) A VL : 认可的供货商清单(Approved Vendor List) BOM : 物料清单(Bill Of Material) BPR : 企业流程再造(Business Process Reengineering) BSC : 平衡记分卡(Balanced ScoreCard) BTF : 计划生产(Build To Forecast) BTO : 订单生产(Build To Order) CPM : 要径法(Critical Path Method) CPM : 每一百万个使用者会有几次抱怨(Complaint per Million) CRM : 客户关系管理(Customer Relationship Management) CRP : 产能需求规划(Capacity Requirements Planning) CTO : 客制化生产(Configuration To Order) DBR : 限制驱导式排程法(Drum-Buffer-Rope) DMT : 成熟度验证(Design Maturing Testing) DVT : 设计验证(Design Verification Testing) DRP : 运销资源计划(Distribution Resource Planning) DSS : 决策支持系统(Decision Support System) 返回顶部 EC : 设计变更／工程变更(Engineer Change) EC : 电子商务(Electronic Commerce) ECRN: 原件规格更改通知(Engineer Change Request Notice) EDI : 电子资料交换(Electronic Data Interchange) EIS : 主管决策系统(Executive Information System) EMC : 电磁兼容(Electric Magnetic Capability) EOQ : 基本经济订购量(Economic Order Quantity) ERP : 企业资源规划(Enterprise Resource Planning) FAE : 应用工程师(Field Application Engineer) FCST: 预估(Forecast) FMS : 弹性制造系统(Flexible Manufacture System) FQC : 成品品质管制(Finish or Final Quality Control) IPQC: 制程品质管制(In-Process Quality Control) IQC : 进料品质管制(Incoming Quality Control) ISO : 国际标准组织(International Organization for Standardization) ISAR: 首批样品认可(Initial Sample Approval Request) JIT : 实时管理(Just In Time) KM : 知识管理(Knowledge Management) 返回顶部 L4L : 逐批订购法(Lot-for-Lot)
中英文对照的文件格式要求 1文件表头 文件表头表格及内部文字均居中，中文文件名称为宋体四号加黑，段落行距为固定值20磅，其余文字采用宋体小四，段落行距为固定值15磅，表格指定高度为0.8厘米，文件表头英文字体为Times New Roman小五。 2 固定格式的页眉，首页不同，从第二页开始，格式如下： 内容需填文件名、文件编号及版本号，中文字体采用宋体五号，英文字体采用Times New Roman小五号，表格指定高度为0.8厘米，段落行距为单倍行距。 3 固定格式的页脚，内容如下： HUALAN BIOLOGICAL BACTERIN CO., LTD.Page n of n 左侧为公司的英文名字及标志，右侧为文件页码，字号为小五。页码字体为Times New Roman字体。 4正文 4.1基本要求
正文字体：中文用宋体，英文用Times New Roman。 正文字号：中英文均为小四号。 正文间距：中文1.5倍行间距，段前间距0行，段后间距0行。英文单倍行间距，段前间距0行，段后间距0.5行。 正文缩进：两端对齐。中文左右缩进均为0字符，首行缩进2字符；英文字体左缩进2.24字符。 版本历史中，变更原因无下划线。 单位为ml时，m小写，l小写，需规范：遇到数字和单位组合时，数字和单位之间应空一格，如20μg/ml 4.2 标题 标题的字体要求同4.1所述。 ◆一级标题 小四号，加粗，两端对齐，左右缩进均为0字符，悬挂缩进2字符，段前间距1行，段后间距0.5行，行距1.5倍。形式为：阿拉伯数字序号+1个空格+中文标题+1个空格+英文标题，例如：1 目的Purpose ◆二级标题 小四号，不加粗，两端对齐，左右缩进均为0字符，悬挂缩进2字符，段前间距0.5行，段后间距0行，行距1.5倍。形式为：阿拉伯数字序号+1个空格+中文标题+1个空格+英文标题，例如：4.1 检定要求Test specifications ◆三级标题 小四号，不加粗，两端对齐，左右缩进均为0字符，悬挂缩进2字符，段前间距0行，段后间距0行，行距1.5倍。形式为：阿拉伯数字序号+1个空格+中文标题+1（2）个空格+英文标题，例如：4.1.1 鉴别试验Identity Test ◆四级标题 格式按正文处理。 4.3 各标题样式 1 目的Objective 2范围Scope 3定义Definitions
Revision History
1.0 SCOPE范围 1.1 This work instruction is applicable to Quality Management System (QMS) documents such as System Manual, Procedures, and Working Instructions of SUNMING. 本作业指导书适用于SUNMING的质量管理体系（QMS）文件如体系手册，程序文件和作业 指导书。 1.2 This work instruction also covers numbering of Document Change Notice (DCN) / Temporary Document Change Notice (TDCN) and Engineering Change Notice (ECN) / Temporary Engineering Change Notice (TECN). 本作业指导书也包括对文件变更通知（DCN ）/临时文件变更通知（TDCN ）和工程变更通 知（ECN）/临时工程变更通知（TECN）进行编号。 2.0 ASSOCIATED DOCUMENTS相关文件 2.1 DC20001 : Document Control Procedure 文件管控程序 2.2 DC30002 : Work Instruction for Document Change Notice (DCN) Generation 文件变更通知（DCN）生成作业指导书 2.3 DC30003 : Work Instruction for Engineering Change Notice (ECN) Generation 工程变更通知（ECN）生成作业指导书 2.4 DC30004 : Work Instruction for Releasing Documents to Suppliers 发布文档给供应商之工作指引 2.5 DC30005 : Work Instruction for Retention of Quality Documents and Records 品质文件/记录保存作业指导书 3.0 SAFETY REQUIREMENTS安全要求 3.1 Not applicable.不适用 4.0 GENERAL REQUIREMENTS一般要求 4.1 Document Control Center (DCC) is responsible for the assignment and control of document numbers. 文控中心（DCC）负责分配和控制文件编号。
常用的一些招投标英语词汇 估算/费用估算：estimate/cost estimate; 估算类型：types of estimate; 详细估算：是偏差幅度最小的估算，defined estimate; 设备估算：equipment estimate; 分析估算：analysis estimate; 报价估算:proposal estimate; 控制估算：control estimate; 初期控制估算：interim control estimate/initial control estimate 批准的控制估算：initial approved cost 核定估算：check estimate 首次核定估算：first check estimate 二次核定估算：production check estimate 人工时估算：man hour estimate 材料费用/直接材料费用：material cost/direct material cost 设备费用/设备购买费用：equipment cost/purchased cost of equipment 散装材料费用/散装材料购买费用：bulk material cost/purchased cost of bulk material 施工费用：construction cost 施工人工费用：labor cost/construction force cost 设备安装人工费用：labor cost associated with equipment 散装材料施工安装人工费用：labor cost associated with bulk materials 人工时估算定额：standard manhours 施工人工时估算定额：standard labor manhours 标准工时定额：standard hours 劳动生产率：labor productivity/productivity factor/productivity ratio 修正的人工时估算值：adjusted manhours 人工时单价：manhours rate 施工监督费用：cost of construction supervision 施工间接费用：cost of contruction indirects 分包合同费用/现场施工分包合同费用：subcontract cost/field subcontract cost 公司本部费用：home office cost 公司管理费用：overhead 非工资费用：non payroll 开车服务费用：cost of start-up services 其他费用：other cost 利润/预期利润：profit/expected profit 服务酬金：service gains 风险：risk 风险分析：risk analysis 风险备忘录：risk memorandum 未可预见费：contingency 基本未可预见费：average contingency
安卓系统文件中英文对照 安卓系统文件中英文对照，给你的手机减减肥吧。。。来源：石小田的日志模拟安卓机身内存里的\system\app，app文件夹里就是装系统自带的文件。将那些不要的，也用不到的删了。速度提升很明显的 【文件夹功能简介】 \system\app 这个里面主要存放的是常规下载的应用程序，可以看到都是以APK格式结尾的文件。在这个文件夹下的程序为系统默认的组件，自己安装的软件将不会出现在这里，而是\data\文件夹中。 \system\bin 这个目录下的文件都是系统的本地程序，从bin文件夹名称可以看出是binary二进制的程序，里面主要是Linux系统自带的组件(命令) \system\etc 从文件夹名称来看保存的都是系统的配置文件，比如APN接入点设置等核心配置。 \system\fonts 字体文件夹，除了标准字体和粗体、斜体外可以看到文件体积最大的可能是中文字库，或一些unicode字库，从T-Mobile G1上可以清楚的看到显示简体中文正常，其中DroidSansFallback.ttf文件大小。 \system\framework framework主要是一些核心的文件，从后缀名为jar可以看出是是系统平台框架。
\system\lib lib目录中存放的主要是系统底层库，一些so文件，如平台运行时库。 \system\media \system\media\audio 铃声音乐文件夹，除了常规的铃声外还有一些系统提示事件音。 \system\sounds 默认的音乐测试文件，仅有一个test.mid文件，用于播放测试的文件。 \system\usr 用户文件夹，包含共享、键盘布局、时间区域文件等。 ---------------------------------------------------------------------------------------------------------------------------------下面是app文件夹里面的程序的中英文对照表：注：带*号的千万不能删 *AccountAndSyncSettings.apk 同步与帐户设定 *ApplicationsProvider.apk 应用程序支持服务 Bluetooth.apk 蓝牙（删了就没有蓝牙了） Browser.apk 谷歌浏览器（喜欢UC的可用UC替代） Calculator.apk 计算器（自带计算器较弱，可用其他替代） Calendar.apk 日历（不用日历的可删） CalendarProvider.apk 日历程序支持服务（不用日历的可删） Camera.apk 自带相机（用360的可删） *CertInstaller.apk 证书服务
、Filev 文件> 1. New噺建> 2.Openv打开> 3.OpenAsv打开为> 4.OpenRecentv最近打开文件> 5.Closev 关闭> 6.Savev存储> 7.SaveAsv存储为> 8.SaveforWebv存储为Web所用格式＞ 9. Revertv 恢复> 10. Placev 置入> 11. Importv 输入> v1> PDFImage v2>Annotationsv 注释> 12.Exportv 输出> 13.ManageWorkflowv管理工作流程> v1>CheckInv 登记> v2>UndoCheckOut
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、Editv 编辑> 1. Undoes原> 2.StepForwardv 向前> 3.StepBackwardv 返回> 4.Fadev消退> 5.Cutv 剪 切>6.Copyv拷贝> 7.CopyMergedv合并拷贝> 8. Pastev 粘贴> 9. Pastelntov 粘贴入> lO.CIearv 清 除>11.FiIIv 填充> 12. Strokev 描边> 13. FreeTransformv 自由变形> 14. Transformv 变换> v1>Againv 再次> v2>SacIev 缩放> v3>Rotatev 旋转> v4>Skew^切> v5>Distortv 扭曲> v6>Prespectivev 透视> v7>Rotate180v。旋转180 度>v8>Rotate90C ° W顺时针旋转90度> v9>Rotate90C °CW逆时针旋转90度＞ v10>FlipHpeizontaiv 水平翻转> v11>FIipVerticaIv 垂直翻转> 15. DefineBrushv 定义画笔> 16. DefinePatternv 设置图案> 17. DefineCustomShapev 定义自定形状> 18. Purgev清除内存数据＞ v1>Undov还原> v2>Clipboardv 剪贴板> v3>Histonesv 历史纪 录> v4>AIIv 全部> 19. CoIorSettingsv 颜色设置> 20. PresetManagerv 预置管理器> 21.Preferencesv 预设>
《泰戈尔诗集》经典语录中英文对照版
精品文档 《泰戈尔诗集》经典语录中英文对照版 1.如果你因失去了太阳而流泪，那么你也失去了群星。 If you shed tears when you miss the sun, you also miss the stars. 2.我的心是旷野的鸟，在你的眼睛里找到了它的天空。 My heart, the bird of the wilderness, has found its sky in your eyes. 3.它是大地的泪点，使她的微笑保持着青春不谢。 It is the tears of the earth that keep her smiles in bloom. 4.你看不见你自己，你所看见的只是你的影子。 What you are you do not see, what you see is your shadow. 5.瀑布歌唱道："当我找到了自己的自由时,我找到了我的歌。" The waterfall sing, "I find my song, when I find my freedom." 6.你微微地笑着，不同我说什么话。而我觉得，为了这个，我已等待得久了。 You smiled and talked to me of nothing and I felt that for this I had been waiting long. 7.人不能在他的历史中表现出他自己，他在历史中奋斗着露出头角。 Man does not reveal himself in his history, he struggles up through it. 8.我们如海鸥之与波涛相遇似地，遇见了，走近了。海鸥飞去，波涛滚滚地流开，我们也分别了。 Like the meeting of the seagulls and the waves we meet and come near.The seagulls fly off, the waves roll away and we depart. 9.当我们是大为谦卑的时候，便是我们最接近伟大的时候。 We come nearest to the great when we are great in humility. 10.决不要害怕刹那－－永恒之声这样唱着。 Never be afraid of the moments--thus sings the voice of the everlasting. 11."完全"为了对"不全"的爱，把自己装饰得美丽。 The perfect decks itself in beauty for the love of the Imperfect. 12.错误经不起失败，但是真理却不怕失败。 Wrong cannot afford defeat but right can. 13.这寡独的黄昏，幕着雾与雨，我在我的心的孤寂里，感觉到它的叹息。 In my solitude of heart I feel the sigh of this widowed evening veiled with mist and rain. 14.我们把世界看错了，反说它欺骗我们。 We read the world wrong and say that it deceives us. 15.人对他自己建筑起堤防来。 Man barricades against himself. 16.使生如夏花之绚烂，死如秋叶之静美。 Let life be beautiful like summer flowers and death like autumn leaves. 17.我想起了其他的浮泛在生与死与爱以及被遗忘的川流上的的时代，我便感觉到离开尘世的自由了。 I think of other ages that floated upon the stream of life and love and death and are forgotten, and I feel the freedom of passing away.18.只管走过去，不必逗留着采了花朵来保存，因为一路上花朵自会继续开放的。Do not linger to gather flowers to keep them, but walk on,for flowers will keep themselves blooming all your way. 19.思想掠过我的心上，如一群野鸭飞过天空。我听见它们鼓翼之声了。 Thoughts pass in my mind like flocks of lucks in the sky.I hear the voice of their wings. 20."谁如命运似的催着我向前走呢？""那是我自己，在身背后大跨步走着。" Who drives me forward like fate？The Myself striding on my back. 21.我们的欲望把彩虹的颜色借给那只不过是云雾的人生。 Our desire lends the colours of the rainbow to the mere mists and vapours of life 收集于网络，如有侵权请联系管理员删除
仅供内部使用和参考 读前说明 为了方便大家在工程上对国际咨询工程师联合会编写出版的《土木工程施工国际招标合同第一部分－通用条件》(以下简称FIDIC合同条件) 的使用，本人根据中国航空工业出版社出版发行的本条件的应用指南，已将其第四版发行的内容整理成英汉对照的电子版本。正文里的条款按原文的两种语言对照录入，只在自己认为明显不妥的地方插入了自己的译法，同时对某些句子的措词和修饰也加进了一点改进意见（原文用红色标注，自己插入的译文和改动用蓝色标注）。在此需要说明的是，插入的译文和对原译文的一些改动意见，旨在使原译文更接近于中文习惯及增加它的可读性，并不敢妄加更正，仅供对照原译文参考理解。 附录部分没有对应的译文，如：前言、索引、附件，1988年修订版说明和1992年再版修正说明等。因此，对照英文内容为其增加了中文译文。由于时间仓促和自己的知识面有限，在翻译和录入过程中难免会出现错误，希望各位领导和同事批评指正。 周彦松 2004年8月29日于金边 FOREWORD 前言 (补充译文) The terms of the Fourth Edition of the Conditions of Contract for Works of Civil Engineering Construction have been prepared by the Fédération Internationale des Ingénieurs Conseils (FIDIC) and are recommended for general use for the purpose of construction of such works where tenders are invited on an intemational basis. The Conditions, subject to minor modifications, are also suitable for use on domestic contracts. 土木工程施工合同条件的第四版已由国际咨询工程师联合会（以下简称为FIDIC）起草完成，并被推荐为以国际性招标为主的同类工程施工的通用条件，如果稍加修改，也适用于国内的招标合同。 The version in English of the Conditions is considered by FIDIC as the official and authentic text for the purpose of translation. 本条件的英文版本, FIDIC已将其作为正式的和有效的语言文本，以用于翻译之目的。 In the preparation of the Conditions it was recognised that while there are numerous Clauses which will be generally applicable there are some Clauses which must necessarily vary to take account of the circumstances and locality of the Works. The Clauses of general application have been grouped together in this document and are referred to as Part I - General Conditions. They have been printed in a form which will facilitate their inclusion as printed in the contract documents normally prepared. 在对本条件准备的过程中，发现多数条款是可以通用的，同时还考虑到工程所处的不同环境和地区须对某些条款加以必要的改动。这些通用条款已在本文件里进行了组合，并将其称为“第一部分－通用条件”。本条件已采用常规准备合同文件的形式印刷出版，以便按同样的印刷格式将其编入合同文件之中。