Guidance for Industry Changes to an Approved NDA or ANDA Q&A 中英对照
Changes to an Approved NDA or ANDA Questions and Answers
REPORTING CATEGORIES报告类别 (1)
GENERAL REQUIREMENTS一般要求 (2)
MANUFACTURING SITES生产地址 (3)
MANUFACTURING PROCESS生产工艺 (8)
SPECIFICATIONS规程 (12)
PACKAGE包装 (13)
MISCELLANEOUS CHANGES多重变更 (15)
Guidance for Industry1
Changes to an Approved NDA or ANDA
Questions and Answers
This document provides questions and answers relating to the guidance on Changes to an Approved NDA or ANDA (the guidance).2 The questions are based on those posed to CDER by applicants. The questions and answers are presented using subject headings that correspond to the table of contents in the guidance.
本文提供指南文件的常见问题及解答。常见问题来源于申请人向CDER提出的
问题。常见问题及解答按照指南文件的目录顺序列表。
REPORTING CATEGORIES报告类别
Q1: For a change that is reported in a Supplement — Changes Being Effected in 30 Days, will CDER complete the review of the supplement within 30 Days?
问1：对于按照30日内生效变更申请提交的报告，CDER是否能在30日内将增补文件审核完毕？
A1: Within 30 days CDER will notify the applicant that prior approval is
required for the change (i.e., CDER has designated the supplement a prior
approval supplement) or that the FDA has determined appropriate information is missing, including information that should have been developed by the
applicant in assessing the effects of the change. Supplement reviews will be
performed consistent with standard procedures. It is unlikely that a substantive review and action letter will be completed within 30 days.
答1:30日内，CDER确定增补应该按照批准前增补提交，将通知申请人该项事务；
或者FDA判断应有的信息存在缺陷，包括申请人应当开展的变更影响评估报告，也会通知申请人。增补文件的审核时严格按照既定标准程序开展的，实质性的审核和通知函一般不可能在30日内就能完成。
Q2: If information is missing from a Supplement — Changes Being Effected in 30 Days, will the reporting category be changed to a prior approval supplement?
问2：若20日内生效变更信息缺失，该申请是否变更为优先批准变更增补？
A2: No. If FDA informs the applicant within 30 days of receipt of the
Supplement — Changes Being Effected in 30 Days that information is missing, the reporting category is not changed to a prior approval supplement. However, distribution of the product made with the change must be delayed until the
supplement is amended with the missing information.
答2：不会。即使FDA通知申请人该30日内生效变更申请信息有缺陷，也不会将其变更为优先批准变更增补文件类型。然而，变更后生产的产品
必须在申请者将缺陷信息增补完毕后才能进行销售活动。
Q3: A change (specified change) is planned. The guidance recommends that the change be reported in a supplemental application. However, the data generated indicate that this change does not adversely affect the identity, strength, quality, purity, and potency of the product. Can this change be reported in an annual report?问3：企业做了变更计划。指南文件建议其变更用增补申请提交。而测试数据表明，该变更并不对产品性状、剂量、纯度及药效有不良影响。可否仅将该变更在年报中提交？
A3: No. The recommended reporting category is based on the potential for the change to adversely affect the identity, strength, quality, purity, or potency of
the drug product as these factors relate to the safety or effectiveness of the drug product (see section 506A of the Federal Food, Drug, and Cosmetic Act (the
Act)). CDER expects that the majority of the data and information submitted to support a supplemental change will, in the applicant’s judgment, demonstrate
that the change does not adversely affect the product. However, FDA will
evaluate the completeness of the data and information and decide whether the
applicant’s conclusion (i.e., there is no adverse effect) is appropriate prior to
approving such a change.
答3：不可以。指南文件对变更建议报告类型的分类，是建立在该变更是否对产品的性状、剂量、纯度及药效等与药物安全性、有效性相关的特
性产生不良影响的可能性上的。CDER专家期待，从申请人的角度判断，所提供的支持变更的数据和信息是能够说明该变更对产品并无不良影响
的。然而，FDA会评估数据的完整性，来判断申请人所提出的结论（即
变更不造成不良影响）是否足够可靠，是否足够支持该变更申请。
GENERAL REQUIREMENTS一般要求
Q1: A manufacturing change is planned that can be reported in the annual report. Should the data to support the change be included in the annual report?
问1：若指南文件建议某一可报告的生产变更在年报中报告，是否支持该变更的数据及信息也该包括在年报中？
A2: Yes. After the change is implemented, the information should be included in the next annual report. Moreover, the information to support the change
must be generated prior to distributing the product made with the change
(506A(b)). As stated in section 506A(b) of the Act, “a drug made with a
manufacturing change (whether a major manufacturing change or otherwise)
may be distributed only if, before distribution of the drug as so made, the
holder involved validated the effects of the change on the identity, strength,
quality, purity, and potency of the drug as the identity, strength, quality, purity, and potency may relate to the safety or effectiveness of the drug.”
答2：是的。实施变更后，该变更及其支持信息必须包括在下一年报中。
并且，变更后的产品也必须在支持变更信息发布之后才能销售。按照联
邦食品药品及化妆品法506A（b）部分所述：生产变更（无论是否是重大生产变更）后生产的产品必须在申请者能够完全验证该变更对产品性状、剂量、质量、纯度和药效及其他可能与药品安全性、有效性相关的特性
的影响后，才能进行销售。
MANUFACTURING SITES生产地址
Q1: Can a change in the manufacturing site for a drug substance that involves a different company (i.e., change in source) be reported in a Supplement — Changes Being Effected in 30 Days?
问1：若原料药生产地址变更包含另一个不同的公司（如物料来源），可否在30日内生效变更增补文件中报告？
A1: As stated in section VI.A of the guidance, “A move to a different
manufacturing site that involves other changes (e.g., process, equipment)
should be evaluated as a multiple related change (see section XII) to determine the appropriate reporting category.” Typically, a change from one drug
substance manufacturer to another involves more than simply a site change. In most cases, there will be additional differences (e.g., route of synthesis,
process, solvents, equipment). Without extensive knowledge of the new and
old sources (e.g., access to the drug master file), an applicant cannot
adequately describe the differences between the sources or evaluate the
multiple change. Therefore, when the applicant does not have extensive
knowledge to provide the information and evaluation, the drug substance site
change should be reported in a prior approval supplement. When an applicant
has the extensive knowledge to describe the differences between the sources,
the applicant can report the change as appropriate after evaluation as a multiple change. If the change is not reported in a prior approval supplement, the
applicant should include a statement in the submission that the change involves no changes that should be reported in a prior approval supplement. In either
case, a move to a drug substance manufacturing site should be reported in a
prior approval supplement when the site does not have a satisfactory current
good manufacturing practice (CGMP)) inspection (see guidance for details) for the type of operation.
答1：指南VI.A部分陈述：若生产地址变更到另一生产地址且包含其他变更（工艺，设备），应当按照多重变更提交报告。典型的例子就是将原
料药生产地址变更到另一地点，且只包含地址的变化。但是大多数情况
下，可能都会包含别的变更（如合成路线、工艺、溶剂、设备等变更）。
若没有对新旧两个物料来源公司广泛的信息掌握（如DMF情况），申请
者是无法充分的评估该多重变更的。因此，若申请者无法提供广泛的信
息和评估，则该原料药生产地址变更应该按照优先批准变更报告。若申
请人有很广泛的信息来源，足够描述两个物料来源的区别，则申请人能
在进行适当的评估后按照多重变更提交报告。若变更不安优先批准变更
提交，则在报告中申请人应当做出声明，声明泵本报告中不包含必须在
优先批准变更提交的变更。同样，若变更后的生产地址该类生产操作没
有合格的CGMP条件，则该变更也必须按照优先批准变更提交（细节见
指南）。
Q2: Should a change to a different site be reported when the change is for fabrication of packaging components?
问2：若包装组件的加工地点变更，需要按照生产地址变更提交报告吗？
A2: Section VI.A of the guidance identifies the site changes that should be
reported to CDER. A move to a different site to manufacture or process drug
products should be reported. The guidance defines sites used to manufacture or process drug products to include sites used by the applicant (applicant owned
or contractors) to prepare (e.g., sterilize, depyrogenate, irradiate, wash)
container closure systems or packaging components. A change to a different
site for fabricating packaging components (e.g., bottles) or manufacturing
packaging materials (e.g., resins) need not be reported if there is no other
change (e.g., dimensions, composition, specification, processing aids). If other changes occur, the reporting category should be based on the recommended
reporting categories for the changes (i.e., the manufacturing site change should not be considered when determining the appropriate reporting category).
答2：指南VI.A部分声明，地质变化必须通知CDER。即，生产和加工地址的变化必须报告。而指南定义，申请人使用的生产或加工的地址包括
申请者拥有（自己持有或承包）用来准备（灭菌，去热源，辐照灭菌，
清晰）容器密封系统或包装组件的地址。加工包装组件（如瓶）或生产
包装物料（如树脂）的地址变更若无其他变更（包装规模，物料组成，
规格，加工助剂）则不需要报告。若发生其他变更，要根据变更的建议
报告类别提交报告（考虑报告类别时不用考虑生产地址变更）。
Q3: The guidance states that a move to a different site that results in a restart at the new manufacturing site of a type of operation that has been discontinued for more than twoyears should be reported in a prior approval supplement (section VI.B.1). Two manufacturing sites were approved in the original application. Production at one of the sites has not occurred in 5 years but is going to be restarted. Should this restart be reported in a prior approval supplement?
指南声明，若变更的生产地址该类生产操作已终止了两年以上，测该变更需要按照批准前增补提交。而原申请通过了两个生产地址，其中一个生产地址五年之内没有发生生产操作但即将发生。这个变更也应该按照批准前增补提交吗？
A3: A restart of manufacturing at a site already approved in the application
need not be reported in the application as long as the restart does not involve
any other changes(e.g., equipment, process) that should be reported. If the
restart involves a site that is not approved in the application, a prior approval
supplement should be submitted.
答3：已经通过的申请中的生产地址重新开始生产时，若不包括其他需要报告的变更（设备，工艺等），则不需要报告。若重新生产设计一个未
被批准的生产地址，则申请人必须按照批准前增补提交。
Q4: A packaging site will be added that will enclose two sample cartons, along with some promotional material, into a larger carton or box preprinted with the product name:
·Does the information about the tertiary packaging site need to be submitted to the agency? If yes, can CDER be notified in an annual report?
·Is the tertiary site held to the same CGMP requirements as a secondary site?
For example, if a tertiary site should be submitted to the agency, and this site has not had any CGMP inspection within the last two years, is this change still
annual reportable?
问4：计划增加一个包装地址，此地将两个标准纸箱装入一个大的印有产品名称的纸箱中，同时装入部分宣传资料。
·这个三级包装地址需要向CDER报告吗？若需要，可否按年报方式报告？
·这个三级包装地址是否也要向二级包装地址一样满足同等CGMP要求？例如，若一个三级包装地址必须报告，并且2年内并无任何CGMP检查，这个变更是否依然可以在年报中报告？
A4: The guidance only distinguishes between primary and secondary
packaging sites. The site described would be considered a secondary packaging site. CGMP requirements extend beyond packaging and repackaging
operations that involve direct product contact. For example, a site must register with FDA (21 CFR Part 207) and is subject to CGMP inspection (21 CFR Part 211) when the site is used to attach inserts, or in the case of a cartoning site,
when cartons contain product labels. If registration and/or inspection are
required for the site of this secondary packaging operation, CDER should be
notified of the different site (via the application). The site should have a
satisfactory inspection relating to packaging operations for notification to
occur in the annual report. For the purposes of this guidance, in general, there
is no two-year limit on the CGMP inspection (see Manufacturing Sites Q10). If registration and inspection are not required for the site of this secondary
packaging operation, the applicant need not notify CDER of the site. If you
have any questions on whether this packaging operation is subject to FDA
registration or inspection, you should contact the appropriate CDER inspection and/or compliance staff for advice.
答4：指南只定义了内包和外包。问题中描述的应属于外包。只要是直接与产品接触的操作，无论是内包还是外包，都应满足CGMP要求。例如，若一个生产地址用来给产品加入说明书，或在纸箱包装中加入说明书，
就必须在FDA注册（21CFR,207）并通过CGMP检查(21CFR,211)。若这个外包地址需要在FDA注册和/或需要检查，申请者应通知CDER新的地址。
在年报中报告该变更时应对该包装进行合格性检查。一般来说，指南并
未对CGMP合格性限定两年的标准。若这个操作不需要注册、检查则不
需要通知CDER这个变更。若您对该包装操作是否应该注册有任何疑问，请联系合适的CDER调查员或合规员征询意见。
Q5: Certain changes relating to contract sterilization sites for packaging components can be reported in an annual report (section VI.D.4). Does this also apply to applicant owned sites?
问5：承包的包装组件灭菌场地变更可以在年报中报告。申请人自己拥有的灭菌场地是否也适用该规定？
A5: Yes. Whether the sterilization site is applicant- or contractor-owned, a
change to a different sterilization site for packaging components can be
reported in an annual report when the process is not materially different from
the process described in the approved application, and the facility has a
satisfactory CGMP inspection for the type of operation that is being performed.
答5：是。无论该灭菌地址是承包的还是自有的，包装组件的灭菌场地变更都可以在年报中报告，只要该操作与已批准申请无实质上的差别，且
该类操作符合该类操作的CGMP要求。
Q6: Should a prior approval supplement be submitted for a change in the sterilization site for a primary packaging component of a metered dose inhaler?
问6：定量雾化吸入剂型的内包组件灭菌场地变更是否按照优先批准变更提交？
A6: The change can be reported in an annual report as long as the process is
not materially different from that provided for in the approved application and as long as the facility has a satisfactory CGMP inspection for the type of
operation being performed (section VI.D.4)
答6：只要该操作与已批准申请提供的操作并无实质上的差别，且该类操作符合该类操作的CGMP检查，即可仅在年报中报告。
Q7: If an intermediate or starting material is also a drug substance, would the recommendations on reporting site changes for intermediates or drug substances apply?
问7：若某一中间体或起始物料也是原料药，则其地址变更信息是按照中间体还是原料药提交？
A7: If a drug substance is used as an intermediate in a drug substance
manufacturing process, the guidance on intermediates would apply. This
assumes that the material has been classified appropriately as an intermediate (see relevant definitions in the glossary of the guidance). CDER traditionally
does not consider a drug substance to be a starting material.
答7：若某原料药在生产工序中作为中间体使用，则有关中间体的指南文适用。即此时这个物料被认为是中间体。CDER一般不将原料药作为起始物料。
Q8: Do the recommendations for manufacturing site changes apply to manufacturing sites outside the United States as long as the site has a satisfactory CGMP inspection for the type of operation that will be moved?
问8：只要迁往的生产地符合CGMP检查，即使地址不在美国，对该类操作的地址变更建议报告类型依然适用吗？
A8: Yes. The recommendations in the guidance apply to domestic and foreign manufacturing sites.
答8：是的。本指南在美国本土或其他国家都适用。
Q9: The site where the certificates of analysis and regulatory documentation are reviewed prior to commercial distribution of the product will be relocated. Should this site change be reported in the application?
问9：计划变更产品销售前审核化验证明书和监管文档的场所。该场所变更是否应在申请中报告？
A9: A change in the site where GMP support paperwork operations occur need not be reported in the application.
答9：支持CGMP的文件操作场地变更无需报告。
Q10: The guidance (section VI.B.2) states that a manufacturing site change should be submitted in a prior approval supplement if the new manufacturing site does not have a satisfactory CGMP inspection for the type of operation being moved. In previous guidances it was stated that a satisfactory CGMP inspection within the last two years was needed. Should a prior approval supplement be used if the new facility has a satisfactory CGMP inspection for the type of operation being moved, but the inspection occurred more than two years ago?
问10：指南文件VI.B.2部分陈述，若变更的新生产场地对于该类生产操作并无合格的CGMP条件，则该变更应该按照优先批准变更提交报告。而之前的指南文件则声明需要2年之内的CGMP检查合格。若变更的生产场地2年之前该类生产操作经CGMP检查合格，变更报告是否应采用优先批准变更报告？
A10: For the purposes of the guidance, there is no time limit on the satisfactory CGMP inspection unless the type of operation was discontinued (section
VI.B.1).
答10：只要该类生产操作未被中止，本指南并未对CGMP检查设定有效
期限。
Q11: What is the reporting category for a change to a different manufacturing site for an excipient?
问11：赋形剂的生产地址变更应按何种类型报告？
A11: CDER need not be notified of this type of change.
答11：不需向CDER报告此类变更。
Q12: What is the recommended reporting category for the addition of a new aseptic
filling line for sterile products?
问12：若计划给无菌制剂增加一个添加防腐剂的生产线，该变更建议报告类型是什么？
A12: The addition of a new aseptic filling line should be reported in a prior
approval supplement (section VI.B.4).
答12：新的防腐剂添加生产线按照优先批准变更进行报告。
Q13: Why does the guidance exclude drug substance intermediates when referring to satisfactory CGMP inspections?
问13：为什么在涉及到CGMP合格性检查时，指南文件将原料药中间体排除？
A13: Section 510(a)(2)(B) of the Act requires that all drugs be manufactured,
processed, packed, and held in accordance with CGMPs. No distinction is
made between the manufacture of drug substance and drug product. Although the CGMP regulations under 21 CFR Parts 210 and 211 apply only to drug
products, FDA expects appropriate CGMPs to be applied to all steps of a drug substance manufacturing process beginning with the use of starting materials.
The types of sites identified in the guidance are routinely subject to FDA
inspection with the exception of those facilities or establishments used to
manufacture or process drug substance intermediates. Drug substance
intermediate manufacturing or processing sites are not exempt from inspection, but an inspection is generally discretionary. Moreover, this type of facility is
always subject to for cause inspection. Because drug substance intermediate
sites are not routinely inspected, a satisfactory CGMP inspection was not
included as a condition for submitting the change in a Supplement — Changes Being Effected in 30 Days or annual report. However, when a drug substance
intermediate manufacturing or processing site has been inspected and the
CGMP inspection was not satisfactory, the change in site should be submitted as a prior approval supplement.
答13：法案5 10(a)(2)(B)部分要求，所有药物必须按照CGMP开展生产、
加工、包装和贮藏操作。制剂和原料药的生产并无差别。尽管CGMP的
21CFR210和211只适用于之际，FDA还是希望所有从使用起始物料开始
的原料药生产过程满足合格的CGMP。指南文件的操作场地类型是以
FDA的检查为基础，除了生产或加工原料药中间体的。原料药中间体的
生产和加工场地并不能免除检查，但是基本上按照申请者自由安排。此
外，此种设备通常是“因故”检查。因为原料药中间体的生产地址的
CGMP并不进行例行检查，因此并不是必须在30日内生效变更申请的必
要内容。
MANUFACTURING PROCESS生产工艺
Q1: An applicant intends to add a coarse screen to the opening of a blender, through which all individual components of a granulation would pass prior to granulation. The applicant asks whether this could be considered a change in a control which would be reportable in a Supplement — Changes Being Effected under section VII.C.2.a of the guidance.
问1：申请者意图在混合机出料口增加一个粗孔筛，使所有物料在制粒前过筛。申请社询问，是否可以将该操作按照指南VII.C.2.a.所述，按照中控变更提交即将生效变更申请。
A1: This change is not considered a change in control but an additional step in the manufacturing process. However, it is not considered a fundamental
change in the manufacturing process. This type of change should be reported in
a Supplement — Changes Being Effected in 30 Days (section VII.C.1.a).
A1：该操作不可能被认为是中控变更，但可以认为是增加了生产工序。
然而该变更也不认为是生产工艺的基本变更。该变更可以以30日内生效
变更提交。
Q2: Can changes in mixing steps and elimination of a mixing step be reported in an annual report if these changes are implemented prior to the manufacture of validation batches?
问2：若混合步骤变更或取消在验证批次生产之前实施，可否仅在年报中报告？
A2: The timing of the postapproval change (i.e., pre- or post validation batches) does not affect the recommended reporting category. The type of change
should be submitted in either a Supplement — Changes Being Effected in 30
Days (e.g., VIII.C.1.a.) or prior approval supplement (e.g., VII.B.1) depending on the specifics of each situation such as the type of dosage form.
答2：已批准变更的时间（例如，验证前或验证后的批次）不影响建议报
告类别。应该按照不同的具体情况，例如剂型种类，来判断应该按优先
批准变更提交还是30日内生效变更提交。
Q3: What is the recommended reporting category for a drug product (immediate release solid oral dosage form) scale change beyond 10 times the size of the biobatch? If the change is annual reportable, should the information identified in SUPAC-IR3 for an Level 1 scale change be submitted?
问3：当一个制剂（如速释固体口服制剂）的生产规模超过了生物批次的十倍，建议报告类别是？若变更可以按照年报提交，SUPAC-IR3中所提及的Level 1 规模变更是否也要提交？
A3: All changes in the scale of the nonprotein drug product manufacturing
batches can be reported in an annual report (see section VII.D.1.a).4 However,
if the scale change results in other changes (e.g., equipment, process), the
change would be considered a multiple change, and the recommended
reporting category should be the most restrictive of those for any of the indi
vidual changes (section XII). Recommendations on scale changes for protein
drug products are included in section VII.C.1.c and VII.D.1.a of the guidance.
The information and data recommendations in SUPAC-IR can be used to
support a change. However, the data and information that should be included
in the annual report to support the change depends on the extent of the scale
change. If the scale change is up to and including 10 times the size of the
biobatch, the data and information recommended in SUPAC-IR section V.A
(Level 1) should be submitted. If the scale up is greater than 10 times the size
of the biobatch, the data and information recommended in SUPAC-IR Section V.B (Level 2) should be submitted.
答3：非蛋白质制剂的生产批次规模变更都可按照年报提交。但是，若变更导致了其他的变更（如设备），则该变更应该被视为多重变更，且是
所有单一变更中最具限制性的建议报告类型（见XII部分）。蛋白质类制剂的生产规模变更建议报告类型参见指南VII.C.1.c和VII.D.A.a部分。
SUPAC-IR的建议信息和数据是可以用来支持变更的。然而，年报中所需要包括的支持变更的数据及信息取决于生产规模变更的程度。若规模变
更在生物批次的十倍及以内，建议信息在SUPAC-IR的V.A.部分，一级变更提交。若是变更规模超过生物批的十倍，则建议信息在SUPAC-IR的
V.B.部分，二级变更提交。
Q4: Can changes in the drying process (i.e., tray dryer to cone dryer and associated process changes) of the crude drug substance be reported in an annual report?
问4：计划发生天然原料药的干燥过程中的变更（如盘式干燥器变更为锥桶干燥器），可否仅在年报中报告？
A4: Section VII.B.5 of the guidance recommends a prior approval supplement when any change is made after the final intermediate processing step in the
drug substance manufacture. Changes that occur after the final intermediate for synthetic or semisynthetic drug substances will be addressed in the guidance
on Bulk Active Chemicals – Postapproval Changes II (BACPAC II). Until the BACPAC II guidance is finalized, the appropriate chemistry review division(s) can be consulted for advice if an applicant believes a change made after the
final intermediate processing step is not a major change.
答4：指南的VII.B.5.部分建议，原料药生产工艺中，在最后中间体加工
工序之后所发生的任何变更都按照优先批准变更提交。在合成或半合成
原料药最后中间体后发生的任何变更，可以参考BACPAC指南。直到指
南完成，若申请人认为最后中间体加工工艺后的变更不是重大变更，可
以向化学审核部门征询意见。
Q5: For nonprotein drug substances, how should scale changes be reported when there are no other changes?
问5：对非蛋白质原料药来说，若无其他附加变更，只有生产规模变更，应如何报告？
A5: Changes in the manufacturing scale for a nonprotein drug substance prior
to the final intermediate need not be reported to CDER unless the change
adversely affects the identity, strength, quality, purity, or potency of the drug
product as these factors relate to the safety and effectiveness of the drug
product. Changes in scale for synthetic or semisynthetic drug substances after
the final intermediate will be addressed in the BACPAC II guidance. Until the BACPAC II guidance is finalized, the appropriate chemistry review division(s) can be consulted for advice if an applicant believes a change made after the
final intermediate processing step is not a major change.
答5：非蛋白质原料药发生在最后中间体加工工序之前的生产规模变更无
需向CDER报告，除非该变更对药品的性状，剂量，质量，纯度有效性或其他与药品安全性有效性相关的特性有不良影响。在合成或半合成原料
药最后中间体后发生的任何变更，可以参考BACPAC指南。直到指南完
成，若申请人认为最后中间体加工工艺后的变更不是重大变更，可以向
化学审核部门征询意见。
Q6: Section VII.B.2 of the guidance recommends a prior approval supplement for changes in sterilizer and load configurations that are outside the range of previously validated loads. How should changes in load configuration for manufacturing process equipment (e.g., forceps, stopper bowl) be reported?
问6：指南VII.B.2部分建议，超过原批准验证范围的灭菌及负载变更应提交优
先批准变更，那么生产工序的设备负载变更应该如何报告（如镊子，塞碗等）？
A6: A Supplement — Changes Being Effected in 30 Days is recommended if
the load change is large enough so that the cycle has to be adjusted beyond the previously validated range. If the cycle does not have to be adjusted, an annual
report is recommended.
答6：若负载变更过大，导致生产将在批准的验证范围外进行调整，则将提交30日内生效变更增补。若其他部分不用调整，则在年报中报告即可。
Q7: Can CDER be notified in an annual report when the filling speed line for a sterile product is increased by changing the speed of filling through the fill heads or adding filling heads.
问7：若计划通过加快灌装头灌装速度或增加灌装头数目来增加某无菌制剂的灌装生产速度，可否仅在年报中向CDER提交报告？
A7: Changing the speed of filling through the fill heads or adding fill heads
can be reported in an annual report as long as the total processing time is not
extended beyond the validated limits in the approved application.
答7：只要整个生产时间并未超过已通过申请的验证范围，则通过增加灌装头的灌装速度或灌装头数目来加快生产速度的变更可以仅在年报中报
告。
Q8: A prior approval supplement is recommended for changes in the source material of drug substances or drug products derived from plants, animals, or microorganisms (section VII.B.3). Does this recommendation apply to a substance derived from a natural source that is used as the starting material for the synthetic part of a semisynthetic process?
问8：原料药的起始物料来源变更，或者源自植物、动物或微生物的制剂产品的来源变更都应按照优先批准变更报告。这个建议是否对衍生自天然产物的原料药、而该天然产物又是某合成路线或半合成路线的起始物料的情况也适用？
A8: Yes. This recommendation applies to the starting materials for the
synthetic part of a semi-synthetic process as well as a drug substance or drug
product derived directly from these sources with no further synthetic
modification. For example, the recommendation applies to changes in the
source material for: (1) a plant extract that undergoes synthetic modification to
produce the drug substance, or (2) a cellular metabolite that undergoes
synthetic modification to produce an antibiotic drug substance. This
recommendation does not apply to starting materials derived from natural
sources that are widely available (i.e., used more than just to produce
pharmaceuticals), such as glucose or tartaric acid, that can be used in a
synthetic process.
答8：是的。该建议对半合成工艺合成部分的起始物料，或有他们直接衍生不经过其他合成修饰的原料药和制剂都适用。例如，该建议对以下物
料来源的变更适用：（1）：经过合成修饰后生产原料药的植物提取物；
（2）：经过合成修饰后生产抗菌素原料药的细胞代谢物。本指南不使用天然来源、广泛使用的起始物料（即不止在制剂过程中使用的物料），
如葡萄糖或酒石酸，因其可能在合成工艺中用到。
SPECIFICATIONS规程
Q1: How should a revision of an analytical procedure be reported to allow for the use of a company (i.e., secondary) standard in addition to the U. S. Pharmacopeia (USP) standard?
问1：如何提交报告才能在USP标准之外给分析规程增加一个公司规程（第二标准）？
A1: The revision of an analytical procedure to allow the option to use a
secondary standard should be reported in an annual report. Also, the laboratory reference standards used must comply with CGMP regulations (e.g., 21 CFR
211.194(c)).
答1：允许使用第二标准的修正分析规程应在年报中报告。同时，实验室参考标准也必须符合CGMP规程。
Q2: How should a decrease in the fill volume be reported?
问2：填充体积的减少应该如何上报？
A2: A change in the fill volume of a drug product involves a change to the
specification and must be submitted in a prior approval supplement unless
exempted by regulation or guidance (506A(c)(2)(A) of the Act). There is no
exemption for this type of specification change; therefore, a prior approval
supplement should be submitted.
答2：填充体积的减少包括了规格的变化，并必须提交优先批准变更，除非有法规或指南豁免。而这类规格变更并无豁免。因此必须按照优先批
准变更提交。
Q3: What reporting category should be used if a USP HPLC assay procedure replaces, or is used in addition to, a microbiological assay that is listed in the approved specification as the regulatory analytical procedure?
问3：若计划增加一个USP标准的HPLC分析规程来辅助或替代原批准申请中作为常规分析程序的微生物鉴定，应怎样报告变更？
A3: The addition of the HPLC analytical procedure to comply with an official compendium can be submitted in an annual report (section VIII.D.1). However, if the microbiological assay will also be deleted, the deletion of a test should be reported in a prior approval supplement (section VIII.B.2 and 3).
答3：添加符合药典标准的HPLC分析程序可以在年报中报告。然而，若
微生物鉴定被取消，则该检测手段被取消的变更应按优先批准变更递交
增补。
Q4: In the approved application, it is specified that full product testing will be performed before bulk material is sent to a contract packager and when the packaged material is received from the contractor. Can notification in an annual report be used to replace the full testing of the product after it is received from the contractor with an identity test?
问4：在已批准的申请中规定，在生产厂家向包装承包公司发货之前和从该承包公司接受包装好的产品之后都应该进行完整的产品检测。若计划将接受包装后的完整检测变更为鉴定试验，该如何进行报告？
A4: This change involves a deletion of tests and should be reported in a prior
approval supplement (section VIII.B.2).
to与for的用法和区别
to与for的用法和区别 一般情况下, to后面常接对象; for后面表示原因与目的为多。 Thank you for helping me. Thanks to all of you. to sb.表示对某人有直接影响比如，食物对某人好或者不好就用to; for表示从意义、价值等间接角度来说，例如对某人而言是重要的，就用for. for和to这两个介词，意义丰富，用法复杂。这里仅就它们主要用法进行比较。 1. 表示各种“目的” 1. What do you study English for? 你为什么要学英语？ 2. She went to france for holiday. 她到法国度假去了。 3. These books are written for pupils. 这些书是为学生些的。 4. hope for the best, prepare for the worst. 作最好的打算，作最坏的准备。 2．对于 1．She has a liking for painting. 她爱好绘画。 2．She had a natural gift for teaching. 她对教学有天赋/ 3．表示赞成同情，用for不用to. 1. Are you for the idea or against it? 你是支持还是反对这个想法？ 2. He expresses sympathy for the common people.. 他表现了对普通老百姓的同情。 3. I felt deeply sorry for my friend who was very ill. 4 for表示因为，由于（常有较活译法） 1 Thank you for coming. 谢谢你来。 2. France is famous for its wines. 法国因酒而出名。 5．当事人对某事的主观看法，对于（某人），对…来说（多和形容词连用）用介词to，不用for.. He said that money was not important to him. 他说钱对他并不重要。 To her it was rather unusual. 对她来说这是相当不寻常的。 They are cruel to animals. 他们对动物很残忍。 6．for和fit, good, bad, useful, suitable 等形容词连用，表示适宜，适合。 Some training will make them fit for the job. 经过一段训练，他们会胜任这项工作的。 Exercises are good for health. 锻炼有益于健康。 Smoking and drinking are bad for health. 抽烟喝酒对健康有害。 You are not suited for the kind of work you are doing. 7. for表示不定式逻辑上的主语，可以用在主语、表语、状语、定语中。 1．It would be best for you to write to him. 2．The simple thing is for him to resign at once. 3．There was nowhere else for me to go. 4．He opened a door and stood aside for her to pass.
of与for的用法以及区别
of与for的用法以及区别 for 表原因、目的 of 表从属关系 介词of的用法 （1）所有关系 this is a picture of a classroom （2）部分关系 a piece of paper a cup of tea a glass of water a bottle of milk what kind of football，American of soccer？ （3）描写关系 a man of thirty 三十岁的人 a man of shanghai 上海人 （4）承受动作 the exploitation of man by man．人对人的剥削。 （5）同位关系 It was a cold spring morning in the city of London in England． （6）关于，对于 What do you think of Chinese food？ 你觉得中国食品怎么样？ 介词 for 的用法小结 1. 表示“当作、作为”。如: I like some bread and milk for breakfast. 我喜欢把面包和牛奶作为早餐。What will we have for supper? 我们晚餐吃什么?
2. 表示理由或原因,意为“因为、由于”。如: Thank you for helping me with my English. 谢谢你帮我学习英语。 Thank you for your last letter. 谢谢你上次的来信。 Thank you for teaching us so well. 感谢你如此尽心地教我们。 3. 表示动作的对象或接受者,意为“给……”、“对…… (而言)”。如: Let me pick it up for you. 让我为你捡起来。 Watching TV too much is bad for your health. 看电视太多有害于你的健康。 4. 表示时间、距离,意为“计、达”。如: I usually do the running for an hour in the morning. 我早晨通常跑步一小时。We will stay there for two days. 我们将在那里逗留两天。 5. 表示去向、目的,意为“向、往、取、买”等。如: let’s go for a walk. 我们出去散步吧。 I came here for my schoolbag.我来这儿取书包。 I paid twenty yuan for the dictionary. 我花了20元买这本词典。 6. 表示所属关系或用途,意为“为、适于……的”。如: It’s time for school. 到上学的时间了。 Here is a letter for you. 这儿有你的一封信。 7. 表示“支持、赞成”。如: Are you for this plan or against it? 你是支持还是反对这个计划? 8. 用于一些固定搭配中。如: Who are you waiting for? 你在等谁? For example, Mr Green is a kind teacher. 比如,格林先生是一位心地善良的老师。
常用介词用法(for to with of)
For的用法 1. 表示“当作、作为”。如: I like some bread and milk for breakfast. 我喜欢把面包和牛奶作为早餐。 What will we have for supper? 我们晚餐吃什么? 2. 表示理由或原因,意为“因为、由于”。如: Thank you for helping me with my English. 谢谢你帮我学习英语。 3. 表示动作的对象或接受者,意为“给……”、“对…… (而言)”。如: Let me pick it up for you. 让我为你捡起来。 Watching TV too much is bad for your health. 看电视太多有害于你的健康。 4. 表示时间、距离,意为“计、达”。如: I usually do the running for an hour in the morning. 我早晨通常跑步一小时。 We will stay there for two days. 我们将在那里逗留两天。 5. 表示去向、目的,意为“向、往、取、买”等。如: Let’s go for a walk. 我们出去散步吧。 I came here for my schoolbag.我来这儿取书包。 I paid twenty yuan for the dictionary. 我花了20元买这本词典。 6. 表示所属关系或用途,意为“为、适于……的”。如: It’s time for school. 到上学的时间了。 Here is a letter for you. 这儿有你的一封信。 7. 表示“支持、赞成”。如: Are you for this plan or against it? 你是支持还是反对这个计划? 8. 用于一些固定搭配中。如: Who are you waiting for? 你在等谁? For example, Mr Green is a kind teacher. 比如,格林先生是一位心地善良的老师。 尽管for 的用法较多，但记住常用的几个就可以了。 to的用法: 一：表示相对，针对 be strange (common, new, familiar, peculiar) to This injection will make you immune to infection. 二：表示对比，比较 1：以-ior结尾的形容词，后接介词to表示比较，如：superior ,inferior,prior,senior,junior 2: 一些本身就含有比较或比拟意思的形容词，如equal，similar，equivalent，analogous A is similar to B in many ways.
because,since,as,for的用法区别
because、since、as、for的用法区别 because、since、as、for这几个词都是表示“原因”的连词，语气由强至弱依次为：because→since→as→for。其中because、since和as均为从属连词，引导原因状语从句；而for是并列连词，引导并列句。 ?because because表示直接原因，它所指的原因通常是听话人所不知道的，其语气最强。常用来回答why的提问，一般放在主句之后，也可以单独存在例如： (1)Istayed at home because it rained. 因为下雨，我呆在家里。 (2)B ecause Lingling was ill, she didn’t come to school. 玲玲因为生病，没有上学。 (3)—Why is she absent? 她为什么缺席? —Because she is sick. 因为她病了。 (4)此外，在强调句型中只能用because。例如， It was because I missed the early bus that I was late for school. 我上学迟到是因为我错过了早班车。 ?since since侧重主句，从句表示显然的或已为人所知的理由，常译为“因为、既然”，语气比because稍弱，通常置于句首，表示一种含有勉强语气的原因。例如： (1)Si nce he asks you, you’ll tell him why. 他既然问你了，那就告诉他为什么吧。 (2)Si nce everyone is here, let’s start. 既然大家都到齐了，我们就是出发吧。 (3)Since I understood very little Japanese, I c ouldn’t follow the conversation. 我日语懂得不多，因而听不懂对话。 ?as as是常用词，它表示的“原因”是双方已知的事实或显而易见的原因，由于理由不是很重要，含义与since相同，但语气更弱，没有since正式，常译为“由于，鉴于”。从句说明原因，主句说明结果，主从并重。例如：
of和for的用法
of 1....的,属于 One of the legs of the table is broken. 桌子的一条腿坏了。 Mr.Brown is a friend of mine. 布朗先生是我的朋友。 2.用...做成的;由...制成 The house is of stone. 这房子是石建的。 3.含有...的;装有...的 4....之中的;...的成员 Of all the students in this class,Tom is the best. 在这个班级中,汤姆是最优秀的。 5.(表示同位) He came to New York at the age of ten. 他在十岁时来到纽约。 6.(表示宾格关系) He gave a lecture on the use of solar energy. 他就太阳能的利用作了一场讲演。 7.(表示主格关系) We waited for the arrival of the next bus. 我们等待下一班汽车的到来。
I have the complete works of Shakespeare. 我有莎士比亚全集。 8.来自...的;出自 He was a graduate of the University of Hawaii. 他是夏威夷大学的毕业生。 9.因为 Her son died of hepatitis. 她儿子因患肝炎而死。 10.在...方面 My aunt is hard of hearing. 我姑妈耳朵有点聋。 11.【美】(时间)在...之前 12.(表示具有某种性质) It is a matter of importance. 这是一件重要的事。 For 1.为,为了 They fought for national independence. 他们为民族独立而战。 This letter is for you. 这是你的信。
because, since, as与for用法辨析
because, since, as与for用法辨析 1. because的用法 because语气最强，表示直接原因，可用于回答 why 提出的问题、引导表语从句、用于强调句等，而其余三者均不行。如： A：Why didn’t she come? 她为什么没来? B：Because she was very busy. 因为她很忙。 It is because he is clever that I like him. 是因为他聪明我才喜欢他。 2. since与as 两者所表示的原因都是人们已知的，即对已知事实提供理由，而不是表示直接原因。since 比 as 语气稍强，且比 as 略为正式，它们引导的从句通常放在主句之前，有时也放在主句之后。如： As you weren’t there, I left a message. 由于你不在那儿，我留了个口信。 Since you’ve been here a w hile, you might as well stay. 既然你已经来了一段时间，就不妨继续待下去。 另外，since 可用于省略句，而其他三者不行。如： Since so, I have nothing to say. 既然如此，我无话可说。 3. for的用法
for是并列连词，而其余三者为从属连词。for有时可表示因果关系(通常要放在主句之后，且可与 because 换用)；有时不表示因果关系，而是对前面分句内容的解释或推断(也要放在主句之后，但不能与because 换用)。比较： The ground is wet，for (＝because) it rained last night. 地面是湿的，因为昨晚下过雨。 It must have rained last night，for the ground is wet this morning. 昨晚一定下过雨，你看今天早上地面是湿的。 (此句不能用 because 代 for) 英语微信群是目前学习英语最有效的方法，群里都是说英语，没有半个中文，而且规则非常严格，是一个超级不错的英语学习环境，群里有好多英语超好的超牛逼的人，还有鬼佬和外国美眉。其实坦白说，如果自己一个人学习英语太孤独，太寂寞，没有办法坚持，好几次都会半途而废。只要你加入到那个群里以后，自己就会每天都能在群里坚持学，坚持不停地说和练，由于是付费群，群里的成员学习氛围非常强，每天的训练度都非常猛，本来很懒惰的你一下子就被感染了，不由自主地被带动起来参与操练，不好意思偷懒，别人的刻苦学习精神会不知不觉影响你，EYC英语微信群（群主vx 601332975）可以彻底治好你的拖延症，里面学员都非常友好，总是给你不断的帮助和鼓励，让你学英语的路上重新燃起了斗志，因为每天都在运用，你的英语口语就能得到了迅猛的提升，现在可以随便给一个话题，都能用英文滔滔不绝的发表5分钟以上对这个话题的看法和观点，想提高英语口语的可以加入进来，It really works very well.
for和to区别
1.表示各种“目的”，用for （1）What do you study English for 你为什么要学英语？ （2）went to france for holiday. 她到法国度假去了。 （3）These books are written for pupils. 这些书是为学生些的。 （4）hope for the best, prepare for the worst. 作最好的打算，作最坏的准备。 2．“对于”用for （1）She has a liking for painting. 她爱好绘画。 （2）She had a natural gift for teaching. 她对教学有天赋/ 3．表示“赞成、同情”，用for （1）Are you for the idea or against it 你是支持还是反对这个想法？ （2）He expresses sympathy for the common people.. 他表现了对普通老百姓的同情。 （3）I felt deeply sorry for my friend who was very ill. 4. 表示“因为，由于”（常有较活译法），用for （1）Thank you for coming. 谢谢你来。
（2）France is famous for its wines. 法国因酒而出名。 5．当事人对某事的主观看法，“对于（某人），对…来说”，（多和形容词连用），用介词to，不用for. （1）He said that money was not important to him. 他说钱对他并不重要。 （2）To her it was rather unusual. 对她来说这是相当不寻常的。 （3）They are cruel to animals. 他们对动物很残忍。 6．和fit, good, bad, useful, suitable 等形容词连用，表示“适宜，适合”，用for。（1）Some training will make them fit for the job. 经过一段训练，他们会胜任这项工作的。 （2）Exercises are good for health. 锻炼有益于健康。 （3）Smoking and drinking are bad for health. 抽烟喝酒对健康有害。 （4）You are not suited for the kind of work you are doing. 7. 表示不定式逻辑上的主语，可以用在主语、表语、状语、定语中。 （1）It would be best for you to write to him. （2） The simple thing is for him to resign at once.
大学英语四级基础复习讲义.pdf
plete 指完成一件指派或预定的任务,或完 善、完整未完成的部分 gain 指需要做出比 obtain 更大的努力,往往指通过竞争获得某些有价值的东西obtain 指经过努力或付出代价或经过很长时间儿得到所需要的东西end 指一个动作或一件事情的结束或终止 finish 指把一件事或一个动作做完,强调 事情的了结、终止 7、4 、 accurate , correct , delicate , exact,precise 都含有一定的"正确,精确" 之意 acknowledge,admit,concede,confess,rec ognize 都含有一定的"承认"之意acknowledge 着重”公开承认”,常用来指过去曾隐瞒或否认的事accurate 准确的,精确的,指某人或某事 不仅不出错,而且与事实无出入,强调准 确性 admit 是指在压力下不得不承认已经证实或难以否认的事实,招供(事实,错误等)concede(不情愿地)承认,(在结果确定前)承认失败correct 正确的,指某人或某事合乎事实或 公认的标准或规则,没有错误 delicate 精美、精细的、雅致的 exact 确切的、精确的,语气较 accurate 强, 指某人或某事数量或质量完全符合事实或 标准,而且在细致末节上也丝毫不差 precise 精密的,指具有高度的精确性和准 确性,强调范围界限的鲜明性或细节的精密, 有时略带"吹毛求疵"的贬义 confess 着重承认自己的过错或罪恶recognize 指正式承认主权、权利等8、affirm,assert,allege,claim 都含有一定的"宣称,断言"之意affirm 断言,肯定,指根据事实坚定不移地宣称,有无可争辩之意assert 宣称,坚持,指不管事实如何,主观自信地宣称5、accuse,charge,indict 都含有一定的 "指控,控告"之意 allege 宣称,断定,指在无真实根据情况下宣称,硬说accuseaccusesb.ofdoingsth. 为 … 指 责 某 人,控告某人 claim 声称,主张,往往表示说话者反对或不同意某一观点chargechargesb.withdoingsth. 指 控 某 人… 英语四级温习资料 2(2006-12-1116:02:10)分类：大学英语四六级温习资料征服大学英语四级考试（阅读篇）（一）存在问题6、achieve,acquire,attain,gain,obtain 都含有一定的"获得,达到"之意 achieve 强调由于极大的努力,克服困难后 达到目标 第一,读不懂acquire 指经过不懈努力才获得的技术,知 识等抽象的东西,也指养成习惯等 attain 正式用语,指经过艰苦努力才使人达 到完美境地所谓读不懂,就是考生拿过文章,满头雾水,即使硬着头皮读文章,也是一知半解。然后匆忙做体,仅凭感觉去蒙,因此做体准确率必然不高。
双宾语 to for的用法
1.两者都可以引出间接宾语，但要根据不同的动词分别选用介词to 或for：(1) 在give, pass, hand, lend, send, tell, bring, show, pay, read, return, write, offer, teach, throw 等之后接介词to。 如： 请把那本字典递给我。 正：Please hand me that dictionary. 正：Please hand that dictionary to me. 她去年教我们的音乐。 正：She taught us music last year. 正：She taught music to us last year. (2) 在buy, make, get, order, cook, sing, fetch, play, find, paint, choose,prepare, spare 等之后用介词for 。如： 他为我们唱了首英语歌。 正：He sang us an English song. 正：He sang an English song for us. 请帮我把钥匙找到。 正：Please find me the keys. 正：Please find the keys for me. 能耽搁你几分钟吗(即你能为我抽出几分钟吗)? 正：Can you spare me a few minutes? 正：Can you spare a few minutes for me? 注：有的动词由于搭配和含义的不同，用介词to 或for 都是可能的。如：do sb a favour＝do a favour for sb 帮某人的忙 do sb harm＝do harm to sb 对某人有害
双宾语tofor的用法
1. 两者都可以引出间接宾语，但要根据不同的动词分别选用介词to 或for： (1) 在give, pass, hand, lend, send, tell, bring, show, pay, read, return, write, offer, teach, throw 等之后接介词to。 如： 请把那本字典递给我。 正：Please hand me that dictionary. 正：Please hand that dictionary to me. 她去年教我们的音乐。 正：She taught us music last year. 正：She taught music to us last year. (2) 在buy, make, get, order, cook, sing, fetch, play, find, paint, choose,prepare, spare 等之后用介词for 。如： 他为我们唱了首英语歌。 正：He sang us an English song. 正：He sang an English song for us. 请帮我把钥匙找到。 正：Please find me the keys. 正：Please find the keys for me. 能耽搁你几分钟吗(即你能为我抽出几分钟吗)? 正：Can you spare me a few minutes? 正：Can you spare a few minutes for me? 注：有的动词由于搭配和含义的不同，用介词to 或for 都是可能的。如： do sb a favou r do a favour for sb 帮某人的忙 do sb harnn= do harm to sb 对某人有害
for和of的用法
for的用法： 1. 表示“当作、作为”。如: I like some bread and milk for breakfast. 我喜欢把面包和牛奶作为早餐。 What will we have for supper? 我们晚餐吃什么? 2. 表示理由或原因,意为“因为、由于”。如: Thank you for helping me with my English. 谢谢你帮我学习英语。 Thank you for your last letter. 谢谢你上次的来信。 Thank you for teaching us so well. 感谢你如此尽心地教我们。 3. 表示动作的对象或接受者,意为“给……”、“对…… (而言)”。如: Let me pick it up for you. 让我为你捡起来。 Watching TV too much is bad for your health. 看电视太多有害于你的健康。 4. 表示时间、距离,意为“计、达”。如:
I usually do the running for an hour in the morning. 我早晨通常跑步一小时。 We will stay there for two days. 我们将在那里逗留两天。 5. 表示去向、目的,意为“向、往、取、买”等。如: Let’s go for a walk. 我们出去散步吧。 I came here for my schoolbag.我来这儿取书包。 I paid twenty yuan for the dictionary. 我花了20元买这本词典。 6. 表示所属关系或用途,意为“为、适于……的”。如: It’s time for school. 到上学的时间了。 Here is a letter for you. 这儿有你的一封信。 7. 表示“支持、赞成”。如: Are you for this plan or against it? 你是支持还是反对这个计划? 8. 用于一些固定搭配中。如:
英语连接词大全
英语连接词大全 ( 转) 英语写作中常见问题就是如何连接各个句子，使之能够流畅地承上启下，更顺畅地表达出自己的观点。 这份连接词大全，提供了常用、常见的连接词，方便大家在学习、工作上的使用。建议分享收藏，以便需要时可以拿出来用噢～ 1)先后次序关系： atthistime;first;second;atlast;next；previously;simultaneously同时地;eventually；lastbutnotleast；tobeginwith；tostartwith；toendwith；finally；seeing...由于，因为；sincethen；firstofall；afterwards后来;followingthis;preceding先前的;originally最初的ultimate最终的，极限的，根本的 2)因果关系： because；becauseofthis；beingthat（口语）既然，因为；anotherimportantfactor／reasonof...；since；as；for；inthat...；owingto由于，通常负面；dueto由于；forthereasonthat...；inviewof 鉴于，考虑到resultfrom归因于thereasonseemstobeobvious;thereareabout...；forthisreason;asaresultofthis；therefore；...andso...；consequently所以，因此；asaresult；thus 这样，如此，因而；hence因此；so；sothat...；inconsequence结果，结果；asaconsequence；accordingly因此，于是，相应地;inevitably不可避免地;undertheseconditionsthereupon因此于 是upon迫近 3)转折关系： but；evenso；however；though；eventhough；independentof；recklessof不顾；despitethat；inspiteofthat；regardlessof不顾;yet...；andyet；butunless.Nonetheless尽管如此 4)并列关系： and;also；too；aswellas；either...，or...；both...and... 5)(补充)递进关系： furthermore此外，而且；moreover而且，此外；further进一步地，此外；Inthisway；still；notonly...butalso...；not...but...；inaddition(to)； additionally,muchmoreinteresting,morespecifically更具体地说,next,besides；asfaras...isconcerned 至于;moreover此外；inotherwords； alongthislineofconsideration；on(the)onehand...在一方面，ontheotherhand...；even；asasayinggoes...；inordertodoit...;meanwhile同时；atthesametime；accordingly因此；Inthefirstplace...，inthesecondplace...;equallyimportant;ofevengreaterappeal. 6)比较关系： similarly;inlikemanner,incomparisonwith；whencomparedwith；comparedwith；wheninfact...;like...；likewise同样地，也；similarlyimportant； apartfrom(doing)...；...ratherthan...，bydoingso；both…and...;inthesameway;notonly...but(also). 7)对照(不同点)：
英语形容词和of for 的用法
加入收藏夹 主题： 介词试题It’s + 形容词 + of sb. to do sth.和It’s + 形容词 + for sb. to do sth.的用法区别。 内容： It's very nice___pictures for me. A.of you to draw B.for you to draw C.for you drawing C.of you drawing 提交人：杨天若时间：1/23/2008 20:5:54 主题：for 与of 的辨别 内容：It's very nice___pictures for me. A.of you to draw B.for you to draw C.for you drawing C.of you drawing 答：选A 解析：该题考查的句型It’s + 形容词+ of sb. to do sth.和It’s +形容词+ for sb. to do sth.的用法区别。 “It’s + 形容词+ to do sth.”中常用of或for引出不定式的行为者，究竟用of sb.还是用for sb.，取决于前面的形容词。 1) 若形容词是描述不定式行为者的性格、品质的，如kind，good，nice，right，wrong，clever，careless，polite，foolish等，用of sb. 例： It’s very kind of you to help me. 你能帮我，真好。 It’s clever of you to work out the maths problem. 你真聪明，解出了这道数学题。 2) 若形容词仅仅是描述事物，不是对不定式行为者的品格进行评价，用for sb.，这类形容词有difficult，easy，hard，important，dangerous，（im）possible等。例： It’s very dangerous for children to cross the busy street. 对孩子们来说，穿过繁忙的街道很危险。 It’s difficult for u s to finish the work. 对我们来说，完成这项工作很困难。 for 与of 的辨别方法： 用介词后面的代词作主语，用介词前边的形容词作表语，造个句子。如果道理上通顺用of，不通则用for. 如： You are nice.(通顺，所以应用of)。 He is hard.(人是困难的，不通，因此应用for.) 由此可知，该题的正确答案应该为A项。 提交人：f7_liyf 时间：1/24/2008 11:18:42
to和for的用法有什么不同(一)
to和for的用法有什么不同（一） 一、引出间接宾语时的区别 两者都可以引出间接宾语，但要根据不同的动词分别选用介词to 或for，具体应注意以下三种情况： 1. 在give, pass, hand, lend, send, tell, bring, show, pay, read, return, write, offer, teach, throw 等之后接介词to。如： 请把那本字典递给我。 正：Please hand me that dictionary. 正：Please hand that dictionary to me. 她去年教我们的音乐。 正：She taught us music last year. 正：She taught music to us last year. 2. 在buy, make, get, order, cook, sing, fetch, play, find, paint, choose, prepare, spare 等之后用介词for 。如： 他为我们唱了首英语歌。 正：He sang us an English song. 正：He sang an English song for us. 请帮我把钥匙找到。 正：Please find me the keys. 正：Please find the keys for me. 能耽搁你几分钟吗(即你能为我抽出几分钟吗)? 正：Can you spare me a few minutes?
正：Can you spare a few minutes for me? 3. 有的动词由于用法和含义不同，用介词to 或for 都是可能的。如： do sb a favor＝do a favor for sb 帮某人的忙 do sb harm＝do harm to sb 对某人有害 在有的情况下，可能既不用for 也不用to，而用其他的介词。如： play sb a trick＝play a trick on sb 作弄某人 请比较： play sb some folk songs＝play some folk songs for sb 给某人演奏民歌 有时同一个动词，由于用法不同，所搭配的介词也可能不同，如leave sbsth 这一结构，若表示一般意义的为某人留下某物，则用介词for 引出间接宾语，即说leave sth for sb；若表示某人死后遗留下某物，则用介词to 引出间接宾语，即说leave sth to sb。如： Would you like to leave him a message? / Would you like to leave a message for him? 你要不要给他留个话？ Her father left her a large fortune. / Her father left a large fortune to her. 她父亲死后给她留下了一大笔财产。 二、表示目标或方向的区别 两者均可表示目标、目的地、方向等，此时也要根据不同动词分别对待。如： 1. 在come, go, walk, move, fly, ride, drive, march, return 等动词之后通常用介词to 表示目标或目的地。如： He has gone to Shanghai. 他到上海去了。 They walked to a river. 他们走到一条河边。
while、when和as的用法区别
as when while 的区别和用法 as when while的用法 一、as的意思是“正当……时候”,它既可表示一个具体的时间点，也可以表示一段时间。as可表示主句和从句的动作同时发生或同时持续，即“点点重合”“线线重合”；又可表示一个动作发生在另一个动作的持续过程中，即“点线重合”， 但不能表示两个动作一前一后发生。如果主句和从句的谓语动词都表示持续性的动作，二者均可用进行时，也可以一个用进行时，一个用一般时或者都用一般时。 1、As I got on the bus，he got off. 我上车，他下车。（点点重合）两个动作都是非延续性的 2、He was writing as I was reading. 我看书时，他在写字。（线线重合）两个动作都是延续性的 3、The students were talking as the teacher came in. 老师进来时，学生们正在讲话。（点线重合）前一个动作是延续性的，而后一个动作时非延续性的 二、while的意思是“在……同时（at the same time that )”“在……期间(for as long as, during the time that）”。从while的本身词义来看，它只能表示一段时间，不能表示具体的时间点。在时间上可以是“线线重合”或“点线重合”，但不能表示“点点重合”。例如： 1、He was watching TV while she was cooking. 她做饭时，他在看电视。（线线重合） 2、He was waiting for me while I was working. 我工作的时候，他正等着我。（线线重合） 3、He asked me a question while I was speaking. 我在讲话时，他问了我一个问题。（点线重合）
202X中考英语：to和for的区别与用法.doc
202X中考英语：to和for的区别与用法中考栏目我为考生们整理了“202X中考英语：to和for的区别与用法”，希望能帮到大家，想了解更多考试资讯，本网站的及时更新哦。 202X中考英语：to和for的区别与用法 to和for的区别与用法是什么 一般情况下, to后面常接对象; for后面表示原因与目的为多。 Thank you for helping me. Thanks to all of you. to sb. 表示对某人有直接影响比如，食物对某人好或者不好就用to; for 表示从意义、价值等间接角度来说，例如对某人而言是重要的，就用for. for和to这两个介词，意义丰富，用法复杂。这里仅就它们主要用法进行比较。 1. 表示各种“目的” 1. What do you study English for? 你为什么要学英语? 2. She went to france for holiday. 她到法国度假去了。 3. These books are written for pupils. 这些书是为学生些的。 4. hope for the best, prepare for the worst. 作最好的打算，作最坏的准备。
2.对于 1.She has a liking for painting. 她爱好绘画。 2.She had a natural gift for teaching. 她对教学有天赋。 3.表示赞成同情，用for不用to. 1. Are you for the idea or against it? 你是支持还是反对这个想法? 2. He expresses sympathy for the common people.. 他表现了对普通老百姓的同情。 3. I felt deeply sorry for my friend who was very ill. 4 for表示因为，由于(常有较活译法) 1.Thank you for coming. 谢谢你来。 2. France is famous for its wines. 法国因酒而出名。 5.当事人对某事的主观看法，对于(某人)，对?来说(多和形容词连用)用介词to，不用for.. He said that money was not important to him. 他说钱对他并不重要。 To her it was rather unusual. 对她来说这是相当不寻常的。 They are cruel to animals. 他们对动物很残忍。