1、Digitalis is one of the most frequently used medications in the treatment of heart failure and arrhythmia. It increases the contractility of the heart muscle and modifies vascular resistance. It also slows conduction through the atrioventricular node in the heart, making it useful in the treatment of atrial fibrillation and other rapid heart rhythms
洋地黄是其中一个最常用的药物治疗心力衰竭和心律失常。它增加了的心肌收缩血管阻力和修改。它也减慢传导通过传导节点的心使它有用的治疗房颤和其他快速心律
2、The formulation of a parenteral product involves the combination of one or more ingredients
with a medicinal agent to enhance the convenience，acceptability ，or effectiveness of the product. Rarely is it preferable to dispense a drug singly as a sterile dry powder unless the formulation of a stable liquid preparation is not possible
非肠道用产品的配方涉及一个或者更多组成部分间的结合，这些组成部分（各自）都含有一种用以提高产品方便性、可接受性或者疗效的有效成分。（人们）很少愿意把药物仅仅以一种无菌的、干燥的粉末（的形式）配售，除非（把它做成）稳定的液体制剂的配方是行不通的。
3、Production 生产
The production process includes all of the steps from the accumulation and combining of the ingredients of the formula to the enclosing of the product in the individual container for distribution. Intimately associated with these processes are the personnel who carry them out and the facilities in which they are performed. The most ideally planned processes can be rendered ineffective by personnel who do not have the right attitude or training，or by facilities that do not provide an efficiently controlled environment.
生产过程包括从配方的各个组成部分的积聚和结合到产品封装入用于分售的单个包装内的所有步骤。和这些过程有紧密联系的是搬运人员和执行这些步骤的设备。计划出来的最理想的过程也会因为没有正确态度或没有接受正确培训的人员或者不能提供一个有效的控制环境的设备而变得无效。
To enhance the assurance of successful manufacturing operation ，all process steps must be carefully reduced to writing after being shown to be effective. These written process steps are often called standard. operating procedures (SOPs)⑥.No extemporaneous changes are permitted to be made in these procedures; any change must go through the same approval steps as the original written SOP. Further ，extensive records must be kept to give assurance at the end of the production process that all steps have been performed as prescribed，an aspect emphasized in the FDA's Good Manufacturing Practices. Such in-process control is essential to assuring the quality of the product，since these assurances are even more significant than those from product release testing. The production of .a quality product is a result of the continuous ,dedicated effort of the quality assurance，production ，and quality control personnel within the plant in developing，performing ，and confirming effective sops
为了增加成功的生产操作的保证，所有的过程步骤在证明是有效的之后都要仔细地归纳成书面材料，这些书面的过程步骤经常被称为标准操作规程（SOPs ）。这些规程是不允许进行临时改动的, 任何改动都必须经过和原有的书面规程一样
的证明步骤的证明。而且，还需要做大量的记录，以便在生产过程的最后用来保证：所有的步骤都是按照规定执行的。这是美国食品及药物管理局药品生产质量管理规范, 这样的过程中的控制是必不可少的保证了产品的质量，因为这些保证甚至比那些从产物释放测试更显著。 ，高品质的产品的生产厂在开发，执行，并确认有效的SOP 中的质量保证，生产和质量控制人员的连续，专用努力的结果
4、Reactor technology comprises the underlying principles of chemical reaction engineering(CRE)and the practices used in their application. The focuses of reactor technology are reactor configurations ，operating conditions ，external operating environments ，developmental history，industrial application，and evolutionary change. Reactor designs evolve from the pursuit of new products and uses，higher conversion，more favorable reaction selectivity，reduced fixed and operating costs，intrinsically safe operation，and environmentally acceptable processing
反应堆技术包括化学反应工程（CRE ），并在其应用程序中使用的惯例的基本原则。反应器技术的重点是反应器构型，经营状况，外部经营环境，发展历史，工业应用和进化改变。反应堆设计从追求新产品和用途的发展，更高的转换，更有利的反应选择性，减少了固定和运营成本，本质安全的操作，并符合环保要求处理
5、Drug development aims to produce a novel therapeutic agent which is superior in efficacy to existing remedies and which causes less frequent or less severe adverse effects.
药物研制旨在生产出在疗效上优于现存药品，且副作用发生率减少、程度降低的新型治疗药物。
6、Phase 1 involves small scale studies in normal volunteers. These studies should determine whether the drug can be given to man without serious symptoms or toxicity, and whether it has desired pharmacological effects .These studies often begin with a dose ranging study, using 1/50 to 1/100 the effective dose in animals and increasing until the desired effect, or adverse effects, are seen. These studies should only be performed on volunteers who are informed about the implications of the tests, and who give their consent freely Studies should include careful assessment of clinical, haematological evidence before and after drug administration to identify pharmacological actions and adverse effects. Phase 1 studies should only be performed by experienced staff, under medical supervision, and in premises with appropriate resuscitative facilities and support.
第一阶段，新药小规模运用在正常志愿者身上的研究。这个阶段的研究应确定药物是否能让正常人产生严重副反应和毒性反应，以及能否有明显的药理作用。这些研究往往从一个剂量范围开始，在1/100 到 1/50范围内的动物有效剂量开始逐次增加使用剂量，直到出现明显药理作用或者副作用为止。这些研究只能在这样的志愿者身上进行，他们应该了解实验的影响并且自愿同意进行实验。研究还应包括仔细的评估临床，根据实验前后的血药浓度来确定的药物的药理作用及不良影响。这一阶段的研究只能在有经验的工作人员和医生监督下进行，并且有抢救设备和复苏技术的支持。
Phase 2 studies determine whether the new drug has the desired effect on patients
with the appropriate disease .In Britain these investigations can be performed only after submission of preclinical and phase 1 study results to the Committee on Safety of Medicines. This body either issues a clinical trial certificate (CTC) or authorizes limited clinical trials under an exemption procedure (CTE).Phase 2 studies initially may be open, uncontrolled, dose-ranging experiments but should include controlled studies under single or Double-blind conditions. they may involve comparisons with inactive placebo or known active agents.
第二阶段的研究要确定新药在患有相关疾病的人身上是否有明显的疗效。在英国，这些研究有且只有在提交前期和第一期研究结果到药物安全委员会的情况下才可以进行。这个部分主要是发行一份临床试验证明(CTC)或根据豁免做法(CTE)批准有限的临床试验。第二阶段的研究也许最初是开放的，没条件限制的，药量排列的实验，但是研究应该控制在唯一或双盲情况下进行。研究中可包括一些只服用非活性安慰剂或已知的活性药物的对照组。
Phase 3：If results of therapeutic efficacy and safety justify it, the next step is progression to large scale clinical trials to determine how the new drug compare in clinical practice with existing remedies, and to establish its profile of action and frequency of adverse effects.
第三阶段：如果治疗的有效性和安全性被证明，下一步就是发展到大规模的临床试验，以确定新的药物在临床实践中如何比较与现有的补救措施，并建立行动的不利影响和频率的分布。After Phase 3 studies the evidence from all stages of development is assembled and if the conclusions indicate a useful action, the drug may be submitted to the regulatory authorities with a request for a product license. 继第三阶段研究之后，在第三阶段研究之后，来自各发展阶段的证据将被分析，如果结论表明了有益的作用，新药会被许可向药物监管机构申请获得一个产品的许可证。
Phase 4 A new drug is usually marketed after only a few hundred, or at the most a few thousand, patients have been exposed to it for a relatively short period (weeks or months). Post-marketing surveillance is increasingly undertaken to assess efficacy and toxicity of new drugs on a large scale. No uniform scheme for Phase 4 supervision has yet been established, but few doubt the necessity of collecting this information on low-frequency adverse effects
第四阶段：一个新的药物通常是上市后仅过了几百年，或在最几千年，患者接触到药物的时间都相对较短（数周或数月）。大规模的上市后监测越来越多地承担了评估新药的疗效和毒性的方法。对第四阶段的监管虽然没有规定统一的操作，但很少有人怀疑收集阶段低频副作用的必要性
7、Under current law, all new drugs need proof that they are effective, as well as safe, before they can be approved for marketing. But it’s important to realize that no drug is absolutely safe. There is always some risk of an adverse reaction. It’s when the benefits outweigh the risks that FDA considers a drug safe enough to approve.
现有的法律要求，所有的新药在被批准上市前都必须出具其有效、安全的证据。但必须认识到没有任何药品是绝对安全的，总有不良反应的危险，只有当益处超过风险时，FDA 才会认为该药品足够安全，可以批准。
8、
Full reports of a drug’s studies must be submitted because they are the basis of
FDA’s evaluation of safety and effecti veness. The controlled clinical trials are especially important because they involve the greatest number of patients.
制药商必须提供药物研究的所有报告，因为它是FDA 评估其安全性和有效性的基础。有对照组的临床实验尤其重要因为涉及众多病人。
By providing for the appropriate comparisons to judge the drug’s effectiveness and by revealing less common (even rare) side effects and adverse reactions, they help to clarify the drug’s benefit-to-risk relationship. The final human studies also generate information that will be in the drug’s professional labeling, the guidance approved by FDA on how to use the drug. This is the package insert that accompanies a drug in all shipments to physicians and pharmacies.
通过提供适当的比较，以判断药物的有效性，并揭示不常见（甚至罕见的）副作用和不良反应，它们有助于澄清该药物的益处与风险的关系。最终人类的研究也产生信息，这将是在药物的专业标签，就如何使用这种药物通过美国FDA 认证的指导。这是伴随着药物在所有出货给医生和药店的药品说明书。
9、Anytime during an NDA review, FDA may contact the sponsor or the investigators to discuss problems concerning the data
随时在NDA 的审查，FDA 可能与保荐人或调查人员讨论有关数据的问题
Indeed, FDA staff may visit the sites of some of the studies to compare results provid ed in the NDA with the physicians’ patient records. If there are major deficiencies with any part of the NDA, substantially more work by the sponsor may be needed.
实际上，FDA 的工作人员可能会亲临一些研究地点，以将NDA 中的结果与医生的患者记录进行比较。如果与NDA 的任何部分有较大的分歧，赞助商还需做大量的工作。
FDA frequently asks one of its 17 standing advisory committees on drugs and biologics for advice. This is especially true when an approval decision is a “close call”.
FDA 经常向其17个药物和生物制品常务顾问委员会之一征求意见，特别是当是否批准的决定“千钧一发”时，更是如此。
In the final analysis, FDA’s decision whether to approve a new drug for marketing boils down to two questions
在最后的分析中，FDA 的决定是否批准一种新药的营销归结为两个问题 Do the results provide substantial evidence of effectiveness?
This may be easy to figure out in a study with a drug to treat high blood pressure —if the drug works, the blood pressure goes down. But other studies, such as those testing a drug to treat depression, are more complicated.
请执行结果的有效性提供了大量的证据？
这可能很容易搞清楚与药物来治疗高血压，如果药物工程研究，血压下降。但其他研究中，如那些测试一种药物来治疗抑郁症，比较复杂。
Do the results show the product is safe under the conditions of use in the proposed labeling? Reviewers note whether the adverse reactions show any disturbing pattern of occurrence. They “tease” out, so to speak, whether certain symptoms—such as headache or constipation —were caused by the drug or whether they occurred independently
不要结果显示使用条件下的产品是安全的建议的标签？审稿人注意不良反应是否显示发生任何令人不安的模式。他们“挑逗”出来的，可以这么说，是否有某些症状，如头痛，或便秘是由药物或引起他们是否独立发生。
10、To be sure approval decisions reflect the most recent safety data, FDA requires safety updates four months after the NDA is submitted, again after it sends the firm an “approvable letter” and at other times as appropriate—before an advisory committee meeting, for instance.
为了确定批准决定反映了最新的安全数据，FDA 要求新药申请递交后的4个月更新安全资料，以及在寄给公司“可能批准信”后、在其他适当的时候，如在顾问委员会开会之前，都要更新安全资料。
Updates must report new adverse reactions and important changes in the frequency or severity of effects that are known. Thus, new data suggesting that an adverse effect occurs more often than previously thought might change a “precaution” to a “warning” in the labeling.
更新信息须报告新的不良反应和已知不良反应的频率和严重性的重要变化。因此，新数据若反映不良反应比以前认定的更严重，说明书中的“注意事项”可能会被改为“警告”.
1、Digitalis is one of the most frequently used medications in the treatment of heart failure and arrhythmia. It increases the contractility of the heart muscle and modifies vascular resistance. It also slows conduction through the atrioventricular node in the heart, making it useful in the treatment of atrial fibrillation and other rapid heart rhythms
洋地黄是其中一个最常用的药物治疗心力衰竭和心律失常。它增加了的心肌收缩血管阻力和修改。它也减慢传导通过传导节点的心使它有用的治疗房颤和其他快速心律
2、The formulation of a parenteral product involves the combination of one or more ingredients
with a medicinal agent to enhance the convenience，acceptability ，or effectiveness of the product. Rarely is it preferable to dispense a drug singly as a sterile dry powder unless the formulation of a stable liquid preparation is not possible
非肠道用产品的配方涉及一个或者更多组成部分间的结合，这些组成部分（各自）都含有一种用以提高产品方便性、可接受性或者疗效的有效成分。（人们）很少愿意把药物仅仅以一种无菌的、干燥的粉末（的形式）配售，除非（把它做成）稳定的液体制剂的配方是行不通的。
3、Production 生产
The production process includes all of the steps from the accumulation and combining of the ingredients of the formula to the enclosing of the product in the individual container for distribution. Intimately associated with these processes are the personnel who carry them out and the facilities in which they are performed. The most ideally planned processes can be rendered ineffective by personnel who do not have the right attitude or training，or by facilities that do not provide an efficiently controlled environment.
生产过程包括从配方的各个组成部分的积聚和结合到产品封装入用于分售的单个包装内的所有步骤。和这些过程有紧密联系的是搬运人员和执行这些步骤的设备。计划出来的最理想的过程也会因为没有正确态度或没有接受正确培训的人员或者不能提供一个有效的控制环境的设备而变得无效。
To enhance the assurance of successful manufacturing operation ，all process steps must be carefully reduced to writing after being shown to be effective. These written process steps are often called standard. operating procedures (SOPs)⑥.No extemporaneous changes are permitted to be made in these procedures; any change must go through the same approval steps as the original written SOP. Further ，extensive records must be kept to give assurance at the end of the production process that all steps have been performed as prescribed，an aspect emphasized in the FDA's Good Manufacturing Practices. Such in-process control is essential to assuring the quality of the product，since these assurances are even more significant than those from product release testing. The production of .a quality product is a result of the continuous ,dedicated effort of the quality assurance，production ，and quality control personnel within the plant in developing，performing ，and confirming effective sops
为了增加成功的生产操作的保证，所有的过程步骤在证明是有效的之后都要仔细地归纳成书面材料，这些书面的过程步骤经常被称为标准操作规程（SOPs ）。这些规程是不允许进行临时改动的, 任何改动都必须经过和原有的书面规程一样
的证明步骤的证明。而且，还需要做大量的记录，以便在生产过程的最后用来保证：所有的步骤都是按照规定执行的。这是美国食品及药物管理局药品生产质量管理规范, 这样的过程中的控制是必不可少的保证了产品的质量，因为这些保证甚至比那些从产物释放测试更显著。 ，高品质的产品的生产厂在开发，执行，并确认有效的SOP 中的质量保证，生产和质量控制人员的连续，专用努力的结果
4、Reactor technology comprises the underlying principles of chemical reaction engineering(CRE)and the practices used in their application. The focuses of reactor technology are reactor configurations ，operating conditions ，external operating environments ，developmental history，industrial application，and evolutionary change. Reactor designs evolve from the pursuit of new products and uses，higher conversion，more favorable reaction selectivity，reduced fixed and operating costs，intrinsically safe operation，and environmentally acceptable processing
反应堆技术包括化学反应工程（CRE ），并在其应用程序中使用的惯例的基本原则。反应器技术的重点是反应器构型，经营状况，外部经营环境，发展历史，工业应用和进化改变。反应堆设计从追求新产品和用途的发展，更高的转换，更有利的反应选择性，减少了固定和运营成本，本质安全的操作，并符合环保要求处理
5、Drug development aims to produce a novel therapeutic agent which is superior in efficacy to existing remedies and which causes less frequent or less severe adverse effects.
药物研制旨在生产出在疗效上优于现存药品，且副作用发生率减少、程度降低的新型治疗药物。
6、Phase 1 involves small scale studies in normal volunteers. These studies should determine whether the drug can be given to man without serious symptoms or toxicity, and whether it has desired pharmacological effects .These studies often begin with a dose ranging study, using 1/50 to 1/100 the effective dose in animals and increasing until the desired effect, or adverse effects, are seen. These studies should only be performed on volunteers who are informed about the implications of the tests, and who give their consent freely Studies should include careful assessment of clinical, haematological evidence before and after drug administration to identify pharmacological actions and adverse effects. Phase 1 studies should only be performed by experienced staff, under medical supervision, and in premises with appropriate resuscitative facilities and support.
第一阶段，新药小规模运用在正常志愿者身上的研究。这个阶段的研究应确定药物是否能让正常人产生严重副反应和毒性反应，以及能否有明显的药理作用。这些研究往往从一个剂量范围开始，在1/100 到 1/50范围内的动物有效剂量开始逐次增加使用剂量，直到出现明显药理作用或者副作用为止。这些研究只能在这样的志愿者身上进行，他们应该了解实验的影响并且自愿同意进行实验。研究还应包括仔细的评估临床，根据实验前后的血药浓度来确定的药物的药理作用及不良影响。这一阶段的研究只能在有经验的工作人员和医生监督下进行，并且有抢救设备和复苏技术的支持。
Phase 2 studies determine whether the new drug has the desired effect on patients
with the appropriate disease .In Britain these investigations can be performed only after submission of preclinical and phase 1 study results to the Committee on Safety of Medicines. This body either issues a clinical trial certificate (CTC) or authorizes limited clinical trials under an exemption procedure (CTE).Phase 2 studies initially may be open, uncontrolled, dose-ranging experiments but should include controlled studies under single or Double-blind conditions. they may involve comparisons with inactive placebo or known active agents.
第二阶段的研究要确定新药在患有相关疾病的人身上是否有明显的疗效。在英国，这些研究有且只有在提交前期和第一期研究结果到药物安全委员会的情况下才可以进行。这个部分主要是发行一份临床试验证明(CTC)或根据豁免做法(CTE)批准有限的临床试验。第二阶段的研究也许最初是开放的，没条件限制的，药量排列的实验，但是研究应该控制在唯一或双盲情况下进行。研究中可包括一些只服用非活性安慰剂或已知的活性药物的对照组。
Phase 3：If results of therapeutic efficacy and safety justify it, the next step is progression to large scale clinical trials to determine how the new drug compare in clinical practice with existing remedies, and to establish its profile of action and frequency of adverse effects.
第三阶段：如果治疗的有效性和安全性被证明，下一步就是发展到大规模的临床试验，以确定新的药物在临床实践中如何比较与现有的补救措施，并建立行动的不利影响和频率的分布。After Phase 3 studies the evidence from all stages of development is assembled and if the conclusions indicate a useful action, the drug may be submitted to the regulatory authorities with a request for a product license. 继第三阶段研究之后，在第三阶段研究之后，来自各发展阶段的证据将被分析，如果结论表明了有益的作用，新药会被许可向药物监管机构申请获得一个产品的许可证。
Phase 4 A new drug is usually marketed after only a few hundred, or at the most a few thousand, patients have been exposed to it for a relatively short period (weeks or months). Post-marketing surveillance is increasingly undertaken to assess efficacy and toxicity of new drugs on a large scale. No uniform scheme for Phase 4 supervision has yet been established, but few doubt the necessity of collecting this information on low-frequency adverse effects
第四阶段：一个新的药物通常是上市后仅过了几百年，或在最几千年，患者接触到药物的时间都相对较短（数周或数月）。大规模的上市后监测越来越多地承担了评估新药的疗效和毒性的方法。对第四阶段的监管虽然没有规定统一的操作，但很少有人怀疑收集阶段低频副作用的必要性
7、Under current law, all new drugs need proof that they are effective, as well as safe, before they can be approved for marketing. But it’s important to realize that no drug is absolutely safe. There is always some risk of an adverse reaction. It’s when the benefits outweigh the risks that FDA considers a drug safe enough to approve.
现有的法律要求，所有的新药在被批准上市前都必须出具其有效、安全的证据。但必须认识到没有任何药品是绝对安全的，总有不良反应的危险，只有当益处超过风险时，FDA 才会认为该药品足够安全，可以批准。
8、
Full reports of a drug’s studies must be submitted because they are the basis of
FDA’s evaluation of safety and effecti veness. The controlled clinical trials are especially important because they involve the greatest number of patients.
制药商必须提供药物研究的所有报告，因为它是FDA 评估其安全性和有效性的基础。有对照组的临床实验尤其重要因为涉及众多病人。
By providing for the appropriate comparisons to judge the drug’s effectiveness and by revealing less common (even rare) side effects and adverse reactions, they help to clarify the drug’s benefit-to-risk relationship. The final human studies also generate information that will be in the drug’s professional labeling, the guidance approved by FDA on how to use the drug. This is the package insert that accompanies a drug in all shipments to physicians and pharmacies.
通过提供适当的比较，以判断药物的有效性，并揭示不常见（甚至罕见的）副作用和不良反应，它们有助于澄清该药物的益处与风险的关系。最终人类的研究也产生信息，这将是在药物的专业标签，就如何使用这种药物通过美国FDA 认证的指导。这是伴随着药物在所有出货给医生和药店的药品说明书。
9、Anytime during an NDA review, FDA may contact the sponsor or the investigators to discuss problems concerning the data
随时在NDA 的审查，FDA 可能与保荐人或调查人员讨论有关数据的问题
Indeed, FDA staff may visit the sites of some of the studies to compare results provid ed in the NDA with the physicians’ patient records. If there are major deficiencies with any part of the NDA, substantially more work by the sponsor may be needed.
实际上，FDA 的工作人员可能会亲临一些研究地点，以将NDA 中的结果与医生的患者记录进行比较。如果与NDA 的任何部分有较大的分歧，赞助商还需做大量的工作。
FDA frequently asks one of its 17 standing advisory committees on drugs and biologics for advice. This is especially true when an approval decision is a “close call”.
FDA 经常向其17个药物和生物制品常务顾问委员会之一征求意见，特别是当是否批准的决定“千钧一发”时，更是如此。
In the final analysis, FDA’s decision whether to approve a new drug for marketing boils down to two questions
在最后的分析中，FDA 的决定是否批准一种新药的营销归结为两个问题 Do the results provide substantial evidence of effectiveness?
This may be easy to figure out in a study with a drug to treat high blood pressure —if the drug works, the blood pressure goes down. But other studies, such as those testing a drug to treat depression, are more complicated.
请执行结果的有效性提供了大量的证据？
这可能很容易搞清楚与药物来治疗高血压，如果药物工程研究，血压下降。但其他研究中，如那些测试一种药物来治疗抑郁症，比较复杂。
Do the results show the product is safe under the conditions of use in the proposed labeling? Reviewers note whether the adverse reactions show any disturbing pattern of occurrence. They “tease” out, so to speak, whether certain symptoms—such as headache or constipation —were caused by the drug or whether they occurred independently
不要结果显示使用条件下的产品是安全的建议的标签？审稿人注意不良反应是否显示发生任何令人不安的模式。他们“挑逗”出来的，可以这么说，是否有某些症状，如头痛，或便秘是由药物或引起他们是否独立发生。
10、To be sure approval decisions reflect the most recent safety data, FDA requires safety updates four months after the NDA is submitted, again after it sends the firm an “approvable letter” and at other times as appropriate—before an advisory committee meeting, for instance.
为了确定批准决定反映了最新的安全数据，FDA 要求新药申请递交后的4个月更新安全资料，以及在寄给公司“可能批准信”后、在其他适当的时候，如在顾问委员会开会之前，都要更新安全资料。
Updates must report new adverse reactions and important changes in the frequency or severity of effects that are known. Thus, new data suggesting that an adverse effect occurs more often than previously thought might change a “precaution” to a “warning” in the labeling.
更新信息须报告新的不良反应和已知不良反应的频率和严重性的重要变化。因此，新数据若反映不良反应比以前认定的更严重，说明书中的“注意事项”可能会被改为“警告”.