【转载】314Part B 314.50

【转载】314Part B 314.50(4/4）  

2014-10-16 22:51:56|  分类： FDA|举报|字号 [url=]订阅[/url]

本文转载自aimerjiaer《314Part B 314.50(4/4）》


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(j)Claimed exclusivity. A new drug product, upon approval, may be entitled to a period of marketing exclusivity under the provisions of 314.108. If an applicant believes its drug product is entitled to a period of exclusivity, it shall submit with the new drug application prior to approval the following information:

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(j)市场专营期  根据314.08条款，新药一旦批准将获得一定期限的市场专营权。如果新药申请人认为自己有权获得市场专营期，应在申请批准前递交以下信息：

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(1) A statement that the applicant is claiming exclusivity.

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(1)提供一份陈述，说明申请人要求给予市场专营权

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(2) A reference to the appropriate paragraph under 314.108 that supports its claim.

(2)引用314.108中的段落以支持该诉求

(3) If the applicant claims exclusivity under 314.108(b)(2), information to show that, to the best of its knowledge or belief, a drug has not previously been approved under section 505(b) of the act containing any active moiety in the drug for which the applicant is seeking approval.

(3)如果申请人依据314.108(b)(2)条款主张市场专营权，以申请人的认知和信念，提供信息证明所申请药品的活性成分，先前没有在任何法案505(b)所批准的药品中出现过。（NCE,新的活性成分）

(4) If the applicant claims exclusivity under 314.108(b)(4) or (b)(5), the following information to show that the application contains "new clinical investigations" that are "essential to approval of the application or supplement" and were "conducted or sponsored by the applicant:"

(4)如果申请人依据314.108(b)(4)或(b)(5)条款主张市场专营权，需提供以下信息证明申请包含“新的临床研究”，这些研究是“申请或者补充得到批准的要素”并且“由申请人实施或赞助”。

(i)"New clinical investigations." A certification that to the best of the applicant's knowledge each of the clinical investigations included in the application meets the definition of "new clinical investigation" set forth in 314.108(a).

(i)“新的临床研究” 以申请人的认知提供一份声明，声明申请中包含的所有临床研究都符合314.08(a)对“新的临床研究”的定义。

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(ii)"Essential to approval." A list of all published studies or publicly available reports of clinical investigations known to the applicant through a literature search that are relevant to the conditions for which the applicant is seeking approval, a certification that the applicant has thoroughly searched the scientific literature and, to the best of the applicant's knowledge, the list is complete and accurate and, in the applicant's opinion, such published studies or publicly available reports do not provide a sufficient basis for the approval of the conditions for which the applicant is seeking approval without reference to the new clinical investigation(s) in the application, and an explanation as to why the studies or reports are insufficient.

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(ii) “批准的要素”  申请人对寻求批准的使用条件所相关的临床研究进行文献搜索，将搜索到的所有公开的研究和公开的报告做一份清单，同时提供一份声明，声明申请人已经查阅了所有的科学文献并且以申请人的认知，所提供的清单是完整并且正确的。声明以申请人的观点，上述的研究和报告倘若不引用申请中新的临床研究，就不足以为寻求批准的使用条件提供充分的基础，同时需说明这些研究或报告不充分的理由。

(iii)"Conducted or sponsored by." If the applicant was the sponsor named in the Form FDA-1571 for an investigational new drug application (IND) under which the new clinical investigation(s) that is essential to the approval of its application was conducted, identification of the IND by number. If the applicant was not the sponsor of the IND under which the clinical investigation(s) was conducted, a certification that the applicant or its predecessor in interest provided substantial support for the clinical investigation(s) that is essential to the approval of its application, and information supporting the certification. To demonstrate "substantial support," an applicant must either provide a certified statement from a certified public accountant that the applicant provided 50 percent or more of the cost of conducting the study or provide an explanation of why FDA should consider the applicant to have conducted or sponsored the study if the applicant's financial contribution to the study is less than 50 percent or the applicant did not sponsor the investigational new drug. A predecessor in interest is an entity, e.g., a corporation, that the applicant has taken over, merged with, or purchased, or from which the applicant has purchased all rights to the drug. Purchase of nonexclusive rights to a clinical investigation after it is completed is not sufficient to satisfy this definition.

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(iii) “由谁实施或赞助”  如果申请人是调研性新药申请（IND）表格FDA-1571中指定的赞助人，作为IND批准要素，新的临床试验已实施的，提供IND号。如果申请人不是IND（新的临床研究已实施）的赞助人，需提供一份声明，声明申请人或其前身有意向为作为批准要素的临床研究提供实质性的支持，同时提供信息支持该声明。为了证明是“实质性的支持”，申请人必须提供一份由注册会计师认证的报表，证明申请人承担了50%或以上的临床研究的费用。如果申请人财政贡献少于50%或者申请人没有赞助IND，需要向FDA解释说明为什么当局应该认为申请人实施或者赞助了研究。有意向的前身指的是一个实体，例如申请人已接管，合并，购买的一家公司，或者申请人从该公司购买了产品的所有权限。临床研究实施完成后，没有购买其市场专营权的不属于上述范畴。

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(k)Financial certification or disclosure statement. The application shall contain a financial certification or disclosure statement or both as required by part 54 of this chapter.

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(k) 财政证明或者披露声明  按照本部分54部分的要求，申请人需包括一份财政证明或者披露声明，或者两者兼有。

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(l)Format of an original application --(1)Archival copy. The applicant must submit a complete archival copy of the application that contains the information required under paragraphs (a) through (f) of this section. FDA will maintain the archival copy during the review of the application to permit individual reviewers to refer to information that is not contained in their particular technical sections of the application, to give other agency personnel access to the application for official business, and to maintain in one place a complete copy of the application. Except as required by paragraph (l)(1)(i) of this section, applicants may submit the archival copy on paper or in electronic format provided that electronic submissions are made in accordance with part 11 of this chapter.

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(1)原始申请的格式--（1）归档的复印件  申请人需要提供一份完整的归档件，包括本部分(a)至（f）的内容。FDA在审核期间将保存该归档，允许审核人员参照所审核的技术部分未包含的信息，允许其他当局人员处理公务时可以参照该申请，同时也是为了在固定的地方可以保存一份完整的申请。除了本部分段落(l)(1)(i)要求的信息，申请人可以以纸质版或者电子版的形式递交归档件，电子版递交需符合本章节11部分的要求。

(i)Labeling. The content of labeling required under 201.100(d)(3) of this chapter (commonly referred to as the package insert or professional labeling), including all text, tables, and figures, must be submitted to the agency in electronic format as described in paragraph (l)(5) of this section. This requirement is in addition to the requirements of paragraph (e)(2)(ii) of this section that copies of the formatted label and all labeling be submitted. Submissions under this paragraph must be made in accordance with part 11 of this chapter, except for the requirements of 11.10(a), (c) through (h), and (k), and the corresponding requirements of 11.30.

(i) 标签  根据本章节201.100(d)(3)的要求，标签内容(通常指的是说明书或者专业的标签)包括所有的文本，表格，以及图表，必须以本部分(l)（5）要求的电子版形式递交。这条是对本部分(e)(2)(ii)关于递交格式化标签和其他标识规定的补充。本段落提到的递交内容必须符合本章节11部分的要求，11.10(a), (c) 至 (h),(k)以及11.30相关的要求除外。

(ii) [Reserved][保留部分]

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(2)Review copy. The applicant must submit a review copy of the application. Each of the technical sections, described in paragraphs (d)(1) through (d)(6) of this section, in the review copy is required to be separately bound with a copy of the application form required under paragraph (a) of this section and a copy of the summary required under paragraph (c) of this section.

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(2)审核复印件  申请人必须递交一份审核件。审核件中每个按照本部分章节(d)(1) 至(d)(6)要求递交的技术部分，需要分别与本部分段落(a)要求的申请表复印件以及按照本部分段落(c)要求的摘要放在一起。

(3)Field copy. The applicant must submit a field copy of the application that contains the technical section described in paragraph (d)(1) of this section, a copy of the application form required under paragraph (a) of this section, a copy of the summary required under paragraph (c) of this section, and a certification that the field copy is a true copy of the technical section described in paragraph (d)(1) of this section contained in the archival and review copies of the application.

(3)现场检查用的复印件  申请人必须提供一份现场检查用的复印件，包含本部分段落(d)(1)描述的技术部分，本部分段落(a)要求的申请表格复印件，本部分段落(c)要求的摘要复印件，以及提供一份声明，声明检查用的复印件中(d)(1)的技术部分是归档件以及审核件真实的副本。

(4)Binding folders. The applicant may obtain from FDA sufficient folders to bind the archival, the review, and the field copies of the application.

(4)装订用的文件夹  申请人可以从FDA处获得足够的文件夹用于装订申请的归档件，节选件和审核件。

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(5)Electronic format submissions. Electronic format submissions must be in a form that FDA can process, review, and archive. FDA will periodically issue guidance on how to provide the electronic submission (e.g., method of transmission, media, file formats, preparation and organization of files).

(5)电子格式递交 电子递交必须以FDA能够处理，审核以及归档的格式递交。FDA将会阶段性的发布关于如何进行电子递交的指南（例如，递交的方法，途径，文件格式，文件的准备和组织）

[50 FR 7493, Feb. 22, 1985]

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Editorial Note:

编辑注：

For Federal Register citations affecting 314.50, see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and at www.fdsys.gov .

联邦注册引用到314.50的，请参见联邦法规部分的清单，印刷卷中的清单位于目录索引部分，也可以访问网址www.fdsys.gov

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【转载】314Part B 314.50(3/4）  

2014-10-16 22:56:56|  分类： FDA|举报|字号 [url=]订阅[/url]

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本文转载自aimerjiaer《314Part B 314.50(3/4）》http://zhuyujiao1972.blog.163.com/blog/static/986947272014916105656371/

(e)Samples and labeling. (1) Upon request from FDA, the applicant shall submit the samples described below to the places identified in the agency's request. FDA will generally ask applicants to submit samples directly to two or more agency laboratories that will perform all necessary tests on the samples and validate the applicant's analytical procedures.
（e）样品和标签   （1）如果FDA要求，申请人应当按如下所诉将样品递交到当局申请中确认的地址。FDA一般会要求申请人将样品直接递交给两个或者两个以上当局的实验室，这些实验室将对样品进行所有必要的检测并且将验证申请人的分析方法。
(i) Four representative samples of the following, each sample in sufficient quantity to permit FDA to perform three times each test described in the application to determine whether the drug substance and the drug product meet the specifications given in the application:
（i）提供以下四份代表性的样品，每份药品都要足量以便FDA能够对申请中描述的每个项目都执行三次检测（每一份样品至少是全检量的三倍），以确定原料药或者成品是否能符合申请的质量标准：
(a ) The drug product proposed for marketing;
5 [1 `4 j( N1 G  `（a）用于上市的成品
(b ) The drug substance used in the drug product from which the samples of the drug product were taken; and
7 \, x& m8 x+ C" b# T（b）用于抽样的成品使用到的原料药
+ b" B( q6 p. C0 ]% e(c ) Reference standards and blanks (except that reference standards recognized in an official compendium need not be submitted).
（c）标准品和空白（法定药典中指出的标准品不需要递交）
(ii) Samples of the finished market package, if requested by FDA.
$ b" }" n, J  W" ]! s2 {0 r（ii）市售包装的样品，若果FDA要求的话
- `, n6 X' Q) e/ }9 c/ d(2) The applicant shall submit the following in the archival copy of the application:
) \2 m. w% V+ q1 M（2）申请人应当在用于归档的那份申请中递交以下内容：
8 z% A9 z/ w* }+ w# Z' H) Y(i) Three copies of the analytical procedures and related descriptive information contained in the chemistry, manufacturing, and controls section under paragraph (d)(1) of this section for the drug substance and the drug product that are necessary for FDA's laboratories to perform all necessary tests on the samples and to validate the applicant's analytical procedures. The related descriptive information includes a description of each sample; the proposed regulatory specifications for the drug; a detailed description of the methods of analysis; supporting data for accuracy, specificity, precision and ruggedness; and complete results of the applicant's tests on each sample.
（i）按照本部分段落（d）(1)要求准备的化学，生产和控制部分所包含的的原料药以及成品的分析方法和相关的描述性信息，需提供三份复印件，以便FDA能够对样品进行所有必要的检测并且验证申请人的分析方法。相关的描述性信息包括以下内容：每份样品的描述；药品的受控标准；分析方法的详细描述；分析方法准确性，专属性，精密度和耐用性的支持性数据；以及申请人对每个样品进行检测的完整的检测结果。
(ii) Copies of the label and all labeling for the drug product (including, if applicable, any Medication Guide required under part 208 of this chapter) for the drug product (4 copies of draft labeling or 12 copies of final printed labeling).
（ii）标签以及成品所有贴标（如适用，包括任何按照本章节208部分提供的用药指南）的复印件（提供四份标签草案的复印件或者12分最终打印版标签的复印件）
(f)Case report forms and tabulations. The archival copy of the application is required to contain the following case report tabulations and case report forms:
（f）病例报告表      用于归档的那份申请需要包括以下CRFs和CRTs：
2 r1 C4 j4 J- z/ P2 }(1)Case report tabulations. The application is required to contain tabulations of the data from each adequate and well-controlled study under 314.126 (Phase 2 and Phase 3 studies as described in 312.21 (b) and (c) of this chapter), tabulations of the data from the earliest clinical pharmacology studies (Phase 1 studies as described in 312.21(a) of this chapter), and tabulations of the safety data from other clinical studies. Routine submission of other patient data from uncontrolled studies is not required. The tabulations are required to include the data on each patient in each study, except that the applicant may delete those tabulations which the agency agrees, in advance, are not pertinent to a review of the drug's safety or effectiveness. Upon request, FDA will discuss with the applicant in a "pre-NDA" conference those tabulations that may be appropriate for such deletion. Barring unforeseen circumstances, tabulations agreed to be deleted at such a conference will not be requested during the conduct of FDA's review of the application. If such unforeseen circumstances do occur, any request for deleted tabulations will be made by the director of the FDA division responsible for reviewing the application, in accordance with paragraph (f)(3) of this section.
（1）CRTs   申请需包含以下数据的表格：按照314.126执行的充分受控的研究（本章节321.21 (b)和(c)描述的II期和III期的研究）所得的数据，最早的临床药理学研究的数据（本章节312.21(a)所描述的I期研究），以及来源于其他临床研究的安全性数据。来源于非受控研究的其他病患数据的常规递交不作要求。表格需包括每项研究中每个病患的数据，事先得到当局同意，与药品安全性有效性审核无关，申请人可以删除的表格除外。根据申请人的请求，FDA将与申请人召开“Pre-NDA”的会议，讨论那些适用于这类删除的表格。除了不可预见的情况下，上述会议中同意删除的表格，FDA审核申请时不会要求这类表格的审核。如果不可预见的情况确实发生了，任何删除表格的申请由FDA负责审核部门的负责人按照本部分段落f（3）的要求出具。
(2)Case report forms. The application is required to contain copies of individual case report forms for each patient who died during a clinical study or who did not complete the study because of an adverse event, whether believed to be drug related or not, including patients receiving reference drugs or placebo. This requirement may be waived by FDA for specific studies if the case report forms are unnecessary for a proper review of the study.
4 g/ U" m, k7 P" Z7 q. l+ _. T" ~2 X: v（2）CFRs     申请中需要包括临床研究过程中死亡病患，以及因为不良反应未完成研究病患的个体病例报告的复印件，无论死亡或者不良反应是否与药物有关，同时包括服用对照药或者安慰剂的病患的个体病例报告表。对于具体的研究，如果上述的病例报告表对于审核来说是不必要的，这条要求可能会被FDA豁免。
(3)Additional data. The applicant shall submit to FDA additional case report forms and tabulations needed to conduct a proper review of the application, as requested by the director of the FDA division responsible for reviewing the application. The applicant's failure to submit information requested by FDA within 30 days after receipt of the request may result in the agency viewing any eventual submission as a major amendment under 314.60 and extending the review period as necessary. If desired by the applicant, the FDA division director will verify in writing any request for additional data that was made orally.
（3）额外的数据    如果FDA审核部门的负责人提出请求，申请人应当向FDA递交额外的CRFs和CRTs，以便对申请实施适当的审核。申请人在接收请求30日内若没有向FDA递交信息，FDA可能会将任何最终的递交视作按照314.60递交的重大修订并且按照需要延长审核周期。若申请人要求，FDA审核部门的负责人将以书面的方式确认任何口头要求额外数据的请求。
" ?) l: z/ V1 N% V9 g5 ?(4) Applicants are invited to meet with FDA before submitting an application to discuss the presentation and format of supporting information. If the applicant and FDA agree, the applicant may submit tabulations of patient data and case report forms in a form other than hard copy, for example, on microfiche or computer tapes.
（4）申请递交前，申请人被邀请与FDA会面，讨论递交信息的形式和格式，如果申请人和FDA同意，申请人不以硬拷贝的形式，而是以，比如缩微平片或者计算机磁带的形式递交患者数据的表格和病例报告表。
. h( Z# l) F8 P( m) B7 C(g)Other. The following general requirements apply to the submission of information within the summary under paragraph (c) of this section and within the technical sections under paragraph (d) of this section.
' r7 c; s3 o. |/ t（g）其他   以下的一般要求，适用于本部分段落（c）总结的递交信息以及本部分（d）的技术部分。
- g# O# r. K) u1 D5 Q- q(1) The applicant ordinarily is not required to resubmit information previously submitted, but may incorporate the information by reference. A reference to information submitted previously is required to identify the file by name, reference number, volume, and page number in the agency's records where the information can be found. A reference to information submitted to the agency by a person other than the applicant is required to contain a written statement that authorizes the reference and that is signed by the person who submitted the information.
1 D. P! o; f% B2 M  g! D2 w(1)一般不要求申请人重复递交之前已经递交的信息，但是可以通过引用的方式包含之前的信息。对先前信息的引用需要确认当局记录中文件的名字，索引号，卷号和页码。申请者以外的人员引用已递交给当局的信息，需要包含一份授权引用的书面声明并且由递交信息的人签字授权。
4 m4 ^5 {- ?/ V(2) The applicant shall submit an accurate and complete English translation of each part of the application that is not in English. The applicant shall submit a copy of each original literature publication for which an English translation is submitted.
$ Y* b3 o9 U, C(2) 对于申请中非英语的部分，需递交准确完整的翻译。递交英语翻译的应同时递交一份原始文件的复印件。
$ P$ x! x2 S* Y4 [, A(3) If an applicant who submits a new drug application under section 505(b) of the act obtains a "right of reference or use," as defined under 314.3(b), to an investigation described in clause (A) of section 505(b)(1) of the act, the applicant shall include in its application a written statement signed by the owner of the data from each such investigation that the applicant may rely on in support of the approval of its application, and provide FDA access to, the underlying raw data that provide the basis for the report of the investigation submitted in its application.
/ I( u1 t8 ]" v4 X& O% i9 Q（3）如果按照法案505（b）递交的新药申请包含一份314.3（b）定义的“right of reference or use”，引用或者使用法案505(b)(1)条款（A）所描述的研究，申请人需在申请中包括一份由研究数据拥有人签署的书面声明，申请人需要依赖这些研究数据用于支持申请的批准，并且授权FDA查看原始数据，这些原始数据是所递交申请中研究报告的基础。
(h)Patent information. The application is required to contain the patent information described under 314.53.
: Q2 x5 t! _# |, ^7 d$ D（h）专利信息   申请应当包含314.53中描述的专利信息
(i)Patent certification --(1)Contents. A 505(b)(2) application is required to contain the following:
(i)专利声明--（1）内容 505(b)(2)的申请需要包含以下内容：
6 |, b' d" ^& }9 |(i)Patents claiming drug, drug product, or method of use. (A) Except as provided in paragraph (i)(2) of this section, a certification with respect to each patent issued by the United States Patent and Trademark Office that, in the opinion of the applicant and to the best of its knowledge, claims a drug (the drug product or drug substance that is a component of the drug product) on which investigations that are relied upon by the applicant for approval of its application were conducted or that claims an approved use for such drug and for which information is required to be filed under section 505(b) and (c) of the act and 314.53. For each such patent, the applicant shall provide the patent number and certify, in its opinion and to the best of its knowledge, one of the following circumstances:
; ~) j/ I" O4 y% {& V（i）药物，药品或者药品使用的专利 （A）本部分段落(i)(2)情况除外，申请人按照自己的观点和知识，提供美国专利局和商标局发布的每项专利的声明，对于药物（成品或者作为成品组分的原料药），声明申请人所依赖的用于药物申请批准的研究已经实施，或者对于上述药物已批准的使用的声明，以及需要按照法案505（b）和(c)， 314.53归档的其他专利信息的声明。对于每一个上述的专利，申请人应当提供专利号，并且，按照自己的观点和知识，对以下任一情况进行确认：
(1 ) That the patent information has not been submitted to FDA. The applicant shall entitle such a certification "Paragraph I Certification";
2 i. O& ^+ Q3 M（1）专利信息从未递交给FDA。申请人应当称此类专利声明为“P I”的声明
  `4 G, K& l! {4 _(2 ) That the patent has expired. The applicant shall entitle such a certification "Paragraph II Certification";
（2）专利已过期。申请人应当称此类专利声明为“P II”的声明
(3 ) The date on which the patent will expire. The applicant shall entitle such a certification "Paragraph III Certification"; or
5 B! ~: N5 q, Z2 m7 ~: y（3）专利即将失效的日期。申请人应当称此类专利声明为“P III”的声明
(4 ) That the patent is invalid, unenforceable, or will not be infringed by the manufacture, use, or sale of the drug product for which the application is submitted. The applicant shall entitle such a certification "Paragraph IV Certification". This certification shall be submitted in the following form:
（4）专利无效，不能强制履行，或者药品的生产，使用或者销售不会对所递交的专利造成侵权。申请人应当称此类专利声明为“P IV”的声明。这类的专利声明应当递交以下表格：
I, (name of applicant ), certify that Patent No. ______ (is invalid, unenforceable, or will not be infringed by the manufacture, use, or sale of ) (name of proposed drug product ) for which this application is submitted.
I，（申请人姓名），证明专利号为       的专利（无效，不能强制履行或者生产，使用，或者销售（提议的药品名称）不会侵权）
/ V2 S! n* |* t' Q: ?: \7 T$ xThe certification shall be accompanied by a statement that the applicant will comply with the requirements under 314.52(a) with respect to providing a notice to each owner of the patent or their representatives and to the holder of the approved application for the drug product which is claimed by the patent or a use of which is claimed by the patent and with the requirements under 314.52(c) with respect to the content of the notice.
9 Z, ]% N$ B. N. H专利声明应附带一份承诺，承诺申请人将会按照314.52（a）的要求通知药品专利或者药品使用专利的每个拥有人或者其代表，以及药品已批准申请的拥有人，并且按照314.52(c)的要求提供通知的内容。
(B) If the drug on which investigations that are relied upon by the applicant were conducted is itself a licensed generic drug of a patented drug first approved under section 505(b) of the act, the appropriate patent certification under this section with respect to each patent that claims the first-approved patented drug or that claims an approved use for such a drug.
& C$ _  c& O! a6 a# B4 W(B)如果申请人依赖的研究已经实施的药品，其本身是某专利药首次按照法案505(b)批准的授权仿制药，针对首个批准的专利药物或者上述药品已批准的使用的每个专利，需要按照本部分提供适当的专利声明
(ii)No relevant patents. If, in the opinion of the applicant and to the best of its knowledge, there are no patents described in paragraph (i)(1)(i) of this section, a certification in the following form:
(ii)没有相关专利   如果根据申请人自己的观点和知识，不存在本部分(i)(1)(i)描述的专利，专利声明按照以下表格提供：
In the opinion and to the best knowledge of (name of applicant ), there are no patents that claim the drug or drugs on which investigations that are relied upon in this application were conducted or that claim a use of such drug or drugs.
4 A, d% e5 S; Q2 k- o" |3 J按照（申请人的姓名）的观点和知识，本申请中所依赖的研究已实施的药品的专利或者此类药品的使用专利不存在。
(iii)Method of use patent. (A) If information that is submitted under section 505(b) or (c) of the act and 314.53 is for a method of use patent, and the labeling for the drug product for which the applicant is seeking approval does not include any indications that are covered by the use patent, a statement explaining that the method of use patent does not claim any of the proposed indications.
; ?6 M5 X  ]( ~' B% z. B（iii）使用专利 （A）如果按照法案505(b)或(c)，314.53递交的信息是关于使用专利，并且申请人寻求批准的药品的标签不包含任何使用专利保护范围内的适应症，需提供一份声明，证实使用专利的保护范围不涉及任何提议的适应症。
(B) If the labeling of the drug product for which the applicant is seeking approval includes an indication that, according to the patent information submitted under section 505(b) or (c) of the act and 314.53 or in the opinion of the applicant, is claimed by a use patent, the applicant shall submit an applicable certification under paragraph (i)(1)(i) of this section.
) N0 S3 B, E7 W8 n（B）如果根据法案505(b)或(c)，314.53递交的专利信息或者按照申请人自己的观点，申请人寻求批准的药品的标签包括了一项适应症，在使用专利的保护范围内，申请人应当按照本部分段落(i)(1)(i)的要求提供一份适用的专利声明。
5 L  U0 d) G$ d& q0 t, B(2)Method of manufacturing patent. An applicant is not required to make a certification with respect to any patent that claims only a method of manufacturing the drug product for which the applicant is seeking approval.
8 m4 A5 L9 {4 V  i（2）生产工艺的专利   如果相关的专利只涉及一项产品生产工艺的专利，申请人不要求出具专利声明。
(3)Licensing agreements. If a 505(b)(2) application is for a drug or method of using a drug claimed by a patent and the applicant has a licensing agreement with the patent owner, the applicant shall submit a certification under paragraph (i)(1)(i)(A)(4 ) of this section ("Paragraph IV Certification") as to that patent and a statement that it has been granted a patent license. If the patent owner consents to an immediate effective date upon approval of the 505(b)(2) application, the application shall contain a written statement from the patent owner that it has a licensing agreement with the applicant and that it consents to an immediate effective date.
（3）许可协议   如果一个505(b)（2）申请是为了专利药品或者有使用专利的药品而递交的，并且申请人与专利拥有人有一份许可协议，申请人应当针对那项专利按照(i)(1)(i)(A)(4 )的要求递交一份声明（即PIV专利声明）并且陈述该专利已经被授权。如果专利拥有人同意505(b)（2）批准后立刻生效的日期，申请应当包含一份来自专利拥有人的书面证明，证实其与申请人有许可协议并且同意申请批准后立即生效的日期。
(4)Late submission of patent information. If a patent described in paragraph (i)(1)(i)(A) of this section is issued and the holder of the approved application for the patented drug does not submit the required information on the patent within 30 days of issuance of the patent, an applicant who submitted a 505(b)(2) application that, before the submission of the patent information, contained an appropriate patent certification is not required to submit an amended certification. An applicant whose 505(b)(2) application is filed after a late submission of patent information or whose 505(b)(2) application was previously filed but did not contain an appropriate patent certification at the time of the patent submission shall submit a certification under paragraph (i)(1)(i) or (i)(1)(ii) of this section or a statement under paragraph (i)(1)(iii) of this section as to that patent.
0 f( W" s; G4 Y5 I1 C7 c* r* y(4)后期递交的专利信息   如果本部分(i)(1)(i)(A)描述的被发布并且专利药物已批准申请的拥有人在专利发布30日内没有递交专利所需的信息，申请人在专利信息递交之前递交了一份505(b)(2)的申请，包含了一份合适的专利声明，不需要递交补充声明。申请人的505(b)(2)申请在后期递交的专利信息之后递交，或者该申请在之前已递交但是在专利信息递交时并未包含合适的专利声明，应当按照(i)(1)(i) 或(i)(1)(ii)的要求递交专利声明或者按照(i)(1)(iii)递交一份陈述。
; [4 q+ n6 J, a' u1 {7 `(5)Disputed patent information. If an applicant disputes the accuracy or relevance of patent information submitted to FDA, the applicant may seek a confirmation of the correctness of the patent information in accordance with the procedures under 314.53(f). Unless the patent information is withdrawn or changed, the applicant must submit an appropriate certification for each relevant patent.
（5）有争议的专利信息   如果申请人对递交给FDA的专利信息的准确性或者关联性存在争议，申请人应按照314.53(f)的流程寻求专利信息正确性的证明。除非专利信息被撤销或者变更，申请人必须针对每个相关专利递交一份适当的专利声明。
( h. Q5 `; F, g9 E(6)Amended certifications. A certification submitted under paragraphs (i)(1)(i) through (i)(1)(iii) of this section may be amended at any time before the effective date of the approval of the application. An applicant shall submit an amended certification as an amendment to a pending application or by letter to an approved application. If an applicant with a pending application voluntarily makes a patent certification for an untimely filed patent, the applicant may withdraw the patent certification for the untimely filed patent. Once an amendment or letter for the change in certification has been submitted, the application will no longer be considered to be one containing the prior certification.
6 Y, f8 \2 o) g* [+ `) r（6）补充声明   按照本部分段落(i)(1)(i)至(i)(1)(iii)递交的专利声明，在申请批准生效前任何时间都可以进行补充。申请人可以递交一份补充声明，作为待批准申请补充的形式递交，或者通过已批准申请申请信的形式递交。如果待批准申请的申请人自愿递交一份不合时宜的专利的声明，申请人可以撤销该专利声明。一旦变更专利声明的补充或者信息递交，申请将不再被认为是包含先前专利声明的申请了。
(i)After finding of infringement. An applicant who has submitted a certification under paragraph (i)(1)(i)(A)(4 ) of this section and is sued for patent infringement within 45 days of the receipt of notice sent under 314.52 shall amend the certification if a final judgment in the action is entered finding the patent to be infringed unless the final judgment also finds the patent to be invalid. In the amended certification, the applicant shall certify under paragraph (i)(1)(i)(A)(3 ) of this section that the patent will expire on a specific date.
(i) 发现侵权之后   申请人递交了PIV专利声明并且按照314.52发布通知的45日内被起诉，如果最终判决专利被侵权，申请人应当补充声明，除非最终判决同时发现专利是无效的。补充声明应当按照本部分(i)(1)(i)(A)(3 )要求声明专利将在某具体的日期失效（即递交一份PIII的声明）
: o, E" A1 p1 a9 \3 N( S(ii)After removal of a patent from the list. If a patent is removed from the list, any applicant with a pending application (including a tentatively approved application with a delayed effective date) who has made a certification with respect to such patent shall amend its certification. The applicant shall certify under paragraph (i)(1)(ii) of this section that no patents described in paragraph (i)(1)(i) of this section claim the drug or, if other relevant patents claim the drug, shall amend the certification to refer only to those relevant patents. In the amendment, the applicant shall state the reason for the change in certification (that the patent is or has been removed from the list). A patent that is the subject of a lawsuit under 314.107(c) shall not be removed from the list until FDA determines either that no delay in effective dates of approval is required under that section as a result of the lawsuit, that the patent has expired, or that any such period of delay in effective dates of approval is ended. An applicant shall submit an amended certification as an amendment to a pending application. Once an amendment for the change has been submitted, the application will no longer be considered to be one containing a certification under paragraph (i)(1)(i)(A)(4 ) of this section.
9 e- l9 F+ y4 Q( E3 d( ^( T. m(ii) 专利从清单上删除   如果一项专利从清单上删除，任何待批准申请的申请人（包括获得条件批准的推迟生效的申请）包括此专利声明的，应当补充其声明。申请人应当按照本部分(i)(1)(ii)证明药品不存在本部分(i)(1)(i)的专利，或者药品有其他相关的专利，申请人应当修订声明，只引用那些相关的专利。在补充中，申请人应当说明变更声明的理由（因为专利正在或者已经从清单上删除）。按照314.107(c)的要求处于诉讼期的专利，在FDA判定没有必要因为诉讼的关系而延迟申请的生效，专利失效，或者任何此类延迟批准生效的时期结束之前，不应当从清单上删除。申请人应当以待批准申请补充的形式递交补充声明。一旦变更专利声明的补充递交，申请将不再被认为是包含先前PIV专利声明的申请了。
(iii)Other amendments. (A) Except as provided in paragraphs (i)(4) and (i)(6)(iii)(B) of this section, an applicant shall amend a submitted certification if, at any time before the effective date of the approval of the application, the applicant learns that the submitted certification is no longer accurate.
（iii）其他修订   （A）除了本部分段落(i)(4)和(i)(6)(iii)(B)的情况外，申请批准生效前的任何时期，申请人在意识到已递交的声明不再正确时，都应当对已递交的声明进行补充。
(B) An applicant is not required to amend a submitted certification when information on an otherwise applicable patent is submitted after the effective date of approval for the 505(b)(2) application.
' v) X( m/ k7 m8 M/ Q7 C: e（B）如果专利的信息在505(b)（2）申请批准生效之后递交，申请人不要求补充已递交的声明。
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【转载】314Part B 314.50(2/4）  

2014-10-16 22:57:44|  分类： FDA|举报|字号 [url=]订阅[/url]

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本文转载自aimerjiaer《314Part B 314.50(2/4）》http://zhuyujiao1972.blog.163.com/blog/static/986947272014916105744142/

(2)非临床药理学和毒理学部分     本部分结合图表描述药品的动物研究和体外研究，包括以下内容：
) ?. R" ?" c* }( ]1 Y+ x, s5 W) ]  }(i) Studies of the pharmacological actions of the drug in relation to its proposed therapeutic indication and studies that otherwise define the pharmacologic properties of the drug or are pertinent to possible adverse effects.
（i）与药品提议的治疗症相关的药理学研究，以及定义药品药理学性质的研究或者与潜在不良反应相关的研究。
(ii) Studies of the toxicological effects of the drug as they relate to the drug's intended clinical uses, including, as appropriate, studies assessing the drug's acute, subacute, and chronic toxicity; carcinogenicity; and studies of toxicities related to the drug's particular mode of administration or conditions of use.
4 h, r0 B. t( {& p1 ~3 I（ii）药品与目标的临床使用相关的毒理学研究，包括，若适用，评估药品急性，亚急性，慢性毒性的研究；致癌性；与药品具体的给药途径或者使用条件相关的毒理学研究。
(iii) Studies, as appropriate, of the effects of the drug on reproduction and on the developing fetus.
（iii）研究药品对生殖和胎儿的影响，若适用
(iv) Any studies of the absorption, distribution, metabolism, and excretion of the drug in animals.
! r9 M  @. \: I+ M% r（iv）动物体内药物的吸收，分布，代谢和排泄的研究
(v) For each nonclinical laboratory study subject to the good laboratory practice regulations under part 58 a statement that it was conducted in compliance with the good laboratory practice regulations in part 58, or, if the study was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance.
（v）每一个非临床实验室研究遵守GLP的要提供一份声明证实研究的实施过程符合GLP的规定，或者，如果研究的实施不符合上述法规，需要对不遵守的原因作一个简短的声明。
- Y2 ]+ w0 t5 B/ ~' k2 @1 _6 h(3)Human pharmacokinetics and bioavailability section. A section describing the human pharmacokinetic data and human bioavailability data, or information supporting a waiver of the submission of in vivo bioavailability data under subpart B of part 320, including the following:
: C4 B  f5 x! g* \9 D6 ~（3）人体药代动力学和生物利用度部分    本部分描述人体药代动力学的数据和人体生物利用度的数据，或者按照320章节，副章节B的要求提供信息支持体内生物利用度数据的豁免，包括以下内容：
(i) A description of each of the bioavailability and pharmacokinetic studies of the drug in humans performed by or on behalf of the applicant that includes a description of the analytical procedures and statistical methods used in each study and a statement with respect to each study that it either was conducted in compliance with the institutional review board regulations in part 56, or was not subject to the regulations under 56.104 or 56.105, and that it was conducted in compliance with the informed consent regulations in part 50.
（i）每个由申请人实施或代理实施的人体内药品药代动力学和生物利用度的研究，需要包括每个研究中使用的分析方法和统计方法的描述，以及声明每个研究的实施符合56部分的机构审查委员会条例，或者不遵循56.104或者56.105的条款，以及研究的实施符合50部分知情同意的条款。
(ii) If the application describes in the chemistry, manufacturing, and controls section tests, analytical procedures, and acceptance criteria needed to assure the bioavailability of the drug product or drug substance, or both, a statement in this section of the rationale for establishing the tests, analytical procedures, and acceptance criteria, including data and information supporting the rationale.
（ii）如果在化学，生产和控制部分描述的检测，分析方法和接受限度需要确保药品或者原料药，或两者的生物利用度，需要在本部分声明建立检测，分析方法以及接受限度的原理，包括支持这一原理的数据和信息。
(iii) A summarizing discussion and analysis of the pharmacokinetics and metabolism of the active ingredients and the bioavailability or bioequivalence, or both, of the drug product.
6 x2 c) \8 F/ N* ~4 ~2 ~(iii)对原料药的药代动力学和代谢，成品的生物利用度或者生物等效性，或者两者兼有，做一个总结性的讨论和分析。
(4)Microbiology section. If the drug is an anti-infective drug, a section describing the microbiology data, including the following:
1 C7 e4 H$ Y5 H! l+ S# [8 _（4）微生物部分   本部分是针对抗感染药物，描述微生物的数据，包括以下内容：
(i) A description of the biochemical basis of the drug's action on microbial physiology.
（i）描述药物对微生物生理学作用的生化基础。
(ii) A description of the antimicrobial spectra of the drug, including results of in vitro preclinical studies to demonstrate concentrations of the drug required for effective use.
（ii）药物抗菌谱的描述，包括证明药物有效抗菌浓度的体外临床前研究的结果。
" O4 ]0 p& ^9 u5 `2 ](iii) A description of any known mechanisms of resistance to the drug, including results of any known epidemiologic studies to demonstrate prevalence of resistance factors.
（iii）描述任何已知的耐药机制，包括任何已知的证明耐药因子流行的流行病学研究的结果。
(iv) A description of clinical microbiology laboratory procedures (for example, in vitro sensitivity discs) needed for effective use of the drug.
% G0 R! D/ [) n: f' [（iv）描述为了药品有效使用所实施的临床微生物实验程序（例如，体外的药敏试验）
(5)Clinical data section. A section describing the clinical investigations of the drug, including the following:
（5）临床数据部分     本部分描述药品临床研究，包括以下内容：
(i) A description and analysis of each clinical pharmacology study of the drug, including a brief comparison of the results of the human studies with the animal pharmacology and toxicology data.
0 }) z6 |. v( r# X3 i1 @(i) 药品每个临床药理学研究的描述和分析，包括把人体研究的结果与动物药理学和毒理学数据做一个简要的对比。
(ii) A description and analysis of each controlled clinical study pertinent to a proposed use of the drug, including the protocol and a description of the statistical analyses used to evaluate the study. If the study report is an interim analysis, this is to be noted and a projected completion date provided. Controlled clinical studies that have not been analyzed in detail for any reason (e.g., because they have been discontinued or are incomplete) are to be included in this section, including a copy of the protocol and a brief description of the results and status of the study.
' j* I- p$ S! X, q1 t（ii）与提议的药品使用相关的每个受控的临床研究进行描述和分析，包括研究方案以及用于评估研究的统计分析的描述。如果研究报告是一份期中分析，需要备注说明并且需提供预计完成的时间。受控的临床研究，因任何原因未能完成详细分析的（例如临床研究被中断或者未完成），应包括在本部分中，需提供研究方案的复印件，并对研究的结果和状态做一份简要的描述。
; ~0 |, a2 s+ B: n$ Y: J(iii) A description of each uncontrolled clinical study, a summary of the results, and a brief statement explaining why the study is classified as uncontrolled.
( m. ^1 I9 }1 ^9 u. F6 Z（iii）描述每个非受控的临床研究，对结果进行总结，并且做一个简要的声明解释研究为何被划分为非受控。
5 U  Q: u7 ]" o( A(iv) A description and analysis of any other data or information relevant to an evaluation of the safety and effectiveness of the drug product obtained or otherwise received by the applicant from any source, foreign or domestic, including information derived from clinical investigations, including controlled and uncontrolled studies of uses of the drug other than those proposed in the application, commercial marketing experience, reports in the scientific literature, and unpublished scientific papers.
7 U3 I: m- S6 {4 l& c（iv）描述和分析其他评估药品安全性有效性相关的数据和信息，这些数据和信息由申请人从任何国内的或者国外的途径接收或者获得，包括临床研究产生的信息，包括对未体现在申请中，药品其他使用所进行的的受控和非受控的研究，商业批上市的经验，科学文献中的报告，以及未发表的科学论文。
(v) An integrated summary of the data demonstrating substantial evidence of effectiveness for the claimed indications. Evidence is also required to support the dosage and administration section of the labeling, including support for the dosage and dose interval recommended. The effectiveness data shall be presented by gender, age, and racial subgroups and shall identify any modifications of dose or dose interval needed for specific subgroups. Effectiveness data from other subgroups of the population of patients treated, when appropriate, such as patients with renal failure or patients with different levels of severity of the disease, also shall be presented.
0 W9 w( ]& f& G(v)能实质上证明药品对适应症有效的数据，需要提供一份综合的数据汇总。同样也需要证据支持标签的给药途径和剂量部分，包括支持建议的给药间隔和剂量的证据。有效性的数据应当按照性别，年龄，种族亚组的类别递交，并且针对具体亚组所做的任何剂量或者给药间隔的调整都应当确认。来源于受治疗病患人群其他亚组的有效性数据，若适用，例如肾衰竭的病患，或者疾病不同严重程度的病患，都应当递交。
(vi) A summary and updates of safety information, as follows:
1 h! G: z( X5 \（vi）安全性信息的总结和更新，按照以下要求：
! v* E. P8 l5 c9 ^8 c$ D(a ) The applicant shall submit an integrated summary of all available information about the safety of the drug product, including pertinent animal data, demonstrated or potential adverse effects of the drug, clinically significant drug/drug interactions, and other safety considerations, such as data from epidemiological studies of related drugs. The safety data shall be presented by gender, age, and racial subgroups. When appropriate, safety data from other subgroups of the population of patients treated also shall be presented, such as for patients with renal failure or patients with different levels of severity of the disease. A description of any statistical analyses performed in analyzing safety data should also be included, unless already included under paragraph (d)(5)(ii) of this section.
! C  C6 v. D# p2 `. q/ x: i8 b# y. j9 y（a）所有有关药品安全性的有效信息，申请人应当递交一份完整的总结，包括动物实验相关的数据，药品已证实的或者潜在的不良反应，临床上重要的药品之间的相互作用，以及其他的安全性考量，例如从相关药物流行病学研究中得来的数据。安全性的数据应当按照性别，年龄，种族亚组的类别递交。来源于受治疗病患人群其他亚组的安全性数据，若适用，例如肾衰竭的病患，或者疾病不同严重程度的病患，也应当递交。任何分析安全性数据时使用的统计分析的描述，也应当被包括进去，这部分内容已经在（d）（5）（ii）中体现的情况除外。
0 t6 U/ g% ~* l7 _) K! g2 _  A(b ) The applicant shall, under section 505(i) of the act, update periodically its pending application with new safety information learned about the drug that may reasonably affect the statement of contraindications, warnings, precautions, and adverse reactions in the draft labeling and, if applicable, any Medication Guide required under part 208 of this chapter. These "safety update reports" are required to include the same kinds of information (from clinical studies, animal studies, and other sources) and are required to be submitted in the same format as the integrated summary in paragraph (d)(5)(vi)(a ) of this section. In addition, the reports are required to include the case report forms for each patient who died during a clinical study or who did not complete the study because of an adverse event (unless this requirement is waived). The applicant shall submit these reports (1 ) 4 months after the initial submission; (2 ) in a resubmission following receipt of a complete response letter; and (3 ) at other times as requested by FDA. Prior to the submission of the first such report, applicants are encouraged to consult with FDA regarding further details on its form and content.
+ k" }1 a7 w% ?' O（b）按照法案505（j）的要求，申请人应当定期更新待批准申请，增加新获悉的药品的安全信息，这些安全信息可能对标签草案上的禁忌症，警示语，注意事项以及不良反应的声明，以及若适用，对按照本章节208部分递交的用药指南造成一定的影响。这些“安全性更新报告”需要递交的信息类型（临床研究，动物实验以及其他来源）以及作为综合总结递交的格式按照(d)(5)(vi)(a)同样的要求执行。此外，报告需包括每个在临床研究期间的死亡病例或者因不良反应未完成研究病例的报告表（除非该条要求被豁免）。申请人应当按照以下要求递交报告：（1）首次递交4个月后；（2）包含在CR不足信回复的重新递交中；（3）FDA要求的其他时间段。第一次递交这类报告时，鼓励申请人就报告格式和内容向FDA咨询进一步的细节。
, b% I) f/ Q5 U7 k(vii) If the drug has a potential for abuse, a description and analysis of studies or information related to abuse of the drug, including a proposal for scheduling under the Controlled Substances Act. A description of any studies related to overdosage is also required, including information on dialysis, antidotes, or other treatments, if known.
) @4 ?; P3 a. a5 p（vii）如果药物存在潜在的成瘾性，需要对药品成瘾相关的研究或者信息进行描述和分析，包括建议将药品列入受管制药品法案管理。同时还需要对任何药物过量相关的研究进行描述，若可以获得信息，需包括用于透析，解毒，或其他治疗的信息。
(viii) An integrated summary of the benefits and risks of the drug, including a discussion of why the benefits exceed the risks under the conditions stated in the labeling.
（viii）对药物的利弊进行综合的总结，包括讨论为何在标签声明的使用条件下利大于弊。
) u+ y0 p8 S5 |" ?9 u(ix) A statement with respect to each clinical study involving human subjects that it either was conducted in compliance with the institutional review board regulations in part 56, or was not subject to the regulations under 56.104 or 56.105, and that it was conducted in compliance with the informed consent regulations in part 50.
（ix）声明每个包含受试者的临床研究的实施符合机构审查委员会条例 56部分，或者不遵循56.104或者56.105的条款，以及研究的实施符合50部分知情同意的条款。
& l6 z1 b: P6 U' L% c(x) If a sponsor has transferred any obligations for the conduct of any clinical study to a contract research organization, a statement containing the name and address of the contract research organization, identification of the clinical study, and a listing of the obligations transferred. If all obligations governing the conduct of the study have been transferred, a general statement of this transfer--in lieu of a listing of the specific obligations transferred--may be submitted.
* ?8 m7 N( h3 T/ n1 y) J（x）如果发起人将任何实施临床研究的义务转让给一家合同研究组织，需要一份声明，包含合同研究组织的名称和地址，临床研究的确认，以及所转让义务的清单。如果所有研究管理的义务都被转让，可以递交一份一般的转让声明，替代具体转让义务的清单。
0 a8 ]- ?" g7 P7 Z9 Y(xi) If original subject records were audited or reviewed by the sponsor in the course of monitoring any clinical study to verify the accuracy of the case reports submitted to the sponsor, a list identifying each clinical study so audited or reviewed.
（xi）如果在任何临床研究的监测过程中，赞助人为了确认所递交病例报告的准确性，对原始病例记录进行了审查和审核，需要出具一份清单确认每个被审查或者审核的临床研究。
6 p5 g) m  L' R0 v5 {7 [; ~4 r* K. O(6)Statistical section. A section describing the statistical evaluation of clinical data, including the following:
0 ^# ?0 V( S4 B8 \$ C& T9 D& S（6）统计部分   本部分描述对临床数据的统计学评估，包括以下内容：
(i) A copy of the information submitted under paragraph (d)(5)(ii) of this section concerning the description and analysis of each controlled clinical study, and the documentation and supporting statistical analyses used in evaluating the controlled clinical studies.
8 w. y, \0 t- B. K' a) F（i）按照本部分(d)(5)(ii)递交的，有关每个受控的临床研究，以及评估这些研究所用的文件和支持性的统计学分析的描述和分析的信息，提供一份复印件。
(ii) A copy of the information submitted under paragraph (d)(5)(vi)(a ) of this section concerning a summary of information about the safety of the drug product, and the documentation and supporting statistical analyses used in evaluating the safety information.
(ii)按照本部分(d)(5)(vi)(a)递交的，有关药品安全性，以及评估安全性信息所用的文件和支持性的统计学分析的信息摘要，提供一份复印件。

# [! X( o4 Q0 E/ ?. A" B4 L' U(7)Pediatric use section. A section describing the investigation of the drug for use in pediatric populations, including an integrated summary of the information (the clinical pharmacology studies, controlled clinical studies, or uncontrolled clinical studies, or other data or information) that is relevant to the safety and effectiveness and benefits and risks of the drug in pediatric populations for the claimed indications, a reference to the full descriptions of such studies provided under paragraphs (d)(3) and (d)(5) of this section, and information required to be submitted under 314.55.
(7)儿科用药部分    本部分描述儿科用药的研究，包括对儿科药物用于适应症时与药品安全性有效性以及利弊有关的信息（临床药理学研究，受控的临床研究，或者非受控的临床研究，或者其他数据或者信息）做一份综合的摘要，对按照本部分段落（d）（3）和（d）（5）要求提供的此类研究的详细描述做一份引用，以及提供按照314.55需要递交的信息。

【转载】314Part B 314.50(1/4）  

2014-10-16 22:58:05|  分类： FDA|举报|字号 [url=]订阅[/url]

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本文转载自aimerjiaer《314Part B 314.50(1/4）》http://zhuyujiao1972.blog.163.com/blog/static/98694727201491610585727/
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Subpart B--Applications
Subpart B—申请
* x7 j0 l7 E, m# T+ F3 fSec. 314.50 Content and format of an application.申请的内容与格式
Applications and supplements to approved applications are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the application are required: An archival copy, a review copy, and a field copy. An application for a new chemical entity will generally contain an application form, an index, a summary, five or six technical sections, case report tabulations of patient data, case report forms, drug samples, and labeling, including, if applicable, any Medication Guide required under part 208 of this chapter. Other applications will generally contain only some of those items, and information will be limited to that needed to support the particular submission. These include an application of the type described in section 505(b)(2) of the act, an amendment, and a supplement. The application is required to contain reports of all investigations of the drug product sponsored by the applicant, and all other information about the drug pertinent to an evaluation of the application that is received or otherwise obtained by the applicant from any source. FDA will maintain guidance documents on the format and content of applications to assist applicants in their preparation.
申请以及已批准申请的补充需按照本部分的要求，按照具体递交适用的格式以及内容递交，申请需要三份：一份用于存档，一份用于审核，一份用于现场检查。新的化合物的申请一般需要包含一份申请表，一份索引，一份摘要，五个或者六个技术部分，病患数据的病例报告表，病例报告表，药品样本，以及标签，如果适用，还包括任何本章节208部分要求的用药指南。其他类型的申请一般只包括以上一部分项目，并且信息仅限于支持具体递交所需要的信息。其他类型的申请包括法案505（b）（2）描述的申请，以及修订和补充。申请需要包含申请人赞助的所有药品调查的报告，以及其他所有与评估申请相关的，申请人通过任何途径接收或者获得的药品信息。FDA将针对申请的格式和内容维护指南文件以帮助申请人准备申请。
(a)Application form. The applicant shall submit a completed and signed application form that contains the following:
# {  F' x  j, P/ w$ K& ^  y（a）申请表。申请人需要递交一份完整并且签字的申请表，包含以下内容：
& M$ }# D6 u( |) Z0 b+ x(1) The name and address of the applicant; the date of the application; the application number if previously issued (for example, if the application is a resubmission, an amendment, or a supplement); the name of the drug product, including its established, proprietary, code, and chemical names; the dosage form and strength; the route of administration; the identification numbers of all investigational new drug applications that are referenced in the application; the identification numbers of all drug master files and other applications under this part that are referenced in the application; and the drug product's proposed indications for use.
（1）申请人的姓名和地址；申请日期；申请号，若先前已经发布（例如，如果申请是一份重新递交的申请，是一份修订或者补充）；产品的名称，包括已有的名称，专利名，暗码名，以及化学名；剂型和规格，给药途径；申请中引用的所有创新药（IND）申请的ID号；申请中引用的所有DMF号以及本部分中其他申请的识别号；药品提议的适应症。
(2) A statement whether the submission is an original submission, a 505(b)(2) application, a resubmission, or a supplement to an application under 314.70.
（2）声明所递交的类型，是原始递交，505（b）（2）申请，重新递交，还是按照314.70要求递交的申请的补充。
+ R- g0 e2 |8 R* y  t# Y(3) A statement whether the applicant proposes to market the drug product as a prescription or an over-the-counter product.
（3）声明申请人提议药品是按照处方药还是OTC药上市
(4) A check-list identifying what enclosures required under this section the applicant is submitting.
（4）提供一份审核清单，以确认按照本部分的要求申请人递交了哪些附件。
/ Q" r9 j  ^( E: D) F" b" D(5) The applicant, or the applicant's attorney, agent, or other authorized official shall sign the application. If the person signing the application does not reside or have a place of business within the United States, the application is required to contain the name and address of, and be countersigned by, an attorney, agent, or other authorized official who resides or maintains a place of business within the United States.
（5）申请者，申请者法律事务的代理人，商业事务的代理人，或者其他授权人员应当签署该申请。如果签署申请的人员，其居住地点或者营业地点不在美国，申请需要包含居住地点或者营业地点在美国的法律事务的代理人，商业事务的代理人或者其他授权人员的姓名和地址，并且需要上述人员会签。
8 \1 N. D; |& q(b)Index. The archival copy of the application is required to contain a comprehensive index by volume number and page number to the summary under paragraph (c) of this section, the technical sections under paragraph (d) of this section, and the supporting information under paragraph (f) of this section.
" t# H- |" F0 R! T4 f（b）索引        用于归档的那份申请需要包含一份综合的，按照本部分（c）所准备的摘要的卷号和页码的索引。
1 ~" e: F% |1 x- J# W' E(c)Summary. (1) An application is required to contain a summary of the application in enough detail that the reader may gain a good general understanding of the data and information in the application, including an understanding of the quantitative aspects of the data. The summary is not required for supplements under 314.70. Resubmissions of an application should contain an updated summary, as appropriate. The summary should discuss all aspects of the application, and synthesize the information into a well-structured and unified document. The summary should be written at approximately the level of detail required for publication in, and meet the editorial standards generally applied by, refereed scientific and medical journals. In addition to the agency personnel reviewing the summary in the context of their review of the application, FDA may furnish the summary to FDA advisory committee members and agency officials whose duties require an understanding of the application. To the extent possible, data in the summary should be presented in tabular and graphic forms. FDA has prepared a guideline under 10.90(b) that provides information about how to prepare a summary. The summary required under this paragraph may be used by FDA or the applicant to prepare the Summary Basis of Approval document for public disclosure (under 314.430(e)(2)(ii)) when the application is approved.
（c）摘要       (1)申请需要包含一份足够详细的摘要，以便让阅读申请的人对数据和信息有好的，大致的了解，包括对数据定量方面的了解。按照314.70递交的补充不需要提供摘要。重新递交需要包含一份更新的摘要，若适用。应当对申请的每个部分都进行摘要，并且将信息整合成一份结构良好并且统一的文档。摘要书写的详细级别大致与学术期刊和医学期刊上要求的出版物一致，并且符合上述期刊要求的编辑标准。摘要除了提供给FDA员工审核，FDA还可能将摘要提供给职责内需要了解该申请的FDA的咨询委员会的人员以及机构人员。摘要中的数据尽量以表格或者图表的形式提供。FDA已经按照10.90（b）的要求提供了一份关于如何准备摘要的指南。本段要求的摘要可能在申请批准时，被FDA或者申请人用来准备公开的the Summary Basis of Approval（批文要略）文件（按照314.430（e）(2)(ii)的要求）
$ z' x5 @9 T: V$ c- V. x/ s/ D& m- Y(2) The summary is required to contain the following information:
% n4 |1 ]$ o1 `1 Q（2）摘要需要以下的信息：
(i) The proposed text of the labeling, including, if applicable, any Medication Guide required under part 208 of this chapter, for the drug, with annotations to the information in the summary and technical sections of the application that support the inclusion of each statement in the labeling, and, if the application is for a prescription drug, statements describing the reasons for omitting a section or subsection of the labeling format in 201.57 of this chapter.
（i）标签文本，若适用，应包括本章节208部分要求的药品的用药指南，并且在标签文本中注释用于支持标签中每句话内容的，申请的摘要以及技术部分的信息，如果是处方药的申请，还应包括声明，描述省略本章节201.57一部分标签格式的理由。
' ]$ }' H7 O/ B: o(ii) A statement identifying the pharmacologic class of the drug and a discussion of the scientific rationale for the drug, its intended use, and the potential clinical benefits of the drug product.
% W8 i/ y. P: E- @（ii）确认药品类别的声明以及有关药品科学原理，既定用途，以及药品潜在的临床价值的讨论。
; v! C! ]* c! o4 f/ F(iii) A brief description of the marketing history, if any, of the drug outside the United States, including a list of the countries in which the drug has been marketed, a list of any countries in which the drug has been withdrawn from marketing for any reason related to safety or effectiveness, and a list of countries in which applications for marketing are pending. The description is required to describe both marketing by the applicant and, if known, the marketing history of other persons.
（iii）药品在美国以外营销历史的简要描述，如果有的话，包括药品一直在上市的国家的清单，药品因为任何与安全性有效性相关的原因被撤市的国家的清单，以及药品上市的申请等待批准的国家的清单。描述不仅需要包括申请人自己的营销情况，并且如果知晓的话，也需要包括其他人的营销历史。
(iv) A summary of the chemistry, manufacturing, and controls section of the application.
2 l/ \2 u; r! m; D（iv）申请的化学，生产以及控制部分的摘要
(v) A summary of the nonclinical pharmacology and toxicology section of the application.
6 U0 U. v7 @) q, j5 Q（v）申请中非临床的药理学毒理学部分的摘要
(vi) A summary of the human pharmacokinetics and bioavailability section of the application.
7 m* t1 x9 k8 A1 g, h（vi）申请中人体药代动力学以及生物利用度部分的摘要
(vii) A summary of the microbiology section of the application (for anti-infective drugs only).
（vii）申请中微生物部分的摘要（仅适用于抗感染药物）
  n2 U( @9 o! Q: z3 Q% ~(viii) A summary of the clinical data section of the application, including the results of statistical analyses of the clinical trials.
2 m1 ?! D- [! M" K* G2 @（viii）申请中临床数据的摘要，包括临床研究统计学分析的结果。
' Z" o$ L0 |! B1 Y* J(ix) A concluding discussion that presents the benefit and risk considerations related to the drug, including a discussion of any proposed additional studies or surveillance the applicant intends to conduct postmarketing.
（ix）一份体现药品相关的效益和风险考量的总结，包括申请人在药品上市后将实施的任何提议的额外的研究或者监测的讨论。
(d)Technical sections. The application is required to contain the technical sections described below. Each technical section is required to contain data and information in sufficient detail to permit the agency to make a knowledgeable judgment about whether to approve the application or whether grounds exist under section 505(d) of the act to refuse to approve the application. The required technical sections are as follows:
/ O$ M6 {4 J5 w& T: ~; j（d）技术部分      申请需要包括以下技术部分的内容。每个技术部分都需要包括足够的数据和信息，能够使当局对是否批准申请，是否存在法案505（d）中描述的拒绝理由而拒绝批准申请作出明智的选择。需要的技术部分如下：
3 \1 o. E* y9 j' Q% K( J(1)Chemistry, manufacturing, and controls section. A section describing the composition, manufacture, and specification of the drug substance and the drug product, including the following:
5 ?; A, |* i+ }2 y$ n$ |$ f+ S（1）化学，生产和控制部分 本部分描述原料药或者成品的组成，生产和质量标准，包括以下内容：
* F, d) P) U! |5 s# _4 O(i)Drug substance . A full description of the drug substance including its physical and chemical characteristics and stability; the name and address of its manufacturer; the 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 and the bioavailability of the drug products made from the substance, including, for example, tests, analytical procedures, and acceptance criteria relating to stability, sterility, particle size, and crystalline form. The application may provide additionally for the use of alternatives to meet any of these requirements, including alternative sources, process controls, and analytical procedures. Reference to the current edition of the U.S. Pharmacopeia and the National Formulary may satisfy relevant requirements in this paragraph.
; z5 [5 k3 G% k3 R（i）原料药 完      整的原料药的描述包括该原料药物理和化学的性质以及稳定性；生产商的名称和地址；原料药合成（或者分离）以及提纯的方法；生产和包装过程中的工艺控制；确保原料药性质，规格，质量以及纯度以及该原料药制剂生物利用度所必须的质量标准，包括，例如与稳定性，无菌，颗粒度或晶型相关的检测，分析方法以及接受限度。申请可能额外提供替代的方案以符合上述的要求，包括，替代的来源，工艺控制以及分析方法。引用现行版美国药典或者国家处方集的方法可以符合本段相关的要求。
(ii)(a)Drug product . A list of all components used in the manufacture of the drug product (regardless of whether they appear in the drug product) and a statement of the composition of the drug product; the specifications for each component; the name and address of each manufacturer of the drug product; a description of the manufacturing and packaging procedures and in-process controls for the drug product; the specifications necessary to ensure the identity, strength, quality, purity, potency, and bioavailability of the drug product, including, for example, tests, analytical procedures, and acceptance criteria relating to sterility, dissolution rate, container closure systems; and stability data with proposed expiration dating. The application may provide additionally for the use of alternatives to meet any of these requirements, including alternative components, manufacturing and packaging procedures, in-process controls, and analytical procedures. Reference to the current edition of the U.S. Pharmacopeia and the National Formulary may satisfy relevant requirements in this paragraph.
(ii)(a)成品        成品生产中使用的所有化合物的清单（无论化合物是否出现在成品中）以及成品组分的声明；每个化合物的质量标准；成品所有生产商的名称和地址；成品生产包装过程以及中间控制过程的描述；确保成品鉴别，规格，质量，纯度，效价和生物利用度所必须的质量标准，包括，例如与无菌，溶出速率，容器密闭系统，以及提议的有效期限内稳定性数据相关的检测，分析方法以及接受限度。申请可能额外提供替代的方案以符合上述的要求，包括，替代的化合物，生产或者包装程序，中间控制，以及分析方法。引用现行版美国药典或者国家处方集的方法可以符合本段相关的要求。
(b ) Unless provided by paragraph (d)(1)(ii)(a ) of this section, for each batch of the drug product used to conduct a bioavailability or bioequivalence study described in 320.38 or 320.63 of this chapter or used to conduct a primary stability study: The batch production record; the specification for each component and for the drug product; the names and addresses of the sources of the active and noncompendial inactive components and of the container and closure system for the drug product; the name and address of each contract facility involved in the manufacture, processing, packaging, or testing of the drug product and identification of the operation performed by each contract facility; and the results of any test performed on the components used in the manufacture of the drug product as required by 211.84(d) of this chapter and on the drug product as required by 211.165 of this chapter.
! }: C1 Q5 A6 a! K- T（b）(d)(1)(ii)(a )情况除外，用于本章节320.38或者320.63描述的生物利用度或者生物等效性研究的产品批次或者用于实施初始稳定性研究的批次需提供以下内容：批生产记录；每个组分以及成品的质量标准；原料药，非药典辅料，以及成品容器与密闭系统来源的名称和地址；参与药品生产，加工，包装和检测的所有合同工厂的名称和地址，以及对合同工厂操作的确认；根据本章节211.84（d）要求对药品生产过程中使用的化合物的检测结果，以及根据本章节211.165对成品的检测结果。
0 \6 i' W, j8 X" v$ V1 m(c ) The proposed or actual master production record, including a description of the equipment, to be used for the manufacture of a commercial lot of the drug product or a comparably detailed description of the production process for a representative batch of the drug product.
（c）商业批或者执行批批记录，包括将用于药品的商业批次生产的设备的描述，或者对药品代表批次的生产过程相对具体的描述。
(iii)Environmental impact. The application is required to contain either a claim for categorical exclusion under 25.30 or 25.31 of this chapter or an environmental assessment under 25.40 of this chapter.
(iii)环境影响。申请需要包含一份按照本章节25.30或者25.31出具的绝对除外的声明或者按照本章节25.40提供一份环境评估。
(iv) The applicant may, at its option, submit a complete chemistry, manufacturing, and controls section 90 to 120 days before the anticipated submission of the remainder of the application. FDA will review such early submissions as resources permit.
（iv）申请人按照自已的意愿，可能在预期提交申请剩余部分前90天至120天， 递交完整的化学，生产和控制部分。若资源许可，FDA将审核这类早期的递交。
7 _3 d2 R: {. U/ \( H% K(v) The applicant shall include a statement certifying that the field copy of the application has been provided to the applicant's home FDA district office.
% I2 M/ Q6 E! p% \4 T9 ]7 |( A（v）申请人应当包括一份声明证实用于现场检查的复印件已经提供给申请人所在的当地的FDA办公室。

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