hovGuidance for Industry Controlled Correspondence Related to Generic Drug
Development
chancenlos行业指南：有关仿制药研发的书面咨询
This guidance reprents the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can u an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.
该指南代表了FDA对该主题目前的看法。它并不会赋予任何人任何权利，也不会约束FDA或公众，如果有替代的方法能够满足法律法规的要求，可以使用替代的方法。如果想探讨替代的方法，请联系该指南首页中FDA 负责执行该指南的工作人员。
I.INTRODUCTION 简介
This guidance provides information regarding the process by which generic drug manufacturers and related industry can submit correspondence to FDA requesting information related to generic drug dev
elopment. This guidance also describes the Agency’s process for providing communications related to such correspondence. FDA is issuing this guidance as part of its implementation of the Generic Drug Ur Fee Amendments of 2012 (Public Law 112-144, Title III), commonly referred to as GDUFA.
该指南描述了仿制药生产商以及相关行业向FDA提交书面咨询，询问有关仿制药研发信息的过程，同时还描述了FDA针对这些书面咨询提供交流的过程。该指南作为2012《仿制药申报者付费法案》（简称GDUFA）（Public Law 112-144, Title III）实施的一部分。
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The u of the word should in Agency guidances means that something is suggested or recommended, but not required.
FDA的指南文件（包括该指南）不会构成任何法律强制职责，而是代表了FDA对该主题的目前想法，仅作为参考意见，除非引用了特定的法规或法定要求。该指南中“should”一词表示的是建议执行的内容，而不是必须执行的。
II.BACKGROUND 背景
helmet什么意思On July 9, 2012, GDUFA was signed into law by the President. GDUFA is designed to speed the delivery of safe and
effective generic drugs to the public and to reduce costs to industry. The law is bad on an agreement negotiated by FDA and reprentatives of the generic drug industry to address a growing number of regulatory challenges. GDUFA reflects input received during an open process that included regular public meetings, posting of meeting minutes, and consideration of comments from a public docket. Agreed-upon recommendations were nt to Congress, and Congress held hearings on GDUFA that included testimony from FDA, the generic drug industry, and other interested parties.
美国电影分级2012年7月9日，GDUFA被总统作为法律签署。制定GDUFA的目的是希望公众能够越来越快速地获得安全且有效的仿制药，同时降低制药成本。为了应对一系列的监管挑战，在FDA以及仿制药行业代表的讨论中奠定了GDUFA的基础。GDUFA体现了在公开过程（包括定期公开会议、会议纪要、对来自公众诉讼的评论）接收到的信息。商定后的建议被发送到国会，国会举行有关GDUFA（包括来自FDA、仿制药行业和其他利益相关方的证词）的听证会。
GDUFA requires that FDA and human generic drug manufacturers alike must meet certain requirem
ents and commitments. Under GDUFA, FDA has agreed to specific program enhancements and performance goals, as t forth in the GDUFA Commitment Letter that accompanied the legislation. The GDUFA Commitment Letter included detail on FDA’s commitment to respond to questions submitted as “controlled correspondence” within certain time frames. Specifically, the Agency agreed that:
GDUFA要求FDA和人用仿制药生产商必须符合相应要求，承担相应义务。依据GDUFA，FDA承诺了明确的提升目标和绩效目标，这些内容在GDUFA中的GDUFA承诺书中都有描述。GDUFA承诺书中包括FDA承诺在固定时间内回复所咨询问题的详细内容。特别是，FDA承诺了如下内容：
∙FDA will respond to 70 percent of controlled correspondence within 4 months from date of submission in fiscal year (FY) 2015.
2015财年，70%书面咨询会在提交日期4个月内得到FDA回复。
∙FDA will respond to 70 percent of controlled correspondence within 2 months from date of submission in FY 2016.
2016财年，70%书面咨询会在提交日期2个月内得到FDA回复。
∙FDA will respond to 90 percent of controlled correspondence within 2 months from date of submission in FY 2017.
2017财年，90%书面咨询会在提交日期2个月内得到FDA回复。
∙If the controlled correspondence requires input from the clinical division, one additional month will be added to the goals outlined above.
如果回复书面咨询需要临床部门的信息，那么上述目标期限需要多延长一个月。
The GDUFA Commitment Letter described controlled correspondence as follows:
FDA’s Office of Generic Drugs provides assistance to pharmaceutical firms and related industry regarding a variety of questions po d as “controlled documents.” See
[v/ForIndustry/UrFees/GenericDrugUrFees/ucm411122.htm]. Controlled correspondence does not include citizen petitions, petitions for reconsideration, or requests for stay.
GDUFA承诺书中描述了书面咨询：
针对一些问题，FDA仿制药办公室通过一种受控文件的形式为制药企业和相关行业提供帮助。请见
[v/ForIndustry/UrFees/GenericDrugUrFees/ucm411122.htm]。书面咨询不包括：公民请愿、复议申请和终止申请。
This guidance provides additional detail and recommendations concerning:
该指南针对以下内容提供了详细信息和建议：
∙What inquiries FDA considers to be controlled correspondence for the purpos of meeting the Agency’s GDUFA commitment
什么样的咨询FDA认为是符合GDUFA承诺的书面咨询。
∙What information requestors can include in a controlled correspondence to facilitate FDA’s consideration of and respon to a controlled correspondence
offer什么意思
什么样的信息可以包括在书面咨询中。
∙What information FDA will provide in its communications to requestors that have submitted controlled correspondence
FDA在与递交书面咨询的人进行交流时会提供什么样的信息。
Many of the recommendations in this guidance incorporate FDA’s historical practices in responding to controlled correspondence that were detailed on the Web page cited in the GDUFA Commitment Letter referenced above. 本指南的许多建议包含了以往FDA回复书面咨询的经验，具体请见上述GDUFA承诺书中引用的网页。
III.CONTROLLED CORRESPONDENCE 书面咨询
最好听的背景音乐
A.Definition of Controlled Correspondence 书面咨询的定义
As detailed in the GDUFA Commitment Letter, the aims of the generic drug ur fee program include (1) ensuring the safety of generic drug products; (2) enhancing access by expediting the availability of the products; and (3) enhancing transparency by, among other things, improving FDA’s communications with and feedback to industry to expedite product access. Each of the goals is designed to directly benefit the public health. FDA and industry identified controlled correspondence in the GDUFA Commitment Letter as one mechanism to support the aims.
正如GDUFA承诺书中所详述的，仿制药申报者付费计划的目标是（1）确保仿制药的安全性（2）通过提高仿制药的可用性加快其进入市场（3）另外，通过改进FDA与企业的交流及对企业的反馈，提升透明度，从而推进仿制药进入市场。上述目标对公众健康都有直接的好处。GDUFA承诺书中所谓的
FDA和企业之间的书面咨
询其实就是支持这些目标的一种机制。
The GDUFA Commitment Letter did not provide a preci definition of controlled correspondence, however. The Agency thus has determined that the term should be further defined in a manner that best supports the principles. Accordingly, FDA defines controlled correspondence for the purpos of GDUFA as follows: GDUFA承诺书对书面咨询没有给出明确的定义，但是FDA决定对该术语进一步规定，以便最大程度上支持GDUFA这些目标的实现。为此，FDA对书面咨询给出的定义如下：
A correspondence submitted to the Agency, by or on behalf of a generic drug manufacturer or related industry, requesting information on a specific element of generic drug product development.
书面咨询是由或代表仿制药生产商或相关行业提交给FDA的书面文件，主要咨询的是有关仿制药研发的特定内容。
We believe that this definition encompass the broad spectrum of issues that can ari as generic drug manufacturers and related industry (e.g., contract rearch organizations conducting bioanalytical or bioequivalence (BE) clinical trials, active pharmaceutical ingredient manufacturers, a
nd excipient manufacturers) begin drug development that can benefit from targeted Agency consideration and, at the same time, helps to ensure that Agency resources supported by ur fees are focud on facilitating and expediting development of generic drug products. Examples of topics that fall within and outside the definition are described in ctions IV.C-D, below.
我们相信我们对书面咨询的定义可以涉及到仿制药生产商和相关行业（例如：执行生物分析或生物等效性临床试验的合同研究机构、APIs生产商和辅料生产商）在开始药物研发时会出现的普遍问题，从而有助于仿制药生产商和相关行业获得FDA的定向指导，同时，还可以确保《仿制药申报者付费法案》所支持的FDA资源主要集中在促进和推进仿制药的研发。有关该定义范围内和范围外的一些主题实例请见下文第4节的C和D部分。
B.Additional Guidance on Inquiries Inside the Scope of Controlled Correspondence 有关咨询（书面咨询范围内）的额外指南
moves like jagger什么意思1.Controlled Correspondence Concerning Issues Raid in a Pending Citizen Petition, Petition for Reconsideration, or Request for Stay
在待处理的公民请愿、复议申请和终止申请中提出的书面咨询问题
If a controlled correspondence is submitted that rais an issue that is the same as or related to an issue or question that is the subject of one or more pending citizen petitions, petitions for reconsideration, or requests for a stay, the goal dates t forth in the GDUFA Commitment Letter for controlled correspondence will apply from the date FDA issues respons to the pending petitions.Likewi, if a citizen petition, petition for
reconsideration, or request for stay is submitted that rais an issue that is the same as or related to an issue or question in a pending controlled correspondence, the goal date for that controlled correspondence will apply from the date FDA issues a respon to the related citizen petition, petition for reconsideration, or stay request. For example, if a controlled correspondence is submitted in FY 2015 that relates to an issue in a pending petition, and the Agency responds in FY 2016 to that petition, the 4-month goal date for FY 2015, the year in which the controlled correspondence was submitted, will apply to the controlled correspondence from the 2016 date that the petition is answered. FDA will notify the requestor if we determine that the controlled correspondence is the subject of or related to an issue or question raid in a citizen petition, request for reconsideration, or request for a stay. When the Agency issues the respon, it will commence consideration of the controlled correspondence.
非主流男生昵称
如果提交的书面咨询中所提出的问题和待处理的公民请愿、复议申请及终止申请的一个或多个主题相同或相关，那么GDUFA承诺书中对于书面咨询的回复期限由FDA回复待处理请愿书的日期开始计算。相反，如果提交的公民请愿、复议申请及终止申请中所提出的问题和待处理的书面咨询的一个或多个主题相同或相关，那么书面咨询的回复期限由FDA回复相关的公民请愿、复议申请及终止申请的日期开始计算。例如：如果2015年提交的书面咨询和待处理的请愿书中问题相关，且FDA在2016年对该请愿书做出回复，那么原本在2015年4个月之内回复的书面咨询将在2016年对请愿书做出回复后的4个月之内回顾。FDA会通知咨询人面咨询中所提出
的问题是否和公民请愿、复议申请及终止申请中的主题/问题相关。当FDA对公民请愿、复议申请及终止申请做出回复后，将开始着手考虑书面咨询。
2.Requests Related to Matters Still Under Consideration by the Agency 有关FDA仍在考虑中的问题的咨询
FDA occasionally receives requests for information on issues that the Agency is considering, but for which no scientific or regulatory decision has been made or for which there is no clear clinical connsus. For a request for which controlled correspondence is the appropriate pathway but the subject is still under consideration at the time of the respon goal date, FDA will notify the requester
that the goal date has been misd becau the request raid issues about which FDA has not made a decision. In such instances, the request will remain open until FDA issues a respon.
heartbeats有时FDA在书面咨询的目标回复日期截止时，仍在考虑书面咨询中的问题，无法做出科学合理的决定或是没
gonna是什么意思有明确的临床共识，那么FDA将通知咨询人因为还没有做出决定而错过了目标回复日期。这种情况下，在FDA 给出回复前，书面咨询保持公开状态。
3.Requests More Appropriately Addresd Through Other Mechanisms 更适合通过其他机制回复的书面咨询
In certain circumstances, the controlled correspondence mechanism may not be the optimal mechanism to gain FDA feedback on such a topic. For example, a pre-ANDA meeting that is more iterative in nature may provide a better forum in which to discuss certain issues, e.g., methods of characterization for complex products or clinically critical BE considerations. Other topics that are general in nature would be more appropriately considered as part of the Regulatory Science Initiative, e.g., the propod u of in vitro data to support demonstration of BE for a new class of products. For such questions, the Agency will notify the requestor of the
