仿制药研发相关的受控通信

201509 FDA行业指南：仿制药研发相关的受控通信

Controlled Correspondence Related to Generic DrugDevelopment

Guidance for Industry

行业指南：仿制药研发相关的受控通信

Office of Communications, Division ofDrug Information

Center for Drug Evaluation and Research

Food and Drug Administration

10001 New Hampshire Ave., HillandaleBldg., 4thFloor

Silver Spring, MD 20993-0002

Phone: 855-543-3784 or 301-796-3400;Fax: 301-431-6353

Email: druginfo@fda.hhs.gov

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and HumanServices

Food and Drug Administration

Center for Drug Evaluation and Research(CDER)

September 2015

Generics

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TABLE OF CONTENTS目录

I. INTRODUCTION.	概述
II. BACKGROUND	背景
III. CONTROLLED CORRESPONDENCE	受控通信
A. Definition of Controlled Correspondence	受控通信的定义
B. Additional Guidance on Inquiries Inside the Scope  of Controlled Correspondence	在受控通信范围内所需的其它指南
1. Controlled Correspondence Concerning Issues  Raised in a Pending Citizen Petition, Petition for Reconsideration, or  Request for Stay	未决市民请愿、重审请愿或要求暂停中提出的相关问题的受控通信
2. Requests Related to Matters Still Under  Consideration by the Agency	与药监当局仍在考虑中的事务相关的申请
C. Guidance on Inquiries Outside the Scope of  Controlled Correspondence	在受控通信范围以外所需的指南
1. Exceptions to the Definition of Controlled  Correspondence	受控通信定义之外的例外
2. Topics Outside the Scope of Controlled  Correspondence	受控通信范围以外的议题
3. Entities Outside the Scope of Controlled  Correspondence	受控通信范围以外的实体
IV. SUBMITTING A CONTROLLED CORRESPONDENCE	提交一个受控通信
A. How to Submit a Controlled Correspondence	如果提前一个受控通信
B. Content of a Controlled Correspondence	受控通信的内容
C. Additional Recommendations on the Content of  Specific Types of Controlled Correspondence Inquiries	受控通信申请的指定类型的内容的其它建议
1. Requests Related to Inactive Ingredients	与非活性成分相关的申请
2. Requests for Q1/Q2 Formulation Assessment	Q1/Q2处方评估申请
3. Requests Requiring Review by More than One  Discipline	要求由不止一个学科进行评估的申请
D. Controlled Correspondence Review Disciplines	受控通信审核原则
V. INFORMATION ON COMMUNICATIONS FROM FDA TO  REQUESTORS THAT SUBMIT CONTROLLED CORRESPONDENCE	FDA对提交受控通信的申请者的沟通信息

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Guidance for Industry[1]

行业指南

Controlled Correspondence Related to

Generic Drug Development

仿制药研发相关受控通信

This guidance represents 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 use 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.    本指南代表FDA当前对本问题的想法。它不赋予任何人任何权利，对FDA或公众亦无强制力。如果满足适用的法律和法规要求，你也可以使用替代的方法。如需讨论替代方法，请联系FDA负责本指南的人员，联系方式列在标题页。

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I. INTRODUCTION概述

This guidance provides informationregarding the process by which generic drug manufacturers and related industrycan submit correspondence to FDA requesting information related to generic drugdevelopment. This guidance also describes the Agency’s process for providingcommunications related to such correspondence. FDA is issuing this guidance aspart of its implementation of the Generic Drug User Fee Amendments of 2012(Public Law 112-144, Title III), commonly referred to as GDUFA.

本指南提供了关于仿制药生产和相关行业向FDA提交其索取的有关仿制药研发信息流程。本指南还描述了药监当局提供这类通信的流程。FDA签发本指南是作为其2012年GDUFA实施的一部分。

FDA’s guidance documents, including thisguidance, do not establish legally enforceable responsibilities. Instead,guidances describe the Agency’s current thinking on a topic and should beviewed only as recommendations, unless specific regulatory or statutoryrequirements are cited. The use of the word shouldin Agency guidances means that somethingis suggested or recommended, but not required.

FDA的指南文件，包括本指南，并未建立法律强制义务。指南描述的只是药监当局目前对某个议题的思考，除引用的特定法规或法律要求外，应仅被当作为是建议。单词“应”在药监当局的指南中表示建议做某事，但不强制。

II. BACKGROUND背景

On July 9, 2012, GDUFA was signed intolaw by the President[2]. GDUFA is designed to speed the deliveryof safe and effective generic drugs to the public and to reduce costs toindustry. The law is based on an agreement negotiated by FDA andrepresentatives of the generic drug industry to address a growing number of regulatorychallenges. GDUFA reflects input received during an open process that includedregular public meetings, posting of meeting minutes, and consideration ofcomments from a public docket. Agreed-upon recommendations were sent toCongress, and Congress held hearings on GDUFA that included testimony from FDA,the generic drug industry, and other interested parties.

在2012年7月9日，GDUFA由总统签发生效。GDUFA的设计是为了加快将安全有效的仿制药提供给患者的速度，减少行业成本。法律是基于FDA和仿制药行业代表的谈判协议的，其中讨论了日益增加的法规挑战。GDUFA反映了在公开流程中收集到的反馈，包括法规公开会、会议纪要公开，以及从公众信息收集到的建议的考量。根据建议达成的一致意见被提交给议会，议会召开了关于GDUFA的听证会，其中听取了包括FDA、仿制药行业和其它利益相关方的证词。

GDUFA requires that FDA and humangeneric drug manufacturers alike must meet certain requirements andcommitments. Under GDUFA, FDA has agreed to specific program enhancements and performancegoals, as set forth in the GDUFA Commitment Letter[3] that accompanied the legislation. TheGDUFA Commitment Letter included detail on FDA’s commitment to respond toquestions 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特定的要求和承诺。根据GDUFA，FDA同意加强指定的流程，达到GDUFA承诺函以及立法要求的绩效目标。GDUFA承诺函包括FDA的承诺在一定时间限度内答复作为“受控通信”所提交的问题的详细信息。药监当局特别承认以下内容：

l  FDA will respond to 70 percent ofcontrolled correspondence within 4 months from date of submission in fiscalyear (FY) 2015.

l  在2015财年，FDA将在收到申报4个月内回复70%的受控通信

l  FDA will respond to 70 percent ofcontrolled correspondence within 2 months fromdate of submission in FY 2016.

l  在2016财年，FDA将在收到申报的2个月内回复70%的受控通信

l  FDA will respond to 90 percent ofcontrolled correspondence within 2 months from date of submission in FY 2017.

l  在2017财年，FDA将在收到申报的2个月内回复90%的受控通信

l   If the controlled correspondencerequires input from the clinical division, one additional month will be addedto the goals outlined above[4].

l  如果受控通信需要临床部门的信息，则上述目标时限相应延长一个月

The GDUFA Commitment Letter described controlled correspondenceas follows:

GDUFA承诺描述受控信息如下：

FDA’s Office of Generic Drugs providesassistance to pharmaceutical firms and related industry regarding a variety ofquestions posed as “controlled documents.” See [http://www.fda.gov/ForIndustry/U ... rFees/ucm411122.htm]. Controlled correspondence does notinclude citizen petitions, petitions for reconsideration, or requests for stay[5].

FDA的仿制药办公室为药业公司和相关行业提供协助，对于具有“受控文件”特性的大量问题作为受控信息处理。参见上述网站。受控通信并不包括市民请愿、重审请愿或暂停要求。

This guidance provides additional detailand recommendations concerning:

本指南提供关于以下内容的其它详细内容和建议：

l  What inquiries FDA considers to becontrolled correspondence for the purposes of meeting the Agency’s GDUFAcommitment

l  FDA认为哪些要求是受控通信，以符合当局的GDUFA承诺的要求

l  What information requestors can includein a controlled correspondence to facilitate FDA’s consideration of andresponse to a controlled correspondence

l  申请人在受控通信里可以包括哪些信息，以便FDA考虑和给受控通信以回复

l   What information FDA will provide in itscommunications to requestors that have submitted controlled correspondence

l  FDA会在其沟通中提供哪些信息给提交了受控通信的申请人。

Many of the recommendations in thisguidance incorporate FDA’s historical practices in responding to controlledcorrespondence that were detailed on the Web page cited in the GDUFA CommitmentLetter referenced above[6].

本指南中许多建议结合了FDA回复受控通信的历史实践，这些在上述所指的GDUFA承诺函中所引用的网页中的详细说明。

III.CONTROLLED CORRESPONDENCE受控通信

A. Definition ofControlled Correspondence受控通信的定义

As detailed in the GDUFA CommitmentLetter, the aims of the generic drug user fee program include (1) ensuring thesafety of generic drug products; (2) enhancing access by expediting theavailability of these products; and (3) enhancing transparency by, among otherthings, improving FDA’s communications with and feedback to industry toexpedite product access. Each of these goals is designed to directly benefitthe public health. FDA and industry identified controlled correspondence in theGDUFA Commitment Letter as one mechanism to support these aims.

正如GDUFA承诺函中所详述，仿制药用户费用程度的目的包括（1）确保仿制药品的安全，（2）增加这些仿制药品上市的速度，以及（3）通过加强FDA与行业的沟通及反馈，推进产品上市进程来提高透明度。上述每个目的的均是为了公众健康的直接利益。FDA和行业认为GDUFA承诺函中的受控通信是支持这些目标的一个机制。

The GDUFA Commitment Letter did notprovide a precise definition of controlled correspondence, however. The Agency thus hasdetermined that the term should be further defined in a manner that bestsupports these principles. Accordingly, FDA defines controlled correspondencefor the purposes of GDUFA as follows:

尽管这样，但GDUFA承诺函并没有给出受控通信的准确定义。药监当局因此决定应进一步对该术语进行定义，这样可以最好地支持这些原则。相应地，根据GDUFA的目的，FDA定义受控通信如下：

A correspondence submitted to theAgency, by or on behalf of a generic drug manufacturer or related industry,requesting information on a specific element of generic drug productdevelopment.

由仿制药生产商或相关行业或其代表者提交给药监当局的信函，其中要求索取仿制药研发的特定内容相关的信息。

We believe that this definitionencompasses the broad spectrum of issues that can arise as generic drugmanufacturers and related industry (e.g., contract research organizationsconducting bioanalytical or bioequivalence (BE) clinical trials, activepharmaceutical ingredient manufacturers, and excipient manufacturers) begindrug development that can benefit from targeted Agency consideration and, atthe same time, helps to ensure that Agency resources supported by user fees arefocused on facilitating and expediting development of generic drug products.Examples of topics that fall within and outside the definition are described insections IV.C-D, below.

我们相信这个定义将指导仿制药生产商和相关企业（例如，合同研发机构、实施生物分析或生效等效性临床试验（BE）、活性药用成分生产商，和辅料生产商）在开始药品研发时所提出很宽范围的问题，这些企业可以从当局考量中受益，同时，有助于确保当局由用户费用支持的资源可以集中在有利于加快仿制药研发方面。属于定义内和定义外的议题在以下IV.C-D部分中举例描述。

B. Additional Guidance on InquiriesInside the Scope of Controlled Correspondence受控通信范围内申请的其它指南

1.Controlled Correspondence ConcerningIssues Raised in a Pending Citizen Petition, Petition for Reconsideration, orRequest for Stay 未决市民请愿、重审请愿或要求暂停中提出的相关问题的受控通信

If a controlled correspondence issubmitted that raises an issue that is the same as or related to an issue orquestion that is the subject of one or more pending citizen petitions,petitions for reconsideration, or requests for a stay, the goal dates set forthin the GDUFA Commitment Letter for controlled correspondence will apply fromthe date FDA issues responses to the pending petitions[7]. Likewise, if a citizen petition,petition for reconsideration, or request for stay is submitted that raises anissue that is the same as or related to an issue or question in a pendingcontrolled correspondence, the goal date for that controlled correspondence willapply from the date FDA issues a response to the related citizen petition,petition for reconsideration, or stay request[8]. For example, if a controlledcorrespondence is submitted in FY 2015 that relates to an issue in a pendingpetition, and the Agency responds in FY 2016 to that petition, the 4-month goaldate for FY 2015, the year in which the controlled correspondence wassubmitted, will apply to the controlled correspondence from the 2016 date thatthe petition is answered. FDA will notify the requestor if we determine thatthe controlled correspondence is the subject of or related to an issue orquestion raised in a citizen petition, request for reconsideration, or requestfor a stay. When the Agency issues the response, it will commence considerationof the controlled correspondence.

如果所提交的受控通信提出的问题与一个或多个未决市民请愿、重审请愿或暂停要求的问题相关或相同，在GDUFA承诺函中所设定的回复期限将自FDA回复未决请愿起计时。类似的，如果所提交的市民请愿、重审请愿或暂停要求提出的问题与未决受控通信中的问题相关或相同，则在GDUFA承诺函中所设定的回复期限将自FDA回复未决请愿起计时。例如，如果一个受控通信在2015财年提交，其中问题与一个市民请愿相关，药监当局在2016财年回复了那个市民请愿，则对受控通信的回复期限4个月要从2016财年FDA回复市民请愿开始计时。如果FDA决定受控通信与市民请愿中提出的问题相关或相同，FDA会通知申请人。如果当局签发了回复，则表示已着手考虑受控通信所提出的问题。

2. Requests Related to Matters StillUnder Consideration by the Agency与药监当局仍在考虑中的事务相关的申请

FDA occasionally receives requests forinformation on issues that the Agency is considering, but for which noscientific or regulatory decision has been made or for which there is no clearclinical consensus. For a request for which controlled correspondence is theappropriate pathway but the subject is still under consideration at the time ofthe response goal date, FDA will notify the requester that the goal date hasbeen missed because the request raised issues about which FDA has not made adecision. In such instances, the request will remain open until FDA issues aresponse.

FDA偶然会收到索取当局正在考虑中的问题的信息，但这时还没有科学或法规方面的决定，或者没有明确的临床证据。对于应该通过受控通信提出申请，但仍在考量中的问题，到了回复期限，FDA会通知申请者已过目标回复时间，因为所提交的问题的申请FDA尚未做出决定。此情形申请将持续有效直到FDA签发回复。

3. Requests More Appropriately AddressedThrough Other Mechanisms通过其它系统说明更为适当的申请

In certain circumstances, the controlledcorrespondence mechanism may not be the optimal mechanism to gain FDA feedbackon such a topic. For example, a pre-ANDA meeting that is more iterative innature may provide a better forum in which to discuss certain issues, e.g.,methods of characterization for complex products or clinically critical BEconsiderations. Other topics that are general in nature would be moreappropriately considered as part of the Regulatory Science Initiative, e.g.,the proposed use of in vitro data to support demonstration of BE for a newclass of products. For such questions, the Agency will notify the requestor ofthe recommended alternative pathway and close the control[9].

在特定情形下，受控通信机制可能并不是获取FDA关于此类问题的反馈的最好的途径。例如，ANDA提交前的会议可能更有效，可以提供一个更好的论坛来讨论特定的问题，例如，复杂产品的定性方法，或临床关键性BE考量。其它一般性的问题可能更适合考虑作为法规科学倡议的一部分，例如，提议使用体内试验数据来支持证明新产品类型的BE。这些问题，当局将通知申请人建议通过哪个途径进行申请，并关闭该控制。

C. Guidance on Inquiries Outside theScope of Controlled Correspondence受控通信范围以外的申请指南

1. Exceptions to the Definition ofControlled Correspondence受控通信定义例外情况

Historically, three types of inquiriesfall within the above definition of controlled correspondencethat FDA has treated differently fromother inquiries on generic drug development: (1) requests for recommendationson the appropriate design of BE studies for a specific drug product (BEguidance requests); (2) requests for review of BE clinical protocols (clinicalprotocol requests); and (3) requests for meetings to discuss generic drugdevelopment prior to ANDA submission (pre-ANDA meeting requests). FDA willcontinue to respond to these inquiries consistent with its current practices,and to exclude these inquiries from the goal dates in the GDUFA CommitmentLetter, as described below.

历史上，三种类型的申请属于上述受控通信范围内，FDA曾经将其与其它仿制药研发的申请区分开来：（1）特定药品的BE研究适当设计建议申请（BE指南申请）；（2）申请审核BE临床方案（临床方案申请）；以及（3）申请在ANDA提交申请前召开会议讨论仿制药研发问题（ANDA之前会议申请）。FDA将一如既往继续回复此类申请，对这些申请的回复不受GDUFA承诺函里指定的日期限制，描述如下：

First, FDA will continue to address BEguidance requests consistent with the public process described in the Agency’sguidance for industry on Bioequivalence Recommendations forSpecific Products[10]. Under this approach, FDA publishes BErecommendations in product-specific guidances, the availability of which areannounced in the Federal Registerand are open to comment for a designatedperiod. Before establishing this public process, FDA responded to requests forguidance on BE studies on an individual basis. Under that process, informationabout BE studies was only provided to those parties specifically requestingsuch information, and it created a significant burden on those FDA employeesresponsible for reviewing both the BE data in ANDAs and requests forrecommendations on BE methodologies. The product-specific guidance processenhances transparency, provides a mechanism for public comment on recommendedBE studies, and provides for more efficient use of Agency resources.

首先，FDA将持续对BE指南申请进行回复，与当局的行业指南“特定药品的生物等效性建议”中所述的公众流程相一致。据此流程，FDA公布各产品的BE指南建议，这些指南公布在联邦注册上，公开征求意见一段时间。在建立此公开程序之前，FDA会单独回复给BE研究指南申请。在此流程中，关于BE研究的信息仅提供给指定要求这些信息的企业，它对

With this public process, FDA can beproactive in developing and publishing guidance for new drug products withoutwaiting for inquiries on BE methodologies from individual requestors. Ascontemplated in the GDUFA Commitment Letter, this effort will also includeguidance development resulting from the regulatory science initiatives fundedby generic drug user fees. FDA anticipates that this process will continue toexpedite the availability of BE methodologies to generic drug developers. Thisprocess involves time frames that differ from the goal dates for controlledcorrespondence, however, and the Agency has determined that it would not beappropriate to circumvent this public process by responding to individualrequestors in order to meet the GDUFA goal dates for controlled correspondence.Parties may submit BE guidance requests for proposed products to GenericDrugs@fda.hhs.gov[11] so that the Agency can continue to consider theserequests in prioritizing BE guidance development[12].

根据此公开流程，FDA可以主动研究和公布新的药品指南，不需要等待单个申请人在BE方法学方面的申请。正如GDUFA承诺函所述，此努力也包括从仿制药费用投资的法规科学倡议中建立的指南。FDA期望该流程能持续加快向仿制药研发者提供BE方法学。该流程牵涉到的时间框架不同于受控通信的日期限制，但是，当局已确定不会为了符合GDUFA对受控通信设定的回复期限而向单个申请人进行回复，这样绕开公开流程是不恰当的。相关方可以向上述邮箱提交所拟药品的BE指南申请，这样当局会继续考虑申请来优先建立BE指南。

Second, FDA will continue to excludeclinical protocol requests from controlled correspondence, and the related goaldates. These are requests for review of clinical protocols for in vivo BEstudies with pharmacokinetic, pharmacodynamic, or clinical end-point studiesconducted to support demonstration of BE for a proposed generic product.Historically, FDA has not considered such requests as controlledcorrespondence, because these requests are more time- and resource-intensivethan other requests and often call for consultation with multiple disciplineswithin the Office of Generic Drugs (OGD), as well as with other offices in theCenter for Drug Evaluation and Research (CDER). Notwithstanding exclusion fromthe category of controlled correspondence for the purposes of GDUFA goal dates,we recommend that parties continue to submit clinical protocol requests to GenericDrugs@fda.hhs.gov so the correct discipline can reviewthem promptly. FDA will respond to clinical protocol requests as expeditiouslyas practicable.

其次，FDA会继续将临床方案申请排除在受控通信之外以及相关的回复期限之外。这些申请都是要求对临床体内药动学、药理学或支持所拟仿制药BE结果的临床终点试验的BE研究方案进行审核。以前，FDA并未将这些申请作为受控通信，因为这些要求比起其它要求来说需要更多时间和资源，通常需要在仿制药办公室（OGD），以及药品评审中心（CDER）内部召开多学科讨论。尽管将其排除在GDUFA对受控通信承诺的回复期限之外，我们建议相关方继续向上述邮箱提交临床方案，这样会有适当的学科组来及时审核它们。FDA将在可行情况下，尽可能加快回复临床方案申请。

Third, FDA will not treat pre-ANDAmeeting requests as controlled correspondence with related GDUFA goal dates,because such requests serve a different purpose than controlled correspondenceand should include different information from an inquirer. The purpose of thecontrolled correspondence process is to provide a mechanism for a directinquiry on FDA’s position with respect to a particular element of generic drugdevelopment, and for the Agency’s direct response. The purpose of a pre-ANDAmeeting request, by contrast, is to seek a dialogue with the Agency on aparticular matter for which the controlled correspondence process is notsuitable. Similarly, materials and information submitted with a controlledcorrespondence should provide the Agency with the relevant information on whichto base its considerations, while the materials submitted in support of ameeting request should help the Agency determine whether a meeting isappropriate. Accordingly, we will treat these meeting requests separately. LikeBE guidance requests and clinical protocol requests, however, we recommend thatparties continue to submit pre-ANDA meeting requests toGenericDrugs@fda.hhs.gov so the Agency can consider themexpeditiously.

第三，FDA不会将ANDA前的会议申请作为受控通信来处理，不会适用GDUFA回复期限，因为这样的申请比起受控通信来说有多个目的，应包括申请者提交的不同资料。受控通信流程的目的是提供一个机制，处理直接提交给FDA的与仿制药研发特定要素相关的立场的申请，让当局来直接回复。ANDA之前的会议申请则相反，是要让当局对于一个特定的方法进行对话，它不适合受控通信流程。类似的，在受控通信中提交的资料和信息应向当局提供考虑所需的相关信息，而会议申请中提交的支持资料则应帮助当局决定召开一个会议是否恰当。相应地，我们会将这些会议申请单独处理。象BE指南申请和临床方案申请一样，我们建议各方继续向上述邮箱提交ANDA前会议申请，这样当局将尽快考虑。

2. Topics Outside the Scope ofControlled Correspondence受控通信范围内的议题

This section provides additionalguidance on the types of inquiries or topics that do not fall within thedefinition of controlled correspondencedescribed above. First, the Agencyconsiders any question related to a pending or approved ANDA a review issue.Such inquiries will not be treated as controlled correspondence and should besubmitted only to the ANDA so they can be included as part of the fulladministrative record for that application[13].

本部分提供关于不属于上述受控通信定义的申请或主题分类的指南。首先，当局将所有与未决或已批准的ANDA相关的所有问题是审核问题。这样的申请将不会当作是受控通信来处理，仅应提交ANDA，这样可以将其包括作为该申报全面行政记录的一部分。

Second, inquiries that are submitted toFDA that are not directly related to generic drug development will not beconsidered controlled correspondence for the purposes of GDUFA. For example,inquiries requesting information on the administrative practices of OGD, or ondevelopment of generic products for which there has never been a U.S.-approvedreference listed drug (RLD) identified in FDA’s Approved Drug Products with TherapeuticEvaluations(the Orange Book)[14], will not be considered controlledcorrespondence.

其次，提交给FDA的不直接与仿制药研发相关的申请从GDUFA的角度来看不会被当作受控通信。例如，索取关于OGD行政实践的申请信息，或关于并未在FDA批准药品中识别并经过治疗评估（橙皮书），并列入美国批准的参考药（RLD）仿制药研发，将不会被作为受控通信来对待。

Third, as reflected in the definition of controlled correspondence, FDA expects that a controlledcorrespondence will contain inquiries on a specific elementof generic drug development, not generalquestions related to product planning. Consistent with FDA’s past practices,general or insufficiently detailed questions related to product development arenot the appropriate subject of controlled correspondence. For example, aninquiry seeking information on general approval standards for a particularproduct is not the appropriate subject of a controlled correspondence for thepurposes of GDUFA. Likewise, an inquiry about the acceptability of an excipientwithout a proposed level for a specific RLD (which includes a specific productstrength), or a question about the general acceptability of a particulardevice, provides insufficient detail for the Agency to respond. FDA providesinformation to stakeholders on its approval standards and general submissionrecommendations through FDA regulations and guidances[15]. The controlled correspondence process isintended to facilitate, not supplant, the generic drug developmental endeavor.

第三，正如受控通信定义中所反映的，FDA期望受控通信包括关于仿制药研发的特定要素，而不是关于药品计划的一般问题。与FDA以前的做法一样，与药品研发相关的一般问题或不够详细的问题不是受控通信的适当的主题。例如，从GDUFA角度来说，索取关于特殊药品的一般批准标准就不是受控通信的适当的主题。同样，关于一个辅料的可接受程度而并没有指定RLD的拟定水平（其中包括特定的产品剂量），或关于一种特殊器械是否会被接受的问题，未提供足够的详细信息让当局可以回复的问题。FDA通过FDA法规和指南向关系方提供关于其批准标准和一般申报建议。受控通信的流程是为了方便，但并不是取代仿制药研发方面的工作。

3. Entities Outside the Scope ofControlled Correspondence受控通信范围以外的主体

The controlled correspondence process,historically (and under the definition above), is available to generic drugmanufacturers and related industry or their representatives, because thismechanism exists to facilitate generic drug development. Other parties (e.g.,private citizens, financial firms, or public advocacy groups that are notdirectly involved in developing generic drug products) should submit theirinquiries related to generic drugs to CDER’s Division of Drug Information[16].

受控制通信过程，之前（在上述定义下）仿制药生产商和相关行业或其代表可以使用，因为此机制存在就是为了方便仿制药三发。其它方面（例如，不直接参与仿制药研发的个人、经济公司或上市支持集团）应将其与仿制药相关的原咨询提交给CDER药品信息部。

IV. SUBMITTING A CONTROLLEDCORRESPONDENCE受控通信的提交

A. How to Submit a ControlledCorrespondence如何提交一份受控通信

Consistent with the agreement withindustry described in the GDUFA Commitment Letter, requestors seeking FDA’sresponse to a controlled correspondence by the goal dates articulated in theGDUFA Commitment Letter (and listed above) should submit the correspondenceelectronically, via email toGenericDrugs@fda.hhs.gov.[17] This will facilitate prompt consideration of and responseto the controlled correspondence by the appropriate discipline. The emailshould be sent from a corporate email address. For this reason, we do notintend to consider emails generated from general, personal accounts ascontrolled correspondence.

与GDUFA承诺函中所述的与行业之间的协议一致，要求FDA在GDUFA承诺函中给出期限前回复给一个受控通信的申请人应通过EMAIL将其通信以电子方式提交到GenericDrugs@fda.hhs.gov。这有利于由适当的学科专家及时考虑和回复受控通信。EMAIL应从公司邮箱发出。因此，我们不倾向于考虑一般的个人邮箱地址发出的邮件作为受控通信来对待。

FDA strongly discourages submittingcontrolled correspondence to individual FDA employees, and submittingadditional copies of a controlled correspondence in paper form, by courier, orby facsimile. As described in section V below, FDA intends to provide requestorsnotification via email on the status of a request soon after it is submitted,which should provide a requestor adequate assurance that the Agency hasreceived the communication. The Agency’s response will either state that FDA isconsidering the request as a controlled correspondence or provide the basis fornot responding to it as a controlled correspondence, as described in thisguidance.

FDA强烈反对提交受控通信对单个FDA雇员，或者通过快递或传真提交额外的受控通信纸质备份。正如以下V部分所述，FDA倾向于通过EMAIL给申请人提供通知，在收到申请后很快通知其申请的状态，这些能充分保证当局已收到该信息。当局的回复要么是说FDA正在将其申请作为受控制通信来考虑，或者告知申请人不会将其作为受控通信来回复的原因，如本指南所述。

B. Content of a ControlledCorrespondence受控通信内容

FDA recommends the following informationbe included at the beginning of a controlled correspondence:

FDA建议在受控通信前面包括以下信息：

l  Name, title, address, phone number, andentity (e.g., corporate affiliation) of the person submitting the controlledcorrespondence.

l  名称、标题、地址、电话、以及提交受控通信的人员所在实体（例如，公司关系）

FDA intends to provide a response to theU.S. agent or representative of a foreign company, similar to FDA practice whenan ANDA is submitted. Please identify the company for which you are the agentand include a copy of a letter of authorization with each controlledcorrespondence.[18]

FDA倾向于向国外公司的美国代理或代表提交回复，与ANDA提交时的FDA做法相似。请明你代表的公司名称，在每个受控通信中包括一份授权信。

l  An email address to which a response tothe controlled correspondence can be sent.

l  一个收取受控通信回复的邮件地址

A requestor (or its U.S. agent) mayapply for a secure email pathway by contactingsecureemail@fda.hhs.gov.

申请人（或其美国代理）[url=mailto:%E5%8F%AF%E4%BB%A5%E9%80%9A%E8%BF%87%E8%81%94%E7%B3%BBsecureemail@fda.hhs.gov]可以通过联系secureemail@fda.hhs.gov[/url]来使用受到保护的EMAIL途径。

l  The FDA-assigned control number andsubmission date of any previous, related controlled correspondence, if any, aswell as a copy of that previous controlled correspondence and FDA’s response,if any.

l  FDA给定控制号，和之前相关受控通信的申请日期（如有），以及之前受控通信和FDA回复的副本（如有）

l   Relevant RLD(s), as applicable,including application number, proprietary (brand) name, manufacturer, activeingredient, dosage form, and strength(s).

l  相关的RLD（s），适当时，包括申报号、专用名（商用名）、生产商、活性成分、剂型和剂量

l  A concise statement of the inquiry forwhich the controlled correspondence is being submitted.

l  简洁的说明所提交的受控通信的要求

l  A recommendation of the appropriate FDAreview discipline to review the controlled correspondence.

l  由适当的FDA审核学科来审核受控通信的建议

General information regarding reviewdisciplines is provided in section IV.D, below.

在IV.D部分提供了关于审核学科方面的一般信息。

l  Relevant prior research and supportingmaterials.

l  相关的之前研究和支持性材料

FDA recommends that a requestor includein its controlled correspondence the pertinent prior research and supportinginformation on the specific element of generic drug development about which itseeks information. If FDA determines, upon receipt of a controlledcorrespondence, that the correspondence lacks sufficient information toconsider the inquiry, it will notify the requestor of this deficiency and closethe controlled correspondence. If FDA determines, during the substantive reviewof the inquiry, that the inquiry lacks sufficient information, it can eitherclose the control at that time or contact the requestor for additionalinformation. If the Agency decides to close the control, it will notify therequestor of that decision and the basis for that decision. If FDA contacts therequestor for additional information, the goal date period will be extended bythe amount of time that the Agency’s request for additional information isoutstanding with the requestor.

FDA建议申请人在其受控通信中包括其在所要求信息的仿制药研发中特定要素方面的已有研究和支持性资料。如果FDA根据所收到的受控通信，认为通信缺乏足够的资料来对申请进行考虑，FDA会通知申请人该缺陷，并关闭受控通信。如果FDA在对申请的后续审核中，认为申请缺乏足够的资料，也可以在那时关闭控制，或联系申请人索取其它信息。如果当局决定关闭控制，则它会通知申请人其决定，以及做出决定的原因。如果FDA联系申请人索取更多资料，其回复期限则会相应延长。

C. Additional Recommendations on theContent of Specific Types of Controlled Correspondence Inquiries受控通信申请的特殊类型内容其它建议

This section provides additionalrecommendations for the content of specific types of inquiries submitted ascontrolled correspondence.

本部分提供了作为受控通信提交的申请的特殊类型的内容方面的其它建议。

1. Requests Related to InactiveIngredients与非活性成分相关的申请

The Agency often receives requests forinformation pertaining to whether particular inactive ingredients present athigher levels than the maximums listed in the Agency’s Inactive IngredientDatabase are permissible in a generic drug product. FDA recommends that arequestor submit for evaluation no more than three inactive ingredients, andunder any circumstances no more than three proposed formulations total for adrug product at a given time. For example, a request that proposes threedifferent ranges for a single inactive ingredient would be considered toinclude three proposed formulations, and a requestor should wait for FDA’sresponse to the controlled correspondence prior to submitting a differentformulation for consideration.

当局经常会收到含有在仿制药中是否特殊的非活性成分可以高于当局非活性成分数据库中列出的最高水平的问题。FDA建议申请人提交评估不要超过三种非活性成分，在任何情况下，不能同时提交超过三种拟定配方。例如，一个申请提议同一个非活性成分有三种不同范围，将被会认为是包括三种不同配方，在提交不同的配方考量之前，申请人应等待FDA对受控通信的回复。

The Agency believes this is thereasonable limit based on what can be evaluated for a particular drug productwithin the GDUFA goal date period. This encourages sponsors to provide targetedsubmissions to the Agency, and allows firms to refine their subsequentformulation proposals based on FDA’s previous responses. In addition, suchrequests should include reference to a relevant RLD (including the specificdrug product strength(s)) in order for FDA to evaluate the potentialacceptability of an excipient in the context of a specific proposed drugproduct. Absent that information, there is no means for OGD to evaluate use ofthat inactive ingredient safely, which depends on many factors, including theconditions of use for the reference product. We note that FDA evaluates theultimate acceptability of an excipient in the context of a specific proposeddrug product formulation during ANDA review, when the Agency has the fullcomplement of data and information in support of ANDA approval to consider.

基于在GDUFA回复期限内，给一个特殊药品能做出何中评估的前提，当局相信这是一个合理的限度。这就鼓励发起人提供有目的的申请给当局，允许公司根据FDA之前的回复制订其随后的配方提议。另外，这样的要求应包括对相关RLD的引用（包括特定的药品剂量），以使FDA能评估一个辅料在特定药品中可能被接受的程序。没有这些信息的话，OGD无法评估使用这种非活性成份的安全性，这取决于许多因素，包括参考药品的使用条件。我们注意到在ANDA评审期间，如果当局具有全面的补充数据和资料来支持ANDA批准供考量，FDA就能评估一个辅料在特定药品处方中无限可接受程度。

Parties seeking to provide informationto update FDA’s Inactive Ingredients Database (for example, to correctinformation on FDA-approved products contained in the database or to providedata for FDA-approved products not in the database) should send suchnotifications to IIDUpdate@fda.hhs.gov. Such updates should not be submittedto GenericDrugs@fda.hhs.gov.

想要提供信息让FDA更新其非活性成分数据库的各方（例如，纠正数据库中包含的FDA已批准的药品的信息，或提供数据库中没有包括的FDA已批准药品的数据）[url=mailto:%E5%BA%94%E5%B0%86%E8%AF%A5%E7%B1%BB%E9%80%9A%E7%9F%A5%E5%8F%91%E9%80%81%E5%88%B0IIDUpdate@fda.hhs.gov]应将该类通知发送到IIDUpdate@fda.hhs.gov[/url]。[url=mailto:%E6%AD%A4%E7%B1%BB%E6%9B%B4%E6%96%B0%E4%B8%8D%E5%BA%94%E5%8F%91%E9%80%81%E7%BB%99GenericDrugs@fda.hhs.gov]此类更新不应发送给GenericDrugs@fda.hhs.gov[/url]。

2. Requests for Q1/Q2 FormulationAssessment Q1/Q2处方评审申请

For certain types of products, FDA’sregulations generally require that proposed products be qualitatively (Q1) andquantitatively (Q2) the same as the RLD with respect to inactive ingredients[19]. In addition, FDA’s guidances sometimesrecommend certain BE studies for drug products that are Q1/Q2 with respect tothe RLD. When seeking review of proposed Q1/Q2 formulations, we recommend thecontrolled correspondence include the following information (which can be foundin the Orange Book):

对于特定类型的药品，FDA的法规一般要求所拟药品在非活性成分配方内容（Q1）和配方比例（Q2）两方面与RLD相同。另外，FDA的指南有时建议采用RLD对Q1/Q2相关的药品进行特定的BE研究。在要求对所拟Q1/Q2配方进行审核时，我们建立受控通信中包括以下信息（可以在橙皮书上找到这些信息）：

l  relevant RLD sponsor

l  相关RLD上市人

l  application number

l  申请编号

l  proprietary name

l  专用名

l  active ingredient

l  活性成分

l  dosage form

l  剂型

l  route of administration

l  给药途径

l  RLD approval date

l  RLD批准日期

l  whether the product is prescription,over-the-counter, or in the “Discontinued” section of the Orange Book, whichlists drug products that have been withdrawn from the market.

l  药品是否处方药、非处方药，还是橙皮书中的“退市药”，在其中有列出已从市场撤出的药品

FDA recommends that no more than threeproposed Q1/Q2 formulations of a single drug product be submitted in onecontrolled correspondence at a given time. Limiting a single control to no morethan three formulation requests provides for FDA’s targeted and timely reviewof such requests. In addition, the Agency recommends against submitting arequest for evaluation of Q1/Q2 and a separate request for evaluation of aproposed inactive ingredient at the same time. The formulation descriptionsshould include adequate details, including salt and hydration forms of theactive ingredients and excipients[20].

FDA建议在同一时间的一个受控通信里，不要提议同一个药品超过3个Q1/Q2处方。限制单个控制不超过3个处方申请让FDA可以达到及时审核这类申请的目标。另外，当局建议一个Q1/Q2审核申请，而同时提交另一个评估提议的非活性成分的单独申请。处方描述应包括足够的详细信息，包括活性成分和辅料的盐和水合形态。

If a requestor is seeking formulationassessment for multiple drug products, FDA recommends that each request besubmitted in a separate controlled correspondence. Thus, a requestor should notseek Q1/Q2 formulation assessment for generic products with different RLDs in asingle controlled correspondence. This also includes separate formulationassessment requests for drug products with multiple strengths, because eachstrength is a separate drug product.

如果申请人希望对多个药品的配方进行评估，FDA建议在单个受控通信中分别提交申请。因此，申请人不应该在同一个受控通信中提交不同RLD的仿制药的Q1/Q2处方评估。这也包括多剂量药品配方评估，因为每个剂量是一个单独的药品。

Consistent with the Agency’s pastpractice, FDA does not intend to review proposed formulations that are notrequired or FDA-recommended in guidance to be Q1/Q2 to the RLD. Non-Q1/Q2formulations are permissible for certain products so long as the differences donot affect the safety or effectiveness of the product. The acceptability ofsuch differences would be considered in the context of an ANDA review.

与当局过去的实践一样，FDA不倾向于审核指南中说明不属于RLD的Q1/Q2的配方提案。到目前为止，非Q1/Q2配方对特定药品是允许的，因为差异不并影响药品的有效性和安全性。这类差异的可接受程度将在ANDA审核时进行考虑。

3. Requests Requiring Review by Morethan One Discipline需要不止一个学科审核的申请

If a requestor seeks information relatedto separate elements of generic drug product development (e.g., information onproposed formulation and proposed product labeling), FDA recommends that therequestor submit separate requests regarding the product. This will facilitatetimely review and response.

如果一个申请人要求的信息与仿制药研发的独立要素有关（例如，所拟处方和所拟药品标签信息），FDA建议申请人分开提交申请。这会有助于及时审核和回复。

D. Controlled Correspondence ReviewDisciplines受控通信审核原则

This section provides additionalinformation on the different disciplines that might review and respond to acontrolled correspondence. In addition, this section provides examples of thetypes of inquiries a discipline might review. The Agency anticipates that thisinformation will assist requestors in recommending the appropriate disciplineto review a particular controlled correspondence, as suggested above. Thesedescriptions are not intended to be exhaustive, and FDA has the discretion todetermine which discipline should review and respond to a controlledcorrespondence.

本部分提供了可能会参与审核并回复受控通信的不同学科的额外信息。此外，本部分给出了各学科可能会审核的类型例子。当局期望这些信息会有助于申请人推荐适当的学科专家来审核特别的受控通信，如上所建议。这些学科并不代表仅限于，FDA有权自由裁量决定哪个学科应审核和回复给一个受控通信。

l  OGD’s Office of Bioequivalence

l  OGD的生物等效性办公室

FDA anticipates that the Office ofBioequivalence will review correspondence containing inquiries related to theplanning of BE studies. Within the Office of Bioequivalence, we anticipate thatthe Division of Clinical Review will review correspondence containing clear,concrete questions related to the planning of a BE study with clinicalendpoints, and questions related to adverse events that occur during theconduct of a BE study. The Division of Clinical Review also reviews questionsrelated to inactive ingredients.

FDA期望生物等效性办公室审核包括有关于BE研究计划方面的申请通信。在生物等效性办公室内，我们期望临床审核部审核包括有与临床终点BE研究计划有关的明确的、具体问题，以及与BE研究中发生的不良事件有关的问题。临床审核部也要审核关于非活性成分相关的问题。

l  OGD’s Office of Research and Standards

l  OGD研发和标准办公室

FDA anticipates that the Office ofResearch and Standards will review correspondence containing questions, forexample, on complex drug products or drug-device combination products.

FDA期望研发和标准办公室审核包括有，例如，复杂药品或药品-器械复合产品方面问题的通信。

l  OGD’s Office of Operations, Division ofFiling Review

l  OGD营运办公室，文件审核部

We anticipate that the Division ofFiling Review will review correspondence containing inquiries regarding FDA’sInactive Ingredient Database and drug product formulation.

我们期望文件审核部审核关于FDA非活性成分数据库和药品处方方面的通信申请。

l  OGD’s Office of Operations, Division ofLabeling Review

l  OGD营运办公室，标签审核部

FDA anticipates that the Division ofLabeling Review will review, for example, correspondence regarding labelingstandards for container/closure systems that are different from the RLD’s, andappropriate labeling differences.

FDA期望标签审核部审核，如，关于不同于RLD的容器/密闭系统的标签标准，以及适当的标签差异的通信。

l  OGD’s Office of Generic Drug Policy

l  OGD的仿制药政策办公室

We anticipate that the Office of GenericDrug Policy, which includes the Orange Book staff, will review, for example,correspondence regarding patent listings or RLD questions.

我们期望仿制药政策办公室，其中包括橙皮书员工，审核如关于专利列表或RLD问题方面的通信。

l  OPQ’s Office of Policy forPharmaceutical Quality

l  OPQ的药品质量政策办公室

FDA anticipates that the Office ofPolicy for Pharmaceutical Quality will coordinate OPQ’s review ofcorrespondence amongst the sub-offices listed below. For example, OPQ willreview correspondence containing inquiries regarding chemistry, manufacturing,and controls, as well as product quality microbiology for generic drugs. Inaddition, we anticipate that OPQ will review inquiries related to Type II drugmaster files for drug substances submitted in support of generic drugapplications.

FDA期望药品质量政策办公室协助OPQ在以下分部办公室里对通信进行审核。例如，OPQ将审核包括关于研发、生产和控制，以及仿制药产品质量微生物方面要求的通信。另外，我们期望OPQ审核与支持仿制药申报所提交的原料药II类DMF有关的申请。

l  OPQ’s Office of Lifecycle Drug Products

l  OPQ的药品生命周期办公室

l  OPQ’s Office of New DrugProducts/Division of Lifecycle API and Division of Biopharmaceutics

l  OPQ的新药/原料药生命周期部和生物药品部办公室

l  OPQ’s Office of Process and Facilities

l  OPQ的工艺和设施办公室

V. INFORMATION ON COMMUNICATIONS FROMFDA TO REQUESTORS THAT SUBMIT CONTROLLED CORRESPONDENCEFDA对提交受控通信的申请者的沟通信息

For inquiries submitted to GenericDrugs@fda.hhs.gov, FDA will provide the followinginformation to a requestor regarding its receipt and consideration of theinquiry.

对于提交至上述邮箱的申请，FDA提供以下信息给申请人，告知其收到申请以及对申请的考量。

Upon receipt of a submission, FDA willevaluate whether the submission will be considered a controlled correspondencefor the purposes of GDUFA. FDA then will send the requestor one of two emails1) an email confirming acceptance of the submission as a controlledcorrespondence for the purposes of GDUFA, which will include a controlledcorrespondence tracking number; or (2) an email informing the requestor eitherthat the Agency does not consider the submission a controlled correspondenceand the basis for that decision, or that FDA lacks adequate information to makethis determination. In most instances, we anticipate confirming acceptance ofthe submission within seven calendar days, which communication will contain areceipt date that the requestor can use to calculate the goal date. If arequestor resubmits a request for information that addresses any problem thatFDA identified with a previous request, the Agency will consider this a newcontrolled correspondence and process it as such.

在收到申请资料后，FDA会评估该申请是否根据GDUFA应作为受控通信。随后FDA会给申请人发送一个或两个EMAIL：（1）一个EMAIL确认接受该申请作为GDUFA下的受控通信，其中包括一个受控通信跟踪号；或者（2）一个EMAIL通知申请人当局不认为该申请是一个受控通信及判定的原因，或者FDA没有足够的信息来做出决定。在多数情况下，我们期望在7个自然日内确认收到申请，其中会包括一个收到日期，申请人可以基于此日期计算回复期限。如果申请人重新提交了一个申请，其中要求说明的问题是FDA之前已收到的咨询，则当局会将之作为一个新的受控通信，并按程序处理。

After reviewing the request forinformation in the controlled correspondence, FDA will respond in written formvia email to the email address from which the original controlledcorrespondence was sent. The length and content of FDA’s response will dependon the nature of the inquiry submitted. We intend that the comments we providein response to a controlled correspondence will be comprehensive as of the dateof the response. We note that response comments represent the Agency’s currentthinking on a topic at that time, and that our scientific thinking may evolvein the future.

对审核了受控通信中的要求后，FDA会通过EMAIL书面回复给原始发送受控通信的邮箱。FDA回复的长度和内容取决于所提交要求的性质。我们力求给受控信息提供的回复在当时足够全面。我们的回复代表了当局目前对该问题的思考，但我们的科学考虑在将来可能会有改进。

FDA will not respond to status requestsregarding pending controlled correspondence prior to the goal date[21]. If the Agency does not respond to thecontrolled correspondence by the goal date, we will send an acknowledgement tothe requestor with notification that the request is still under consideration.

FDA不会在回复期限之前答复关于未决受控通信的状态咨询。如果当局到期没有回复，我们会发送一份知悉函给申请人，通知申请人其申请仍在处理中。

We recognize that upon receipt of FDA’sresponse to a controlled correspondence, requestors might have follow-upquestions or wish to request related, additional information. Because Agencystaff would have to expend resources to review and respond to these follow-upquestions and requests for additional information, FDA will treat the requestsas new controlled correspondence. This ensures that the follow-up question istracked and that all requestors are treated equitably. In these instances, werecommend that a requestor submit a new controlled correspondence and includethe controlled correspondence tracking number(s) of the previous inquiry tofacilitate FDA’s review and response.

我们知道在收到FDA对受控通信的回复后，申请者可能会有后续问题，或希望申请相关的其它信息。由于当局人员需要更多资源来审核和回复这些后续的问题以及要求更多信息的申请，FDA会将这些申请作为新的受控通信来处理。这样能确保后续问题被追踪，所有申请者受到公平对待。在这种情况下，我们建议申请者提交一个新的受控通信，包括之前申请的受控通信跟踪号，以便FDA审核和回复。

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[1] The Office of Generic Drugs in the Center for DrugEvaluation and Research at the Food and Drug Administration prepared thisguidance.

[2] On October 5, 2012, the President signed into law the FDAUser Fee Corrections Act of 2012 (Public Law 112-193). This act amended GDUFAso that due dates for GDUFA user fees in fiscal year 2013 were not dependent onenactment of an appropriations act.  

[3] See Generic Drug User Fee Act Program Performance Goalsand Procedures (GDUFA Commitment Letter) for fiscal years 2013 through 2017,available at http://www.fda.gov/downloads/For ... Fees/UCM282505.pdf.

[4] GDUFA Commitment Letter at 12. Any controlledcorrespondence submitted before October 1, 2014, does not fall under the timeframes and goal dates identified in the GDUFA Commitment Letter.Notwithstanding, FDA intends to respond to those controlled correspondence asexpeditiously as practicable.

[5] GDUFA Commitment Letter at 15. We note that the Web pagelink quoted in the definition above has been updated to reflect the currentlink, because the link provided in the GDUFA Commitment Letter is no longeraccessible.  

[6] See Recommendationsfor Improving Submissions of a “Controlled Correspondence” to the Office ofGeneric Drugs, available athttp://www.fda.gov/ForIndustry/U ... rFees/ucm411122.htm

[7] As set forth in the GDUFA Commitment Letter, controlled correspondencedoes not include citizen petitions, petitions forreconsideration, or requests for stay, even if they raise issues related togeneric drug development (GDUFA Commitment Letter at 12).  正如GDUFA承诺函中所设定，受控通信并不包括市民请愿、重审请愿或暂停要求，即使他们提出的问题与仿制药研发有关（GDUFA承诺函）。

[8] FDA considers a controlled correspondence to be relatedto an issue or question that is the subject of a pending citizen petition if wedetermine that a decision regarding the issue or question raised in the citizenpetition could affect our response to the controlled correspondence.  FDA可能将与市民请愿有关的问题作为受控通信，如果我们认为请愿中提出的问题所作出的决定

[9] Controlled correspondence are intended to requestinformation on a specific element of generic drug development, so they are notappropriate for requests that ask FDA to develop a new regulatory policy orchange an existing policy. As described below, however, FDA intends to monitorsubjects of controlled correspondence to consider issues for developingguidance documents.

[10] We updateguidances periodically. To make sure you have the most recent version of aguidance, check the FDA Drugs guidance Web page at

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  

[11] This email address is a general OGD address to whichcertain submissions related to generic drugs may be submitted. This emailaddress is monitored daily and submissions, including requests for BE guidance,pre-ANDA meetings, clinical protocol reviews, and controlled correspondence,are routed to the appropriate discipline or personnel.

[12] We encourage requests for consideration of BE methodsthat modify or deviate from those proposed for a specific product to besubmitted to the public docket of the particular product-specific BE guidance.As an alternative, the inquirer can submit such a request to GenericDrugs@fda.hhs.gov and it will be forwarded to the appropriate division. Inaddition, if a requestor wants clarification on a BE study recommended in therelated product-specific draft guidance to support development of a genericdrug product, the requestor can submit an inquiry as a controlledcorrespondence.  

[13] The Agency will consider a request for information in acontrolled correspondence regarding development of a new strength for a productfor which the submitter is a sponsor of a pending or approved ANDA for otherstrengths. The Agency also will consider a request for information in acontrolled correspondence regarding development of a different packageconfiguration for a product for which the submitter is a sponsor of a pendingor approved ANDA for other package configurations. For example, if an inquirypertaining to a gel in a metered-dose pump is submitted and there is a pendingor approved ANDA for gel in a unit-dose package, the controlled correspondencecould still be accepted for review.

[14] An RLD is the “listed” (i.e., approved) drug that FDA hasidentified as the drug product upon which an applicant relies in seekingapproval of its abbreviated application (21 CFR 314.3). RLDs are identified inthe Orange Book and are available on FDA’s Web site at http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm.  

[15] FDA intends to monitor the subjects raised in controlledcorrespondence to identify future topics for Agency guidance.

[16] See contact information for the Division of Drug Informationon the second title page of this guidance.

[17] Controlled correspondence that are not submittedelectronically will be responded to, but will not receive a goal date. GDUFACommitment at 7 (“Review metric goals […] only apply to submissions madeelectronically, following the eCTD format in effect at the date ofsubmission”.)  

[18] When possible, FDA recommends identification of thesponsor of the potential ANDA, which facilitates linkage of the controlledcorrespondence to the ANDA when submitted.

[19] See, e.g., 21 CFR 314.94(a)(9)(iii).

[20] Tofacilitate consideration of the request, FDA recommends that the inactiveingredient and/or the formulation information be presented in the format inwhich it would be submitted in an ANDA.

[21] For pre-FY 2015 controlled correspondence, OGD willstrive to respond to these controls as expeditiously as practicable.

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