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This draft guidance, when finalized, will represent the current thinking of the Foodand Drug Administration (FDA or Agency) on this topic.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.
本草案在定稿时，将代表FDA当前对该主题的看法。它并不赋予任何人任何权力，对FDA和公众亦无强制效力。可使用满足适用法律法规要求方法替代。如需对替代方法进行讨论，请联系本标题页上所列的FDA本指南负责人员。
TABLEOF CONTENTS
I. INTRODUCTION 概述
II. BACKGROUND 背景
III. QUESTIONS AND ANSWERS 问答
A. General Inquiries About the Content andFormat of the Orange Book 关于橙皮书内容和格式的一般询问
B. Petitioned ANDAs 请愿性ANDA
C. The Movement of Drug Products Between theActive and Discontinued Sections of the Orange Book 橙皮书活跃部分和退市部分之间的药品移动
D. Patent Listings 专利列表
I. INTRODUCTION 概述
This guidance is intended to assist interested parties (including prospective drug product applicants, drug product applicants, and approved application holders) in utilizing the Approved Drug Products With Therapeutic Equivalence Evaluations publication (the Orange Book ). This guidance provides answers to commonly asked questions that we have received from these interested parties regarding the Orange Book .
本指南意在帮助相关方（包括未来和当前的药品申报人以及已批准的药品申报持有人）利用《已批准药品及其一致性评价》出版物（橙皮书）。本指南回答了我们所收到的相关方关于橙皮书的常见问题。
Ingeneral, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking ona topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
一般来说，FDA的指南文件并不构成法律强制义务。相反，指南所述仅为FDA当前对某主题的想法，应仅作为建议看待，其中所引用的具体法律法规要求除外。在FDA指南中使用“应当（SHOULD）”一词表示建议或推荐某事但并非强制要求。
II. BACKGROUND 背景
The Orange Book identifies (1) drug products approved by FDA under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and (2) patent and exclusivityinformation related to approved drug products. In particular, the main criteria for the inclusion of a drug product inthe Orange Book are that the drug product is the subject of an approved application and that FDA has not determined the drug product to have been withdrawn from sale for safety or effectiveness reasons .
橙皮书列出信息包括（1）FDA根据FDCA批准的药品，和（2）与所批准药品有关的专利信息和独占信息。尤其是如果一个药品进入橙皮书的主要标准是该药品为一份已批准的申报资料的对象，并且FDA并因安全性或有效性原因而确定其退出销售。
The Orange Book is composed of four main parts:
橙皮书主要包括4个部分：
(1) The Prescription Drug Product List, which isa list of approved marketed prescription drug products with therapeutic equivalence evaluations (which along with the OTC Drug Product List is referredto as the “Active Section”);
处方药列表，它是已批准上市的处方药品及其治疗等同性评价的清单（与OTC药品列表一起称为“活跃部分”）；
(2) The OTC Drug Product List, which is a list of marketed over-the-counter (OTC) drug products that have been approved in new drug application (NDAs) or abbreviated new drug applications (ANDAs) (which along with the Prescription Drug Product List is referred to as the “Active Section”);
OTC药品列表，它是通过新药申报（NDA）或简略新药申报（ANDA）程序已批准上市的非处方药（OTC）药品清单（与处方药列表一起称为“活跃部分”）；
(3) The Drug Products with Approval under Section 505 of the FD&C Act Administered by the Center for Biologics Evaluation and Research List; and
根据FDCA第505条款获得生物制品审评与研究中心（CBER）批准的药品，以及
(4) The Discontinued Drug Product List, which isa cumulative list of approved drug products that have never been marketed, are for exportation (e.g., only marketed outside the United States), are formilitary use, are not commercially distributed by a United States federal or state government entity, have been discontinued from marketing and FDA has not determined that they were withdrawn from sale for reasons of safety or effectiveness, or have had their approvals withdrawn for reasons other than safety or effectiveness subsequent to being discontinued from marketing (commonly referred to as the “Discontinued Section”).
退市药品列表，它是一份从未上市销售的、用于出口（例如，仅在美国以外上市销售）、用于军事用途、美国联邦或州政府实体未进行商业化销售、退市、FDA未确定其因安全性或有效性原因退出销售，或因非安全性非有效性原因撤销其批准退出销售的已批准药品的累积清单（一般称为“退市部分”）。
The Orange Book contains additional information, including three appendices and two addenda related to patents and exclusivity. The Orange Book website also has a number of additional resources that can assist stakeholders with using the Orange Book and related questions .
橙皮书中还有其它信息，包括3个附录和2个与专利和独占有关的补充部分。橙皮书网页还有大量其它资源，可帮助相关方使用橙皮书和相关问题。
In addition, the Orange Book contains therapeutic equivalence evaluations for approved multisource prescription drug products, which are reflected for drug products in the Active Section. These evaluations have been prepared to serve as public information and advice to state health agencies, prescribers, and pharmacists to promote public education on drug product selection and to foster containment of health care costs .
橙皮书还有已批准多源处方药的一致性评价信息，反映的是活跃部分的药品。这些评价内容是为州卫生部分、处方开具者和药师提供的公开信息和建议，促进公众对药品选择的教育，推进健康护理成本控制。
The coding system for therapeutic equivalence evaluations is designed (1) to allowusers to determine quickly whether the Agency has determined that a particularapproved drug product (e.g., a particular strength, dosage form, and route of administration of an approved drug) is therapeutically equivalent to other pharmaceutically equivalent drugproducts and (2) to provide additional information to users on the basis of FDA’s evaluations; the first item (i.e., therapeutic equivalence) is reflected in the first letter of the therapeutic equivalence code, and the second item (i.e., additional information) is reflected in the second letter of the code.
治疗等同性评价的代码系统是设计用于（1）让用户可快速确定FDA是否已批准该药品（例如，已批准药品的特定剂量、剂型、给药途径），（2）基于FDA的评价结果为使用者提供更多信息，第一条（即治疗等同性）反映在治疗等同性代码的第一位字母中，第二条（即更多信息）反映在代码的第二个字母中。
As noted in the Introduction, this guidance provides answers to questions that have been received by the FDA staff that publishes and manages the Orange Book. The questions and answers in this guidance cover the following topics:
正如概述中所言，本指南是回答FDA职员所收到的关于橙皮书发布和管理方面的问题。本指南中的问答包括以下主题：
• General inquiries about the content and format of the Orange Book
• 关于橙皮书内容和格式的一般询问
• Petitioned ANDAs
• 请愿性ANDA
• The movement of drug products between the Active and Discontinued Sections of the Orange Book
• 药品在橙皮书活跃部分和退市部分之间移动的情况
• Patent listings
• 专利列表
III. QUESTIONS AND ANSWERS 问答
A. General Inquiries About the Content and Format of the Orange Book 关于橙皮书内容和格式的一般询问
Q1.Which applications are not listed in the Orange Book? 哪些申报是不列入橙皮书的？
A1. The Orange Book does not include: (1) approved drug products that were discontinued either before the first edition in October1980 or discontinued between 1980 and 1987, prior to the identification of discontinued products; (2) drug products that have a tentative approval ; (3) drug products marketed before 1962 for which a Drug Efficacy Study Implementation review has not been completed; (4) biological products licensed by FDA under the Public Health Service Act (42 U.S.C. 262 ); (5) marketed drug products that are not the subject of an approved NDA or ANDA (e.g., under OTC monograph); and (6) drug products compounded by a pharmacy pursuant to section 503A of the FD&C Act and drug products compounded by an outsourcing facility pursuant to section 503B of the FD&C Act. Approved drug products are removed from the Orange Book when, for example, an approval is withdrawn under section 505(e) or 505(j)(6) of the FD&C Act , when FDA has determined that the drug product was withdrawn from sale for reasons of safety or effectiveness , or when the status of an approval is converted from final approval to tentative approval.
橙皮书中没有（1）在1980年橙皮书首版之前已退市的已批准药品，和1980-1987年之间尚未识别退市药品之前退市的药品，（2）临时批准的药品，（3）在1962年之前上市的药品，这些药品未进行药品有效性研究审评，（4）由FDA根据公众卫生服务法案（42.U.S.C.262）批准的生物制品，（5）不是已批准NDA或ANDA（例如，根据OTC各论）对象的已上市药品，以及（6）由药房根据FDCA第503A条款配制的药品，和根据FDCA第503B条款委托给外包场所配制的药品。已批准药品会从橙皮书中删除，例如，当根据FDCA第505(e) 或505(j)(6)条款撤销批准，FDA已认定因安全性或有效性原因决定撤回该药品，或批准状态从最终批准转为临时批准时。
Q2.Can I access the current data files for the Orange Book? How are data provided? 我能否访问当前的橙皮书数据文件？数据会以何种方式提供？
A2. Yes. The Orange Book Data Files contain current Orange Book data for approved drug products and unexpired patent and exclusivity data, which are updated monthly. They are available in a compressed ZIP file under “Additional Resources.”
可以。橙皮书数据文件中有当前的橙皮书已批准药品数据和未过期专利和独占数据，每月更新。在“其它资源”中以ZPI压缩文件提供。
Q3. Is it possible to obtain previous editions ofthe Orange Book or an Orange Book Data File? 是否有可能获得橙皮书之前的版本或数据文件？
A3. Requests for previous editions of the Orange Book or an Orange Book Data File should be made under the Freedom of Information Act. Requests should be submitted either online viahttps://www.accessdata.fda.gov/scripts/foi/FOIRequest/index.cfm or in writing to FDA’s Freedom of Information Staff at the following address:
如需之前版本，请按信息自由法案流程提交申请。申请可在线提交，亦可以书面方式按以下地址提交给FDA信息自由职员。
Foodand Drug Administration, Division of Freedom of Information Office of the Executive Secretariat, OC 5630 FishersLn., Rm. 1035，Rockville, MD 20857 .
Q4.For daily updates to the Orange Book (e.g.,posting of newly submitted or revised patent information or newly approved generic drug products), is there a specific time of the day when the electronic Orange Book is updated? 橙皮书电子版的日常更新内容（例如，发布最新提交或修订的专利信息，或最新批准的仿制药）是在当天的固定时间更新的吗？
A4. Updates to the electronic Orange Book are generally posted in the afternoon, Eastern Time.
电子橙皮书的更新通常在东部时间下午发布。
Q5.When are newly approved NDA drug products listed in the Orange Book? 新批准的NDA药品何时会录入橙皮书？
A5. Newly approved NDA drug products will generally appear in the Active Section of the Orange Book in the month following their approval, and will remain there, unless the NDA holder notifies FDA that the drug product will not be available for sale within 180 days of approval. If the NDA holder notifiesFDA that it does not intend to market upon approval, the NDA drug product will,in the month following such approval, appear in the Discontinued Section. The monthly cumulative supplement of the Orange Book is generally updated at the end of the second full week of each month.
新批准的NDA药品一般会在其批准后次月出现在橙皮书的活跃部分，并保持在该部分直到NDA持有人在批准后180天内通知FDA该药品不再销售。如果NDA持有人通知FDA其在批准之后不准备上市，则NDA药品会在该批准之后次月出现在退市部分。橙皮书的月度累积增补册一般会在每月的第二个全工作周结束时更新。
Q6.Are the marketing reports required under section 506I of the FD&C Act available to the public ? FDCA第506I部分所要求的销售报告是否会公开？
A6. No. Consistent with section 506I(f) of the FD&C Act, FDA will not publish copies of marketing reports submitted to the Agency, but will update the Orange Book, as appropriate, as the reports are reviewed and processed.
不公开。根据FDCA第506I(f)条，FDA不会发布其收到的上市报告的副本，仅会在审核和处理报告时更新橙皮书（适当时）。
B. Petitioned ANDAs 请愿性ANDA
Q7.A petitioned ANDA drug product is listed in the Orange Book without a therapeutic equivalence code. What is its reference listed drug (RLD )? Should a therapeutic equivalence code be assigned to that ANDA? 请愿性ANDA药品列入橙皮书时没有治病等同性代码。其参比制剂（RLF）是什么？这种ANDA会指定治疗等同性代码吗？
A7. For a petitioned ANDA, the RLD should be the listed drug referenced in the approved suitability petition. The firstpetitioned ANDA approved will not be pharmaceutically equivalent to the RLD andthus no therapeutic equivalence code would be assigned to it. However, after the first petitioned ANDA is approved, FDA generally will assign therapeutic equivalence codes to all ANDAs that contain the same petitioned differences(i.e., in dosage form, route of administration, strength, or active ingredient (in a drug product with more than one active ingredient)) as the first petitioned ANDA.
对于请愿性ANDA，RLD应为已批准的适用请愿中引用的列表药品。首个已批准请愿性ANDA不会在药学方面与RLD一致，因此不会为其给定一致性代码。但是在首个请愿性ANDA批准之后，FDA通常会为所有含有相同已请愿差异（即，剂型、给药途径、剂量或活性成分（当药品在有不止一种活性成分时））的ANDA给定一致性代码。
C. The Movement of Drug Products Between the Active and Discontinued Sections of the Orange Book 药品在橙皮书活跃部分和退市部分之间移动
Q8. Are only those drug products for which approval of the application has been withdrawn (i.e., the approval of the drug product application has been withdrawn by FDA) considered withdrawn from sale by FDA? FDA是否只将申报批准被撤销的药品（即FDA撤销了对该药品的批准）认为是“退出销售”？
A8. No. Adrug product considered withdrawn from sale is not limited to the withdrawal of approval of a drug product application. The Agency has previously indicated that withdrawal from sale is not limited to a permanent withdrawal of a product but can include drug products for which “any decision to discontinue marketing ” has been made. In particular, FDA previously explained its interpretation that a drug is considered to have been “withdrawn from sale” for purposes of section 505(j)(5) and 505(j)(6)(C) of the FD&C Act if:
不是。药品退出销售不仅仅限于药品申报批准的撤销。FDA之前说过退出销售不仅限于药品永久退出，还有做出“中止销售决定”的药品。尤其是FDA之前解释过根据FDAC第505(j)(5) 和 505(j)(6)(C)款以下情形时的药品会被作为“退出销售”：
the applicant has ceased its own distribution of the drug, whether or not it has ordered recall of previously distributed lots of the drug. A routine, temporary interruption in the supply of a drug product would not be considered a withdrawal from sale, however, unless triggered by safety or effectiveness concerns .
申报人停止其药品销售，无论是否因要求召回之前已销售的药品批次。除因安全或有效性关切理由退出外，药品销售的临时中断不是退出销售。
Likewise, FDA has considered a drug product to have been withdrawn from sale if the NDA or ANDA holder has notified FDA that the drug product is not being marketed.
类似地，如果NDA或ANDA持有人通知FDA其药品暂不上市，则FDA亦将该药品作为退出销售。
Q9. How should an NDA or ANDA holder notify FDA, under section 506I of the FD&C Act, that a drug product is or will be withdrawn from sale? 为符合FDCA506I要求，NDA或ANDA持有人要如何通知FDA某个药品已经或将要退出销售？
A9. The NDA or ANDA holder should submit a notification of withdrawal from sale in a letter to the applicable NDA or ANDA file through the electronic submissions gateway. The notification should prominently identify the submission as an “ADMINISTRATIVE CHANGE / NOTAVAILABLE FOR SALE .”
NDA或ANDA持有人应提交一份退出销售的通知函，通过电子申报端口提交至对应的NDA或ANDA文件。通知应突出写明该申请为“行政变更/不再销售”。
NDA and ANDA holders are required to provide a written notification to FDA 180 days prior to withdrawing an approved drug product from sale. If it is not practicable to submit the notification 180 days before withdrawing the drug product from sale, that submission should be made “as soon as practicable, but not later than the date of withdrawal” from sale.
NDA和ANDA持有人要在将已批准药品退出销售之前180天向FDA提交一份书面通知。如果在退出销售之前180提交通知不现实，则通知的提交应“尽可能早，但不得迟于退出销售之日”。
Q10. How and when should an NDA or ANDA holder request that an application be moved from the Discontinued Section of the Orange Book to the Active Section? NDA或ANDA持有人要如何申请将一份申报从橙皮书的退市部分移入活跃部分呢？
A10. Prior to requesting that an applicationbe moved from the Discontinued Section to the Active Section, the application holder should determine whether the submission of a supplement under 21 CFR314.70 or 314.97 is required prior to or at the time of introduction of the drug product into the marketplace.
在申请将一个申报从退市部分移入活跃部分之前，申报持有人应确定根据21 CFR 314.70或 314.97是否需要在上市销售该药品之前提交一份补充资料。
Ifa prior approval supplement under 21 CFR 314.70(b) is required:
如果需要根据21 CFR 314.70(b)提交预批准补充资料，则
• The application holder should notify the Orange Book 1-2 months prior to the approval of the supplement that the application holder is seeking market entry or re-entry via submission to the application file identified as an “ADMINISTRATIVE CHANGE / NOTIFICATION OF COMMERCIAL MARKETING.”
• 申报持有人应在上市或重新上市补充资料批准之前1-2个月通知橙皮书，通知方式为提交一份申报文件，标明“行政变更/商业化销售通知”
• The Orange Book will move the product from the Discontinued Section to the Active Section upon approval of the supplementin the subsequent monthly cumulative supplement.
• 橙皮书会在后续月度累积增补册中根据批准情况将药品从退市部分移入活跃部分
If a Changes Being Effected supplement under 21 CFR 314.70(c) is required:
如果需要根据21 CFR 314.70(c)提交CBE补充资料，则：
• The application holder should determinethe anticipated launch date, which is generally the date the drug product isput into the marketplace for distribution.
• 申报持有人应确定预期上市日期，通常是药品上市销售的日期
• The application holder should notify the Orange Book that the application holder is seeking market entry or re-entry approximately 1 – 2 months before the anticipated launch date via submission to the application file identified as an “ADMINISTRATIVE CHANGE / NOTIFICATION OF COMMERCIAL MARKETING.”
• 申报持有人应在其预期上市或重新上市日期前约1-2个月时通知橙皮书，通知方式为提交申报文件，标明“行政变更/商业化销售通知”
• The Orange Book will move the product from the Discontinued Section to the Active Section upon the anticipated launch datein the subsequent monthly cumulative supplement.
• 橙皮书会根据预期上市日期将药品从退市部分移入活跃部分，放在后续的月度累积补充卷。
Q11. When will a move of a drug product to orfrom the Discontinued Section be reflected in the Orange Book? 橙皮书何时会反映出药品移入/移出退市部分的情况？
A11. A move to or from the Discontinued Section will generally be reflected in a future Orange Book monthly cumulative supplement update. The monthly electronic Orange Book is generally updated by the end of the following month’s second work week (e.g., November’s edition of the electronic Orange Book willbe updated by the end of the second full work week in December ).
橙皮书以后一般会每月更新退市部分，以累积补充方式更新。每月的电子橙皮书一般会在每月第二周结束时更新（例如，11月电子版橙皮书会在12月的第二个全工作周结束时更新）。
D. Patent Listings 专利列表
1. Listing Patents 列表专利
Q13. How does an NDA holder ensure that Form FDA 3542 (Patent Information Submitted Upon and After Approval of an NDA or Supplement ) is timely filed? NDA持有人要如何确保FDA3542表（在NDA或补充资料批准时或批准后提交的专利信息）的提交是及时的？
A13. An NDA holder must submit information foreach patent that claims the drug or method of using the drug and for which aclaim of patent infringement could reasonably be asserted against a person engaged in the unlicensed manufacture, use, or sale of the drug product . The NDA holder must submit this patent information to the NDA on a Form FDA 3542 . FDA publishes this patent information in the Orange Book. For a patent to be considered timely filed, a Form FDA 3542 must be submitted to the NDA within 30 days after the date of approval of the NDA or supplement or within 30 days of issuance of a patent for each patent that claims the drug substance (active ingredient), drug product (formulation or composition), and/or approved method of using the approved drug product .
NDA持有人必须为每项声明该药品或药品使用方法的专利提交信息，未获授权生产、使用或销售此该药品的人员将被合理认定侵权。NDA持有人必须使用FDA3542表提交此类专利信息至NDA。FDA会将该专利信息发布在橙皮书中。如果在NDA或增补批准后30天内，或在声明药用物质（活性成分）、药品（制剂配方或组成），和/或已批准药品的已批准使用方法的专利授权后30日内提交了FDA3542表，则认为是“及时”提交了专利。
With respect to any errors or omissions that FDA identifies in a Form FDA 3542, 21CFR 314.53(c)(2)(ii) provides:
如果FDA发现表格3542有错误或遗漏， 21 CFR314.53(c)(2)(ii)提到：
If the applicant submits the required patent information within the 30 days, but we notify an applicant that a declaration form is incomplete or shows that thepatent is not eligible for listing, the applicant must submit an acceptable declaration form within 15 days of FDA notification to be considered timely filed.
如果申报人在30天内提交了所要求的专利信息，但我们通知申报人说申报表不完整，或者该专利不符合列表要求，则申报人必须在收到FDA通知之后15天内提交一份合格的申报表，此时认为满足“及时提交”的要求。
Under the terms of the regulation, to be considered timely filed as of the date of the original submission of patent information, the NDA holder must submit an acceptable Form FDA 3542 within 15 days of FDA’s original notification. NDA holders should carefully read the instructions to Form FDA 3542 in correcting such deficiencies.
根据法规条款，NDA持有人必须在收到FDA原始通知15天以内提交一份满意的FDA3542表，该专利信息首次提交日期方可被认为“及时”。NDA持有人应仔细阅读FDA3542表中的指导，避免此类缺陷。
Q14. How does an NDA holder ensure that an amendment to the description of an approved method of use claimed by the patentis timely filed? NDA持有人要如何确保及时提交专利所声明的已批准使用方法描述修订内容？
A14. An NDA holder’s amendment to the description of an approved method(s) of use (MOU) claimed by the patent will be considered timely filed if it is submitted within 30 days of (1) patent issuance, (2) approval of a corresponding change to the drug product labeling, or (3) a decision by the U.S. Patent and Trademark Office or a Federal court that is specific to the patent and alters the construction of a method-of-useclaim(s) of the patent. Outside of these circumstances, and except as provided in the patent listing dispute regulations , an amendment to the description of the approved MOU claimed bythe patent will not be considered timely filed .
NDA持有人对已批准专利声明的使用方法（MOU）描述的修订在（1）专利授权之后，（2）药品标签相应变更批准之后，或（3）美国专利商标局或负责专利的联邦法庭判定变更专利声明的使用方法结构之后，30天内提交则认为是及时的。不在上述范围的情形，除专利列表质疑规定范围情形外，对已批准的专利声明MOU描述的修改不在及时报告之列。
Q15. How can an NDA holder submit a reissued patent to the Orange Book for listing? NDA持有人要如何提交一份再版专利要求列入橙皮书？
A15. An NDA holder is required to request that the original patent be removed from the Orange Book once a patent is reissued because, upon patent reissuance, the original patent is surrendered and ceases to have legal effect . Consistent with our regulationsfor any request to withdraw a patent from the Orange Book, the original patent will remain listed in the Orange Book until FDA determines that no first applicant is eligible for 180-day exclusivity based on a paragraph IV certification to that patent or after the 180-day exclusivity period of a first applicant based on that patent has expired or has been extinguished or relinquished .
专利再版时，NDA持有人要申请从橙皮书上删除原版专利，因为专利再版后，原版专利即告失效，法律效力中止。与申请从橙皮书上其它撤销专利的法规要求一样，原版专利会保持列于橙皮书中，直到FDA确定并无首仿人因四段挑战获得该专利180天独占期，或如获得但已过期、撤销或弃权。
Q16. How does FDA receive and process a request from an NDA holder for removal of a patent from the Orange Book? FDA是怎么从NDA持有人处接收到从橙皮书上删除某个专利的申请并执行删除的呢？
A16. If an NDA holder determines that a patentor patent claim no longer meets the statutory requirements for listing (e.g.,if a court finds a listed patent invalid or unenforceable, from which no appeal has been or can be taken), the NDA holder must promptly notify FDA to amend or withdraw the patent information and request that the patent information be removed from the Orange Book . If the NDA holder is required by court order to amend patent information or withdraw a patent from the Orange Book, the NDA holder must submit an amendment to its NDA that includes a copy of the order within 14 days of the date of order entry. As described above, FDA will remove apatent from the Orange Book if there is no first applicant eligible for 180-day exclusivity based on a paragraph IV certification to that patent or after the expiration, extinguishment, or relinquishment of any 180-day exclusivity period for a first applicant .
如果一个NDA持有人确定某项专利或专利声明不再符合列表法规要求（例如，如果法院宣布所列专利无效或不具有可执行性，且未申诉或不能申诉者），则NDA持有人必须立即通知FDA修改或撤回其专利信息，申请从橙皮书上删除该专利信息。如果法庭裁定该NDA持有人修改专利信息或从橙皮书上撤回某项专利，则该NDA持有人必须在裁定生效后14日之内提交NDA修订，在其中包括有一份裁定书副本。如上所述，如果没有该专利四段挑战的首个申办人获得180天排他优先权，或首个申办人的180天排他优先权过期、撤销或弃权之后，则FDA将从橙皮书上删除该专利。
An NDA holder may submit a withdrawal of a patent and request for removal of the patent from the Orange Book by letter to the NDA file . The letter must contain the NDA number, each product to which the request applies, and the patent number. A Form FDA 3542 is not required to be submitted for this request, but the NDA holder should clearly and prominently identify that it is seeking patent withdrawal and removal from the Orange Book under 21 CFR 314.53(f)(2)(iv).
NDA持有人可通过递交一份NDA文件函，请求撤销专利，要求从橙皮书上删除该专利。该函中必须包括有NDA编号，专利号及申请适用的所有产品。提交该申请时不需要填写FDA3542表，但NDA持有人应清楚突出写明其根据21 CFR314.53(f)(2)(iv)要求撤回专利列表，申请从橙皮书上删除该专利。
Q17. An NDA holder has requested that a patent be removed from the Orange Book. The patent remains in the Orange Book with a delist request flag. When will the patent be removed? NDA持有人已要求从橙皮书上删除某项专利，但该专利仍在橙皮书中，标有“从列表删除申请”符号，该专利要何时才会删除？
A17. A patent may remain listed for a certain period even if the NDA holder requests that it be removed because a first applicant may retain eligibility for 180-day exclusivity based on a paragraph IV certification to this patent .
即使NDA持有人因首个申报人因对该专利提起四段挑战成功获得180天独占期且仍在效期内而申请删除该专利，但该专利仍会留在橙皮书上一段时间。
Until the patent is removed from the Orange Book ― after any associated 180-day exclusivity has expired or has been extinguished or relinquished ― ANDA applicants must submit or maintain appropriate certifications to the patent not withstanding the NDA holder’s request to remove the patent . Applicants submitting a section 505(b)(2) application are not required to certify to a patent when the delist request flag is set to Y in the Orange Book .
在相关的180独占权过期、撤销或弃权之后，橙皮书上将该专利删除之前，无论NDA持有人是否申请了删除该专利，ANDA申请人均必须提交或保持适当的专利声明。如果橙皮书上某项专利“从列表删除”栏为“Y”，申请人不需要提交505(b)(2)申请对该专利进行认证。
2. Patent Listing Disputes 专利列表质疑
Q18. Can a patent listing be disputed? 可以质疑专利列表吗？
A18. Yes. 21 CFR 314.53(f)(1) outlines a process through which a person other than the NDA holder can dispute the accuracy or relevance of patent information published in the Orange Book, as well as the process for the relevant NDA holder to respond to such disputes. If any person either “disputes the accuracy or relevance of patent information submitted to the Agency” and published by the Agency in the Orange Book or “believes that an NDA holder has failed to submit required patent information, that person must first notify the Agency in a written or electronic communication titled ‘314.53(f) Patent Listing Dispute .’” The patent listing dispute may be sent to the Orange Book Staff at orangebook@fda.hhs.gov .
可以。21 CFR 314.53(f)(1)中列出了非NDA的持有人可以质疑橙皮书上所列专利信息的准确性或相关性的流程，以及相关NDA持有人回应此类质疑的流程。如果有任何人“质疑提交给FDA”且被FDA列入橙皮书发布“的专利信息的准确性或相关性”，或“相信有NDA持有人未提交所需专利信息，则该人必须首先书面或电子方式通知FDA，标题写明‘314.53(f)专利列表质疑’”。可通过orangebook@fda.hhs.gov将专利列表质疑发送给橙皮书职员。
The patent listing dispute “must include a statement of dispute that describes the specific grounds for disagreement regarding the accuracy or relevance of patent information,” which FDA will send to the applicable NDA holder . 21 CFR 314.53(f)(1) states:
专利列表质疑“必须包括有质疑声明，写明不同意专利信息的准确性或相关性的具体原因”，FDA会将此类信息发给适当的NDA持有人。21 CFR 314.53(f)(1)要求：
Fora dispute regarding the accuracy or relevance of patent information regarding an approved method of using the drug product, this statement of dispute must be only a narrative description (no more than 250 words) of the person’s interpretation of the scope of the patent. This statement of dispute must only contain information for which the person consents to disclosure because FDA will send the text of the statement to the applicable NDA holder without review or redaction.
对于已批准药品使用方法的专利信息准确性或相关性的质疑，质疑声明必须只采用叙述性说明（不超过250字），解释专利范围。质疑声明只能包括有该人认为可披露的信息，因为FDA不会再行审核或遮盖而是直接将原文转给适当的NDA持有人。
FDA will forward the dispute to the NDA holder as described in the regulation.
FDA会按法规所述将质疑发给NDA持有人。
Q19. How does FDA provide notification of whether a patent listing dispute has been submitted? FDA会如何发布已提交专利质疑通知？
A19. For all patent listing disputes, FDA promptly posts information to a Patent Listing Dispute List website indicating whether (1) a patent listing dispute has been submitted to FDA and (2) the NDA holder has timely responded to the patent listing dispute. The Patent Listing Dispute List contains relevant drug product information andinformation on the disputed patent. This list is cumulative in nature and isorganized by the drug product established name and patent number(s).
FDA会即刻将所有专利列表质疑发布在专利列表质疑清单页面，注明（1）专利列表质疑是否已提交给FDA，以及（2）NDA持有人是否及时回应专利列表质疑。专利列表质疑清单中包括有相关的药品信息，以及受质疑的专利信息。该清单为累积清单，按药品注册名称和专利编号排列。
文章来源：蒲公英
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