DRAFT GUIDANCE

Orange Book Questions and Answers Guidance for Industry

行業(yè)指南草案：橙皮書問答

This draft guidance, when finalized, will represent the current thinking of the Foodand Drug Administration (FDA or Agency) on this topic.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.

本草案在定稿時，將代表FDA當(dāng)前對該主題的看法。它并不賦予任何人任何權(quán)力，對FDA和公眾亦無強制效力?？墒褂脻M足適用法律法規(guī)要求方法替代。如需對替代方法進(jìn)行討論，請聯(lián)系本標(biāo)題頁上所列的FDA本指南負(fù)責(zé)人員。

TABLEOF CONTENTS

I.     INTRODUCTION  概述

II.  BACKGROUND 背景

III.   QUESTIONS AND ANSWERS 問答

A.    General Inquiries About the Content andFormat of the Orange Book 關(guān)于橙皮書內(nèi)容和格式的一般詢問

B.    Petitioned ANDAs 請愿性ANDA

C.   The Movement of Drug Products Between theActive and Discontinued Sections of the Orange Book 橙皮書活躍部分和退市部分之間的藥品移動

D.   Patent Listings 專利列表

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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 .

本指南意在幫助相關(guān)方（包括未來和當(dāng)前的藥品申報人以及已批準(zhǔn)的藥品申報持有人）利用《已批準(zhǔn)藥品及其一致性評價》出版物（橙皮書）。本指南回答了我們所收到的相關(guān)方關(guān)于橙皮書的常見問題。

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.

一般來說，F(xiàn)DA的指南文件并不構(gòu)成法律強制義務(wù)。相反，指南所述僅為FDA當(dāng)前對某主題的想法，應(yīng)僅作為建議看待，其中所引用的具體法律法規(guī)要求除外。在FDA指南中使用“應(yīng)當(dāng)（SHOULD）”一詞表示建議或推薦某事但并非強制要求。

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 .

橙皮書列出信息包括（1）FDA根據(jù)FDCA批準(zhǔn)的藥品，和（2）與所批準(zhǔn)藥品有關(guān)的專利信息和獨占信息。尤其是如果一個藥品進(jìn)入橙皮書的主要標(biāo)準(zhǔn)是該藥品為一份已批準(zhǔn)的申報資料的對象，并且FDA并因安全性或有效性原因而確定其退出銷售。

The Orange Book is composed of four main parts:

橙皮書主要包括4個部分：

(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”);

處方藥列表，它是已批準(zhǔn)上市的處方藥品及其治療等同性評價的清單（與OTC藥品列表一起稱為“活躍部分”）；

(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藥品列表，它是通過新藥申報（NDA）或簡略新藥申報（ANDA）程序已批準(zhǔn)上市的非處方藥（OTC）藥品清單（與處方藥列表一起稱為“活躍部分”）；

(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

根據(jù)FDCA第505條款獲得生物制品審評與研究中心（CBER）批準(zhǔn)的藥品，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”).

退市藥品列表，它是一份從未上市銷售的、用于出口（例如，僅在美國以外上市銷售）、用于軍事用途、美國聯(lián)邦或州政府實體未進(jìn)行商業(yè)化銷售、退市、FDA未確定其因安全性或有效性原因退出銷售，或因非安全性非有效性原因撤銷其批準(zhǔn)退出銷售的已批準(zhǔn)藥品的累積清單（一般稱為“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 .

橙皮書中還有其它信息，包括3個附錄和2個與專利和獨占有關(guān)的補充部分。橙皮書網(wǎng)頁還有大量其它資源，可幫助相關(guān)方使用橙皮書和相關(guān)問題。

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 .

橙皮書還有已批準(zhǔn)多源處方藥的一致性評價信息，反映的是活躍部分的藥品。這些評價內(nèi)容是為州衛(wèi)生部分、處方開具者和藥師提供的公開信息和建議，促進(jìn)公眾對藥品選擇的教育，推進(jìn)健康護(hù)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.

治療等同性評價的代碼系統(tǒng)是設(shè)計用于（1）讓用戶可快速確定FDA是否已批準(zhǔn)該藥品（例如，已批準(zhǔn)藥品的特定劑量、劑型、給藥途徑），（2）基于FDA的評價結(jié)果為使用者提供更多信息，第一條（即治療等同性）反映在治療等同性代碼的第一位字母中，第二條（即更多信息）反映在代碼的第二個字母中。

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職員所收到的關(guān)于橙皮書發(fā)布和管理方面的問題。本指南中的問答包括以下主題：

·      General inquiries about the content and format of the Orange Book

·      關(guān)于橙皮書內(nèi)容和格式的一般詢問

·      Petitioned ANDAs

·      請愿性ANDA

·      The movement of drug products between the Active and Discontinued Sections of the Orange Book

·      藥品在橙皮書活躍部分和退市部分之間移動的情況

·      Patent listings

·      專利列表

III.   QUESTIONS AND ANSWERS 問答

A.    General Inquiries About the Content and Format of the Orange Book 關(guān)于橙皮書內(nèi)容和格式的一般詢問

Q1.Which applications are not listed in the Orange Book? 哪些申報是不列入橙皮書的？

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.

橙皮書中沒有（1）在1980年橙皮書首版之前已退市的已批準(zhǔn)藥品，和1980-1987年之間尚未識別退市藥品之前退市的藥品，（2）臨時批準(zhǔn)的藥品，（3）在1962年之前上市的藥品，這些藥品未進(jìn)行藥品有效性研究審評，（4）由FDA根據(jù)公眾衛(wèi)生服務(wù)法案（42.U.S.C.262）批準(zhǔn)的生物制品，（5）不是已批準(zhǔn)NDA或ANDA（例如，根據(jù)OTC各論）對象的已上市藥品，以及（6）由藥房根據(jù)FDCA第503A條款配制的藥品，和根據(jù)FDCA第503B條款委托給外包場所配制的藥品。已批準(zhǔn)藥品會從橙皮書中刪除，例如，當(dāng)根據(jù)FDCA第505(e) 或505(j)(6)條款撤銷批準(zhǔn)，F(xiàn)DA已認(rèn)定因安全性或有效性原因決定撤回該藥品，或批準(zhǔn)狀態(tài)從最終批準(zhǔn)轉(zhuǎn)為臨時批準(zhǔn)時。

Q2.Can I access the current data files for the Orange Book? How are data provided? 我能否訪問當(dāng)前的橙皮書數(shù)據(jù)文件？數(shù)據(jù)會以何種方式提供？

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。橙皮書數(shù)據(jù)文件中有當(dāng)前的橙皮書已批準(zhǔn)藥品數(shù)據(jù)和未過期專利和獨占數(shù)據(jù)，每月更新。在“其它資源”中以ZPI壓縮文件提供。

Q3. Is it possible to obtain previous editions ofthe Orange Book or an Orange Book Data File? 是否有可能獲得橙皮書之前的版本或數(shù)據(jù)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./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，請按信息自由法案流程提交申請。申請可在線提交，亦可以書面方式按以下地址提交給FDA信息自由職員。

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? 橙皮書電子版的日常更新內(nèi)容（例如，發(fā)布最新提交或修訂的專利信息，或最新批準(zhǔn)的仿制藥）是在當(dāng)天的固定時間更新的嗎？

A4.  Updates to the electronic Orange Book are generally posted in the afternoon, Eastern Time.

電子橙皮書的更新通常在東部時間下午發(fā)布。

Q5.When are newly approved NDA drug products listed in the Orange Book? 新批準(zhǔn)的NDA藥品何時會錄入橙皮書？

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.

新批準(zhǔn)的NDA藥品一般會在其批準(zhǔn)后次月出現(xiàn)在橙皮書的活躍部分，并保持在該部分直到NDA持有人在批準(zhǔn)后180天內(nèi)通知FDA該藥品不再銷售。如果NDA持有人通知FDA其在批準(zhǔn)之后不準(zhǔn)備上市，則NDA藥品會在該批準(zhǔn)之后次月出現(xiàn)在退市部分。橙皮書的月度累積增補冊一般會在每月的第二個全工作周結(jié)束時更新。

Q6.Are the marketing reports required under section 506I of the FD&C Act available to the public ?FDCA第506I部分所要求的銷售報告是否會公開？

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.

不公開。根據(jù)FDCA第506I(f)條，F(xiàn)DA不會發(fā)布其收到的上市報告的副本，僅會在審核和處理報告時更新橙皮書（適當(dāng)時）。

B.   Petitioned ANDAs 請愿性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? 請愿性ANDA藥品列入橙皮書時沒有治病等同性代碼。其參比制劑（RLF）是什么？這種ANDA會指定治療等同性代碼嗎？

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.

對于請愿性ANDA，RLD應(yīng)為已批準(zhǔn)的適用請愿中引用的列表藥品。首個已批準(zhǔn)請愿性ANDA不會在藥學(xué)方面與RLD一致，因此不會為其給定一致性代碼。但是在首個請愿性ANDA批準(zhǔn)之后，F(xiàn)DA通常會為所有含有相同已請愿差異（即，劑型、給藥途徑、劑量或活性成分（當(dāng)藥品在有不止一種活性成分時））的ANDA給定一致性代碼。

C.   The Movement of Drug Products Between the Active and Discontinued Sections of the Orange Book 藥品在橙皮書活躍部分和退市部分之間移動

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是否只將申報批準(zhǔn)被撤銷的藥品（即FDA撤銷了對該藥品的批準(zhǔn)）認(rèn)為是“退出銷售”？

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。藥品退出銷售不僅僅限于藥品申報批準(zhǔn)的撤銷。FDA之前說過退出銷售不僅限于藥品永久退出，還有做出“中止銷售決定”的藥品。尤其是FDA之前解釋過根據(jù)FDAC第505(j)(5) 和 505(j)(6)(C)款以下情形時的藥品會被作為“退出銷售”：

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 .

申報人停止其藥品銷售，無論是否因要求召回之前已銷售的藥品批次。除因安全或有效性關(guān)切理由退出外，藥品銷售的臨時中斷不是退出銷售。

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.

類似地，如果NDA或ANDA持有人通知FDA其藥品暫不上市，則FDA亦將該藥品作為退出銷售。

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? 為符合FDCA506I要求，NDA或ANDA持有人要如何通知FDA某個藥品已經(jīng)或?qū)⒁顺鲣N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持有人應(yīng)提交一份退出銷售的通知函，通過電子申報端口提交至對應(yīng)的NDA或ANDA文件。通知應(yīng)突出寫明該申請為“行政變更/不再銷售”。

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持有人要在將已批準(zhǔn)藥品退出銷售之前180天向FDA提交一份書面通知。如果在退出銷售之前180提交通知不現(xiàn)實，則通知的提交應(yīng)“盡可能早，但不得遲于退出銷售之日”。

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持有人要如何申請將一份申報從橙皮書的退市部分移入活躍部分呢？

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.

在申請將一個申報從退市部分移入活躍部分之前，申報持有人應(yīng)確定根據(jù)21 CFR 314.70或 314.97是否需要在上市銷售該藥品之前提交一份補充資料。

Ifa prior approval supplement under 21 CFR 314.70(b) is required:

如果需要根據(jù)21 CFR 314.70(b)提交預(yù)批準(zhǔn)補充資料，則

·      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.”

·      申報持有人應(yīng)在上市或重新上市補充資料批準(zhǔn)之前1-2個月通知橙皮書，通知方式為提交一份申報文件，標(biāo)明“行政變更/商業(yè)化銷售通知”

·      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.

·      橙皮書會在后續(xù)月度累積增補冊中根據(jù)批準(zhǔn)情況將藥品從退市部分移入活躍部分

If a Changes Being Effected supplement under 21 CFR 314.70(c) is required:

如果需要根據(jù)21 CFR 314.70(c)提交CBE補充資料，則：

·      The application holder should determinethe anticipated launch date, which is generally the date the drug product isput into the marketplace for distribution.

·      申報持有人應(yīng)確定預(yù)期上市日期，通常是藥品上市銷售的日期

·      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.”

·      申報持有人應(yīng)在其預(yù)期上市或重新上市日期前約1-2個月時通知橙皮書，通知方式為提交申報文件，標(biāo)明“行政變更/商業(yè)化銷售通知”

·      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.

·      橙皮書會根據(jù)預(yù)期上市日期將藥品從退市部分移入活躍部分，放在后續(xù)的月度累積補充卷。

Q11.      When will a move of a drug product to orfrom the Discontinued Section be reflected in the Orange Book? 橙皮書何時會反映出藥品移入/移出退市部分的情況？

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 ).

橙皮書以后一般會每月更新退市部分，以累積補充方式更新。每月的電子橙皮書一般會在每月第二周結(jié)束時更新（例如，11月電子版橙皮書會在12月的第二個全工作周結(jié)束時更新）。

D.   Patent Listings 專利列表

1.    Listing Patents 列表專利

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持有人要如何確保FDA3542表（在NDA或補充資料批準(zhǔn)時或批準(zhǔn)后提交的專利信息）的提交是及時的？

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持有人必須為每項聲明該藥品或藥品使用方法的專利提交信息，未獲授權(quán)生產(chǎn)、使用或銷售此該藥品的人員將被合理認(rèn)定侵權(quán)。NDA持有人必須使用FDA3542表提交此類專利信息至NDA。FDA會將該專利信息發(fā)布在橙皮書中。如果在NDA或增補批準(zhǔn)后30天內(nèi)，或在聲明藥用物質(zhì)（活性成分）、藥品（制劑配方或組成），和/或已批準(zhǔn)藥品的已批準(zhǔn)使用方法的專利授權(quán)后30日內(nèi)提交了FDA3542表，則認(rèn)為是“及時”提交了專利。

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發(fā)現(xiàn)表格3542有錯誤或遺漏， 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.

如果申報人在30天內(nèi)提交了所要求的專利信息，但我們通知申報人說申報表不完整，或者該專利不符合列表要求，則申報人必須在收到FDA通知之后15天內(nèi)提交一份合格的申報表，此時認(rèn)為滿足“及時提交”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.

根據(jù)法規(guī)條款，NDA持有人必須在收到FDA原始通知15天以內(nèi)提交一份滿意的FDA3542表，該專利信息首次提交日期方可被認(rèn)為“及時”。NDA持有人應(yīng)仔細(xì)閱讀FDA3542表中的指導(dǎo)，避免此類缺陷。

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持有人要如何確保及時提交專利所聲明的已批準(zhǔn)使用方法描述修訂內(nèi)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持有人對已批準(zhǔn)專利聲明的使用方法（MOU）描述的修訂在（1）專利授權(quán)之后，（2）藥品標(biāo)簽相應(yīng)變更批準(zhǔn)之后，或（3）美國專利商標(biāo)局或負(fù)責(zé)專利的聯(lián)邦法庭判定變更專利聲明的使用方法結(jié)構(gòu)之后，30天內(nèi)提交則認(rèn)為是及時的。不在上述范圍的情形，除專利列表質(zhì)疑規(guī)定范圍情形外，對已批準(zhǔn)的專利聲明MOU描述的修改不在及時報告之列。

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專利要求列入橙皮書？

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 .

專利再版時，NDA持有人要申請從橙皮書上刪除原版專利，因為專利再版后，原版專利即告失效，法律效力中止。與申請從橙皮書上其它撤銷專利的法規(guī)要求一樣，原版專利會保持列于橙皮書中，直到FDA確定并無首仿人因四段挑戰(zhàn)獲得該專利180天獨占期，或如獲得但已過期、撤銷或棄權(quán)。

Q16.      How does FDA receive and process a request from an NDA holder for removal of a patent from the Orange Book? FDA是怎么從NDA持有人處接收到從橙皮書上刪除某個專利的申請并執(zhí)行刪除的呢？

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 .

如果一個NDA持有人確定某項專利或?qū)＠暶鞑辉俜狭斜矸ㄒ?guī)要求（例如，如果法院宣布所列專利無效或不具有可執(zhí)行性，且未申訴或不能申訴者），則NDA持有人必須立即通知FDA修改或撤回其專利信息，申請從橙皮書上刪除該專利信息。如果法庭裁定該NDA持有人修改專利信息或從橙皮書上撤回某項專利，則該NDA持有人必須在裁定生效后14日之內(nèi)提交NDA修訂，在其中包括有一份裁定書副本。如上所述，如果沒有該專利四段挑戰(zhàn)的首個申辦人獲得180天排他優(yōu)先權(quán)，或首個申辦人的180天排他優(yōu)先權(quán)過期、撤銷或棄權(quán)之后，則FDA將從橙皮書上刪除該專利。

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持有人可通過遞交一份NDA文件函，請求撤銷專利，要求從橙皮書上刪除該專利。該函中必須包括有NDA編號，專利號及申請適用的所有產(chǎn)品。提交該申請時不需要填寫FDA3542表，但NDA持有人應(yīng)清楚突出寫明其根據(jù)21 CFR314.53(f)(2)(iv)要求撤回專利列表，申請從橙皮書上刪除該專利。

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持有人已要求從橙皮書上刪除某項專利，但該專利仍在橙皮書中，標(biāo)有“從列表刪除申請”符號，該專利要何時才會刪除？

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持有人因首個申報人因?qū)υ搶＠崞鹚亩翁魬?zhàn)成功獲得180天獨占期且仍在效期內(nèi)而申請刪除該專利，但該專利仍會留在橙皮書上一段時間。

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 .

在相關(guān)的180獨占權(quán)過期、撤銷或棄權(quán)之后，橙皮書上將該專利刪除之前，無論NDA持有人是否申請了刪除該專利，ANDA申請人均必須提交或保持適當(dāng)?shù)膶＠暶?。如果橙皮書上某項專利“從列表刪除”欄為“Y”，申請人不需要提交505(b)(2)申請對該專利進(jìn)行認(rèn)證。

2.    Patent Listing Disputes 專利列表質(zhì)疑

Q18.      Can a patent listing be disputed? 可以質(zhì)疑專利列表嗎？

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的持有人可以質(zhì)疑橙皮書上所列專利信息的準(zhǔn)確性或相關(guān)性的流程，以及相關(guān)NDA持有人回應(yīng)此類質(zhì)疑的流程。如果有任何人“質(zhì)疑提交給FDA”且被FDA列入橙皮書發(fā)布“的專利信息的準(zhǔn)確性或相關(guān)性”，或“相信有NDA持有人未提交所需專利信息，則該人必須首先書面或電子方式通知FDA，標(biāo)題寫明‘314.53(f)專利列表質(zhì)疑’”。可通過orangebook@fda.hhs.gov將專利列表質(zhì)疑發(fā)送給橙皮書職員。

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:

專利列表質(zhì)疑“必須包括有質(zhì)疑聲明，寫明不同意專利信息的準(zhǔn)確性或相關(guān)性的具體原因”，F(xiàn)DA會將此類信息發(fā)給適當(dāng)?shù)腘DA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.

對于已批準(zhǔn)藥品使用方法的專利信息準(zhǔn)確性或相關(guān)性的質(zhì)疑，質(zhì)疑聲明必須只采用敘述性說明（不超過250字），解釋專利范圍。質(zhì)疑聲明只能包括有該人認(rèn)為可披露的信息，因為FDA不會再行審核或遮蓋而是直接將原文轉(zhuǎn)給適當(dāng)?shù)腘DA持有人。

FDA will forward the dispute to the NDA holder as described in the regulation.

FDA會按法規(guī)所述將質(zhì)疑發(fā)給NDA持有人。

Q19.      How does FDA provide notification of whether a patent listing dispute has been submitted? FDA會如何發(fā)布已提交專利質(zhì)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會即刻將所有專利列表質(zhì)疑發(fā)布在專利列表質(zhì)疑清單頁面，注明（1）專利列表質(zhì)疑是否已提交給FDA，以及（2）NDA持有人是否及時回應(yīng)專利列表質(zhì)疑。專利列表質(zhì)疑清單中包括有相關(guān)的藥品信息，以及受質(zhì)疑的專利信息。該清單為累積清單，按藥品注冊名稱和專利編號排列。

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文章來源：Julia法規(guī)翻譯   免責(zé)聲明：上述內(nèi)容僅供交流學(xué)習(xí)使用，對文中陳述、觀點判斷保持中立，不對所包含內(nèi)容的準(zhǔn)確性、可靠性或完整性提供任何明示或暗示的保證。僅作參考，并請各位自行承擔(dān)全部責(zé)任。版權(quán)歸原作者所有，如遇版權(quán)問題請聯(lián)系小編刪除。。