Evaluation of Therapeutic Equivalence Guidance for Industry1

治疗等效性评估

2022 年 07 月 20 日 发布

中译为机翻简校版
This draft guidance， when finalized， will represent the current thinking of the Food and Drug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.
本指南草案定稿后，将代表 FDA 目前对此主题的看法。它没有确立任何人的任何权利，对 FDA 或公
众没有约束力。如果替代方法满足适用的法令和法规的要求，则可以使用替代方法。要讨论替代方
法，请联系标题页上列出的负责本指南的 FDA 工作人员。
目录
 I. INTRODUCTION
 II. THERAPEUTIC EQUIVALENCE EVALUATIONS
o A. The Fundamentals of Therapeutic Equivalence
 1. Pharmaceutical Equivalence
 2. Bioequivalence
 3. Same Clinical Effect and Safety Profile
o B. Products Evaluated for Therapeutic Equivalence
 1. Drug Products Approved Under Section 505（c） of the FD&C Act
 2 Drug Products Approved Under Section 505（j） of the FD&C Act
o C. The Therapeutic Equivalence Coding System26
 1. A Codes
 2. B Codes
 3. Three-Character Codes
o D. Revisions to Therapeutic Equivalence Evaluations
 III. FREQUENTLY ASKED QUESTIONS

I. INTRODUCTION
I.介绍
This guidance explains FDA's therapeutic equivalence evaluations， including the assignment of
therapeutic equivalence codes （or TE codes）. As defined in 21 CFR 314.3（b）， therapeutic
equivalents are
本指南解释了 FDA 的治疗等效性评估，包括治疗等效性代码（或 TE 代码）的分配。 如 21 CFR
314.3（b）所定义， 治疗等效物
approved drug products that FDA has determined are pharmaceutical equivalents for
which bioequivalence has been demonstrated ， and that can be expected to have the
same clinical effect and safety profile when administered to patients under the conditions
specified in the labeling.

第 1 页 / 共 20 页
 是 FDA 已确定为已被证明具有生物等效性的已获批药品，在标签规定的条件下给予患者可预
期具有相同的临床效果和安全性的药品。
FDA's therapeutic equivalence evaluations are listed for multisource2 prescription drug products
approved under section 505 of the Federal Food， Drug， and Cosmetic Act （FD&C Act） （21
U.S.C. 355） in the active section of the Approved Drug Products With Therapeutic Equivalence
Evaluations （commonly known as the Orange Book）3. As FDA explained when it first proposed
to make available a list of all approved drug products， together with therapeutic evaluations of
listed products that are available from more than one manufacturer， therapeutic equivalence
evaluations have been prepared to serve as public information and advice to state health
agencies， prescribers， and pharmacists to promote public education in the area of drug
product selection and to foster containment of health care costs.4 For example， the Orange
Book can assist in the establishment of formularies that States and other entities may use in
determining when drug products may be substituted for one another. If lower-cost，
therapeutically equivalent drug products are available， American consumers are more likely to
receive savings on these products.5 Therapeutic equivalence evaluations are a scientific judgment
based upon evidence， while generic substitution may involve social and economic policy
administered by the states， e.g.， reducing the cost of drugs to consumers. These evaluations
do not constitute determinations that any product is in violation of the FD&C Act or that any product
is preferable to any other.
FDA 的治疗等效性评估列于多源 2 依据《联邦食品、药品和化妆品法案》（FD&C Act）（21U.SC
355）第 505 节批准的处方药活性部分 经治疗等效性评价的获批药品 （俗称橙皮书）3 .正如 FDA
在首次提出提供所有获批药品清单以及来自多个生产商的产品的治疗性评估时所解释的那样，治疗
等效性评估已经准备好作为公共信息和对州卫生的建议。 机构、处方医师和药剂师促进药品选择领
域的公众教育，并促进对医疗保健费用的控制。 4 例如，橙皮书有助于建立处方集，各州和其它实体
可使用该集来确定何时可以相互替代药品。 如果可以获得成本更低、治疗等效的药品，美国消费者
更有可能在这些药品上节省开支。 5 治疗等效性评估是基于证据的科学判断，而仿制药替代可能涉及
各州管理的社会和经济政策，例如，降低消费者的药品成本。这些评估并不构成任何产品违反 FD＆
C 法案或任何产品优于任何其它产品的判定。
The contents of this document do not have the force and effect of law and are not meant to bind
the public in any way， unless specifically incorporated into a contract. This document is intended
only to provide clarity to the public regarding existing requirements under the law. FDA guidance
documents， including this guidance， should be viewed only as recommendations， unless
specific regulatory or statutory requirements are cited. The use of the word should in FDA
guidance means that something is suggested or recommended， but not required.
本文件的内容不具备法律效力，不以任何方式约束公众，除非明确纳入合同。本文件仅旨在就法律
规定的现有要求向公众提供澄清。FDA 指南文件，包括本指南，应仅被视为建议，除非引用了具体
的监管或法定要求。 这个词的用法 应该 在 FDA 指南中的意思是建议或推荐某事，但不是必需
的。
II. THERAPEUTIC EQUIVALENCE EVALUATIONS
II.治疗等效性评价
A. The Fundamentals of Therapeutic Equivalence
A.治疗等效性的基本原理
The scientific and regulatory foundation for the evaluation of therapeutic equivalence of
prescription drug products involves:
处方药治疗等效性评价的科学和监管基础包括：

第 2 页 / 共 20 页
  Pharmaceutical equivalence，
 药学等效性
 Bioequivalence， and
 生物等效性，以及
 Same clinical effect and safety profile for the conditions of use specified in the labeling. 6
 对于标签说明的使用条件，具有相同的临床效果和安全性。6
Therapeutic equivalence can be evaluated only for products that are （or will become upon
approval） multisource prescription drug products.7 FDA approval includes， among other
things， a determination that the drug product is adequately labeled， and that the methods used
in， and the facilities and controls used for， the manufacture， processing， and packaging of
a drug product are adequate to preserve its identity， strength， quality， and purity.8
治疗等效性只能对是（或将成为）多源处方药的产品进行评估。 7 FDA 的批准包括确定药品经充分标
识，药品生产、加工和包装所用的方法、设施和控制足以保持其特性、规格、质量和纯度。8
FDA believes products classified as therapeutically equivalent can be substituted with the full
expectation that the substituted product will produce the same clinical effect and safety profile as
the prescribed product when administered to patients under the conditions specified in the labeling.
FDA 认为治疗等效性的产品可以被替代，完全期望在标签规定的条件下给予患者时，被替代的产品
将产生与处方产品相同的临床效果和安全性。
1. Pharmaceutical Equivalence
1 药物等效性
To be therapeutically equivalent， drug products must be pharmaceutically equivalent.9 As defined
in 21 CFR 314.3（b）， pharmaceutical equivalents are drug products:
要具有治疗等效性，药品必须是药学等效的。9 如 21 CFR 314.3（b）所定义， 药品等同物 是药
品：
 in identical dosage form and route（s） of administration；
 以相同的剂型和给药途径；
 Contain identical amounts of the identical active drug ingredient， i.e.， the same salt
or ester of the same therapeutic moiety， or， in the case of modified-release dosage
forms that require a reservoir or overage or such forms as prefilled syringes where
residual volume may vary， that deliver identical amounts of the active drug ingredient
over the identical dosing period；
 含有相同量的相同活性药物成分，即相同治疗性成分的相同盐或酯，或者对于需要贮存器
或过量的改良释放剂型，或者诸如残留体积可能的预填充注射器。 变化，在相同的给药
期内释放相同量的活性药物成分；
 Do not necessarily contain the same inactive ingredients； and
 不一定含有相同的非活性成分；和
 Meet the identical compendial or other applicable standard of identity， strength，
quality， and purity， including potency and， where applicable， content
uniformity， disintegration times， and/or dissolution rates.10
 符合相同的药典或其它适用的鉴别、规格、质量和纯度标准，包括效价，适用时，含量均
匀度、崩解时间和/或溶出速率。10
2. Bioequivalence
2 生物等效性
To be therapeutically equivalent， drug products must also be bioequivalent.11 Bioequivalence is，
in pertinent part:
为了在治疗上等效，药品也必须是生物等效的。11 生物等效性 在相关方面：

第 3 页 / 共 20 页
 the absence of a significant difference in the rate and extent to which the active ingredient
or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes
available at the site of drug action when administered at the same molar dose under similar
conditions in an appropriately designed study.12
在适当设计的研究中，当以相同摩尔剂量给药时，药物等同物或药物替代物中的活性成分或
活性基团在药物作用部位可用的速率和程度无显着差异。12
For drug products that are not intended to be absorbed into the bloodstream， applicants may
assess bioequivalence by conducting scientifically valid measurements that are intended to reflect
the rate and extent to which the active ingredient or active moiety becomes available at the site of
action.13 FDA has promulgated regulations regarding demonstrating bioequivalence，14 and the
Agency routinely publishes guidances for industry and product-specific guidances to assist
applicants and sponsors in demonstrating bioequivalence.15
对于不吸收进入血液的药品，申请人可以通过进行科学有效的测定来评估生物等效性，这些测定旨
在反映活性成分或活性基团在作用部位变得可用的速度和程度。 13 FDA 已颁布关于证明生物等效性
的法规，14 FDA 定期发布行业指南和具体产品指南，以帮助申请人和申办者证明生物等效性。15
3. Same Clinical Effect and Safety Profile
3 相同的临床效果和安全性
Therapeutic equivalents are expected to have the same clinical effect and safety profile when
administered to patients under the conditions of use specified in the labeling.16 Labeling plays a
critical role in the therapeutic equivalence evaluation. FDA evaluates the labeling to determine
whether the drug products have the same clinical effect and safety profile under the conditions of
use that the labeling specifies. As a result， pharmaceutically equivalent products with differences
in labeling may not be considered therapeutically equivalent to one another.
当在标签规定的使用条件下给予患者相同的治疗效果和安全性时，预期具有相同的临床效果和安全
性。16 标签在治疗等效性评估中起着关键作用。FDA 对标签说明进行评估，以确定药品在其使用条
件下是否具有相同的临床效果和安全性。 因此，标签不同的药学等效产品可能不被认为是治疗等效
的。
The evaluation of whether drug products have the same clinical effect and safety profile is product-
specific. For example， whether a proposed generic drug-device combination product with a user
interface that contains differences from that for the RLD17 can be substituted with the full
expectation that the generic combination product will produce the same clinical effect and safety
profile as the RLD under the conditions specified in the labeling is a product specific
determination， and additional information and/or data relating to the user interface may be
appropriate to support approval and to perform this evaluation.
药品是否具有相同的临床效果和安全性的评价因产品而异。 例如，仿制药-器械组合产品的用户界
面是否包含与 RLD 的不同之处 17 可以替换为在标签规定的条件下仿制药将产生与 RLD 相同的临床效
果和安全性的完全期望适用于支持批准和执行此评估。
B. Products Evaluated for Therapeutic Equivalence
B.产品治疗等效性评价
FDA only evaluates certain drug products approved under section 505 of the FD&C Act for
therapeutic equivalence. Section 505 establishes the following approval pathways for drug
products: "stand-alone" new drug applications （NDAs）； 505（b）（2） applications； and
abbreviated new drug applications （ANDAs）， which include petitioned ANDAs.18
FDA 仅评估根据 FD＆C 法案第 505 节批准的某些药品的治疗等效性。 第 505 节规定了药品的以下
批准途径：“独立”新药申请（NDA）； 505（b）（2） 申请；简化新药申请（ANDA），其中包

第 4 页 / 共 20 页
括已请求的 ANDA。18
1. Drug Products Approved Under Section 505（c） of the FD&C Act
1 依据 FD&C 法案第 505（c）节获批的药品
A "stand-alone NDA" is an application submitted under section 505（b）（1） and approved
under section 505（c） of the FD&C Act that contains full reports of investigations of safety and
effectiveness that were conducted by or for the applicant or for which the applicant has a right of
reference or use.
“独立 NDA”是指依据 FD＆C 法案第 505（b）（1）节提交并获批的申请，其中包含由申请人或为申
请人进行的安全性和有效性调查的完整报告或申请人有权引用或使用。
A 505（b）（2） application is an NDA submitted under section 505（b）（1） and approved
under section 505（c） of the FD&C Act that contains full reports of investigations of safety and
effectiveness， where at least some of the information required for approval comes from studies
not conducted by or for the applicant and for which the applicant has not obtained a right of
reference or use （e.g.， the Agency's finding of safety and/or effectiveness for a listed drug，
published literature）.19 FDA generally will refuse to file a 505（b）（2） application for a drug
that is a duplicate20 of a listed drug and eligible for approval under section 505（j） of the FD&C
Act.21
505（b）（2）申请是根据 FD＆C 法案第 505（b）（1）节提交并获批的 NDA，其中包含安全性和
有效性调查的完整报告，其中至少有一些批准所需的信息来自于申请人未进行的研究或为申请人进
行的研究，并且申请人未获得引用或使用权（例如，FDA 对已登记药品的安全性和/或有效性的发现，
已发表的文献）。19 FDA 通常会拒绝重复药品的 505（b）（2）申请 20 根据 FD＆C 法案第 505（j）
节获得批准的上市药品。21
FDA generally does not conduct therapeutic equivalence evaluations upon approval of drug
products in stand-alone NDAs. In most cases， a stand-alone NDA drug product would not be
pharmaceutically equivalent—and thus not therapeutically equivalent—to another approved stand-
alone NDA drug product. Drug products approved in stand-alone NDAs are generally designated
as reference listed drugs upon which prospective generic drug applicants can rely in developing
their ANDA drug products.
FDA 在批准 NDA 单机版产品时通常不进行治疗等效性评价。 在大多数情况下，单机版 NDA 药品与
另一种已获批的单机版 NDA 药品不具有药学等效性，因此也不具有治疗等效性。 单机版 NDA 中
获批的药品通常被指定为参照药品，潜在仿制药申请人可以依据这些药品开发 ANDA 药品。
FDA does not routinely conduct therapeutic equivalence evaluations for every product approved in
a 505（b）（2） application. A person seeking to have a therapeutic equivalence rating for a drug
product approved in a 505（b）（2） application may petition the Agency through the citizen
petition procedure （see 21 CFR 10.25（a） and 21 CFR 10.30）.22 When therapeutic
equivalence is evaluated， the differences between a product approved in a 505（b）（2）
application and another listed drug may preclude a finding that the products are therapeutically
equivalent. These differences may include， for example， a different active ingredient or a new
indication， dosage form， strength， or route of administration， or
certain formulation differences.23 See question and answer 3， 4， and 5 for more information
specifically on 505（b）（2） applications and TE codes， including information on requesting a
therapeutic equivalence evaluation for a drug product that is the subject of an approved or
pending 505（b）（2） application. Like those in stand-alone NDAs， drug products approved in
505（b）（2） applications are generally designated as reference listed drugs upon which
prospective generic drug applicants can rely in developing their ANDA drug products.
FDA 不会对 505（b）（2）申请中批准的每种产品进行常规治疗等效性评估。 寻求获得 505（b）

第 5 页 / 共 20 页
（2）申请中批准的药品的治疗等效性评级的人可以通过公民请愿程序向 FDA 请愿（参见 21 CFR
10.25（a）和 21 CFR 10.30）。22 当评估治疗等效性时，505（b）（2）申请中批准的产品与另一
种上市药品之间的差异可能会妨碍产品治疗等效性的发现。 这些差异可能包括，例如，不同的活性
成分或新的适应症、剂型、规格或给药途径，或某些处方差异。 23 关于 505（b）（2）申请和 TE 代
码的更多信息，包括对已获批或待批的 505 药品申请治疗等效性评价的信息，请参见问答 3、4 和
5。 b）（2） 申请。 与单机版 NDAs 一样，505（b）（2）申请中批准的药品通常被指定为参照
药品，潜在仿制药申请人可以依据这些药品开发 ANDA 药品。
2 Drug Products Approved Under Section 505（j） of the FD&C Act
2 依据 FD&C 法案第 505（j）节获批的药品
An ANDA24 generally is an application submitted and approved under section 505（j） of the
FD&C Act for a drug product that is a duplicate of a previously approved drug product， the RLD.
An ANDA generally must contain information to show that the proposed generic product （1） is
the same as the RLD with respect to the active ingredient（s）， conditions of use， route of
administration， dosage form， strength， and labeling （with certain permissible differences）
and （2） is bioequivalent to the RLD. If the statutory requirements are met， an ANDA may rely
on FDA's finding that the previously approved drug product， the RLD， is safe and effective.
一个 ANDA24 通常是根据 FD＆C 法案第 505（j）节提交并批准的药品申请，该药品是之前已获批药
品的重复产品，参照药品。 ANDA 通常必须包含信息以表明拟定仿制药（ 1）在活性成分、使用条
件、给药途径、剂型、规格和标签（有某些允许的差异）方面与 RLD 相同，并且（2）与 RLD 生物
等效。如果符合法定要求，ANDA 可能依赖于 FDA 关于之前批准的药品 RLD 是安全有效的发现。
A "petitioned" ANDA is a type of ANDA for a drug product that differs from the RLD in its dosage
form， route of administration， strength， or active ingredient （in a product with more than one
active ingredient） and for which FDA has determined， in response to a petition submitted
under section 505（j）（2）（C） of the FD&C Act （suitability petition）， that studies are not
necessary to establish the safety and effectiveness of the proposed drug product. For approval，
the drug product approved in a petitioned ANDA may rely on the finding of safety and effectiveness
for the RLD that was the basis of the suitability petition， but would not be therapeutically
equivalent to its RLD because the differences permissible in a petitioned ANDA would render the
product not pharmaceutically equivalent to the RLD.
“请愿”ANDA 是指制剂在剂型、给药途径、规格或活性成分（含有多个活性成分的产品）方面不同
于 RLD，并且 FDA 已确定的 ANDA 类型。作为对依据 FD＆C 法案第 505（j）（2）（C）节提交的
请愿（适用性请愿）的回应，研究不是确定拟议药品的安全性和有效性所必需的。对于批准，在请
愿 ANDA 中批准的药品可能依赖于作为适用性请愿基础的 RLD 的安全性和有效性，但不会与 RLD
在治疗上等效，因为请愿 ANDA 中允许的差异将使产品在药学上不等同于 RLD。
In general， with the exception of a drug product approved in a petitioned ANDA， when FDA
approves a drug product under an ANDA it is therapeutically equivalent to its RLD because the
requirements for ANDA approval include the data and information that establish therapeutic
equivalence. Accordingly， an ANDA applicant does not need to request a therapeutic
equivalence evaluation from the Agency. In contrast to FDA's general practice to designate stand-
alone NDAs and 505（b）（2） applications as reference listed drugs upon approval， FDA's
general practice has not been to designate ANDAs as reference listed drugs upon approval
because ANDAs do not contain independent findings of safety and effectiveness upon which other
ANDAs can rely. 25
一般而言，除了在请愿 ANDA 中批准的药品外，当 FDA 批准 ANDA 下的药品时，该药品在治疗上与
其 RLD 是等效的，因为 ANDA 批准的要求包括建立治疗等效性的数据和信息。因此，ANDA 申请人
不需要向 FDA 请求治疗等效性评估。与 FDA 在批准时将单机版 NDAs 和 505（b）（2）申请指定为

第 6 页 / 共 20 页
参照药品不同，FDA 的一般做法是在批准时将 ANDA 指定为参照药品，因为 ANDA 不包含独立的发
现项其它 ANDA 可以依赖的安全性和有效性。25
C. The Therapeutic Equivalence Coding System26
C. 治疗等效性编码系统 26
FDA lists its therapeutic equivalence evaluations in the Orange Book using a system of multi-letter
codes assigned to multi-source drug products. The coding system is designed to allow users to
determine quickly whether the Agency has evaluated a particular approved drug product as
therapeutically equivalent to another approved pharmaceutically equivalent drug product.
Generally， the first letter of the code indicates whether the Agency has determined that a
particular approved drug product is therapeutically equivalent to another drug product.
FDA 使用分配给多来源药品的多字母代码系统在橙皮书中列出其治疗等效性评估。编码系统旨在允
许使用者快速确定 FDA 是否已将某特定获批药品评估为与另一种已获批药学等效药品的治疗等效性。
通常，代码的第一个字母表示 FDA 是否已确定某种获批药品与另一种药品在治疗上是等效的。
The coding system also uses additional specific letters to provide further information based on
FDA's evaluations.
编码系统还使用额外的特定字母来提供基于 FDA 评估的进一步信息。
1. A Codes
1 A 代码
Drug products are assigned an A as the first letter of their therapeutic equivalence code if FDA
considers them to be therapeutically equivalent to other pharmaceutically equivalent products.
Drug products considered to be therapeutically equivalent are grouped together in the Orange
Book.
药品被指定为 一个 如果 FDA 认为其与其它药学等效产品治疗等效，则将其作为其治疗等效性代
码的首字母。被认为具有治疗等效性的药品在橙皮书中归为一组。
For products that are therapeutically equivalent （i.e.， those codes in which an A is the first
letter）， the second letter in the code identifies that either:
对于治疗等效的产品（即那些代码 A 是第一个字母），代码中的第二个字母表示：
（ 1 ） actual or potential bioequivalence problems have been resolved with adequate
evidence， or
（1）实际或潜在的生物等效性问题已得到解决并有足够的证据，或
（2） there are no known or suspected bioequivalence problems.
（2）不存在已知或可疑的生物等效性问题。
In the former case， for pharmaceutically equivalent products that have raised questions of
bioequivalence and for which in vivo and/or in vitro methods were used to establish
bioequivalence， FDA assigns them an AB code. In the latter case （when there are no known or
suspected bioequivalence problems）， the second letter in the therapeutic equivalence code
（i.e.， the A， N， O， P， or T in AA， AN， AO， AP， or AT） identifies
the dosage form.27 For active ingredients or dosage forms for which no in vivo bioequivalence issue
is known or suspected， the information necessary to show bioequivalence （between
pharmaceutically equivalent products） is either presumed and considered self-evident （based
on other information in the application for some dosage forms （e.g.， solutions）），28 or
satisfied by a showing that an acceptable in vitro approach is met.
在前一种情况下，对于引起生物等效性问题并且使用体内和/或体外方法建立生物等效性的药学等效
性产品，FDA 指定为 AB 代码。在后一种情况下（当没有已知或可疑的生物等效性问题时），治疗
等 效 性 代 码 中 的 第 二 个 字 母 （ 即 ， A， N， O， P， 或 T

第 7 页 / 共 20 页
在 AA ， AN ， AO ， AP ， 或 AT ）标识剂型。27 对于不存在已知或疑似体内生物等效性
问题的活性成分或剂型， 证明生物等效性（药学等效产品之间）的必要信息是假定的和不证自明的
（基于某些剂型（例如，溶液）申请中的其它信息），28 或通过证明可接受符合体外方法。
2. B Codes
2. B 代码
Drug products are assigned a B as the first letter of their therapeutic equivalence code if， at this
time， actual or potential bioequivalence problems have not been resolved with adequate
evidence of bioequivalence. Until actual or potential bioequivalence questions are resolved， FDA
considers such products not to be therapeutically equivalent to other pharmaceutically equivalent
products.
药品被指定为 乙 如果此时实际或潜在的生物等效性问题没有得到充分的生物等效性证据的解决，
则将其作为治疗等效性代码的第一个字母。在实际或潜在的生物等效性问题得到解决之前，FDA 认
为此类产品与其它药学等效产品不具有治疗等效性。
For such products， the second letter in the therapeutic equivalence code （i.e.，
the C， D， E， N， P， R， S， T， X， and B*
in BC， BD， BE， BN， BP， BR， BS， BT， BX， or BB*） either identifies the
dosage form or provides further general information regarding why the product is not considered to
be therapeutically equivalent.29 In its description of the B codes， the Orange Book describes
circumstances under which FDA may find that a drug product is not therapeutically equivalent to
another approved pharmaceutically equivalent drug product.30
对于此类产品，治疗等效性代码中的第二个字母（即 C ， D ， E ， N ， P ， R ， S
， T ， X ， and B * in BC ， BD ， BE ， BN ， BP ， BR ， BS ， BT ， BX ，
or BB* ）确定剂型或提供关于为什么该产品不被认为是有效的进一步一般信息治疗等效。 29 在其描
述中 乙 橙皮书描述了 FDA 可能会发现药品与另一种已批准的药学等效药品不等效的情况。30
3. Three-Character Codes
3. 三字符代码
In some instances， a number is added to certain codes to make a three-character code. Three-
character codes generally are assigned only in situations in which more than one RLD of the same
strength has been designated under the same product heading （i.e.， same active
ingredient（s）， dosage form， route（s） of administration， and strength） in the Orange
Book. For example， for the listing for Diltiazem Hydrochloride Capsule， Extended Release，
multiple RLDs are designated， including Tiazac （NDA 020401 for 120， 180， 240， 300，
360， and 420 milligrams （mg））， Cardizem CD （NDA 020062 for 120， 180， 240，
300， and 360 mg）， and Dilacor XR （NDA 020092 for 120， 180， and 240
mg）. ANDAs that reference Tiazac have the AB4 rating， ANDAs that reference Cardizem CD
have the AB3 rating， and ANDAs that referenced Dilacor XR have the AB2 rating.
在某些情况下，将数字添加到某些代码以形成三字符代码。在橙皮书中三字符代码通常仅在同一产
品标题下指定了多个相同规格 RLD 的情况下使用（即相同的活性成分、剂型、给药途径和规格）。
例如，盐酸地尔硫卓缓释胶囊的上市许可指定了多个 RLD，包括 Tiazac（NDA 020401，用于
120、180、240、300、360 和 420 mg）。（mg））， Cardizem CD （NDA 020062 for 120，
180， 300， and 360 mg）， and Dilacor XR （NDA 020092 for 120， 180， and 240 mg）.引
用 Tiazac 的 ANDA AB4 评 级 ， 引 用 Cardizem CD 的 ANDA AB3 评 级 ， 引 用 Dilacor XR 的
ANDA 具有 AB2 评级。
D. Revisions to Therapeutic Equivalence Evaluations
D. 治疗等效性评估的修订

第 8 页 / 共 20 页
FDA may revise its therapeutic equivalence evaluation for a particular drug product if， based on
data or information FDA receives or becomes aware of， FDA determines that such a revision is
warranted. FDA may revise either the first or second letter of the therapeutic equivalence code.
The following is a non-exhaustive list of examples:
如果基于 FDA 收到或意识到的数据或信息，FDA 认为有必要进行这种修订，FDA 可能会对特定药品
的治疗等效性评估进行修订。FDA 可能会修订治疗等效性代码的第一个或第二个字母。以下是示例
的非详尽列表：
 FDA will revise a therapeutic equivalence code if it decides that another therapeutic
equivalence code would be more accurate than the current one.
 如果 FDA 决定另一个治疗等效性代码比当前的更准确，FDA 将修订治疗等效性代码。
 FDA will remove any associated therapeutic equivalence code for a drug product that is
moved from the Active section to the Discontinued Drug Product List section of the
Orange Book.
 对于从橙皮书的在用药品部分移至已停产药品清单部分的药品，FDA 将删除任何相关的
治疗等效性代码。
 FDA will remove the therapeutic equivalence code for a drug product listed in the Active
section of the Orange Book if that drug product becomes a single-source product.
 如果该药品成为单一来源药品，FDA 将删除橙皮书现行部分中列出的药品的治疗等效性
代码。
FDA also may change a drug product's therapeutic equivalence code from an A-rating to a B-rating
if FDA becomes aware of information that raises questions about the data and information that the
Agency relied on in approving that product. For example， if FDA discovers significant issues at a
facility where a drug product was used in testing to support its approval and those issues are
relevant to the underlying therapeutic equivalence evaluation， FDA may change
an AB therapeutic equivalence code to a BX code until the related facility issues and questions
about their impact on the application are resolved.
如果 FDA 意识到有信息对该机构在批准该产品时所依赖的数据和信息产生疑问，FDA 也可以将一个
药物产品的治疗等效代码从 A 级改为 B 级。例如，如果 FDA 在用于支持其批准的检验的设施中发现
重大问题，并且问题与潜在的治疗等效性评估相关，FDA 可能会改变 AB 治疗等效性代码 BX 直
到相关设施问题及其对申请的影响问题得到解决。
III. FREQUENTLY ASKED QUESTIONS
III.常见问题
1. When are therapeutic equivalence codes for ANDAs listed in the Orange Book?
1. 橙皮书什么时候列出 ANDA 的治疗等效性代码？
Because the approval standards for a drug product in an ANDA （other than a drug product in a
petitioned ANDA） require in general， among other things， a demonstration that the proposed
drug product has the same dosage form， route of administration， strength， and active
ingredient as its RLD， is bioequivalent to its RLD， and generally has the same labeling as its
RLD， with limited exceptions，31 a generic drug is considered therapeutically equivalent to its
RLD upon approval. In general， the therapeutic equivalence code for an approved ANDA will be
listed with the approved ANDA at the time that ANDA is added to the Orange Book，32 and the
ANDA holder does not need to request a therapeutic equivalence evaluation to its RLD.
因为 ANDA 中药品的批准标准（申请 ANDA 中的药品除外）通常要求证明拟议药品具有相同的剂型，
给药途径，规格和活性成分与其 RLD 生物等效，并且通常具有与其 RLD 相同的标签，但有限的例外
情况，31 仿制药在批准时被认为与 RLD 治疗等效。 一般而言，已获批 ANDA 的治疗等效性代码将

第 9 页 / 共 20 页
在 ANDA 加入橙皮书时与已获批 ANDA 一起列出，32 ANDA 持有人不需要请求对其 RLD 进行治疗等
效性评价。
2. Are there any instances in which an approved ANDA drug product would not have a
therapeutic equivalence code?
2. 是否存在已获批 ANDA 药品没有治疗等效性代码的情况？
Yes. Generally， FDA assigns a therapeutic equivalence code for an ANDA drug product at the
time of the drug's approval， and this code is included in the listing for that drug product in the
Orange Book. However， there are limited instances in which a drug product approved
under section 505（j） would not have a therapeutic equivalence code. For example:
是的。通常，FDA 在药品批准时为其指定治疗等效性代码，该代码包含在橙皮书中该药品的清单中。
但是，根据第 505（j）节获批的药品在少数情况下没有治疗等效性代码。 例如：
 If an RLD is discontinued or withdrawn from sale for reasons other than safety or
effectiveness33 and a drug product approved under the ANDA that references that RLD
becomes a single-source product， then any assigned therapeutic equivalence codes
for the RLD and the ANDA are removed from the Orange Book； the ANDA will not
have a TE code until it becomes a multisource product， for example through the
approval of a therapeutically equivalent ANDA or 505（b）（2） application.34
 如果 RLD 由于安全性或有效性以外的原因被中止或撤回 33 根据 ANDA 批准的药品，引用
RLD 成为单一来源产品，则 RLD 和 ANDA 的任何指定治疗等效性代码将从橙皮书中删除；
ANDA 在成为多源产品之前不会有 TE 代码，例如通过治疗等效性 ANDA 或 505（b）
（2）申请。34
 If FDA approves an ANDA based on an approved suitability petition for a change
permissible under section 505（j）（2）（C） of the FD&C Act （including a change
in dosage form， route of administration， and strength）， the approved ANDA
would not be pharmaceutically equivalent to its RLD and， therefore， would not be
therapeutically equivalent to the RLD or have a therapeutic equivalence code to the
RLD. If a second ANDA is approved for the petitioned change， that second ANDA and
the first ANDA would be designated as therapeutically equivalent to each other.
 如果 FDA 基于 FD＆C 法案第 505（j）（2）（C）节允许的变更（包括剂型，给药途径
和规格的变更）的适用性请愿批准 ANDA，则获批的 ANDA 药学上不等同于其 RLD，因
此治疗学上不等同于 RLD 或具有治疗等效性代码参照药品如果申请变更的第二个 ANDA
被批准，第二个 ANDA 和第一个 ANDA 将被认定为治疗等效。
3. Are there any instances in which an approved NDA drug product would not have a
therapeutic equivalence code?
3. 是否存在已获批 NDA 药品没有治疗等效性代码的情况？
Yes， there are instances in which an approved NDA drug product listed in the Orange
Book would not have a therapeutic equivalence code. For example， if an NDA drug product does
not have a therapeutic equivalence code， it could indicate that:
是的，在某些情况下，橙皮书中已获批的 NDA 药品没有治疗等效性代码。例如，如果 NDA 药品没
有治疗等效性代码，则可以表明：
 The drug product is one for which there are no therapeutically equivalent products listed
in the Active Section of the Orange Book.
 该药品是一种没有在橙皮书现行部分列出的治疗等效产品。
 The drug product was approved in a 505（b）（2） application and is not
therapeutically equivalent to the listed drug it references because it is not a

第 10 页 / 共 20 页
 pharmaceutical equivalent （for example， it is for a strength that was not approved for
the listed drug）.
 该药品是在 505（b）（2）申请中获批的，与所引用的药品在治疗上不等效，因为它不是
药用等效物（例如，其规格未获批用于所列药品） ）
 The drug product was approved in a 505（b）（2） application and is
pharmaceutically equivalent to a "stand-alone" NDA， but the 505（b）（2）
application holder has not made a request for， and FDA has not conducted， a
therapeutic equivalence evaluation for the 505（b）（2） application.
 该药品在 505（b）（2）申请中获批，药学上等同于“单机版”NDA，但 505（b）
（2）申请持有人未提出请求，FDA 也没有对 505（b）（2）申请进行治疗等效性评价。
4. What is an example of a 505（b）（2） application for which a request for an A rating
may be granted?
4. 505（b）（2）申请的例子是什么？ A 级 可以授予评级吗？
As noted in Section II.B.1， a drug product approved in a 505（b）（2） application may have
differences from other listed drugs which may preclude a finding of therapeutic equivalence.
However， a drug product approved in a 505（b）（2） application that meets the criteria for
therapeutic equivalence as described in 21 CFR 314.3（b） may receive an appropriate
therapeutic equivalence code.
如第 II.B.1 节所述，在 505（b）（2）申请中获批的药品可能与其他上市药品存在差异，这可能会妨
碍治疗性发现。等效性。但是，符合 21 CFR 314.3（b）中描述的治疗等效性标准的 505（b）
（2）申请中批准的药品可能会收到适当的治疗等效性代码。
For example， FDA may determine that an injectable solution drug product submitted under a
505（b）（2） application is therapeutically equivalent to the listed drug it references if that drug
product is pharmaceutically equivalent and bioequivalent to the listed drug but because of a
difference in excipients from the listed drug35 it references it could not have been approved in an
ANDA.
例如，如果依据 505（b）（2）申请提交的注射液药品与上市药品药学等效且生物等效，但由于差
异来自于上市药品的辅料 35 它引用了它不能在 ANDA 中获批。
5. How do I request therapeutic equivalence evaluation of a drug product submitted in
a 505（b）（2） application?
5. 我如何请求对 505（b）（2）申请中提交的药品进行治疗等效性评价？
The holder of an approved 505（b）（2） application drug product may request a therapeutic
equivalence evaluation in a citizen petition submitted under 21 CFR 10.25（a） and 10.30. FDA
will evaluate whether a therapeutic equivalence code for a 505（b）（2） application is
appropriate， after the drug product is approved and FDA has received a therapeutic equivalence
code request from the 505（b）（2） application holder.
已获批 505（b）（2）申请的药品的持有人可以根据 21 CFR 10.25（a）和 10.30 提交公民请愿。
FDA 将评估 505（b）（2）申请的治疗等效性代码是否合适，在药品获批并且 FDA 收到 505（b）
（2）申请持有人的治疗等效性代码之后。
In many cases， FDA will assess therapeutic equivalence for a 505（b）（2） application
utilizing information supporting the safety， effectiveness， and quality of the drug product that is
already contained in the NDA file. If the applicant for a product submitted in a 505（b）（2）
application intends to request a therapeutic equivalence evaluation upon approval， we
recommend that the applicant contact the regulatory project manager for the division to discuss
how the applicant's presentation of data and information will facilitate a therapeutic equivalence
evaluation and/or to discuss which additional information （if any） may be needed.36

第 11 页 / 共 20 页
在许多情况下，FDA 将利用已包含在 NDA 文件中的支持药品安全性、有效性和质量的信息来评估
505（b）（2）申请的治疗等效性。如果 505（b）（2）申请中提交的产品的申请人打算在批准时请
求治疗等效性，我们建议申请人联系该部门的监管项目经理讨论申请人如何呈现数据和信息将有助
于治疗等效性评估和/或讨论可能需要的额外信息（如果有的话）。36
6. Does FDA assign a therapeutic equivalence code to tentatively approved 37 drug
products?
6. FDA 是否为暂时批准的药物分配治疗等效性代码 37 药品？
A drug product that is tentatively approved is not an approved drug product and cannot be
marketed.38 Accordingly， FDA does not list that drug product in the Orange Book and does not
give it a therapeutic equivalence code.
暂时批准的药品不是已批准的药品，不能上市销售。 38 因此，FDA 没有将该药品列入橙皮书，也没
有给出治疗等效性代码。
7. If a drug product is repackaged and distributed by either the applicant or a party other
than the applicant， will it be given its own therapeutic equivalence code?
7. 如果药品由申请人或申请人以外的一方重新包装和分销，是否会给出自己的治疗等效性代码？
No. In the Orange Book， FDA would not include a separate listing with separate TE code for a
product that has been repackaged and distributed.
不可以。在橙皮书中，FDA 不会对再包装和分销的产品单独列名。
8. How do instructions in the labeling regarding reconstitution， dilution， or other
manipulation（s） before dispensing or administration affect FDA's determination
of dosage form?
8. 标签中关于配药或给药前的复溶、稀释或其它操作的说明如何影响 FDA 对剂型的判定？
The labeling for a drug product may include instructions for reconstitution， dilution， or other
manipulation（s） of the drug product before use. FDA evaluates the dosage form of such a drug
product before such reconstitution， dilution， or other manipulation（s）. Thus， for example，
a powder for oral solution drug product39 would have a different dosage form from a ready-to-use
oral solution drug product.40 As a result， a powder for oral solution drug product and a ready-to-
use oral solution drug product would not be pharmaceutically equivalent and therefore not
therapeutically equivalent to each other.
药品的标签说明可包括药品在使用前的复溶、稀释或其它操作说明。FDA 在复溶、稀释或其它操作
之前评估此类药品的剂型。因此，例如，一个口服溶液制剂用粉末 39 与即用型口服溶液制剂不同的
剂型。40 因此，口服溶液制剂的粉末和即用型口服溶液制剂不是药学等效的，因此在治疗上彼此不等
效。
9. Can a drug product be therapeutically equivalent if it has different packaging from the
listed drug it references?
9. 如果药品的包装与其所引用的药品不同，那么该药品是否具有治疗等效性？
Drug products that vary in packaging may or may not be therapeutically equivalent to each other.
For example， if the packaging difference results in a different clinical effect or safety profile of
one drug product to the other or precludes the two products from being pharmaceutical
equivalents， they will not be considered therapeutically equivalent.
包装不同的药品可能在治疗上是等效的，也可能不是。例如，如果包装差异导致一种药品与另一种
药品的临床效果或安全性不同，或妨碍这两种药品成为药学等效品，则认为它们不具有治疗等效性。
10. Can an ANDA drug product receive an A code if its labeling omits an indication（s） or
other condition（s） of use， or other aspect（s） of labeling that is approved for the RLD
but protected by patent or by exclusivity?
10. 如果 ANDA 药品的标签省略了该 RLD 已获批的适应症或其它使用条件，但受专利或专营权保护，

第 12 页 / 共 20 页
该药品能否获得 A 代码？
Yes. An ANDA drug product can be determined to be therapeutically equivalent to its RLD even if
the drug product， due to listed patents or exclusivity for the RLD， is approved for fewer than all
of the indications or other conditions of use for the RLD， or omits， due to listed patents or
exclusivity for the RLD， other aspects of labeling currently approved for the RLD. ANDA drug
products are permitted by statute and FDA's regulations to omit or "carve out，" for patent or
exclusivity reasons， an indication（s） or other condition（s） of use， or other aspect（s）
of labeling approved for the RLD.41 In making a therapeutic equivalence determination， FDA
evaluates whether the two drug products are pharmaceutical equivalents for
which bioequivalence has been demonstrated， and if they can be expected to have the same
clinical effect and safety profile when administered to patients under the conditions specified in the
labeling.42
是的。 即使由于已登记的专利或 RLD 的专营权，ANDA 药品被批准用于少于该 RLD 的所有适应症
或其它使用条件，或者省略了该 RLD ， 由于该 RLD 已登记的专利或专营权，该 RLD 的标签的其它
方面目前已获批。法令和 FDA 法规允许 ANDA 药品出于专利或专营权的原因省略或“剔除”RLD 获
批的适应症或其它使用条件.41 在进行治疗等效性判定时，FDA 会评估这两种药品是否为已被证明具
有生物等效性的药品，以及在标签规定的条件下给予患者时是否预期具有相同的临床效果和安全性。
.42
Because the approval standards for a drug product in an ANDA （other than a drug product with a
permissible change in a petitioned ANDA） mean that， among other things， demonstrations of
pharmaceutical equivalence to its RLD， bioequivalence to its RLD， and generally the same
labeling as its RLD （with limited exceptions， including to allow for the omission， for patent or
exclusivity reasons， of an indication（s） or other condition（s） of use， or other aspect（s）
of labeling）， an approved ANDA drug product is considered therapeutically equivalent to its
RLD and will receive an A code at approval， even if its labeling omits certain indications or other
conditions of use， or other aspects of labeling approved for the RLD but protected by patent or
exclusivity.
因为 ANDA 中药品的批准标准（申请 ANDA 中允许变更的药品除外）意味着，除其他外，与其 RLD
的药学等效性，与其 RLD 的生物等效性，以及通常相同的证明标示为 RLD（有限的例外情况，包括
允许省略）由于专营权原因，适应症或其它使用条件，或标签说明的其它方面，获批 ANDA 药品被
认为在治疗上等同于其 RLD，并且在批准时将获得 A 代码，即使如果其标签省略了 RLD 的某些适应
症或其他使用条件，或标签的其他方面已获批但受专利或专营权保护。
As a hypothetical example， suppose that a drug， Drugex， is approved for three indications:
treatment of type 2 diabetes mellitus， treatment of hypertension， and prevention of heart
disease. A method-of-use patent is listed in the Orange Book， and the use code describes the
approved method of use claimed by the patent as "treatment of hypertension." The Orange
Book also lists a period of three-year exclusivity for Drugex with the exclusivity code of "prevention
of heart disease." In this case， an ANDA applicant could seek approval of a generic drug that
relies on Drugex as its RLD with labeling that retains the type 2 diabetes mellitus indication but
"carves out" the indications for treatment of hypertension and prevention of heart disease， which
are protected by patent and exclusivity， respectively. If FDA found that the omissions did not
render the ANDA drug product less safe or effective than Drugex for the remaining， non-
protected conditions of use， and the ANDA met all other requirements for approval， it would be
approved. The Orange Book would list an A code for the ANDA drug product， reflecting that it is
therapeutically equivalent to Drugex and thus can be expected to have the same clinical effect and
safety profile as Drugex when administered to patients under the conditions specified in the ANDA

第 13 页 / 共 20 页
drug product's labeling.
作为一个假设的例子，假设一种药品 Drugex 获批三年适应症：治疗 2 型糖尿病，治疗高血压，预
防心脏病。橙皮书中列出了使用方法专利，使用代码将该专利所声称的获批使用方法描述为“治疗
高血压”。橙皮书还列出了 Drugex 的三年专营期，专营权代码为“预防心脏病”。在这种情况下，
ANDA 申请人可以寻求批准一种以 Drugex 作为 RLD 的仿制药，其标签保留 2 型糖尿病的适应症，
但“剔除”了治疗高血压和预防心脏病的适应症。分别受专利和专营权保护。如果 FDA 发现这些遗
漏并未导致 ANDA 药品在剩余的非保护使用条件下的安全性或有效性低于 Drugex，并且 ANDA 符合
批准的所有其他要求，则该 ANDA 药品将被批准。橙皮书将列出 ANDA 药品的 A 代码，反映出该药
品在治疗上与 Drugex 相当，因此当在 ANDA 药品规定的条件下给予患者时，可以预期其具有与
Drugex 相同的临床效果和安全性。产品的标签说明。
11. How do inactive ingredients affect a therapeutic equivalence evaluation?
11. 非活性成分如何影响治疗等效性评价？
Differences in inactive ingredients between an ANDA and its RLD of the type permissible in ANDA
products， e.g.， preservatives， generally do not affect FDA's evaluation of therapeutic
equivalence for the ANDA product. FDA evaluates the inactive ingredients in a generic product as
part of the ANDA approval process，43 and， as noted earlier， in general upon approval， an
ANDA product is considered to be therapeutically equivalent to its RLD.
ANDA 产品中允许类型的 RLD 之间的非活性成分的差异，例如防腐剂，通常不会影响 FDA 对该
ANDA 产品的治疗等效性的评估。作为 ANDA 批准程序的一部分，FDA 评估仿制药中的非活性成分，
43
并且，如前所述，通常在批准后，ANDA 产品被认为与其 RLD 在治疗上等效。
Therapeutic equivalence evaluations for a product approved through the 505（b）（2） pathway
consider differences in inactive ingredients between that product and the listed drug to which a TE
code is sought. Inactive ingredients that may be in drug products approved through the 505（b）
（2） pathway and that may differ from the inactive ingredients in the listed drug to which a
therapeutic equivalence evaluation is sought， may influence the bioequivalence， route of
administration， safety profile， dosage form， or labeled indications of the drug products.
Because 505（b）（2） applications are not required to demonstrate pharmaceutical equivalence
or bioequivalence， differences in inactive ingredients may be part of FDA's therapeutic
equivalence evaluation for 505（b）（2） products.
通过 505（b）（2）途径批准的产品的治疗等效性评估考虑该产品与寻求 TE 代码的登记药品之间的
非活性成分的差异。通过 505（b）（2）途径批准的药品中的非活性成分可能与寻求治疗等效性评
估的药品中的非活性成分不同，可能会影响生物等效性，给药途径，安全性药品的概况、剂型或标
示的适应症。由于 505（b）（2）申请不需要证明药物等效性或生物等效性，因此非活性成分的差
异可能是 FDA 505（b）（2）产品治疗等效性评估的一部分。
12. How is therapeutic equivalence evaluated for drug/device combination products
submitted in an ANDA?
12. ANDA 中提交的药品/器械组合产品的治疗等效性是如何评估的？
Therapeutic equivalence evaluations are made between an ANDA and its RLD at the time of
approval， including for ANDAs for drug/device combination products. A generic combination
product classified as therapeutically equivalent to the RLD can be expected to produce the same
clinical effect and safety profile as the RLD under the conditions specified in labeling. This does not
mean， however， that the proposed generic combination product and its RLD need to be
identical in all respects. FDA recognizes that an identical design may not always be feasible and，
in certain instances， differences in the design of the user interface for a generic combination
product as compared to the RLD may exist without precluding approval of the generic combination
product under an ANDA. Any differences in device and labeling identified between a proposed

第 14 页 / 共 20 页
generic combination product and its RLD should be adequately analyzed， scientifically justified，
and otherwise not preclude approval under an ANDA.44 The extent to which differences between
the proposed generic combination product and the RLD affect the approvability of the ANDA
product will be evaluated on a case-by-case basis.45 In some instances in which differences exist，
certain additional information and/or data relating to the user interface of the generic combination
product may be appropriate to support approval of the proposed generic combination product in an
ANDA. Such additional information and/or data are intended to confirm that the differences in
device and labeling for the proposed generic combination product are acceptable and that the
proposed generic combination product can be substituted with the full expectation that the generic
combination product will produce the same clinical effect and safety profile as the RLD under the
conditions specified in the labeling.
治疗等效性评估是在 ANDA 与其 RLD 之间在批准时进行的，包括药品/器械组合产品的 ANDA。在
标签规定的条件下，与 RLD 治疗等效的仿制药组合产品有望产生与 RLD 相同的临床效果和安全性。
然而，这并不意味着拟议仿制药组合产品及其 RLD 需要在所有方面都相同。FDA 认识到，相同的设
计并不总是可行的，在某些情况下，与 RLD 相比，仿制药组合产品的用户界面设计可能存在差异，
而不妨碍根据 ANDA 批准仿制药组合产品。 拟议仿制药组合产品与其 RLD 之间发现的任何器械和
标签差异均应进行充分分析，并进行科学论证，否则不得妨碍 ANDA 的批准。 44 拟议仿制药组合产
品与 RLD 之间的差异对 ANDA 产品可批准性的影响程度将根据具体情况进行评估。 45 在一些存在差
异的情况下，与仿制药组合产品的用户界面相关的某些附加信息和 /或数据可能适用于支持 ANDA 中
拟定仿制药组合产品的批准。此类附加信息和/或数据旨在确认拟议组合产品的器械和标签差异是可
接受的，并且可以完全预期仿制药组合产品将产生相同的临床效果。在标签规定的条件下，效果和
安全性与 RLD 相同。
13. What are "special situations" in the Orange Book?
13. 橙皮书中的“特殊情况”是什么？
Section 1.8 of the Orange Book Preface， "Description of Certain Special Situations，"
identifies， among other things， "special situations" where a more comprehensive explanation of
equivalence scenarios beyond the two- or three-character therapeutic equivalence codes in the
Orange Book may aid healthcare professionals and other interested parties.
橙皮书前言的第 1.8 节“某些特殊情况的描述”确定了“特殊情况”，其中对橙皮书中的两个或三个
字符的治疗等效性代码之外的等效性方案进行更全面的解释可能帮助医疗保健专业人员和其它利益
攸关方。
14. How does an interested party comment on or contest a therapeutic equivalence
evaluation?
14. 利益攸关方如何对治疗等效性评价发表意见或提出异议？
An interested party who wishes to comment on or contest a therapeutic equivalence evaluation
may submit a citizen petition under 21 CFR 10.25（a） and 10.30 or， in general， if a relevant
citizen petition has already been submitted， an interested party may submit a comment to the
docket for that citizen petition.
希望对治疗等效性评估提出意见或提出异议的利益攸关方可依据 21 CFR 10.25（a）和 10.30 提交
公民请愿，或者一般来说，如果相关公民请愿已经提交，利益攸关方可向该公民请愿的摘要提交意
见。
1 This guidance has been prepared by the Office of Generic Drugs in the Center for Drug
Evaluation and Research at the Food and Drug Administration.
1 本指南由 FDA 药品审评和研究中心仿制药办公室编制。
2 For purposes of therapeutic equivalence evaluations， "multisource" drug products are， in
most instances， pharmaceutical equivalence available from more than one manufacturer. In

第 15 页 / 共 20 页
contrast， "single-source" drug products are those products for which there is only one approved
product available for that active ingredient， dosage form， route of administration， and
strength. See Orange Book Preface （42nd edition 2022 ） at xii.
2 出于治疗等效性评估的目的，“多源”药品在大多数情况下是指可从多个生产商处获得的药品等效
性。相比之下，“单一来源”药品是指那些活性成分、剂型、给药途径和规格只有一种获批产品的
产品。参见橙皮书序言 （42nd 2022 年版）在 xii。
3 The electronic version of the Orange Book can be found at url.
3 橙皮书的电子版可在以下网址找到： url.
4 See， e.g.， 44 FR 2932 （January 12， 1979） and 45 FR 72582 （October 31， 1980）.
4 参见，例如，44 FR 2932（1979 年 1 月 12 日）和 45 FR 72582（1980 年 10 月 31 日）。
5 Id.
6 See 21 CFR 314.3（b）.
6 参见 21 CFR 314.3（b）。
7 See id； see also Orange Book Preface （42nd edition 2022 ） at vii and xii. Prescription drug
products are considered multisource when pharmaceutical equivalents are available （i.e.， are
not on the Discontinued Drug Product list in the Orange Book） from more than one manufacturer.
7 见 id；参见橙皮书序言 （42nd 2022 年版）在 vii 和 xii。当有多个生产商的药品等同物（即不在橙
皮书的停产药品清单上）时，处方药被认为是多来源的。
8 See 21 CFR 314.127（a）.
8 参见 21 CFR 314.127（a）。
9 21 CFR 314.3（b）.
10 21 CFR 314.3（b） （bullets added）.
10 21 CFR 314.3（b）（补充说明）
11 Id.
12 Id.
13 Id.
14 See， e.g.， 21 CFR 314.94（a）（7） and 21 CFR part 320.
14 参见，例如，21 CFR 314.94（a）（7） 和 21 CFR part 320。
15 For example， as an initial step for selecting a methodology for generic drug development，
applicants may refer to the draft guidance for industry Bioequivalence Studies With
Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA （August 2021）. When final，
this guidance will represent the FDA's current thinking on this topic. For the most recent version of
a guidance， check the FDA guidance web page at url. Product-specific guidances are available
at url.
15 例如，作为选择仿制药开发方法学的第一步，申请人可以参考行业指南草案。依据 ANDA 提交的
药物的具有药代动力学终点的生物等效性研究 （2021 年 8 月）。当最终版本发布时，本指南将代
表 FDA 目前对这一主题的看法。最新版本的指南，请查看 FDA 指南网页： url 具体产品指南见 u
rl.
16 21 CFR 314.3（b）.
17 The RLD "is the listed drug identified by FDA as the drug product upon which an applicant relies
in seeking approval of its ANDA." 21 CFR 314.3（b）.
17 该 参照药品 “是 FDA 确定的申请人寻求 ANDA 批准所依据的药品。” 21 CFR 314.3（b）。
18 Prescription drug products that have been approved by FDA are generally listed in the Orange
Book. See section 505（j）（7）（A） and （B） of the FD&C Act； 21 CFR 314.3（b）.
The Orange Book includes drug products whose applications became effective before the 1962
Amendments to the FD&C Act （and were deemed approved upon enactment of the 1962

第 16 页 / 共 20 页
amendments） on the basis of a demonstration of safety， where the effectiveness for their
intended use was determined through the Drug Efficacy Study Implementation （DESI） process.
Drugs marketed prior to the enactment of the Federal Food， Drug & Cosmetic Act of 1938 were
not subject to premarket approval procedures and are excluded from the Orange Book.
18 经 FDA 批准的处方药产品通常被列入橙皮书。参见 FD&C 法案第 505（j）（7）（A）和（B）
节； 21 CFR 314.3（b）。橙皮书包括其申请在 1962 年 FD＆C 法案修正案生效之前生效（并在
1962 年修正案颁布时被视为已获批）的药品，其预期用途的有效性是通过以下方式确定的：药效研
究实施（DESI）过程。在 1938 年《联邦食品、药品和化妆品法案》颁布之前上市销售的药品不受
上市前批准程序的约束，被排除在橙皮书之外。
19 For more information on 505（b）（2） applications， see the guidance for
industry Determining Whether to Submit an ANDA or 505（b）（2） Application （May 2019）
and the draft guidance for industry Applications Covered by Section 505（b）（2） （October
1999）. When final， this guidance will represent the FDA's current thinking on this topic.
19 有关 505（b）（2） 申请的更多信息，请参阅行业指南 确定是否提交 ANDA 或 505（b）
（2）申请 （2019 年 5 月）和行业指南草案 第 505（b）（2） 节涵盖的申请 （1999 年 10 月）。
当最终版本发布时，本指南将代表 FDA 目前对这一主题的看法。
20 The term duplicate generally refers to a "drug product that has the same active
ingredient（s）， dosage form， strength， route of administration， and conditions of use as a
listed drug." See 54 FR 28872 at 28877 （July 10， 1989）. However， the term duplicate， as
used in this context， does not mean identical in all aspects to the listed drug.
20 术语 重复 通常是指“与上市药品具有相同活性成分、剂型、规格、给药途径和使用条件的药
品”。参见 54 FR 28872 at 28877（1989 年 7 月 10 日）。但是，该术语 重复在此上下文中使用的
， 并不意味着在所有方面都与所列药品相同。
21 21 CFR 314.101（d）（9） （noting that FDA may refuse to file an NDA if the "NDA is
submitted as a 505（b）（2） application for a drug that is a duplicate of a listed drug and is
eligible for approval under section 505（j） of the [FD&C] Act"）.
21 21 CFR 314.101（d）（9）根据 FD＆C 法案第 505（j）节获得批准”）。
22 See Orange Book Preface （42nd edition 2022 ） at xxiv.
22 参见橙皮书序言 （42nd 2022 年版）在 xxiv。
23 For examples of applications that may be submitted under section 505（b）（2） of the
FD&C Act see the draft guidance for industry Applications Covered by Section 505（b）
（2） （December 1999）. When final， this guidance will represent the FDA's current thinking
on this topic.
23 依据 FD＆C 法案第 505（b）（2）节可能提交的申请示例，请参阅行业指南草案 第 505（b）
（2） 节涵盖的申请 （1999 年 12 月）。当最终版本发布时，本指南将代表 FDA 目前对这一主题
的看法。
24 For purposes of this guidance， the terms "generic"， "abbreviated new drug application"，
and "ANDA" refer to products submitted and approved under section 505（j） of the FD&C Act.
The Orange Book also refers to certain products approved under pre-Hatch-Waxman abbreviated
applications （PANDAs） as ANDAs. In general， the discussion of ANDAs and generics in this
document do not include such products. For more information on PANDAs， see Notice: Drug
Products Approved in Abbreviated New Drug Applications Before the Enactment of the Hatch-
Waxman Amendments； Establishment of a Public Docket； Request for Comments （referred
to as PANDA Notice）， Docket No. FDA-2020-N-1245， available at: url， and Pre-Hatch-
Waxman Abbreviated New Drug Applications in the Orange Book， available at: url.
24 就本指南而 言，术语 “ 仿制药 ”、 “简化 新药 申请 ” 和“ ANDA” 是指 根 据 FD＆C 法案第

第 17 页 / 共 20 页
505（j）节提交和批准的产品。橙皮书还将某些在 Hatch-Waxman 之前的简化申请（PANDA）下获
批的产品称为 ANDA。一般来说，本文件中对 ANDA 和仿制药的讨论不包括此类产品。有关 PANDA
的更多信息，请参见公告：Hatch-Waxman 修正案颁布前在简化新药申请中获批的药品；建立公开
案卷；征求意见稿（称为 PANDA 通知），卷宗号 FDA-2020-N-1245，可在以下网址获取：url， 和
Pre-Hatch-Waxman Abbreviated New Drug Applications in the Orange Book ， 网址： url.
25 We note that PANDAs have been designated as RLDs even though they are described in the
Orange Book as ANDAs （see PANDA Notice）.
25 我们注意到，即使在橙皮书中将 PANDA 描述为 ANDA（参见 PANDA 通知），PANDA 也被指
定为 RLD。
26 The Preface to the Orange Book explains therapeutic equivalence codes in greater detail. See
the Orange Book Preface （42nd edition 2022 ） discussion beginning at p. xii.
26 橙皮书前言更详细地解释了治疗等效性代码。参见橙皮书序言 （42nd 2022 年版）讨论从第 xii 页
开始。
27 At a high level， the A codes， other than AA， indicate the following things. A solution or
powder for aerosolization that is therapeutically equivalent to another such approved product and
for which there are no known or suspected bioequivalence problems would be
coded AN. AA identifies products in conventional dosage forms， e.g.， tablets or capsules， not
presenting bioequivalence problems. All oral dosage forms nonetheless must meet an appropriate
bioequivalence standard for approval. AO identifies injectable oil solutions. AP identifies injectable
aqueous solutions and， in certain instances， intravenous non-aqueous solutions. AT identifies
topical products. See the Orange Book Preface （42nd edition 2022 ） discussion beginning at p.
xiii.
27 在高层次上， A 代码，除了 AA， 请指明以下内容。治疗等效于另一种此类已批准产品并且不
存在已知或可疑生物等效性问题的雾化溶液或粉末，将被编码 AN.AA 确定不存在生物等效性问题的
常规剂型（例如，片剂或胶囊）的产品。尽管如此，所有口服剂型必须符合适当的生物等效性标准
才能获批。AO 确定注射用油溶液。AP 确定可注射的水溶液，在某些情况下，还包括静脉注射的非
水溶液。AT 标识外用产品。参见橙皮书序言 （42nd 2022 年版）讨论从第 xiii 页开始。
28 See 21 CFR 320.22 for a discussion on when bioequivalence may be self-evident.
28 参见 21 CFR 320.22 中关于何时生物等效性不证自明的讨论。
29 At a high level， the B codes indicate the following things. BC identifies extended-release
dosage forms （e.g.， capsules， injectables， and tablets）. BE identifies delayed-release oral
dosage forms. BN identifies products in aerosol-nebulizer drug delivery systems. BR identifies
suppositories or enemas that deliver drugs for systemic absorption. BT identifies topical products
with bioequivalence issues. BD indicates active ingredients and dosage forms with documented
bioequivalence problems. BS indicates that products have drug standard deficiencies. BP indicates
active ingredients and dosage forms with potential bioequivalence problems. B* indicates that a
drug product requires further FDA investigation and review to determine therapeutic equivalence，
and BX indicates that the data available to FDA are insufficient to determine therapeutic
equivalence. See the Orange Book Preface （42nd edition 2022 ） discussion at pp. xviii-xx.
29 在高层次上， B 代码表示以下内容。 BC 确定缓释剂型（例如，胶囊剂，注射剂和片剂）。BE
确定延迟释放的口服剂型。BN 识别气溶胶 - 雾化器给药系统中的产品。BR 确定递送药物供全身吸
收的栓剂或灌肠剂。BT 确定具有生物等效性问题的外用产品。BD 表示存在生物等效性问题的活性
成分和剂型。BS 表示产品存在药品标准缺陷。BP 表示有潜在生物等效性问题的活性成分和剂型。
B* 表明药品需要进一步的 FDA 调查和审评以确定治疗等效性，以及 BX 表明 FDA 可获得的数据不
足以确定治疗等效性。参见橙皮书序言 （42nd 2022 年版）讨论，第 xviii-xx 页。
30 See the Orange Book Preface （42nd edition 2022 ） discussion beginning at p. xviii.

第 18 页 / 共 20 页
30 参见橙皮书序言 （42nd 2022 年版）讨论从第 xviii 页开始。
31 As noted in section II.B.2.c of this guidance， approval of ANDAs under a suitability petition
would not constitute a finding of therapeutic equivalence because the ANDA products are not
pharmaceutical equivalents to their RLDs.
31 如本指南第 II.B.2.c 节所述，根据适用性请愿批准 ANDA 不构成治疗等效性发现，因为 ANDA 产
品不是其 RLD 的药学等效物。
32 The Orange Book Staff provides daily updates to the electronic Orange Book for new generic
drug approvals.
32 橙皮书员工提供新仿制药批准的电子橙皮书的每日更新。
33 See 21 CFR 314.161.
33 参见 21 CFR 314.161。
34 If an RLD is discontinued or withdrawn and there are multiple ANDAs that reference that RLD，
the remaining ANDAs retain their existing therapeutic equivalence codes. Subsequently approved
ANDAs that are pharmaceutical equivalents to the RLD would be assigned the same therapeutic
equivalence code.
34 如果一个 RLD 被中止或撤销，并且有多个 ANDA 引用该 RLD，则剩余的 ANDA 保留其现有的治
疗等效性代码。随后获批的与 RLD 药学等效的 ANDA 将被分配相同的治疗等效性代码。
35 See 21 CFR 314.94（a）（9）（ii） – （v） for a discussion on permissible differences in
exception excipients.
35 关于例外辅料的允许差异的讨论，参见 21 CFR 314.94（a）（9）（ii） – （v）。
36 For more information on contacting the appropriate Office of New Drugs review division，
see url.
36 有关联系相应的新药办公室审评部门的更多信息，请参阅 url.
37 Tentative approval is notification that an NDA or ANDA otherwise meets the requirements for
approval under the FD&C Act， but cannot be approved because there is a 7-year period of
orphan exclusivity for a listed drug under section 527 of the FD&C Act and 21 CFR 316.31， or
that a 505（b）（2） application or ANDA otherwise meets the requirements for approval under
the FD&C Act， but cannot be approved until the conditions in 21 CFR 314.107（b）（1）
（iii）， （b）（3）， or （c） are met； because there is a period of exclusivity for the listed
drug under 21 CFR 314.108； because there is a period of pediatric exclusivity for the listed drug
under section 505A of the FD&C Act； because there is a period of exclusivity for the listed drug
under section 505E of the FD&C Act； or because a court order pursuant to 35 U.S.C. 271（e）
（4）（A） orders that the NDA or ANDA may be approved no earlier than the date specified. A
drug product that is granted tentative approval is not an approved drug and will not be approved
until FDA issues an approval letter after any necessary additional review of the NDA or ANDA. 21
CFR 314.3（b）.
37 暂定批准 通知 NDA 或 ANDA 符合 FD＆C 法案规定的批准要求，但由于 FD＆C 法案第 527 节和
21 CFR 316.31 规定的上市药品有 7 年的孤儿药专营权而不能被批准，或 505（b）（2）申请或
ANDA 符合 FD＆C 法案的批准要求，但在符合 21 CFR 314.107（b）（1）（iii），（b）（3）的
条件之前不能被批准， 或 （c） 符合要求；因为依据 21 CFR 314.108 ， 上市药品有一段时间的
专营权；因为根据 FD＆C 法案第 505A 节 ， 上市药品有一段时间的儿科专营权；因为依据 FD&C
法案第 505E 节 ， 上市药品有一段时间专营权；或者因为依据第 35 USC 271（e）（4）（A） 的
法院命令命令 NDA 或 ANDA 不得早于指定的日期。获得暂时批准的药品不是已获批药品，在 FDA
对 NDA 或 ANDA 进 行 任 何 必 要 的 额 外 审 评 后 发 出 批 准 函 之 前 ， 该 药 品 不 会 被 批 准 。 21 CFR
314.3（b）。
38 Id. See section 505（j）（5）（B）（iv）（II）（dd）（BB） of the FD&C Act （stating that

第 19 页 / 共 20 页
a "drug that is granted tentative approval by the Secretary is not an approved drug and shall not
have an effective approval until the Secretary issues an approval after any necessary additional
review of the application"）； see also 21 CFR 314.105（d）.
38 Id 参见 FD&C 法案第 505（j）（5）（B）（iv）（II）（dd）（BB） 节有效的批准 ， 直到部
长在对申请进行任何必要的额外审核后发布批准”）；参见 21 CFR 314.105（d）。
39 For purposes of this guidance， FDA uses the term "powder for oral solution" drug product to
describe a product in a powder dosage form for oral administration with instructions in the labeling
for reconstitution as a solution before administration.
39 出于本指南的目的 ， FDA 使用术语“口服溶液用粉剂”来描述在标签上有说明的口服粉剂型产
品 ， 以便在给药前以溶液形式溶解。
40 For purposes of this guidance， FDA uses the term "ready-to-use oral solution" drug product to
describe a drug product in an oral solution dosage form for oral administration that does not
include instructions for further manipulation， reconstitution， dilution， etc.， before
administration.
40 出于本指南的目的 ， FDA 使用术语“即用型口服溶液”来描述口服溶液剂型的药品 ， 该制剂
不包括在 给药前进一步处理 ， 重构 ， 稀释等的说明。
41 See section 505（j）（2）（A）（v） and （viii） of the FD&C Act and 21 CFR
314.94（a）（8）（iv）； see also 21 CFR 314.127（a）（7）.
41 参见 FD&C 法案第 505（j）（2）（A）（v） 和 （viii） 节以及 21 CFR 314.94（a）（8）
（iv）；参见 21 CFR 314.127（a）（7）。
42 Prior to approval of an ANDA， FDA will determine the specific language in the labeling of the
RLD that describes the protected use and will assess whether an ANDA that omits the protected
information from its labeling will be rendered less safe or effective than the RLD for the remaining
non-protected conditions of use. 21 CFR 314.127（a）（7）. FDA will not approve an ANDA that
omits protected information from its labeling if that omission renders the ANDA less safe or
effective for the remaining non-protected conditions of use.
42 在批准 ANDA 之前 ， FDA 将确定 RLD 标签中描述受保护用途的具体语言，并将评估在标签中
省略受保护信息的 ANDA 是否会导致其安全性或有效性低于 RLD。其余未受保护的使用条件。 21
CFR 314.127（a）（7）如果省略标签说明中遗漏的受保护信息，会使 ANDA 在剩余的非保护使用
条件下的安全性或有效性降低，FDA 将不会批准该 ANDA。
43 See Section 505（j）（2）（A）（vi） of the FD&C Act （cross-referencing section
505（b）（1）（C））； 21 CFR 314.94（a）（9）.
43 参见 FD&C 法案第 505（j）（2）（A）（vi）节（交叉引用第 505（b）（1）（C）节）； 21
CFR 314.94（a）（9）
44 See draft guidance for industry Comparative Analyses and Related Comparative Use Human
Factors Studies for a Drug-Device Combination Product Submitted in an ANDA （January 2017）.
When final， this guidance will represent the FDA's current thinking on this topic.
44 参见行业指南草案 在 ANDA 中提交的药品-器械组合产品的比较分析和相关的比较使用人为因素
研究 （2017 年 1 月）。当最终版本发布时，本指南将代表 FDA 目前对这一主题的看法。
45 See the Office of Combination Products guidance for industry and FDA staff Principles of
Premarket Pathways for Combination Products （January 2022）.
45 参见针对行业和 FDA 员工的组合产品办公室指南 组合产品上市前途径的原则 （2022 年 1 月）。

第 20 页 / 共 20 页