生产过程违反 cGMP，FDA 发出警告信

2021 年 8 月 FDA 检查了位于印度的一家企业，2022 年 2 月发出警告

信，具体内容如下：

Warning Letter

警告信

Indiana Chem-Port

印度 Chem-Port 制药厂

MARCS-CMS 618173 — FEBRUARY 02, 2022

Dear Mr. Desai:

亲爱的德赛先生：

The U.S. Food and Drug Administration (FDA) inspected your drug
manufacturing facility, Indiana Chem-Port, FEI 3005564386, at 349 GIDC Industrial
Estate, Makarpura, Vadodara, Gujarat, India, from August 2 to 7, 2021.
2021 年 8 月 2 日至 7 日，美国食品和药物管理局（FDA）检查了贵公司
位于印度古吉拉特邦巴罗达 Makarpura GIDC Industrial Estate 349 号印第安纳化
学港（邮编：3005564386）的药品生产工厂。

This warning letter summarizes significant deviations from current good

manufacturing practice (CGMP) for active pharmaceutical ingredients (API).
本警告信总结了与有效药物成分（API）现行良好生产规范（CGMP）的
重大偏差。
 Because your methods, facilities, or controls for manufacturing, processing,
packing, or holding do not conform to CGMP, your drugs are adulterated within the
meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C
Act), 21 U.S.C. 351(a)(2)(B).

由于您的制造、加工、包装或持有方法、设施或控制不符合 CGMP，因
此您的药品在《联邦食品、药品和化妆品法案》（ FD＆C 法案）第 501（a）
（2）（B）节、《美国法典》第 21 卷第 351（a）（2）（B）节中被掺假。

We acknowledge receipt of your October 15, 2021, response to our Form FDA
483.
我们确认收到您 2021 年 10 月 15 日对我们 FDA 483 表格的回复。

During our inspection, our investigator observed specific deviations including,

but not limited to, the following.
在我们的检查过程中，我们的研究人员观察到了具体的 缺陷，包括但不
限于以下内容。

1. Failure to ensure that equipment surfaces in contact with API do not alter
the quality of the API beyond the official or other established specifications.
1.未能确保与 API 接触的设备表面不会改变 API 的质量，超出官方或其
他既定规范。

You failed to ensure the equipment used in the manufacture of API is suitable
for its intended use and is properly maintained. For example:
贵方未能确保 API 生产过程中使用的设备适合其预期用途，并得到适当
维护。例如：

• Rust-like residues were observed on product contact surfaces of your

equipment labeled as clean, including (b)(4) vessels and hoses.
•在标记为清洁的设备（包括（b）（4）容器和软管）的产品接触面上观
察到类似锈迹的残留物。
 • Tape was used on (b)(4) paddles to prevent black material from screws from
contaminating your API.
•在（b）（4）叶片上使用胶带，以防止螺钉的黑色材料污染 API。

• A (b)(4) was used to attach a (b)(4) to a piece of equipment.

•（b）（4）用于将（b）（4）连接到设备上。

• Several holes were observed in a (b)(4).

•在 ab）（4）中观察到几个孔。

Further, you lacked a procedure to qualify your manufacturing and quality

control laboratory equipment. You currently manufacture and test (b)(4) API in
unqualified equipment.
此外，您还缺乏一个程序来鉴定您的制造和质量控制实验室设备。您目
前在不合格的设备中制造和测试（b）（4）API。

In your response you indicated that the rust-like residue cannot be rust. Your
response is inadequate. You failed to identify the source of the brownish residue on
the (b)(4) vessels and hoses. Your response does not adequately address the poor
condition and state of disrepair of your equipment which increases the risk of foreign
material contaminating your (b)(4) API. Notably, your (b)(4) API, is intended for the
production of a sterile injectable drug product, (b)(4).
在您的回复中，您表示类似锈迹的残留物不能是锈迹。你的回答不充
分。您未能确定（b）（4）容器和软管上棕色残留物的来源。贵方的回复没有
充分解决设备状况不佳和年久失修的问题，这会增加异物污染贵方（ b）
（4）API 的风险。值得注意的是，你的（b）（4）原料药是用于生产无菌注射
药物产品（b）（4）。

In response to this letter provide:

针对本函，请提供：
 • Your corrective action and preventive action (CAPA) plan to implement
routine, vigilant operations management, oversight of facilities and equipment. This
plan should ensure, among other things, prompt detection of equipment/facilities
performance issues, effective execution of repairs, adherence to appropriate
preventive maintenance schedules, timely technological upgrades to the
equipment/facility infrastructure, and improved systems for ongoing management
review.
•您的纠正和预防措施（CAPA）计划实施日常、警惕性的运营管理，监
督设施和设备。除其他事项外，该计划应确保及时发现设备/设施性能问题，有
效执行维修，遵守适当的预防性维护计划，及时对设备/设施基础设施进行技术
升级，并改进持续管理审查的系统。

• Provide a plan to ensure that your equipment is of appropriate design,

adequate size, and suitably located for its intended use. The plan should include
CAPAs that ensure product contact surfaces do not alter the quality of the
intermediates and API.
•提供一份计划，以确保您的设备具有适当的设计、足够的尺寸，并适合
其预期用途。该计划应包括 CAPA，以确保产品接触表面不会改变中间体和原
料药的质量。

2. Failure to demonstrate that your manufacturing process can reproducibly

manufacture an API meeting its predetermined quality attributes.
2.未能证明您的制造工艺能够重复制造符合其预定质量属性的原料药。

You failed to validate the manufacturing process for (b)(4) API. You stated
you have not validated the manufacturing process for (b)(4) API because the batches
are manufactured by customer orders. You made several changes to your
manufacturing process without justification or change control. For example, you
changed the amounts of (b)(4) water and (b)(4) added.
您 未 能 验 证 （ b ） （ 4 ） API 的 制 造 过 程 。 您 声 明 您 尚 未 验 证 （ b ）
（4）API 的制造过程，因为批次是根据客户订单制造的。您在没有正当理由或
变更控制的情况下对制造过程进行了多次更改。例如，您更改了（b）（4）水
和（b）（4）添加量。

See FDA’s guidance document Process Validation: General Principles and

Practices for general principles and approaches that FDA considers to be appropriate
elements of process validation at https://www.fda.gov/media/71021/download.
参见 FDA 的指导文件《过程验证：一般原则和实践》，了解 FDA 认为
是当前过程验证适当要素的一般原则和方法 https://www.fda.gov/media/71021/
download.

Process validation evaluates the soundness of design and state of control of a

process throughout its lifecycle. Each significant stage of a manufacturing process
must be designed and controlled to assure the raw materials, in-process materials, and
finished drugs are of the intended quality.
过程验证评估设计的可靠性和过程在其整个生命周期中的控制状态。必
须设计和控制制造过程的每个重要阶段，以确保原材料、过程中材料和成品具
有预期的质量。

Process qualification studies determine whether an initial state of control has

been established. Successful process qualification studies are necessary before
commercial distribution. Thereafter, ongoing vigilant oversight of the variables
affecting process performance and product quality is necessary to ensure you maintain
a stable manufacturing operation throughout the product lifecycle.
工艺鉴定研究确定是否已建立初始控制状态。在商业分销之前，必须
进行成功的工艺鉴定研究。此后，有必要对影响过程性能和产品质量的变量进
行持续的警惕性监督，以确保您在整个产品生命周期中保持稳定的制造操作。

Failure to implement adequate process validation practices can result in

insufficient understanding of process variables or failure to detect a drift in capability,
which increases the risk of drug quality defects.
 未能实施充分的工艺验证实践可能会导致对工艺变量的理解不足或未能
检测到能力漂移，从而增加药品质量缺陷的风险。

In response to this letter provide:

针对本函，请提供：

• A remediation plan that better assures ongoing management oversight

throughout the manufacturing lifecycle of all drug products. Provide a more data-
driven and scientifically sound program that identifies sources of process variability
and assures that manufacturing operations meet appropriate parameters and quality
standards. This includes, but is not limited to, evaluating suitability of equipment for
its intended use, ensuring quality of input materials, determining the capability and
reliability of each manufacturing process step and its controls, and vigilant ongoing
monitoring of process performance and product quality.
•补救计划，更好地确保在所有药物产品的整个生产周期中进行持续的管
理监督。提供一个更加智能和科学合理的程序，以识别过程可变性的来源，并
确保制造操作符合适当的参数和质量标准。这包括但不限于评估设备对其预期
用途的适用性，确保输入材料的质量，确定每个制造过程步骤及其控制的能力
和可靠性，以及对过程性能和产品质量的持续监控。

• A detailed summary of your validation program for ensuring a state of

control throughout the product lifecycle, along with associated procedures. Describe
your program for process performance qualification, and ongoing monitoring of both
intra-batch and inter-batch variation to ensure a continuing state of control.
•验证计划的详细总结，以及相关程序，以确保在整个产品生命周期中处
于受控状态。描述您的工艺性能鉴定计划，以及对批内和批间变化的持续监
控，以确保持续的控制状态。

• A timeline for performing process performance qualification for each of your

marketed drug products.
 •每种上市药品工艺性能鉴定的时间表。

• Include your process performance protocol(s), and written procedures for

qualification of equipment and facilities.

•包括工艺性能协议，以及设备和设施鉴定的书面程序。

• Provide a detailed program for designing, validating, maintaining,

controlling, and monitoring each of your manufacturing processes that includes
vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state
of control. Also, include your program for qualification of your equipment and
facility.
•提供详细的计划，用于设计、验证、维护、控制和监控每个制造过程，
包括对批内和批间变化的警惕性监控，以确保持续的控制状态。此外，还应包
括设备和设施的确认计划。

• A comprehensive, independent assessment of your in-process monitoring and

sampling operations, focusing on each upstream process step that can introduce
variability. Provide your remediation plan to improve: (1) in-process detection of
variation; (2) upstream controls; and (3) sampling plan.
•对过程中的监控和采样操作进行全面、独立的评估，重点关注可能引入
可变性的每个上游过程步骤。提供补救计划以改进：（1）过程中检测变量；
（2） 上游控制；（3）取样方案。

• Provide your updated master batch record for (b)(4) API.

•提供（b）（4）API 现行的批生产记录。

• Provide an independent risk assessment for your distributed (b)(4) API that
may have been impacted by changes made in your manufacturing process without
adequate evaluation.
•为您的分步式（b）（4）API 提供独立的风险评估，该 API 可能受到您
的制造过程中未经充分评估的变更的影响。

3. Failure to adequately validate written procedures for the cleaning and maintenance
of equipment and failure to establish adequate written procedures for cleaning
equipment and its release for use in manufacture of API.

3.未能充分验证设备清洁和维护的书面程序，以及未能建立足够的书面程
序来清洁设备及其确认，以用于 API 的生产。

You failed to adequately validate your cleaning process for non-dedicated

manufacturing equipment as required by your Validation Master Plan. During the
inspection, you did not provide written cleaning procedures for non-dedicated
equipment, including your (b)(4) vessel, (b)(4), and (b)(4). Equipment operators
stated they cleaned equipment without following a procedure. You lack assurance that
your equipment is adequately cleaned to prevent cross-contamination from other
products.
您未能按照验证主计划的要求充分验证非专用制造设备的清洁过程。在
检查期间，您没有提供非专用设备的书面清洁程序，包括您的（ b）（4）容
器，（b）（4）和（b）（4）。设备操作员表示，他们没有按照程序清洁设
备。您无法保证您的设备已充分清洁，以防止其他产品的交叉污染。

In response to this letter provide:

针对本函，请提供：

• Appropriate improvements to your cleaning validation program, with special

emphasis on incorporating conditions identified as worst case in your drug
manufacturing operation. This should include, but not be limited to, identification and
evaluation of all worst-case:
•对清洁验证计划进行适当改进，特别强调在药品生产操作中纳入被确定
为最坏情况的条件。这应包括但不限于识别和评估所有最坏情况：
o drugs with higher toxicities
 o 毒性较高的药物
o drugs with higher drug potencies
o 药效更高的药物
o drugs of lower solubility in their cleaning solvents
o 在清洗溶剂中溶解度较低的药物
o drugs with characteristics that make them difficult to clean
o 具有难以清洗特征的药物
o swabbing locations for areas that are most difficult to clean
o 最难清洁区域的抽、吸位置
o maximum hold times before cleaning
o 清洁前的最大保持时间

In addition, describe the steps that must be taken in your change management
system before introduction of new manufacturing equipment or a new product.
此外，请描述在引入新的制造设备或新产品之前，必须在变更管理系统
中采取的步骤。

• A summary of your updated standard operating procedures that ensure an

appropriate program is in place for verification and validation of cleaning procedures
for products, processes, and equipment.
•修订标准操作程序的总结，确保有适当的程序用于验证和确认产品、工
艺和设备的清洁程序。

• A comprehensive, independent retrospective assessment of your cleaning

effectiveness to evaluate the scope of cross-contamination hazards. Include the
identity of residues, other manufacturing equipment that may have been improperly
cleaned, and an assessment whether cross-contaminated products may have been
released for distribution. The assessment should identify any inadequacies of cleaning
procedures and practices and encompass each piece of manufacturing equipment used
to manufacture more than one product.
•对清洁效果进行全面、独立的回顾性评估，以评估交叉污染危害的范
围。包括残留物、其他可能清洁不当的制造设备，以及是否已发生交叉污染产
品以供放行分发的评估。评估应确定清洁程序和实践中的任何不足之处，并涵
盖用于制造多个产品的每个制造设备。

• A CAPA plan, based on the retrospective assessment of your cleaning

program, that includes appropriate remediations to your cleaning processes and
practices, and timelines for completion. Provide a detailed summary of vulnerabilities
in your process for lifecycle management of equipment cleaning. Describe
improvements to your cleaning program, including enhancements to cleaning
effectiveness; improved ongoing verification of proper cleaning execution for all
products and equipment; and all other needed remediations.
•基于清洁计划回顾性评估的 CAPA 计划，包括对清洁过程和实际行动的
适当补救措施，以及完成时间表。提供设备清洁生命周期管理流程中疏忽的详
细总结。描述清洁计划的改进，包括提高清洁效率；改进所有产品和设备正确
清洁执行的持续验证；以及所有其他需要的补救措施。

4. Failure to design a documented, on-going stability testing program to

monitor the stability characteristics of API and to use the results to confirm
appropriate storage conditions and retest or expiry dates.
4.未能设计一个记录在案的、持续的稳定性测试程序，以监控原料药的
稳定性特征，并使用测试结果确认适当的储存条件和有效期。

You failed to implement an adequate stability program for (b)(4) API. For
example, you lacked appropriate stability protocols. You established the current, (b)
(4) retest date for (b)(4) API by testing reserve samples from one batch (batch (b)(4)).
This batch was manufactured in 2016 and stored in the reserve sample room which is
not controlled for humidity. Despite basing your retest dating on this batch, you
destroyed batch records associated with batch (b)(4).
您未能为（b）（4）API 实施适当的稳定性计划。例如，您缺乏适当的
稳定性协议。您通过测试一批（批次（b）（4））的储存样品，确定了（b）
（4）API 的当前（b）（4）重新测试日期。该批次于 2016 年生产，并储存在
不受湿度控制的备用样品室中。尽管你的复试日期是基于这个批次，你还是销
毁了与批次（b）（4）相关的批次记录。

In addition, this batch record was destroyed while the batch remained in U.S.
distribution. You lacked adequate scientific data to assure that your (b)(4) API will
maintain its quality attributes throughout its purported shelf-life and storage
conditions. This could adversely affect the quality of the drugs that your customers
manufacture from your API.
此外，该批次记录被销毁，而该批次仍在美国销售。您缺乏足够的科学
数据来确保您的（b）（4）原料药在其声称的保质期和储存条件内保持其质量
属性。这可能会对客户使用 API 生产的药物的质量产生不利影响。

In response to this letter provide:

针对本函，请提供：

• A comprehensive, independent assessment and CAPA plan to ensure the

adequacy of your stability program. Your remediated program should include, but not
be limited to:
•全面、独立的评估和 CAPA 计划，以确保稳定计划的充分性。您的补救
计划应包括但不限于：
o Stability indicating methods
o 稳定性测试方法
o Stability studies for each drug product in its marketed container-closure
system before distribution is permitted
o 允许分销前，对每种药品在其上市容器封闭系统中的稳定性进行研
究
o An ongoing program in which representative batches of each product are
added each year to the program to determine if the shelf-life claim remains valid
o 正在进行的计划，每年向计划中添加每种产品的代表批次，以确定
保质期声明是否有效
 o Detailed definition of the specific attributes to be tested at each station
(timepoint)
o 在每个站点（时间点）测试的特定属性的详细定义

• All procedures that describe these and other elements of your remediated
stability program.

•描述补救稳定性计划的这些和其他要素的所有程序。

5. Failure to have a quality unit that is independent of production and fulfills

quality assurance (QA) and quality control (QC) duties.
5.没有独立于生产并履行质量保证（QA）和质量控制（QC）职责的质量
部门。

Your quality unit (QU) lacked adequate responsibilities and authorities to

assure reliable operations. Your QU failed to ensure good documentation practices in
your facility as evidenced by:
你们的质量部门（QU）缺乏足够的责任和权限来确保可靠的操作。您的
QU 不能确保在您有良好的文件记录习惯，这可以从以下方面得到证明：

• A Batch Manufacturing Production logbook was found with pages torn out
•发现一本生产日志，其中有几页被撕掉
• Numerous signed and partially completed batch records which lacked the
“Controlled Copy” stamp were found in the unofficial R&D laboratory
•在非官方研发实验室中发现了大量未加盖“受控副本”印章的签名和部
分完成的批生产记录
• Destruction of (b)(4) API batch record for batch (b)(4) that contained
manufacturing and analysis records, despite this batch remaining in U.S. distribution.
You also destroyed the batch retain sample.
•销毁包含生产和分析 API（b）（4）的（b）（4）批次记录，尽管该批
次仍在美国销售。您还销毁了批次保留样本。

You are responsible for establishing and following appropriate record retention
procedures for your API that remains within retest period.
您有责任为您的 API 建立并遵循适当的记录保留程序，该程序仍在重新
测试期内。

In response to this letter provide:

针对本函，请提供：

• A comprehensive assessment and remediation plan to ensure your QU is

given the authority and resources to effectively function. The assessment should also
include, but not be limited to:
•全面的评估和补救计划，以确保您的 QU 获得有效运行的权限和资源。
评估还应包括但不限于：
o A determination of whether procedures used by your firm are robust and
appropriate
o 确定贵公司使用的程序是否可靠和适当
o Provisions for QU oversight throughout your operations to evaluate
adherence to appropriate practices
o 规定在整个运营过程中对 QU 进行监督，以评估对适当做法的遵守情况
o A complete and final review of each batch and its related information
before the QU disposition decision
o 在做出处置决定之前，对每批产品及其相关信息进行完整的最终审查
o Oversight and approval of investigations and discharging of all other QU
duties to ensure identity, strength, quality, and purity of all products
o 监督和批准调查，并履行所有其他职责，以确保所有产品的特性、强
度、质量和纯度

• How top management supports quality assurance and reliable operations,

including, but not limited to, timely provision of resources to proactively address
emerging manufacturing/quality issues and to assure a continuing state of control.
•最高管理层如何支持质量保证和可靠运营，包括但不限于及时提供资
源，以主动解决新出现的制造/质量问题，并确保持续的控制状态。

• A complete assessment of documentation systems used throughout your

manufacturing and laboratory operations to determine where documentation practices
are insufficient. Include a detailed CAPA plan that comprehensively remediates your
firm’s documentation practices to ensure you retain attributable, legible, complete,
original, accurate, contemporaneous records throughout your operation.
•对整个制造和实验室操作过程中使用的文件系统进行全面评估，以确定
文件实践不足之处。包括一份详细的 CAPA 计划，全面修正贵公司的文件做
法，以确保贵公司在整个运营过程中保留可追溯、清晰、完整、原始、准确的
同期记录。

Your quality system does not adequately ensure the accuracy and integrity of
data to support the safety, effectiveness, and quality of the drugs you manufacture.
See FDA’s guidance document Data Integrity and Compliance with Drug CGMP for
guidance on establishing and following CGMP compliant data integrity practices at
https://www.fda.gov/media/119267/download.
您的质量体系不能充分确保数据的准确性和完整性，以支持您生产的药
物的安全性、有效性和质量可控性。请参阅 FDA 的指导文件《数据完整性和药
物 CGMP 合规性》，以获取关于建立和遵循 CGMP 合规数据完整性实践的指导
https://www.fda.gov/media/119267/download.

We strongly recommend that you retain a qualified consultant to assist in your

remediation.
我们强烈建议您聘请一名合格的顾问协助您进行补救。

In response to this letter, provide the following:

针对本函，请提供以下内容：
 • A comprehensive investigation into the extent of the inaccuracies in data
records and reporting including results of the data review for drugs distributed to the
United States. Include a detailed description of the scope and root causes of your data
integrity lapses.
•对数据记录和报告中的不准确程度进行全面调查，包括对分发给美国的
药物的数据审查结果。包括对数据完整性失效的范围和根本原因的详细描述。

• A current risk assessment of the potential effects of the observed failures on

the quality of your drugs. Your assessment should include analyses of the risks to
patients caused by the release of drugs affected by a lapse of data integrity and
analyses of the risks posed by ongoing operations.
•对观察到的不符合项对药物质量的潜在影响，应进行充分的风险评估。
您的评估应包括对因数据完整性失效而受影响的药物释放对患者造成的风险的
分析，以及对正在进行的手术造成的风险的分析。

• A management strategy for your firm that includes the details of your global
CAPA plan. The detailed corrective action plan should describe how you intend to
ensure the reliability and completeness of all data generated by your firm including
microbiological and analytical data, manufacturing records, and all data submitted to
FDA.
•贵公司的管理战略，包括全部 CAPA 计划的细节。详细的纠正措施计划
应说明您打算如何确保贵公司生成的所有数据的可靠性和完整性，包括微生物
和分析数据、生产记录以及提交给 FDA 的所有数据。

Drug Registration Violation

违反药品注册

Based upon the information obtained from the August 2 to 7, 2021, inspection,
and drug application data for the sterile finished drug product (b)(4), Indiana Chem-
Port (FEI 3005564386) has been identified as a manufacturer of (b)(4) API used to
manufacture the finished drug product. Under section 510(i)(1) of the Act (21 U.S.C.
§ 360(i)(1)), Indiana Chem-Port is required to submit registration information
annually by electronic means for each establishment it owns or operates that is
engaged in the manufacture, preparation, propagation, compounding, or processing of
a drug that is in commercial distribution in the United States. Indiana Chem-Port has
not fulfilled its registration requirement. As a result, all drugs manufactured in this
establishment are misbranded under Section 502(o) of the FD&C Act [21 U.S.C.
352(o)].

根据 2021 年 8 月 2 日至 7 日获得的无菌成品（b）（4）的检验和用药数
据 ， 印 第 安 纳 化 学 港 （ FEI 3005564386 ） 被 认 定 为 用 于 制 造 成 品 的 （ b ）
（4）API 的制造商。根据法案第 510（i）（1）节（《美国法典》第 21 卷第
360（i）（1）条），印第安纳化学港需要每年通过电子方式提交其拥有或经营
的每个机构的注册信息，这些机构从事制造、制备、传播、配制或加工在美国
分销的药物。印第安纳化学港尚未满足其注册要求。因此，根据《FD&C
法案》第 502（o）节【21 美国法典第 352（o）节】的规定，该机构生产的所有
药品都被贴错了品牌。

In addition, according to the records obtained at the time of inspection,

Indiana Chem-Port (FEI 3005564386) manufactures drugs for commercial
distribution in the United States which have not been properly listed with FDA. The
drug includes:
此外，根据检查时获得的记录，印第安纳州化学港（FEI 3005564386）
生产的药品得到美国食品和药物管理局正式批准，用于在美国进行商业分销。
该药物包括：

• (b)(4) API
•(b)(4)原料药 (b)(4)指隐藏了有商业秘密的信息

There are no drug listing submissions to FDA under the name of or labeler
code for Indiana Chem-Port (FEI 3005564386). Under section 510 of the FD&C Act
as amended and 21 CFR (21 U.S.C. 360(j)(1), 21 CFR 207.17 and 207.41), all drugs
manufactured, prepared, propagated, compounded, or processed for U.S. commercial
distribution must be listed with FDA. Failure to properly list drug products is
prohibited and will render the drugs misbranded. (21 U.S.C. 331(p) and 352(o))
没有以印第安纳化学港（FEI 3005564386）的名称或标签代码向 FDA 提
交药物清单。根据修订后的《食品、药品和化妆品法案》第 510 节和《美国联
邦法规》第 21 卷（《美国法典》第 21 卷第 360（j）（1）、第 21 卷第 207.17
和 207.41 节），所有为美国分销而制造、制备、传播、合成或加工的药物必须
得到美国食品和药物管理局（FDA）的批准。禁止未正确列出的药品，这将导
致药品品牌失效。（21《美国法典》第 331（p）和 352（o）节）

Additional API CGMP Guidance

API CGMP 指南附录

FDA considers the expectations outlined in ICH Q7 when determining

whether API are manufactured in conformance with CGMP. See FDA’s guidance
document Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical
Ingredients for guidance regarding CGMP for the manufacture of API at
https://www.fda.gov/media/71518/download.
FDA 在确定原料药的生产是否符合 CGMP 时，会考虑 ICH Q7 中概述的
预期。关于原料药生产的 CGMP 指南，请参见 FDA 的指导文件 Q7《活性药物
成分良好生产规范指南》https://www.fda.gov/media/71518/download.

CGMP Consultant Recommended

CGMP 顾问推荐

Based upon the nature of the deviations we identified at your firm, we strongly
recommend engaging a consultant qualified to evaluate your operations to assist your
firm in meeting CGMP requirements. Your use of a consultant does not relieve your
firm’s obligation to comply with CGMP. Your firm’s executive management remains
responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP
compliance.
根据我们在贵公司发现的偏差的性质，我们强烈建议聘请有资格评估贵
公司运营的顾问，以帮助贵公司满足 CGMP 要求。使用顾问并不能免除贵公司
遵守 CGMP 的义务。贵公司的执行管理层仍然负责解决所有缺陷和系统性缺
陷，以确保持续遵守 CGMP。

Conclusion
结论

The deviations cited in this letter are not intended to be an all-inclusive list of
deviations that exist at your facility. You are responsible for investigating and
determining the causes of any deviations and for preventing their recurrence or the
occurrence of other deviations.
本函中引用的偏差并不是贵公司设施中存在的所有偏差清单。您有责任
调查和确定任何偏差的原因，并防止其再次发生或发生其他偏差。

If you are considering an action that is likely to lead to a disruption in the

supply of drugs produced at your facility, FDA requests that you contact CDER’s
Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can
work with you on the most effective way to bring your operations into compliance
with the law. Contacting the Drug Shortages Staff also allows you to meet any
obligations you may have to report discontinuances or interruptions in your drug
manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as
possible, what actions, if any, may be needed to avoid shortages and protect the health
of patients who depend on your products.
如果您正在考虑可能导致您工厂生产的药品供应中断的行动，FDA 要求
您立即联系 CDER 的药品短缺工作人员，邮箱：drugshortages@fda.hhs.gov，以
便 FDA 能够与您合作，以最有效的方式使您的操作符合法律规定。联系药品短
缺工作人员也可以让您履行《美国法典》第 21 卷第 356C（b）款规定的任何义
务，即报告药品生产中断或中止。这也使 FDA 能够尽快考虑可能需要采取哪些
行动（如有），以避免短缺并保护依赖您产品的患者的健康。

FDA placed your firm on Import Alert 66-40 on December 13, 2021.
2021 年 12 月 13 日，美国食品和药物管理局将贵公司置于进口警戒 66-
40。

Correct any deviations promptly. FDA may withhold approval of new

applications or supplements listing your firm as a drug manufacturer until any
deviations are completely addressed and we confirm your compliance with CGMP.
We may re-inspect to verify that you have completed corrective actions to any
deviations.

请及时纠正任何偏差。FDA 可能会拒绝批准将贵公司列为药品制造商的
新申请或补充申请，直到任何偏差得到完全解决，并且我们确认您符合
CGMP。我们可能会重新检查，以确认您已完成任何偏差的纠正措施。

Failure to address any deviations may also result in the FDA continuing to
refuse admission of articles manufactured at Indiana Chem-Port, at 349 GIDC
Industrial Estate, Gujarat into the United States under section 801(a)(3) of the FD&C
Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated or
misbranded may be detained or refused admission, in that the methods and controls
used in their manufacture do not appear to conform to CGMP within the meaning of
section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B) and are misbranded
under section 502 of the FD&C Act, respectively.
未能解决任何偏差也可能导致美国食品和药物管理局根据《食品和药物
管理法》第 801（a）（3）节、《美国法典》第 21 卷第 381（a）（3）节的规
定，继续拒绝将古吉拉特邦 GIDC 工业区 349 号印地安那化学港制造的物品输
入美国。根据本授权，可能会扣留或拒绝入境看似掺假或贴错标签的物品，因
为其制造过程中使用的方法和控制措施似乎不符合《食品和药品法》第
501（a）（2）（B）节、《美国法典》第 21 卷第 351（a）（2）（B）节所指
的 CGMP，或根据《食品和药品法》第 502 节贴错标签。

This letter notifies you of our findings and provides you an opportunity to
address the above deficiencies. After you receive this letter, respond to this office in
writing within 15 working days. Specify what you have done to address any
deviations and to prevent their recurrence. In response to this letter, you may provide
additional information for our consideration as we continue to assess your activities
and practices. If you cannot complete corrective actions within 15 working days, state
your reasons for delay and your schedule for completion.
本函通知您我们的调查结果，并为您提供了解决上述缺陷的机会。收到
此信后，请在 15 个工作日内以书面形式回复本办公室。详细说明您为解决任何
偏差并防止其再次发生所做的工作。在我方继续评估贵方的活动和做法时，贵
方可提供额外信息供我方参考。如果您无法在 15 个工作日内完成纠正措施，请
说明延迟原因和完成时间表。

Send your electronic reply to CDER-OC-OMQ-

Communications@fda.hhs.gov. Identify your response with FEI 3005564386.

Sincerely,

/S/

Francis Godwin

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research