FDA：海外API试点计划，9个名额，约不？

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近日，就质量管理成熟度（QMM），美国FDA宣布了两项试点计划，分别针对于美国境内的制剂生产商和海外原料药生产商。试点计划的目的是：从对生产商的质量管理系统进行第三方评估，就如何表征质量管理成熟度（QMM）获得信息，确定FDA评级系统的未来发展。

FDA表示，这样的评级系统允许对设施进行横向比较。API设施可以选择向药品生产商披露其设施等级，从而在竞争优势中受益，因为QMM评级信息将使药品生产商在购买API时，可以在设施之间进行区分。有兴趣参与QMM API试点计划的海外设施，可以向FDA提交参与申请，FDA将最终选择9个设施参与该计划。

以下是QMM API试点计划公告的主要内容：

摘要

The Food and Drug Administration (FDA or Agency), Center for Drug Evaluation and Research (CDER) is announcing its Quality Management Maturity for Active Pharmaceutical Ingredients Pilot Program (QMM API Pilot Program) for foreign facilities manufacturing active pharmaceutical ingredients (APIs), including facilities manufacturing drug substance intermediates used to produce APIs, that are used in FDA-regulated prescription and over-the-counter (OTC) drug products. The purpose of the QMM API Pilot Program is to gain insight from third-party assessments of a facility’s quality management system to inform future development of an FDA rating system to characterize quality management maturity (QMM).

美国食品药品监督管理局（FDA）药品评估与研究中心（CDER）宣布：针对海外生产原料药（API）的设施，实施质量管理成熟度试点计划（QMM API试点计划），包括制造用于生产API的原料药中间体的设施，这些原料用于FDA管制的处方药和非处方（OTC）药品。QMM API试点计划的目的是：从对设施质量管理系统的第三方评估中获得见解，就如何表征质量管理成熟度（QMM）获得信息，确定FDA评级系统的未来发展。

Such a rating system would allow a cross-sectional comparison of facilities. Facilities that choose to disclose their facility ratings to drug product manufacturers could benefit from a competitive advantage, as knowledge of QMM ratings would enable drug product manufacturers to differentiate among facilities when purchasing APIs. This notice invites foreign facilities that are interested in participating in the QMM API Pilot Program to submit a request to participate.

这样的评级系统将允许对设施进行横向比较。API设施可以选择向药品生产商披露其设施等级，从而在竞争优势中受益，因为QMM评级信息将使药品生产商在购买API时，可以在设施之间进行区分。有兴趣参与QMM API试点计划的海外设施，请提交参与申请。

DATES: FDA will accept requests to participate in the QMM API Pilot Program through November 30, 2020, and the QMM API Pilot Program will run through December 31, 2021. See the “Participation” section for selection criteria and instructions on how to submit a request to participate.

日期：2020年11月30日前，FDA将接受到参加QMM API试点计划的申请，而QMM API试点计划将在2021年12月31日开始运行。有关选择标准和如何提交参与申请的说明，请参见“参与”部分。

背景

In 2002, FDA launched an initiative “Pharmaceutical CGMPs for the 21st Century--A Risk-Based Approach,” to enhance and modernize the regulation of pharmaceutical manufacturing and product quality.[1] One objective, among others, was to facilitate the implementation of a modern, risk-based pharmaceutical quality assessment system. The desired goal has been described as a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight.

FDA在2002年发起了一项“面向21世纪的制药CGMP——基于风险的方法”倡议，以增强和现代化对药品生产和产品质量的监管。其中一个目标是，促进基于风险的现代药物质量体系的实施。期望的目标可以描述为：制药生产行业需要具有最大效率、敏捷和灵活性，可以可靠地生产高质量的药品，而无需进行太多的法规监管。

There has been significant progress toward this vision as evidenced by FDA programs and initiatives in such areas as pharmaceutical development and quality by design, quality risk management and pharmaceutical quality systems, process validation, and emerging technologies. These programs and initiatives promote use of the best pharmaceutical science and engineering principles throughout the product life cycle.

通过FDA的诺力，已经朝着这一愿景迈出的重要一步。这些项目和举措包括：药品开发和QbD、质量风险管理和药品质量体系、工艺验证以及新兴技术等。这些都可以可在整个产品生命周期中，促进最佳药物科学和工程原理的使用。

Another example is the FDA Quality Metrics Program, described in the November 2016 revised draft guidance for industry, “Submission of Quality Metrics Data” (81 FR 85226). When final, this guidance will represent FDA’s current thinking on this issue. In June 2018, FDA initiated two voluntary programs that sought additional industry input on quality metrics. FDA solicited industry participation for a Site Visit Program (83 FR 30751) for manufacturing establishments to present the advantages and challenges associated with implementing and managing a quality metrics program and for a Quality Metrics Feedback Program (83 FR 30748) to engage stakeholders in identifying mutually useful and objective quality metrics.

另一个例子是FDA的质量度量计划，这在2016年11月修订的行业指南草案“提交质量度量数据”（81 FR 85226）中进行了描述。最终定稿时，该指南将代表FDA当前在此问题上的想法。2018年6月，FDA发起了两项自愿计划，以寻求行业对质量度量的更多投入。FDA要求行业参与者参与工厂访问的现场访问计划（83 FR 30751），以展示与实施和管理质量度量计划相关的优势和挑战，并要求质量度量反馈计划（83 FR 30748），以吸引利益相关者识别有用和客观的质量度量。

The Agency continues to develop the FDA Quality Metrics Program but recognizes that quality metrics are only one element within a manufacturer’s larger effort to increase the maturity of their quality management system. Manufacturers that demonstrate QMM[2] operate under an enhanced quality management system that exceeds the minimum standards specified in current good manufacturing practice regulations and focuses on continual improvement.

FDA继续制定FDA质量度量计划，但认识到：生产商为提高其质量管理体系成熟度需要做很多努力，质量度量只是其中的一个要素。展示QMM的生产商在增强的质量管理体系下运行，该体系超过了cGMP中规定的最低标准，并致力于持续改进。

Characteristics of a mature quality management system include, for example, the ability to consistently and reliably deliver quality product over time, operational stability, and a strong quality culture. Additionally, for manufacturers with a mature quality management system, FDA can exercise a more flexible regulatory approach, leading toward the goal of producing high- quality drug products without extensive regulatory oversight.

成熟的质量管理体系的特征包括，例如：随着时间的推移，能够始终如一地可靠地交付优质产品的能力，运营稳定性和强大的质量文化。此外，对于具有成熟质量管理体系的生产商，FDA可以采用更灵活的监管方法，从而实现在不进行广泛监管的情况下生产高质量药品的目标。

A transparent method of evaluating and communicating QMM is needed to fully realize the 21st century pharmaceutical quality vision. Toward that end, FDA is announcing the start of the QMM API Pilot Program. Through this pilot program, a third-party contractor identified by the FDA will conduct an assessment of a facility’s quality management system, accompanied by FDA staff. The Agency will gain insight from the results of the QMM assessments to inform the development of a rating system to measure and rate QMM. Assessments under the QMM API Pilot Program will cover multiple topics. Examples include but are not limited to:

需要一种透明的评估和沟通QMM的方法，来完全实现21世纪的药品质量愿景。为此，FDA宣布开始QMM API试点计划。通过该试点计划，由FDA确定的第三方将在FDA人员的陪同下对设施的质量管理体系进行评估。FDA将从QMM评估的结果中获得见解，为评估QMM的评级系统的进一步发展，提供信息。QMM API试点计划下的评估将涵盖多个主题，包括但不限于：

• supply chain management;
• manufacturing strategy and operations;
• safety, environmental, and regulatory compliance;
• inventory management;
• performance management and continual improvement;
• risk management;
• management review and responsibility;
• planning;
• workforce management;
• quality culture; and
• customer experience.
  
  
  

供应链管理;

制造策略和运营；

安全、环境和法规合规性；

库存管理;

绩效管理和持续改进；

风险管理;

管理评审和责任；

规划;

劳动力管理；

优质文化；

客户体验。

In the same timeframe as the QMM API Pilot Program, FDA will conduct a QMM pilot program for domestic manufacturers of finished dosage forms (FDF). These pilot programs are funded separately and are intended to provide FDA with representative information about QMM from different types of drug manufacturers (API and FDF). Elsewhere in this issue of the Federal Register, FDA is publishing “Quality Management Maturity for Finished Dosage Forms Pilot Program for Domestic Drug Product Manufacturers; Program Announcement.”

在与QMM API试点计划相同的时间范围内，FDA将为美国国内成品剂型（FDF）生产商实施QMM试点计划。这些试点计划是单独资助的，旨在为FDA提供来自不同类型药品生产商（API和FDF）的有关QMM的代表性信息。FDA在《联邦公报》的其他地方发布了“针对国内药品生产商的制剂试点计划的公告”。

参与

Facilities located outside the United States that manufacture APIs or drug substance intermediates used to produce APIs and are interested in participating in the QMM API PilotProgram should submit a written request directly to Seongjin (Cindy) Pak (see FOR FURTHER INFORMATION CONTACT). Participation is voluntary. Participants in the Quality Metrics Feedback Program are encouraged to participate in the QMM API Pilot Program. FDA will select up to nine participants for the QMM API Pilot Program. Participation in the QMM API Pilot Program is limited to foreign manufacturing facilities since FDA’s funding source for this program is specific to activities related to the surveillance of foreign sites.

位于美国境外的生产API或用于生产API的原料药中间体、且有兴趣参加QMM API 试点计划的设施应直接向Seongjin（Cindy）Pak提交书面申请（请参阅“联系信息”部分）。参与是自愿的。FDA鼓励质量度量反馈计划的参与者参加本试点计划。FDA将为本计划选择最多9个参与设施。参加本计划的设施仅限于海外制造工厂，因为FDA对该计划的资金来源专门用于与监管海外工厂有关的活动。

A. 选择标准

To be considered for the QMM API Pilot Program, participants must meet the following selection criteria:

要被考虑参加QMM API试点计划，参与者必须满足以下选择标准：

Participant is a facility located outside the United States that manufactures APIs or drug substance intermediates used to produce APIs for FDA-regulated prescription and OTC drug products. Facilities located in Puerto Rico or other U.S. territories are not considered to be foreign facilities and thus are not eligible to participate in the QMM API Pilot Program.

参与者需要是位于美国以外的工厂，该工厂生产用于生产FDA管制处方药和OTC药品的API的原料药或原料药中间体。位于波多黎各或其他美国领土的设施不被视为海外设施，因此没有资格参加QMM API试点计划。

All FDA inspection(s) of the manufacturing facility conducted within the 5 years prior to September 15, 2020, received a final classification of “No Action Indicated” or “Voluntary Action Indicated.”

在2020年9月15日之前的5年内对制造厂进行的所有FDA检查，都获得了“无需采取行动”或“自愿采取行动”的最终分类。

Participant agrees to:

参加者需要同意：

a. Permit a third-party contractor to conduct a QMM assessment, whether the assessment is conducted on-site or remotely. FDA will identify an external contractor having the expertise to assess QMM, and FDA staff will join the contractor for the assessment.

允许第三方进行QMM评估，无论评估是在现场进行还是在远程进行。FDA将确定具有评估QMM专业知识的外部合同方，而FDA工作人员会和合同方一起进行评估。

b. Collect and submit metric data to FDA and the contractor by an agreed upon date, prior to the assessment. As part of the scoping discussions for the assessment, FDA will provide the facility with templates and additional details about the data collection.

在评估之前，应在约定的日期之前收集度量数据，并将其提交给FDA和合同方。作为评估范围界定讨论的一部分，FDA将为该设施提供模板，以及有关数据收集的其他详细信息。

c. Be available for consultations with the contractor and FDA prior to and after the assessment, including discussions regarding the participant’s established QMM-related activities and the contractor’s post-assessment recommendations regarding these activities.

在评估之前和之后，可以与合同方和FDA进行磋商，包括与参与者已建立的QMM相关活动的讨论、以及合同方对这些活动的评估后建议。

During this QMM API Pilot Program, the contractor and FDA staff will be available to answer questions and address concerns that arise.

在此QMM API试点计划期间，合同方和FDA工作人员将可以回答问题、并解决出现的问题。

B.申请需要的信息

When submitting a request to participate in the QMM API Pilot Program, include the information below to aid in FDA’s selection and planning. FDA will not consider requests submitted without the following minimal information:

在提交参加QMM API试点计划的申请时，请包括以下信息，以帮助FDA进行选择和规划。没有以下基本信息，FDA将不会考虑提交的申请：

a contact person (name and email);

联系人（姓名和电子邮件）；

facility location;

设施位置；

facility FDA Establishment Identifier and Data Universal Numbering System numbers;

设施的FDA标识号和系统编号；

a brief description of the manufacturing operations conducted at the facility;

该设施生产操作的简要说明；

preferred dates for the assessment;

评估的首选日期；

written confirmation that the facility meets the selection criteria in section II.A, including agreement to items 3a-c;

书面确认设施符合II.A节中的选择标准，包括同意a-c条款；

written confirmation that the facility can handle a visit of up to 10 FDA staff and contractors; and

书面确认：设施最多可以接待10名FDA工作人员和合同方。

a brief description of prior experiences undergoing an assessment related to the maturity of the facility’s quality culture, including the name of the organization that conducted the assessment and date of the assessment.

简要描述与设施质量文化成熟度相关的评估经历，包括进行评估的组织名称和评估日期。

Dated: October 13, 2020.

Lauren K. Roth,

Acting Principal Associate Commissioner for Policy.

日期：2020年10月13日。

劳伦·罗斯（Lauren K. Roth），

FDA 首席政策代理副局长

聚焦FDA/欧盟等全球药监与行业组织

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