FDA发布ICH Q8，Q9，Q10指南新的内部方针

20160616 ECA新闻：FDA发布ICH Q8，Q9，Q10指南新的内部方针  

GMP News
16/06/2016

FDA releases new internal policy on ICH Q8, Q9, Q10 Guidelines

FDA发布ICH Q8，Q9，Q10指南新的内部方针

On May 18, 2016, the US Food and Drug Administration (FDA) released a new policy document (MAPP 5016.1) to clarify how agency staff in the Office of Pharmaceutical Quality (OPQ) should apply ICH Q8, Q9 and Q10 guidelines.

在2016年5月18日，美国FDA发布了新的方针文件（MAPP2016.1）来澄清当局药物质量办公室（OPQ）的人员应如何应用ICH Q8，Q9，Q10指南。

The new policy outlines the responsibilities and procedures FDA expects its staff to adhere to when applying the ICH guidelines:

新的方针列出了FDA期望其员工在适用ICH指南时坚守的职责和程序。

Q8(R2): Pharmaceutical Development, Q9: Quality Risk Management and Q10: Pharmaceutical Quality System.

Q8（R2）：药物研发，Q9：质量风险管理和Q10：药物质量体系

According to FDA, the new policy follows an observed increase in the number of new and supplemental applications for drugs and biologics featuring Quality by Design (QbD) approaches, which are outlined in ICH Q8(R2).

据FDA说，新的方针是随着ICH Q8（R2）中列出的QBD方式研发的药物和生物制品新申报和增补的增长而产生的。

Therefore, "Reviewers should ensure that applications contain at least the minimum information on pharmaceutical development described by ICH Q8(R2) as at a minimum, those aspects of drug substances, excipients, container closure systems and manufacturing processes that are critical to product quality should be determined and control strategies justified," the policy states.

因此，方针中说，“审评人员应确保申报至少包括关于ICH Q8（R2）中列出的药物研发的最少信息，原料药、辅料、容器密闭系统和生产工艺中对药品质量关键的这些方面应进行检测，要论证控制策略。”

Reviewers should check applications to ensure that certain minimal elements described in the Annex of ICH Q8(R2) are included in all applications, namely:

审评人员应检查申报资料，以确保在ICH Q8（R2）中所述的最少特定要素被包括在申报资料中，即：

Quality target product profile (QTPP),
质量目标产品概况（QTPP）
Critical quality attributes (CQAs) of the drug product,
药品关键质量属性（CQA）
CQAs of the drug substance and excipients,
原料药和辅料的CQA
Selection of an appropriate manufacturing process,
选择适当的生产工艺
Control strategy.
控制策略
However, analytical methods are not explicitly mentioned in the document and the introduction of, for example, the Analytical Target profile (ATP) -equivalent to the QTPP- has not yet been established.

但是，在文件和概述里并没有清楚提到分析方法，例如，还没有建立分析目标概况（ATP）--等同于QTPP。

Additionally, FDA says its reviewers should be making sure the applications demonstrate that the manufacturer has enhanced knowledge of the development and manufacturing processes they have identified in their applications. If necessary, quality reviewers should "confer with CMC (chemistry, manufacturing and controls) subject matter experts and members of the extended review team (e.g., medical officer, pharmacology/toxicology reviewer) to establish the relevance of CMC information that supports the drug's safety, efficacy, and performance.

另外，FDA还说他们的审评人员应该确保申报资料证明生产商已经改善了其在申报资料中识别的研发和生产工艺知识。必要时，质量审评人员应“与CMC（研发、生产和检验）专家和扩展审核组（例如，医学官员、药学/毒学审评员）讨论来建立CMC信息相关性，用以支持药物安全性、有效性和性能。”

Additionally more flexible regulatory approaches can be proposed in applications. As described in ICH Q8(R2), manufacturers can justify the use of flexible regulatory approaches in areas where the demonstration of greater understanding of pharmaceutical and manufacturing sciences can create a basis for flexible regulatory approaches. When an application includes information supporting a flexible regulatory approach, the reviewers should determine whether the application "includes sufficient enhanced knowledge that demonstrates the applicant's understanding of material attributes, manufacturing processes, and controls for product quality to support the proposed flexible regulatory approaches."

另外在申报资料中还可以提议更为灵活的法规方法。正如ICH Q8（R2）中所述，生产商可以论证使用灵活的法规方法，证明对药物和生产科学的更多了解可以创建灵活法规方法的基础。如果申报资料包括了支持一个灵活的法规方法的信息，则审评人员应决定是否申报资料“包括足够的强化的知识，可以证明申报人对物料属性、生产工艺和产品质量控制的了解，支持所拟的灵活法规方法。”

FDA gives the following examples of potential flexible regulatory approaches a manufacturer can take:

FDA给出了以下例子，说明生产商可以采取的灵活的法规方法：

Manufacturing process improvements without regulatory notification (e.g., movement within a design space),
无需法规通知即进行生产工艺改进（例如，在设计空间内移动）
Approaches to reduce post-approval submissions through submission of change protocols ("Comparability Protocols"),
通过提交变更方案来减少批准后申报的方法
In-process tests in lieu of end product testing, including real time release testing approaches (PAT, RTRT),
中控测试替代最终产品测试，包括实时放行测试方法（PAT，RTRT）
Mathematical models (e.g., multivariate models) as surrogates for traditional end product testing.
数学模型（例如，多元模型）作为传统最终产品测试的替代
Comparability Protocols together with "established conditions" may be effective tools for the overall product life cycle management. They can also facilitate the management of post-approval CMC changes in a more predictable and efficient manner, as it is the intention of the planned ICH Q12 Guideline "Lifecycle Management". Steps 1 and 2 a/b of ICH Q12 are expected for June 2017.

可比性方案与“已建立的条件”一起可以成为整个产品生命周期管理的有效工具。他们也能促进批准后CMC变更的管理更易预测更为有效，这就是计划中ICH Q12指南“生命周期管理”的目的。该指南已进入第1阶段，预期于2017年6月进入第2a/b阶段。

Risk assessments according to ICH Q9 "are usually the basis for the control strategy and those submitted in the application can justify the proposed flexible regulatory approaches."  However, in order to determine whether a flexible regulatory approach is appropriate, the reviewers should evaluate the risk assessments provided by the manufacturer to support the use of a flexible approach in a "scientific and risk-based" manner.

根据ICH Q9进行的风险管理“一般是控制策略的基础，在申报资料中提交可以论证所拟的灵活的法规方法”。但是，为了决定灵活法规方法是否适当，审评人员应评估由生产商提供的用以支持采用“科学和风险”方法使用灵活方法的风险评估。

Since the manufacturer?s quality system is an important part of ensuring continued product quality (ICH Q10), reviewers should "collaborate with the investigator and compliance officer, as needed, regarding potential risks in the manufacturing process if potential risks are discovered during the course of the review."

由于生产商的质量体系是确保持续产品质量的重要部分（ICH Q10），审评人员应“在必要时结合调查人员和符合性官员对生产工艺潜在风险的意见，看审核期间是否发现潜在风险。”

For further information please see the Manual of Policies and Procedures on Applying ICH Q8(R2), Q9, and Q10 Principles to Chemistry, Manufacturing, and Controls Review.

更多信息，参见官网方针和程序手册。

来源：http://zhuyujiao1972.blog.163.co ... 272016516101751560/