FDA 发布 ICH Q8、Q9 和 Q10 问答文件（R5）正式版
FDA Final: Q8, Q9, and Q10 Questions and Answers (R5)
FDA 发布 ICH Q8、Q9 和 Q10 问答文件（R5）正式版，修订并更新 2011 年 11 月的 R4 版本。文件由 ICH 质量专家工作组制定，2024 年 10 月获 ICH 大会 Step 4 通过，内容涵盖设计空间、实时放行检测、控制策略、药品质量体系、知识管理及软件解决方案等问答。FDA 说明该指南为不具约束力的建议，除非引用了具体法规或法定要求。
文件以问答形式汇总ICH Q8、Q9与Q10实施中的具体问题，可帮助读者按设计空间、控制策略与知识管理等章节定位要点。
FDA guidance: Q8, Q9, and Q10 Questions and Answers (R5)
Status: Final. Guidance contains nonbinding recommendations unless applicable laws or regulations are cited.
FDA directory issue date: 2026-05-29 (MM/DD/YYYY in source).
Directory modification time is retained in source metadata; it is not a new issue date or proof that the PDF was revised.
Products: Drugs
Topics: ICH-Quality
Issuing offices: Center for Drug Evaluation and ResearchCenter for Biologics Evaluation and Research
Document type: Guidance Document
Official detail page: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q8-q9-and-q10-questions-and-answers-r5
Scope: public guidance PDFs from FDA's whole-agency directory, explicitly tagged Drugs/Biologics and manufacturing/quality/ICH-Quality. The complete PDF follows.
PDF 文字版；图形和原始排版请参阅官方 PDF。
第 1 页
Q8, Q9, and Q10
Questions and Answers
(R5)
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
May 2026
ICH-Quality
第 2 页
Q8, Q9, and Q10
Questions and Answers
(R5)
Additional copies are available from:
Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
Phone: 855-543-3784 or 301-796-3400
Email: [email protected]
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs
and/or
Office of Communication, Outreach, and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
Phone: 800-835-4709 or 240-402-8010; Email: [email protected]
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
May 2026
ICH-Quality
第 3 页
Contains Nonbinding Recommendations
FOREWORD
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use (ICH) has the mission of achieving greater regulatory harmonization worldwide to
ensure that safe, effective, and high-quality medicines are developed, registered, and maintained
in the most resource-efficient manner. By harmonizing the regulatory expectations in regions
around the world, ICH guidelines have substantially reduced duplicative clinical studies,
prevented unnecessary animal studies, standardized safety reporting and marketing application
submissions, and contributed to many other improvements in the quality of global drug
development and manufacturing and the products available to patients.
ICH is a consensus-driven process that involves technical experts from regulatory
authorities and industry parties in detailed technical and science-based harmonization
work that results in the development of ICH guidelines. The commitment to consistent
adoption of these consensus-based guidelines by regulators around the globe is critical to
realizing the benefits of safe, effective, and high-quality medicines for patients as well as
for industry. As a Founding Regulatory Member of ICH, the Food and Drug
Administration (FDA) plays a major role in the development of each of the ICH
guidelines, which FDA then adopts and issues as guidance to industry.
第 4 页
Contains Nonbinding Recommendations
TABLE OF CONTENTS
(PREFACE)............................................................................................................................................. 1
I. INTRODUCTION (1)..................................................................................................................... 2
A. For General Clarification (1.1) .............................................................................................. 2
II. QUALITY BY DESIGN TOPICS (2) ........................................................................................... 3
A. Design Space (2.1) ................................................................................................................... 3
B. Real Time Release Testing (RTRT) (2.2) .............................................................................. 5
C. Control Strategy (2.3) ............................................................................................................. 7
III. PHARMACEUTICAL QUALITY SYSTEM (3)......................................................................... 9
IV. ICH QUALITY GUIDELINES’ IMPACT ON GMP INSPECTION PRACTICES (4) ........ 11
V. KNOWLEDGE MANAGEMENT (5) ........................................................................................ 12
VI. SOFTWARE SOLUTIONS (6) ................................................................................................... 14
REFERENCES ..................................................................................................................................... 15
第 5 页
Contains Nonbinding Recommendations
Q8, Q9, and Q10
Questions and Answers (R5)
Guidance for Industry 1
This guidance represents 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 office responsible for this guidance as listed on the title page.
(PREFACE)
This International Council for Harmonisation (ICH) guidance for industry Q8, Q9, and Q10 Questions and Answers (R5) (ICH Q8,
Q9, and Q10 (R5)) provides answers to a number of questions which are relevant to the implementation of the ICH guidances for
industry Q8(R2) Pharmaceutical Development (ICH Q8(R2)) (November 2009), Q9(R1) Quality Risk Management (ICH Q9(R1))
(May 2023), and Q10 Pharmaceutical Quality System (ICH Q10) (April 2009). 2 This guidance revises and updates the November
2011 ICH guidance titled Q8, Q9, and Q10 Questions and Answers (R4).
In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s
current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or recommended but not required.
1
This guidance was developed within the Expert Working Group Quality of the International Council for Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH) and has been subject to consultation by the regulatory parties, in accordance with the ICH process. This
document has been endorsed by the ICH Assembly at Step 4 of the ICH process, October 2024. At Step 4 of the process, the final draft is recommended for
adoption to the regulatory bodies of the ICH regions. Submit comments to Docket No. FDA-2017-D-6821 (available at
https://www.regulations.gov/docket?D=FDA-2017-D-6821). See the instructions in that docket for submitting comments on this and other Level 2 guidances.
2
We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA guidance web page at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
1
第 6 页
Contains Nonbinding Recommendations
I. INTRODUCTION (1) 3
A. For General Clarification (1.1)
Table 1. Q&A for Section I (1) of ICH Q8, Q9, and Q10 (R5)
Date of Questions Answers
Approval
1 June Is the minimal approach accepted by regulators? Yes. The minimal approach as defined in ICH Q8(R2) (sometime also called
2009 ‘baseline’ or ‘traditional’ approach) is the expectation which is to be achieved
for a fully acceptable submission. However, the ‘enhanced’ approach as
described in ICH Q8(R2) is encouraged (Ref. ICH Q8(R2), Appendix 1).
2 Oct. What is an appropriate approach for process The objectives of process validation are unchanged when using ICH Q8, Q9
2009 validation using ICH Q8, Q9 and Q10? and Q10. The main objective of process validation remains that a process
design yields a product meeting its pre-defined quality criteria. ICH Q8, Q9
and Q10 provide a structured way to define product critical quality attributes,
design space, the manufacturing process, and the control strategy. This
information can be used to identify the type and focus of studies to be
performed prior to and on initial commercial production batch. As an
alternative to the traditional process validation, continuous process
verification (see definition in ICH Q8(R2) glossary) can be utilized in process
validation protocols for the initial commercial production and for
manufacturing process changes for the continual improvement throughout the
remainder of the product lifecycle.
3 Oct. How can information from quality risk Like the product itself, process validation also has a lifecycle (process design,
2024 management and continuous process verification process qualification, and ongoing process verification). A risk assessment
provide for a robust continual improvement conducted prior to initial commercial validation batches can highlight the
approach under IH Q8, Q9 and Q10? areas where particular focus and data are needed to demonstrate a high level
of assurance of commercial process robustness. Continual monitoring (e.g.,
via Continuous Process Verification) can further demonstrate the actual level
of assurance of process consistency and provide the basis for continual
improvement of the product. Quality Risk Management methodologies of
ICH Q9(R1) can be applied throughout the product lifecycle to maintain a
state of process control.
3
The numbers in parentheses reflect the organizational breakdown of the document endorsed by the ICH Assembly at Step 4 of the ICH process, October 2024.
2
第 7 页
Contains Nonbinding Recommendations
II. QUALITY BY DESIGN TOPICS (2)
Table 2. Q&A for Section II (2) of ICH Q8, Q9, and Q10 (R5)
Date of Questions Answers
Approval
1 Oct. Is it always necessary to have a Design Space Under Quality by Design, establishing a design space or using RTRT is not necessarily
2024 (DS) or Real Time Release Testing (RTRT) to expected (see ICH Q8(R2)).
implement QbD?
A. Design Space (2.1)
1 Apr. Is it necessary to study multivariate interactions No, the applicant will need to justify the choice of material attributes and parameters for
2009 of all parameters to develop a design space? multivariate experimentation based on risk assessment and desired operational
flexibility.
2 Oct. Can a design space be applicable to scale-up? Yes, when appropriately justified (additional details see ICH Q8(R2), Section II.D.4
2024 (2.4.4), “Relationship of Design Space to Scale and Equipment”).
3 Oct. Can a design space be applicable to a site Yes, it is possible to justify a site change using a site independent design space based on
2024 change? a demonstrated understanding of the robustness of the process and an in-depth
consideration of site-specific factors, e.g., materials, equipment, personnel, utilities,
manufacturing environment, and equipment. There are region-specific regulatory
requirements associated with site changes that need to be followed.
4 Apr. Can a design space be developed for single Yes, it is possible to develop a design space for single unit operations or across a series
2009 and/or multiple-unit operations? of unit operations (see ICH Q8(R2), Section II.D.3 (2.4.3), “Unit Operation Design
Space(s)”).
5 Oct. Is it possible to develop a design space for Yes, it is possible. Manufacturing data and process knowledge can be used to support a
2024 existing products? design space for existing products. Relevant information should be utilized from e.g.,
commercial scale manufacturing, raw materials, process improvement, CAPAs,
development data, and relevant knowledge from risk review.
For manufacturing operations run under narrow operational ranges in fixed equipment,
an expanded region of operation and an understanding of multi-parameter
3
第 8 页
Contains Nonbinding Recommendations
interactions may not be achievable from existing manufacturing data alone and
additional studies may be needed to develop a design space. Sufficient knowledge
should be demonstrated, and the design space should be supported experimentally to
investigate interactions and establish parameter/attribute ranges.
6 Apr. Is there a regulatory expectation to develop a No, development of a design space for existing products is not necessary unless the
2009 design space for an existing product? applicant has a specific need and desires to use a design space to achieve a higher
degree of product and process understanding. This may increase manufacturing
flexibility and/or robustness.
7 Jun. Can a design space be applicable to formulation? Yes, it may be possible to develop formulation (not component but rather composition)
2009 design space consisting of the ranges of excipient amount and its physicochemical
properties (e.g., particle size distribution, substitution degree of polymer) based on an
enhanced knowledge over a wider range of material attributes. The applicant should
justify the rationale for establishing the design space with respect to quality attributes
such as bioequivalence, stability, manufacturing robustness, etc. Formulation
adjustment within the design space depending on material attributes does not need a
submission in a regulatory post approval change.
8 Jun. Does a set of proven acceptable ranges alone No, a combination of proven acceptable ranges (PARs) developed from univariate
2009 constitute a design space? experimentation does not constitute a design space (see ICH Q8(R2), Section II.D.5
(2.4.5), “Design Space Versus Proven Acceptable Ranges”). Proven acceptable ranges
from only univariate experimentation may lack an understanding of interactions
between the process parameters and/or material attributes. However, proven acceptable
ranges continue to be acceptable from the regulatory perspective but are not considered
a design space (see ICH Q8(R2), Section II.D.5 (2.4.5), “Design Space Versus Proven
Acceptable Ranges”). The applicant may elect to use proven acceptable ranges or
design space for different aspects of the manufacturing process.
9 Oct. Should the outer limits of the Design Space be No, there is no need to run the process qualification batches at the outer limits of the
2024 evaluated during process validation studies at the design space during process validation studies at commercial scale. The design space
commercial scale? must be sufficiently explored earlier during development studies (for scale up, see also
page 3, Section II.A (2.1), “Design Space Question 2”; for life cycle approach see page
2, Section A (1.1), “For General Clarification” to Question 3).
4
第 9 页
Contains Nonbinding Recommendations
B. Real Time Release Testing (RTRT) (2.2)
Date of Questions Answers
Approval
1 Oct. How is batch release affected by employing Batch release is the final decision to release the product to the market regardless of
2024 RTRT? whether RTRT or end product testing is employed. End product testing involves
performance of specific analytical procedures on a defined sample size of the final
product after completion of all processing for a given batch of that product. Results of
RTRT are handled in the same manner as end product testing results in the batch release
decision. Batch release involves an independent review of batch conformance to
predefined criteria through the review of testing results and manufacturing records,
together with an effective quality system that ensures GM P compliance, regardless of
which approach is used.
2 Apr. Does RTRT mean elimination of end product RTRT does not necessarily eliminate all end product testing. For example, an applicant
2009 testing? may propose RTRT for some attributes only or not all. If all CQAs (relevant for
RTRT) are assured by in-process monitoring of parameters and/or testing of materials,
then end product testing might not be needed for batch release. Some product testing
will be expected for certain regulatory processes such as stability studies or regional
requirements.
3 Apr. Is a product specification still necessary in the Yes, product specifications (see the ICH guidelines Q6A Specifications: Test
2009 case of RTRT? Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances (finalized October 6, 1999) and Q6B Specifications:
Test Procedures and Acceptance Criteria for Biotechnological/Biological Products)
(finalized March 10, 1999) still need to be established and met, when tested.
4 Oct. When using RTRT, is there a need for stability Even where RTRT is applied, a stability monitoring protocol that uses stability-
2024 test methods? indicating methods is required for all products regardless of the means of release testing
(see the ICH guidances for industry Q1A(R2) Stability Testing of New Drug Substances
and Products (November 2003) and Q5C Quality of Biotechnological Products:
Stability Testing of Biotechnological/Biological Products (July 1996)).
5
第 10 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
5 Oct. What is the relationship between Control Strategy RTRT, if utilized, is an element of the Control Strategy and may enable appropriate in-
2024 and RTRT? process testing (in-line, on-line, at-line) of quality attributes rather than testing on the
end product. This use of RTRT recognizes that under specific circumstances an
appropriate combination of process controls (critical process parameters) together with
pre-defined material attributes may provide greater assurance of product quality than
end product testing and as such be an integral part of the control strategy.
6 Oct. Do traditional sampling approaches apply to No, traditionally sampling plans for in-process and end-product testing involve a
2024 RTRT? discrete sample size that represents the minimal sampling expectations. Generally, the
use of RTRT will include more extensive on-line/in-line measurements. A
scientifically sound sampling approach should be developed, justified, and
implemented.
7 Oct. If RTRT results fail or trending toward failure, No, in principle the RTRT results should be routinely used for the batch release
2024 can end-product testing be used to release the decisions and not be substituted by end-product testing. Any failure should be
batch? investigated, and trending should be followed up appropriately. However, batch release
decisions will need to be made based on the results of the investigations. The batch
release decision needs to comply with the content of the marketing authorization and
GMP compliance.
8 Oct. What is the relationship between in-process In-process testing includes any testing that occurs during the manufacturing process of
2024 testing and RTRT? drug substance and/or finished product. RTRT includes those in-process tests that
directly impact the decision for batch release through evaluation of Critical Quality
Attributes.
9 Jun. What is the difference between ‘real time release’ The definition of RTRT in ICH Q8(R2) is “the ability to evaluate and ensure the
2009 and ‘RTRT’? acceptable quality of in- process and/or final product based on process data, which
typically includes a valid combination of measured material attributes and process
controls.” The term ‘Real time release’ in the ICH Q8(R2), Step 2 document was
revised to RTRT in the final ICH Q8(R2) Part II document to fit the definition more
accurately and thus avoid confusion with batch release.
10 Oct. Can a surrogate measurement be used for RTRT? Yes, RTRT can be based on measurement of surrogate (e.g., process parameter,
2024 material attribute) that has been demonstrated to correlate with an in-process or end-
product specification (see ICH Q8(R2); Section II.E (2.5)).
6
第 11 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
11 Oct. What is the relationship between RTRT and Parametric release is one type of RTRT. Parametric release is based on process data
2024 Parametric Release? (e.g., temperature, pressure, time for terminal sterilization, physicochemical indicator)
rather than the testing of material and/or a sample for a specific attribute.
C. Control Strategy (2.3)
Refer to the definition of control strategy provided in the ICH Q10 glossary definition:
A planned set of controls, derived from current product and process understanding that assures process performance and product quality.
The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and
equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of
monitoring and control.
Date of Questions Answers
Approval
1 Apr. What is the difference in a control strategy for Control strategies are expected irrespective of the development approach. Control
2009 products developed using the minimal approach strategy includes different types of control proposed by the applicant to assure
versus ‘quality-by-design’ approach? product quality (see ICH Q10, Section III.B.1 (3.2.1), “Process Performance and
Product Quality Monitoring System”), such as in-process testing and end-product
testing. For products developed following the minimal approach, the control strategy
is usually derived empirically and typically relies more on discrete sampling and end
product testing. Under QbD, the control strategy is derived using a systematic
science and risk-based approach. Testing, monitoring, or controlling is often shifted
earlier into the process and conducted in-line, on-line or at-line testing.
2 Apr. Are GMP requirements different for batch release No, the same GMP requirements apply for batch release under minimal and QbD
2009 under QbD? approaches.
3 Apr. What is the relationship between a Design Space A control strategy is required for all products. If a Design Space is developed and
2009 and a Control Strategy? approved, the Control Strategy (see ICH Q8(R2), Section II.D (2.4), “Design Space”)
provides the mechanism to ensure that the manufacturing process is maintained
within the boundaries described by the Design Space.
7
第 12 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
4 Jun. What approaches can be taken in the event of on- The control strategy provided in the application should include a proposal for use of
2009 line/in- line/at-line testing or monitoring alternative testing or monitoring approaches in cases of equipment failure. The
equipment breakdown? alternative approach could involve use of end product testing or other options, while
maintaining an acceptable level of quality. Testing or monitoring equipment
breakdown needs to be managed in the context of a deviation under the Quality
System and can be covered by GMP inspection.
5 Oct. Are product specifications different for minimal In principle, no, the same product specifications are needed for minimal and QbD
2009 versus QbD approaches? approaches. For a QbD approach, the control strategy may allow achieving the end
product specifications via RTRT approaches (see ICH Q8(R2), Appendix 1).
Product must meet specifications when tested.
8
第 13 页
Contains Nonbinding Recommendations
III. PHARMACEUTICAL QUALITY SYSTEM (3)
Table 3. Q&A for Section III (3) of ICH Q8, Q9, and Q10 (R5)
Date of Questions Answers
Approval
1 Oct. What are the benefits of implementing a The benefits are:
2024 Pharmaceutical Quality System (in accordance
• A robust manufacturing process, through facilitation of continual improvement
with ICH Q10)?
through science and risk-based post approval change processes;
• Consistency in the global pharmaceutical environment across regions;
• Transparency of systems, processes, organizational and management
responsibility within, and across, companies (e.g., contract organizations);
• Clearer understanding of the application of the Pharmaceutical Quality System
throughout product lifecycle;
• Further reduced risk of product failure and incidence of complaints and recalls,
thereby providing greater assurance of pharmaceutical product consistency and
availability (supply) to the patient;
• Better process performance, supported by effective risk reviews;
• Opportunities to increase understanding between industry and regulators and
more optimal use of industry and regulatory resources. Enhanced manufacturers
and regulators’ confidence in product quality;
• Greater assurance of compliance with GMP, which builds confidence in the
regulators, and which may result in shorter inspections.
• Knowledge-driven and objective risk assessments which help achieve science-and
risk-based control strategies, and which lead to effective risk-based decisions as
well as reduced product availability risks relating to quality/manufacturing issues.
9
第 14 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
2 Apr. How does a company demonstrate implementation When implemented, a company will demonstrate the use of an effective PQS through
2009 of PQS in accordance with ICH Q10? its documentation (e.g., policies, standards), its processes, its training/qualification, its
management, its continual improvement efforts, and its performance against pre-
defined Key Performance Indicators (see ICH Q10 glossary on ‘Performance
indicator’). A mechanism should be established to demonstrate at a site how the PQS
operates across the product lifecycle, in an easily understandable way for
management, staff and regulatory inspectors, e.g., a quality manual, documentation,
flowcharts, procedures. Companies can implement a program in which the PQS is
routinely audited in-house (i.e., internal audit program) to ensure that the system is
functioning at a high level.
3 Oct. Is it necessary to describe the PQS in a regulatory No, however relevant elements of the PQS, such as quality monitoring system,
2024 submission? change management, and deviation management may be referenced as part of the
control strategy as supporting information.
4 Oct. Is there certification that the PQS is in accordance No. There is no specific ICH Q10 certification program.
2024 with ICH Q10?
5 Apr. How should the implementation of the design Inspection should verify/assess that manufacturing operations are appropriately
2009 space be evaluated during inspection of the carried out within the Design Space. The inspector in collaboration with the assessor,
manufacturing site? where appropriate, should also verify successful manufacturing operations under the
Design Space and that movement within the Design Space is managed within the
company’s change system (see ICH Q10, Section III.B (3.2), Table III).
6 Apr. What should be done if manufacturing operations This should be handled as a deviation under GMP. For example, unplanned ‘one-off’
2009 run inadvertently outside of the Design Space? excursions occurring as a result of unexpected events, such as operator error or
equipment failure, would be investigated, documented, and dealt with as a deviation
in the usual way. The results of the investigation may contribute to the process of
knowledge, preventive actions, and continual improvement of the product.
10
第 15 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
7 Oct. What information and documentation of the Pharmaceutical development information (e.g., supporting information on design
2024 development studies should be available at a space, chemometric model, outputs of quality risk management activities) is available
manufacturing site? at the development site. Pharmaceutical development information which is useful to
ensure the understanding of the basis for the manufacturing process and control
strategy, including the rationale for selection of critical process parameters and
critical quality attributes should be available at the manufacturing site.
Scientific collaboration and knowledge sharing between pharmaceutical development
and manufacturing are essential to ensure the successful transfer to production.
8 Jun. Can process parameters be adjusted throughout Process parameters are studied and selected during pharmaceutical development and
2009 the product lifecycle? monitored during commercial manufacturing. Knowledge gained could be utilized
for adjustment of the parameters as part of continual improvement of the process
throughout the lifecycle of the drug product (see ICH Q10, Section III (3),
“Management Responsibility”).
IV. ICH QUALITY GUIDELINES’ IMPACT ON GMP INSPECTION PRACTICES (4)
Table 4. Q&A for Section IV (4) of ICH Q8, Q9, and Q10 (R5)
Date of Questions Answers
Approval
1 Oct. How do product-related inspections differ in an In the case of product-related inspection (in particular pre-authorization) depending
2024 ICH Q8, Q9, and Q10 environment? on the complexity of the product and/or process, there may be a need for greater
collaboration between inspectors and assessors, for example, for the assessment of
development data. The inspection would normally occur at the proposed commercial
manufacturing site and there may be greater focus on enhanced process understanding
and understanding relationships, e.g., Critical Quality Attribute (CQAs), Critical
Process Parameters (CPPs). It may also extend into the application and
implementation of quality risk management principles, as supported by the
Pharmaceutical Quality System (PQS).
11
第 16 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
2 Oct. How do system-related inspections differ in an Such inspections have greater focus (but not only) on how the PQS facilitates the use
2024 ICH Q8, Q9 and Q10 environment? of e.g., Quality Risk Management methods, implementation of design space and
change management (see ICH Q10).
3 Oct. How is control strategy approved in the Elements of the control strategy submitted in the application are reviewed and
2024 application and evaluated during inspection? approved by the regulatory agency. However, additional elements are subject to
inspection (as described in ICH Q10).
V. KNOWLEDGE MANAGEMENT (5)
Table 5. Q&A for Section V (5) of ICH Q8, Q9, and Q10 (R5)
Date of Questions Answers
Approval
1 Oct. How has the implementation of ICH Q8, Q9, and ICH Q10 defines knowledge management as “systematic approach to acquiring,
2024 Q10 changed the significance and use of knowledge analyzing, storing, and disseminating information related to products,
management? manufacturing processes and components.” Knowledge Management is not a new
concept. It is always important regardless of the development approach. ICH Q10
highlights knowledge management because it is expected that more complex
information generated by appropriate approaches (e.g., QbD, PAT, real-time data
generation, and control monitoring systems) need to be captured, managed and
shared during product life cycle. In conjunction with Quality Risk Management,
Knowledge Management can facilitate the use of concepts such as prior knowledge
(including from other similar products), development of design space, control
strategy, technology transfer, and continual improvement across the product life
cycle.
2 April Does ICH Q10 suggest an ideal way to manage No. ICH Q10 provides a framework and does not prescribe how to implement
2009 knowledge? knowledge management. Each company decides how to manage knowledge,
including the depth and extent of information assessment based on their specific
needs.
12
第 17 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
3 Oct. What are examples of sources of information for Some examples of knowledge sources are:
202 Knowledge Management? • Prior knowledge based on experience obtained from similar processes (internal
knowledge, industry, scientific and technical publications) and published
information (external knowledge: literature and peer-reviewed publications);
• Pharmaceutical development studies;
• Mechanism of action;
• Structure/function relationships;
• Technology transfer activities;
• Process validation studies;
• Manufacturing experience e.g.:
- Internal and vendor audits;
- Raw material testing data;
• Innovation;
• Continual improvement;
• Change management activities;
• Stability reports;
• Product Quality Reviews/Annual Product Reviews;
• Complaint Reports;
• Adverse event reports (Patient safety);
• Deviation Reports, Recall Information;
• Technical investigations and/or CAPA reports;
• Suppliers and Contractors;
• Product history and /or manufacturing history;
• Ongoing manufacturing processes information (e.g., trends);
• Risk assessments and other quality risk management activities.
Information from the above can be sourced and shared across a site or company,
between companies and suppliers/contractors, products and across different
disciplines (e.g., development, manufacturing, engineering, quality units).
13
第 18 页
Contains Nonbinding Recommendations
Date of Questions Answers
Approval
4 Apr. Is a specific dedicated computerized information No, but such computerized information management systems can be invaluable in
2009 management system required for the capturing, managing, assessing, and sharing complex data and information.
implementation of knowledge management with
respect to ICH Q8, Q9 and Q10?
5 Oct. Do regulatory agencies expect to see a formal No. There is no regulatory requirement for a formal knowledge management
2024 knowledge management approach during system. However, it is expected that knowledge from different processes and
inspections? systems is appropriately utilized.
Note: ‘formal’ in this context means a structured approach using a recognized
methodology or (IT-) tool, executing and documenting something in a transparent
and detailed manner.
VI. SOFTWARE SOLUTIONS (6)
Table 6. Q&A for Section VI (6) of ICH Q8, Q9, and Q10 (R5)
Date of Questions Answers
Approval
1 Oct. Is it necessary for a pharmaceutical firm to purchase No. ICH has not endorsed any commercial products and does not intend to do so.
2024 products that are marketed as ‘ICH compliant ICH is not a regulatory agency with reviewing authority and thus does not have a
solutions’ or ICH Q8, Q9, and Q10 Implementation role in determining or defining ‘ICH compliance’ for any commercial products. If
software, etc.to achieve a successful considering such products, firms will need to carry out their own evaluation of these
implementation of these ICH guidances within their products relative to their business needs. Computer system validation studies
companies? should be performed by companies to evaluate the reliability of potential software.
14
第 19 页
Contains Nonbinding Recommendations
REFERENCES
The following references are available on the Search for FDA Guidance Documents web page
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. We update
guidances periodically. To make sure you have the most recent version of a guidance, check
the FDA Drugs guidance web page.
ICH Q8(R2) Pharmaceutical Development (November 2009)
Part I: Pharmaceutical Development’
Part II: Pharmaceutical Development (Annex)
ICH Q9(R1) Quality Risk Management (May 2023)
ICH Q10 Pharmaceutical Quality Systems (April 2009)
15
来源：FDA 全域目录：药品／生物制品制造质量指南 · fda.gov