ICH發(fā)布統(tǒng)一的QQQ培訓(xùn)材料實(shí)用教案

1、 ICH, November 2010 DisclaimerThe information within this presentation is based on the ICH Q-IWG members expertise and experience, and represents the views of the ICH Q-IWG members for the purposes of a training workshop.第1頁/共23頁第一頁，共24頁。 ICH, November 2010Outline Workshop Goals and Objectives ICH Q

2、8, Q9 & Q10 How the guidelines are working together throughout the product life cycle Utility of ICH Q8, Q9 & Q10 Key messages Conclusion第2頁/共23頁第二頁，共24頁。 ICH, November 2010Workshop Goals and Objectives This presentation is intended to outline the linkage between Q 8,9 &10 and how the gu

3、idelines are working together This presentation is NOT intended to outline regulatory expectations (assessment and/or inspection) This workshop will: Provide training on the integrated implementation of Q 8, Q9 and Q10 Allow participants to share implementation strategies and experiences Seek partic

4、ipants input and identify implementation issue and concerns第3頁/共23頁第三頁，共24頁。 ICH, November 2010Nov 2005 & Nov 2008November 2005June 2008ICH Q8, Q9 and Q10 High level guidances (not prescriptive) Science and risk-based Encourages systematic approaches Applicable over entire product lifecycle Inte

5、nded to work together to enhance pharmaceutical product quality第4頁/共23頁第四頁，共24頁。 ICH, November 2010Pharmaceutical Development - Q8(R2) Describes science and risk-based approaches for pharmaceutical product and manufacturing process development Introduced concepts of design space and flexible regulat

6、ory approaches Introduced concepts of Quality by Design (QbD) and provided examples of QbD development approaches and design space第5頁/共23頁第五頁，共24頁。 ICH, November 2010Q8(R2) - Example QbD Approach Quality Target Product Profile (QTPP) Determine “potential” critical quality attributes (CQAs)Link raw m

7、aterial attributes and process parameters to CQAs and perform risk assessment Develop a design space (optional and not required) Design and implement a control strategy Manage product lifecycle, including continual improvement第6頁/共23頁第六頁，共24頁。 ICH, November 2010 Quality Risk Management Q9 Describes

8、systematic processes for the assessment, control, communication and review of quality risks Applies over product lifecycle: development, manufacturing and distribution Includes principles, methodologies and examples of tools for quality risk management Assessment of risk to quality should: Be based

9、on scientific knowledge Link to the protection of the patient Extend over the lifecycle of the product第7頁/共23頁第七頁，共24頁。 ICH, November 2010Quality Risk Management Process - Q9ProcessDevelopmentControl StrategyDevelopmentContinual Improvement of the product第8頁/共23頁第八頁，共24頁。 ICH, November 2010Pharmaceu

10、tical Quality System - Q10 Describes key systems that facilitate establishment and maintenance of a state of control for process performance and product quality Facilitates continual improvement Applies to drug substance and drug product throughout product lifecycle Sound pharmaceutical development

11、(Q8R(2) in combination with a robust PQS (Q10) provide opportunities for flexible regulatory approaches. Relevant PQS elements include systems for: Track and trend product quality Maintain and update models as needed Internally verify that process changes are successful第9頁/共23頁第九頁，共24頁。 ICH, Novembe

12、r 2010Pharmaceutical Quality System - Q10第10頁/共23頁第十頁，共24頁。 ICH, November 2010ICH Q8, Q9 and Q10 Working TogetherFormulation Activities: QTPP Definition Pre-Formulation Studies Formulation Screening Optimization & SelectionProcess Development Activities: Process Screening Lab Scale Development S

13、cale-Up StudiesManufacturing Activities: Commercial Scale Manufacturing Batch Release Continual Verification & ImprovementQ8Pharmaceutical DevelopmentQ9Quality Risk ManagementQ10Pharmaceutical Quality Systems第11頁/共23頁第十一頁，共24頁。 ICH, November 2010How can the three guidelines work together The fol

14、lowing four slides (slides 14-17) are intended to show how Q8, Q9, Q10 can work together at different stages of the product lifecycle It is important to note that they are NOT intended to show complete activities at each stage NOR to show the exact timing (stage) for those activities第12頁/共23頁第十二頁，共2

15、4頁。 ICH, November 2010Formulation Development ActivitiesICH Q8(R2) PharmaceuticalDevelopment Related ActivitiesICH Q9 QRMRelated ActivitiesICH Q10 PQSRelated Integrated ActivitiesQuality Target Product Profile (QTPP) Clinical and non-clinical studies on drug substance: bioavailability, PK/PD, and sa

16、fety Informal and/or formal risk assessment to evaluate patient needs and potential medication risks Knowledge Management / Prior Knowledge (relevant information to support the understanding, risk assessment and scope of DOE) - Laboratory note book documentation - Development report - EtcPre-Formula

17、tion Studies Characterization of drug substance (physical properties) Chemical stability of drug substance, degradation and potential formulation interactions Development of analytical tests Determine failure modes and risk factors for drug substance physical and chemical stabilityFormulation Screen

18、ing Excipient compatibility Dissolution method development Screening DOEs Determine failure modes and risk factors for excipient interactionsFormulation Optimization and Selection Excipient and drug substance material property & characterization DOEs for excipient amounts Stability of drug produ

19、ct and storage conditions Develop IVIVC relationships Opportunities for formal risk assessment第13頁/共23頁第十三頁，共24頁。 ICH, November 2010Process Development ActivitiesICH Q8(R2) Pharmaceutical DevelopmentRelated ActivitiesICH Q9 QRM Related ActivitiesICH Q10 PQSRelated Integrated ActivitiesProcess Screen

20、ing Exploration of unit operations Characterization of process intermediates Determine failure modes, risk factors for unit operations and rank risk Batch records and operational guidelines for manufacturing Tech Transfer report Identification and selection of suppliers that meet raw material needsP

21、rocess Development and Optimization (Lab Scale) DOEs for process parameters and interactions with material attributes Development of Design Space Operational ranges for scale- independent parameters understanding of critical process operations Screening risk assessment to determine potential paramet

22、ers impacting product quality (e.g., Ishikawa) Determine critical process steps, process parameters and material attributes (e.g., FMEA) Potential issues of scaleProcess Development and Optimization (Pilot Scale) Pilot to verify lab scale knowledge DOE and modeling effects of scale Development of de

23、sign space Development of on-line measurement technologies Development of control strategy to control risks incl. for scale up第14頁/共23頁第十四頁，共24頁。 ICH, November 2010Technology TransferICH Q8(R2) Pharmaceutical DevelopmentRelated ActivitiesICH Q9 QRMRelated ActivitiesICH Q10 PQSRelated Integrated Acti

24、vities Gain product and process knowledge Knowledge supports transfer between development and manufacturing to achieve product realization Forms the basis for the manufacturing process Improves effectiveness of control strategy Contributes to processes validation and ongoing continual improvement Ad

25、vance understanding through scale- up activities Provide preliminary indication of process performance and successful integration into manufacturing Gain knowledge from transfer and scale up activities to enhance the basis for the control strategy 第15頁/共23頁第十五頁，共24頁。 ICH, November 2010Commercial Man

26、ufacturing ActivitiesICH Q8(R2) Pharmaceutical DevelopmentRelated ActivitiesICH Q9 QRMRelated ActivitiesICH Q10 PQSRelated IntegratedActivitiesCommercial Scale Manufacturing for Drug Product Definition of commercial process design Commercial scale runs to verify process design, with additional sampl

27、ing to verify understanding Implementation of on-line measurement technologies Development of a control strategy for commercial manufacturing, including in- process controls, end-product testing, raw material controls and change control Check procedures in the PQS regarding risk from Process specifi

28、c procedure (e.g., sampling plans, design space and model verification, change control for movement within design space) Process-specific operating procedures (e.g. sampling plans, design space etc.) Documentation to support on-line testing methods Validation to demonstrate process and analytical me

29、thod reproducibility Storage of development reports, risk assessmentsContinual Process Verification and Continual Improvement On-going analysis and trending of process data, (multivariate SPC, etc.) Evaluation of process changes and associated effect on intermediates and products Manage risks of pro

30、cess or material attribute change (including changes within or outside of design space) Review risks in audits/inspections and implement risk-based CAPAs Procedures on process monitoring and action limits Change control procedures including how and when to do risk assessment for process changes and

31、evaluation of the change Maintenance and update of knowledge management第16頁/共23頁第十六頁，共24頁。 ICH, November 2010The Utility of ICH Q8, 9 &10 The implementation of Q8, 9 &10 is valuable for all drug products, pharmaceutical development approaches and regulatory systems New/innovator, marketed/le

32、gacy and generics Simple and complex dosage forms Small molecule and biotech Traditional development and QbD Within and outside ICH regions Good scientific development (Q8) in combination with QRM (Q9) and PQS (Q10) will improve drug quality and efficiency of pharmaceutical manufacturing Quality is

33、important for all drug products throughout product lifecycle (new, legacy and generics)第17頁/共23頁第十七頁，共24頁。 ICH, November 2010Key Messages ICH Q8, Q9 and Q10 are linked together to provide a systematic, modern risk- and science- based approach to pharmaceutical manufacturing and development Comprehen

34、sive implementation of the three guidelines together is essential to achieve ICH Quality Vision Guidelines are applicable over entire product lifecycle Guidelines can be utilized by all stakeholders Industry and regulators Assessors and inspectors are expected to incorporate QRM during regulatory pr

35、ocesses第18頁/共23頁第十八頁，共24頁。 ICH, November 2010Key Messages Traditional development approaches, as outlined in ICH Q8(R2) part I, are acceptable Enhanced approaches (QbD) provide higher assurance of product quality and additional opportunities for manufacturing efficiency and flexibility The use of qu

36、ality risk management process, methodologies and tools (Q9) is beneficial regardless of development or manufacturing approaches used Pharmaceutical Quality Systems (Q10) applies to drug substance and drug product throughout product lifecycle and provide tools to facilitates continual improvement第19頁

37、/共23頁第十九頁，共24頁。 ICH, November 2010Conclusions Workshop materials, plenary presentations, and breakout discussions will provide useful information to facilitate pharmaceutical development and manufacturing, and related regulatory aspects Training materials provide only illustrative examples Training materials are not intended to serve as templates for pharmaceutical development, manufacturing, regulatory assessment or inspection Depending of th