QbD Application in Japan: PMDA Perspective

Transcription

1 CMC Strategy Forum Japan 2013 Hotel Okura, Tokyo, Japan, December 9 10, 2013 QbD Application in Japan: PMDA Perspective Yasuhiro Kishioka, PhD. Reviewer Office of Cellular and Tissue based Products Pharmaceuticals and Medical Devices Agency Disclaimer The views and opinions expressed in this presentation are those of the presenter and should not necessarily represent the views and opinions of the PMDA.

2 Take home messages The application of Quality by Design (QbD) * is for better quality assurance. *: defined in ICH Q8 (R2) The use of QbD will provide a better communication between regulators and industries. ( hopefully) Description in application form (AF) is one of the most important topics. However, AF (with modification(s) (if necessary)) would be a good regulatory system to adopt a QbD concept. 2

3 Outline 1. Introduction 2. QbD Application of Biologics in Japan 3. Future Perspectives 3

4 Guideline Q8(R2): Pharmaceutical Development Q9: Quality Risk Management Q10: Pharmaceutical Quality System Q11: Development and Manufacture of Drug Substances (Chemical/Biotechnological entities) ICH Q IWG Points to Consider (R2) Q IWG on Q8, 9, 10 Q&A s (R4) 4

5 Quality by Design (Q8(R2)) Quality cannot be tested into products; i.e., quality should be built in by design. A systematic approach to development begins with predefined objectives and emphasizes product and process understanding and process control based on sound science and quality risk management. 5

6 Example QbD Approach Product Profile Define Quality Target Product Profile (QTPP) CQAs Determine potential critical quality attributes (CQAs) Risk Assessment Design Space Link raw material attributes and process parameters to CQAs and perform risk assessment Develop a design space (optional and not required) Control Strategy Design and implement a control strategy Continual Improvement Manage product lifecycle, incl. continual improvement Modified from programme for q8q9q10/presentations.html 6

7 Control Strategy (Q10) A planned set of controls, derived from current product and process understanding that ensures 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. 7

8 Critical Quality Attribute (CQA) A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. (Q8(R2)) Quality Attribute criticality is primarily based upon severity of harm and does not change as a result of risk management. (Q IWG PtCs (R2)) 8

9 Critical Process Parameter (CPP) A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (Q8(R2)) Process Parameter criticality is linked to the parameter s effect on any critical quality attribute. It is based on the probability of occurrence and detectability and therefore can change as a result of risk management. (Q IWG PtCs (R2)) 9

10 Critical Process Parameter (CPP) (Cont.) The criticality of a parameter is linked to the risk of the parameter s effect on a CQA. Although the risk associated with a parameter can be reduced by implementing a control strategy that changes the probability of occurrence and detectability as a result of risk management, the parameter remains a CPP. Criticality can evolve long term (during life cycle) when more knowledge is gained. Modified from Dr. Mats Welin s slide 2013 APEC Harmonization Center Biotherapeutics Workshop, September 25 27, 2013 Critical 10

11 Design Space (Q8(R2)) The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval 11

12 QbD Assessment Project (in English)

13 QbD Assessment Project Team Chemical WG Biotech WG Reviewer Inspector Reviewer Reviewer Inspector Reviewer Reviewer Inspector Reviewer Inspector Reviewer 13

14 Outline 1. Introduction 2. QbD Application of Biologics in Japan 3. Future Perspectives 14

15 Pertuzumab application The applicant has applied QbD approach to develop the product, and design space was proposed in the manufacturing process. 15

16 Review points Identification of CQAs Criticality should be primarily based upon severity of harm. Classification of Process Parameters Ranges tested/investigated were discussed. Some non CPPs (classified by the applicant ) should be described in AF. Establishment of Design Space (DS) DS should be defined not only by CPPs * but also by some non CPPs *. (*:classified by the applicant ) Design of Control Strategy Although potential residual risks remain, they will be managed by the modified control strategy. 16

17 Outline 1. Introduction 2. QbD Application of Biologics in Japan 3. Future Perspectives 17

18 Issues We Need to Discuss Identification of CQAs Classification of Process Parameters Establishment of Design Space (DS) Application of QbD concept to Analytical Methods Description in Application Form 16

19 Quality Review/Regulation in Japan Approval Matters Major review document Module 1 Application form (in Japanese) Specification Shelf life Mfg. process Mfg. site Etc. Module 2 (QOS) (in Japanese) 2.3.S.1 General Information 2.3.S.2 Manufacture 2.3.S.3 Characterisation 2.3.S.4 Control of Drug Substance 2.3.S.5 Reference Standards or Materials 2.3.S.6 Container Closure System 2.3.S.7 Stability Module 3 (in Japanese or English) 3.2.S.1 General Information 3.2.S.2 Manufacture 3.2.S.3 Characterisation 3.2.S.4 Control of Drug Substance 3.2.S.5 Reference Standards or Materials 3.2.S.6 Container Closure System 3.2.S.7 Stability Raw data 19

20 Quality Review/Regulation in Japan (Cont.) <Quality information> High Application Form Module 2 (QOS) Specification Mfg. process etc. Mfg. process Process characterization etc. Matters for Partial Change Application (PCA) Matters for Minor Change Notification (MCN) Impact on Quality Low Module 3 Mfg. process Process characterization etc. Regulatory Flexibility Figure Inspired by Dr. Shikano s slide 19

21 Quality Review/Regulation in Japan (Cont.) <Quality information> High Application Form Module 2 (QOS) Specification Mfg. process etc. Mfg. process Process characterization etc. Matters for Partial Change Application (PCA) Matters for Partial Change Application (PCA) Matters for Minor Change Notification (MCN) Matters for Minor Change Notification (MCN) Impact on Quality Low Module 3 Mfg. process Process characterization etc. Regulatory Flexibility Figure Inspired by Dr. Shikano s slide 19

22 Quality Review/Regulation in Japan (Cont.) <Quality information> High Application Form Module 2 (QOS) Specification Mfg. process etc. Mfg. process Process characterization etc. PCA MCN To ensure the quality of the product To clarify/understand mfg. process Impact on Quality Low Module 3 Mfg. process Process characterization etc. Regulatory Flexibility Figure Inspired by Dr. Shikano s slide 20

23 Take home messages The application of Quality by Design (QbD) * is for better quality assurance. *: defined in ICH Q8 (R2) The use of QbD will provide a better communication between regulators and industries. ( hopefully) Description in application form (AF) is one of the most important topics. However, AF (with modification(s) (if necessary)) would be a good regulatory system to adopt a QbD concept. 23

24 Thank you for your attention! Yasuhiro Kishioka, PhD. Office of Cellular and Tissue based Products Pharmaceuticals and Medical Devices Agency Acknowledgements (in Japanese) (in English) Colleagues in the Office of Cellular and Tissue based Products QbD Assessment Project Members