Quality by design.. ppt for RA (1ST SEM

UNIT 5 RA 1ST SEM

1. Quality by design Prepared by: Charmi Shah ( 2308212170009) M. pharm 1 st sem Guided by: Dr. Zanza Patel Assistant professor of Parul Institute of pharmacy FACULTY OF PHARMACY PARUL INSTITUTE OF PHARMACY LIMDA, VADODARA

2. Content Introduction Aim and Goals of QbD Elements of Pharmaceutical Development Regulatory Need Case Study on QbD References 2

3. Introduction [1] Pharmaceutical QbD is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and control, based on sound science and quality risk management. Quality by design is an approach that aims to ensure the quality of medicines by employing statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines. 3

4. Background [2] Quality by design (QbD) is a concept first developed by the quality pioneer Dr. Joseph M. Juran. Dr. Juran believed that quality should be designed into a product, and that most quality crises and problems relate to the way in which a product was designed in the first place. 4

5. QbD follows ICH guidelines: 5

6. Aim and Goals of QbD [3] A more systematic approach to development (also defined as quality by design) can include, incorporation of prior knowledge, use of quality risk management, and use of knowledge management throughout the lifecycle. To increase process capability and reduce product variability and defects by enhancing product and process design, understanding, and control. To increase product development and manufacturing efficiencies. To enhance root cause analysis and post approval change management. 6

7. Comparison between Traditional and Developed approach 7

8. Elements of Pharmaceutical Development Quality Target Product Profile (QTPP) Critical Quality Attribute (CQA) Risk Assessment Design Space Control Strategy Product Lifecycle Management and Continual Improvement 8

9. Quality Target Product Profile (QTPP) QTPP is a prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account the safety and efficacy of the drug product. Considerations in the QTPP could include: R oute of administration, dosage form, and delivery system(s). Dosage strength(s) and Container closure system. Therapeutic moiety release or delivery and attributes affecting pharmacokinetic characteristics (dissolution) appropriate to the drug product dosage form being developed. Drug product quality criteria ( e.g. , sterility, purity, stability, and drug release) appropriate for the intended marketed product. 9

10. Critical Quality Attribute A CQA is 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. 10

11. Risk Assessment Risk assessment is a valuable science-based process used in quality risk management that can aid in identifying which material attributes and process parameters potentially have an effect on product CQAs. Risk assessment is typically performed early in the pharmaceutical development process and is repeated as more information becomes available and greater knowledge is obtained. Risk assessment tools can be used to identify and rank parameters (e.g. equipment, input materials) with potential to have an impact on product quality. 11

12. Example of using a Risk Assessment tool. For example, a team of experts could work together to develop an Ishikawa (fishbone) diagram that identifies potential variables which can have an impact on the desired quality attribute. The team could then rank the variables based on probability and severity using failure mode effects analysis (FMEA) or similar tools based on prior knowledge and experimental data. Here’s a representation of Ishikawa diagram for the Tablet. 12

13. Ishikawa diagram 13

14. Design Space The relationship between the process inputs (material attributes and process parameters) and the critical quality attributes can be described in the design space. The multi-dimensional region which encompasses the various combinations of product design, manufacturing process, manufacturing process operating parameters and raw material quality which ultimately results in quality product. 14

15. Design Space Working within the design space is not considered as a change, rather moving out of design space is counted as a change and would initiate regulatory post approval change process. The applicant can choose to establish independent design spaces for one or more unit operations, or to establish a single design space that spans multiple operations. While a separate design space for each unit operation is often simpler to develop, a design space that spans the entire process can provide more operational flexibility. For example, in the case of a drug product that undergoes degradation in solution before lyophilization, the design space to control the extent of degradation (e.g., concentration, time, temperature) could be expressed. 15

16. Control Strategy A control strategy is designed to ensure that a product of required quality will be produced consistently. The controls should be based on product, formulation and process understanding and should include, at a minimum, control of the critical process parameters and material attributes. Sources of variability that can impact product quality should be identified, appropriately understood, and subsequently controlled. A control strategy can include: Control of input material attributes (e.g., drug substance, excipients, primary packaging materials) based on an understanding of their impact on processability or product quality; Product specification, a monitoring program (e.g., full product testing at regular intervals) . 16

17. Continual Improvement [4] Product quality can be improved throughout the product lifecycle; companies have opportunities to opt inventive approaches to improve quality. Periodic maintenance can be done within a company’s own internal quality system; but design space should be unchanged. The QbD approach avails the continuous improvement throughout products’ life cycle this is distinguishing point from the conventional method. 17

18. QbD Tools [5] 18

19. DOE in simplified way 19

20. Regulatory Need: - Regulatory challenges and inspection [6] 20

21. Case Study on QbD [7] Development of the arzoxifene hydrochloride drug substance manufacturing process, first via a traditional approach and subsequently via an enhanced approach as QbD. The primary focus of this paper is to illustrate the impact and advantages of QbD on the impurity control strategy. By operating the process at the extremes during design space studies, a larger collection of organic impurities and higher levels of typical impurities are observed in the intermediates. 21

22. Cont …. 22

23. Cont …. Drug substance critical quality attribute Rationale Identity Ensures drug product performance Potency Ensures drug product safety Purity Ensures drug product safety and efficacy Particle size distribution It controls dissolution kinetics of the molecule. 23

24. Cont …. Through the rigorous application of an enhanced process development approach, they have designed quality into the arzoxifene hydrochloride drug substance .   24

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26. QbD Assessment in Japan [7] 2007 2008 2009 2010 2011 2012 2013 2014 2015 3 3 2 11 11 12 27 16 26

27. So why QbD approach is Important? 27

28. Provides a higher level of quality assurance Facilitates regulatory assessment Systematic development described in regulatory submissions will improve the regulatory assessment Improves the efficiency of the assessment / inspection Enables science and risk based regulatory decisions Provides more operational flexibility Facilitates innovation Improves communication b etween Regulators and Industry 28

29. To sum up….. 29

30. References Introduction: Pramod K, Tahir MA, Charoo NA, Ansari SH, Ali J. Pharmaceutical product development: A quality by design approach. International journal of pharmaceutical investigation. 2016 Jul;6(3):129. Background: Juran JM. Juran on quality by design: the new steps for planning quality into goods and services. Simon and Schuster; 1992 May 4. Aims and Goals: U. S. Food and Drug Administration. Guidance for Industry: Q8 (2) Pharmaceutical Development. 2009. ( Link: https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf ) Continual improvement: Phil B., Phil N., marion C., Duncan T., Keith T., 2007. Pharma Technol. Available on http://www.pharmtech.com/pharmtech/ Peer-Reviewed+Research /The-Application-of-Quality-by- Designto -Analytical/ ArticleStandard /Article/detail/463580 30

31. References Quality by Design , BySaket Yeotikar Regulatory Need: Anastasia GL, Anurag SR. Regulatory challenges in the QbD paradigm. Bio. Pharm. Int. 2012;25(9):44-53. Case study and Importance from: - https://www.allfordrugs.com/qbd-case-studies/ 31

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