Quality by design (qbd)

Quality by design (qbd)

1. Quality by Design Presented By : A s h i s h R a j e n d r a C h a u d hari M-pharm I st ye a r

2. 2 c Definition of Qbd Current vs Good approach to pharmaceutical development Benefits of Qbd Objectives of Qbd Element of Qbd Ishikawa diagram Conclusion Reference Content...

3. 12/7/2019 3 The Quality Mantra.... “ Quality can not be tested into products; It has to be built in by design” Dr. Joseph M. Juran .

4. Definition of QbD : ICH Q8,QbD has been defined as “A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management”. 12/7/2019 4

5. 12/7/2019 5 ICHQ8. GUIDELINE PART I: PHARMACEUTICAL DEVELOPMENT PART II: ANNEX TO PHARMACEUTICAL DEVELOPMENT

6. 12/7/2019 6 Pharmaceutical Development 2.1 Components of the Drug Product 2.1.1 Drug Substance 2.1.2 Excipients 2.2 Drug Product 2.2.1 Formulation Development 2.2.2 Overages 2.2.3 Physicochemical and Biological Properties 2.3 Manufacturing Process Development 2.4 Container Closure System 2.5 Microbiological Attributes 2.6 Compatibility

7. 12/7/2019 7 ANNEX TO PHARMACEUTICAL DEVELOPMENT 2.1 Quality Target Product Profile 2.2 Critical Quality Attributes 2.3 Risk Assessment: Linking Material Attributes and Process Parameters to Drug Product CQAs 2.4 Design Space 2.4.1 Selection of Variables 2.4.2 Describing a Design Space in a Submission 2.4.3 Unit Operation Design Space(s) 2.4.4 Relationship of Design Space to Scale and Equipment 2.4.5 Design Space Versus Proven Acceptable Ranges 2.4.6 Design Space and Edge of Failure 2.5 Control Strategy

8. 8 QbD and ICH Guidelines Pharmaceutical development Quality Risk Management Pharmaceutical Quality System Development & mfg of drug substance

9. 12/7/2019 9 The Important terms related with QbD that are defined in ICH Q8 Design space : The multidimensional combination and interaction of input variable (e.g. Material attribute) and process parameter that have been demonstrated to provide assurance of quality . PAT ( Process Analytical Technique) : A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e. during processing ) of critical quality and performance attribute of raw and in-process with goal of ensuring final product quality.

10. 12/7/2019 10 Current Approach QbD Approach Quality assured by testing and inspection. Quality built into product & process by design based on scientific understanding Control strategy by testing and inspection Risk based control strategy Use of statistical process control unit method is limited Use of statistical process control unit method is predominant Empirical development Systematic development Product specification are primary means of control Product specification are of the overall quality summary Validation of manufacturing process is primarily based on initial full-scale batches Life cycle approach to validation of manufacturing process and continuous verification Frozen process Flexible process within design space allowing continuous improvement Current Vs. QbD Approach to Pharmaceutical Development 10

11. Benefits of QbD : Less validation burden. Better design of product. Fewer problems in manufacturing. Understanding and mitigation of risk. A reduction in overall cost of manufacturing. More efficient technology transfer to manufacturing. Enabling continuous improvement . 12/7/2019 11

12. Objectives of QbD : To encourages pharmaceutical companies to develop sufficient understanding of their products and manufacture processes . To ensure that their processes are robust. To demonstrate this enhanced understanding to the pharmaceutical regulatory agencies. 12/7/2019 12

13. Advantages of QbD: Patient safety and product efficacy are focused. Scientific understanding of pharmaceutical process and methods is done. It involve product design and process devlopement. Science based risk assessment is carried. Critical quality attributes are identified and their effect on final quality of product is analysed. It offers robust method or process .. Method design concept helps to avoid cost involved with post approval changes. 12/7/2019 13

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15. Define an objective : As per ICH guideline Q8 R2 Quality Target Product Profile can be defined as “Summary of the quality characteristics of a drug product that ideally will be achieved to ensure that the desired quality, and thus the safety and efficacy of a drug product is realised ”. The Quality target product profile forms the basis for design and the development of the product . 12/7/2019 15

16. Consideration for the Quality Target Product Profile (QTPP): 12/7/2019 16

17. Determination of Critical Quality Attributes (CQA ) According to ICH Q8 R2 “A CQA is a physical, chemical, biological , or, microbiological property or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality . CQAs are generally linked with the drug substance, excipients intermediates and drug products. It is stated in ICH Q9 that in case of potential drug substance CQAs are used to guide process development. 12/7/2019 17

18. Risk Assessment: Risk assessment consist of the identification of hazards and analysis an evaluation of risk associated with exposure to those hazards . Principle of management are : Scientific knowledge based evaluation of the risk to quality which eventually link to the protection of the patient . Adequate effort should be taken; formality and documentation of the quality risk management process should be done with the level of risk involved It is joint responsibility of quality unit, business development, engineering, regulatory affairs production operations, sales and marketing, legal, statistics and clinical department. 12/7/2019 18

19. Methods of Risk Assessment Methods of risk assessments are mentioned in ICH guideline Q9as follows: Failure mode effects analysis (FMEA) Failure mode, effects and critically analysis (FMCEA) Fault tree analysis (FTA) Hazard analysis and critical control points (HACCP) Hazard operability analysis (HAZOP) Preliminary hazard analysis (PHA) Risk ranking and filtering Supporting statistical tools. 12/7/2019 19

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21. Development of Experimental Design Experimental design is the multidimensional combination and interaction of input variables and process parameters that have demonstrated to provide assurance of quality. Pharmaceutical development scientist have just began to making use of computer-aided process design (CAPD) and process simulation to support process development and optimization of manufacturing. 12/7/2019 21

22. Designing and implementing control strategy Control strategy is required to ensure that material and process is within the expected lower and upper limits. parameter and material are routinely controlled during production in order to assurer reproducibility. 12/7/2019 22

23. Continuous Improvements Product quality can be improved throughout the product lifecycle; companies have opportunities to inventive approaches to improve quality . Process performance can be monoitored to make sure consistency in quality . The QbD approach avails the continuous improvement throughout product life cycle this is distinguish point from the conventionl method which must frozen process. 12/7/2019 23

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25. CONCLUSION 12/7/2019 25 Quality by Design (QbD) is increasingly becoming an important and widely used technique in pharmaceutical development. It means designing and developing formulations and manufacturing processes to ensure predefined product quality objectives. Implementing QbD concept in product development provide quality medicines to patients, production improvements to Manufacturers with significantly reduced batch failures and drug regulatory bodies will have greater confidence in the robust quality of products they are being asked to approve. As such QbD ng a promising scientific tool in quality assurance in pharma industry.

26. References 18/10/2019 26 Sangshetti, J.N., Zaheer, Z., Mahaparale P.R., Chitlange S.S., August 2015, Quality By Design In Pharmaceuticals, Published By Unique Publication, First Edition, Pp. 12-20,30-44,113-114. Jaiprakash N. Sangshetti A, Mrinmayee Deshpande A, Zahid Zaheer A, Devanand B. Shinde B, Rohidas Arote C, Feb 2014 Review Article Quality By Design Approach: Regulatory Need, Arabian Journal Of Chemistry ICH Q8 (R1) Pharmaceutical Development: Quality By Design, May 2006. Ich Harmonised Tripartite Guideline, November 2005. Quality Risk Management Q9.

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