QbD in Pharmaceutical development

In this slide contains QbD approach in Pharmaceutical development.
Presented by: V NABI RASOOL (Department of pharmaceutical analysis and quality assurance).RIPER, anantapur

1. Quality-by-Design in Pharmaceutical development A Seminar as a part of curricular requirement for M. Pharm I year II semester Presented by V.NABI RASOOL. (20L81S0401). Department of Pharmaceutical Quality Assurance. 1

2. 2 DEFINITION Quality by design (QbD) is a systematic approach to product development that begins with predefined objectives and emphasizes product and process understanding and controls based on sound science and quality risk management (ICH Q8). Quality-by-design

3. 3 The main objective of QbD is to achieve the quality products. To achieve positive performance testing. Ensures combination of product and process knowledge gained during development. From knowledge of data process, desired attributes may be constructed. Objectives :

4. Benefits of QbD for Industry : Eliminate batch failures. Minimize deviations and costly investigations. Empowerment of technical staff. Better understanding of the process. Continuous improvement. Ensure better design of product with less problem . 4

5. 5 Aspects Traditional QbD Pharmaceutical development Empirical (Experimental) Systematic and multivariate experiments. Manufacturing process Fixed Adjustable with experiment design space. Process control Offline and has wide or slow response PAT (Process Analytical Technique) utilized for feed back. Product specification Based on batch data Based on the desired product performance. Control strategy By end product testing Risk based, controlled shifted up stream, real time release. Life cycle management Post approval changes needed Continual improvement enable within design space. Approaches to Pharmaceutical Development

6. 6 Flow of QbD :

7. 7 “A prospective summary of the quality characteristics of drug product that ideally will be achieved to ensure the desired quality, taking into account safety & efficacy of drug product.”(ICH Q8) Target product profile should includes- Dosage form Route of administration Dosage strength Pharmacokinetics Stability  Target Product Profile(TPP)

8. 8 QTPP is a quantitative substitute for aspects of scientific safety & efficacy that can be used to design and optimize a formulation and manufacturing process. QTPP should only include patient relevant product performance. The Quality Target product profile is a term that is an ordinary addition of TPP for product quality. QTPP is related to identity, assay, dosage form, purity, stability in the label. Quality Target Product Profile (QTPP)

9. 9 A CQA has been defined as “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”. Critical Quality Attributes are generally associated with the drug substance, excipients, intermediates and drug product. Critical Quality Attributes(CQAs)

10. 10 The quality attributes of a drug product may include identity, assay, content uniformity, degradation products, residual solvents, drug release, moisture content, microbial limits. Physical attributes such as color, shape, size, odor, and friability. These attributes can be critical or not critical.

11. 11 A CMA of a drug substance, excipient, and in-process materials is a physical, chemical, biological, or microbiological characteristic of an input material that should be consistently , The CMA is likely to have an impact on CQA of the drug product. A material attributes can be an excipients , raw material, drug substances, reagents, solvents, packaging & labeling materials. Critical Material Attributes(CMA)

12. 12 A CPP of manufacturing process are the parameters which, when changed, can potentially impact product CQA and may result in failure to meet the limit of the CQA. Critical Process Parameters(CPP) Operations during tableting CPP Wet granulation Mixing time, temperature, method of binder addition Drying Drying time, Inert air flow Milling Milling speed, screen size, feeding rate Compression Pre compression force, main compression force, dwell time, hopper design, ejection force Coating Inert air flow, time, temperature, spray pattern and rate

13. 13 Design Space As per ICH Q8- This is the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. A design space may be built for a single unit operation or for the ensure process. Design Space :

14. 14 Design of Experiment (DoE): This is a systematic approach applied to conduct experiments to obtain maximum output. We have capability and expertize to perform DoE in product development using software like Minitab and Statistica.  Tools applied in QbD approach

15. 15 Design of experiments done by 2 methods- 1. Screening: Designs applied to screen large number of factors in minimal number of experiments to identify the significant ones. Main purpose of these designs is to identify main effects and not the interaction effects. For such studies common designs used are- Placket- Burman design Fractional factorial design.

16. 16 2. Optimization: Experimental designs considered to carry out optimization are mainly full factorial design, surface response methodology . e.g. Central composite Box- Behnken and Mixture designs. These designs include main effects and interactions and may also have quadratic and cubic terms require to obtain curvature.

17. 17 Process Analytical Techniques : Assurance of product quality during intermittent steps using Process Analytical Technology (PAT) is recommended by regulatory authorities, which is yet to be extensively accepted by the pharmaceutical industry over conservative methodologies. It involves advanced online monitoring systems like NIR (Near IR), Handheld Raman Spectrometer, Online Particle Size Analyzer etc., These technologies further make assurance of continuous improvement in process and product quality through its life cycle.

18. 18 As defined by an FDA official (Woodcock, 2004), “The QbD concept represents product and process performance characteristics scientifically designed to meet specific objectives, not merely empirically derived from performance of test batches.” Another FDA representative (Shah, 2009) states that “introduction of the QbD concept can lead to cost savings and efficiency improvements for both industry and regulators.” Regulatory views on QbD

19. 19 Pfizer was one of the first companies to implement QbD and PAT concepts. Through these concepts, the company gained enhanced process understanding, higher process capability, better product quality, and increased flexibility to implement continuous improvement change. Industry views on QbD

20. 20 Industry Regulatory agency Development of scientific understanding of critical process and product attributes. Scientifically based assessment of product and manufacturing process design and development. Controls and testing are designed based on limits of scientific understanding at development stage. Evaluation and approval of product quality specifications in light of established standards ( e.g : purity, stability, content uniformity, etc.,) Utilization of knowledge gained over the product’s lifecycle for continuous improvement. Evaluation of post-approval changes based on risk and sciences. QbD for industry and regulatory bodies

21. 21 Quality by Design is intended to enhance process knowledge and is based on existing guidance and reference documents. QbD can be viewed as a process defined by series of document requirements as per process knowledge and understanding. The goals of implementing pharmaceutical QbD are to reduce product variability and defects, thereby enhancing product development and manufacturing efficiencies and post approval change management. Finally, QbD is challenge & the current challenges to QbD implementation from an industry perspective are numerous because industry has yet to fully embrace its application to pharmaceutical product development.  Conclusion

22. 22 Lan Zhang, Shirui Mao (2016 ). Application of quality by design in the current drug development: Asian journal of pharmaceutical sciences 12 (2017) 1–8.  Sushila D. Chavan , Nayana V. Pimpodkar , Amruta S. Kadam , Puja S.Gaikwad . Quality by Design : Research and Reviews: Journal of Pharmaceutical Quality Assurance|Volume 1 | Issue 2 | October- December, 2015.  D. M. Patwardhan , S. S. Amrutkar , T. S. Kotwal and M. P. Wagh , APPLICATION OF QUALITY BY DESIGN TO DIFFERENT ASPECTS OF PHARMACEUTICAL TECHNOLOGIES : IJPSR, 2017; Vol. 8(9): 3649-3662. References

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