Pharmaceutical Quality by Design (QbD)

QbD is new concept in pharmaceutical industries which is beneficial for producing and maintaining quality in product. With help of QbD a quality is built in product during manufacturing.

1. QUALITY Risk STRATEGY Improvement PHARMACEUTICAL QUALITY BY DESIGN Presented By :- Chinmay H. Gramopadhye 1 st M.Pharm QA Guided By : Prof. Ms.V.V. Kunjir 1 RD’s College of Pharmacy, Bhor

2. INTRODUCTION NEED OF QBD BENEFIT FOR INDUSTRY OBJECTIVES KEY ELEMENTS CONCLUSION REFERENCE CONTENT 2

3. Quality by Design (QbD) has become a new concept for development of quality pharmaceutical products, It is an essential part of the modern approach to pharmaceutical quality, QbD is a best solution to build a quality in all pharmaceutical products.   “Quality by Design means designing and developing manufacturing processes during the product development stage to consistently ensure a predefined quality at the end of the manufacturing process.” The FDA publication defined Quality by Design as: Developing a product to meet predefined product quality, safety and efficacy Designing a manufacturing process to meet predefined product quality, safety and efficacy INTRODUCTION 3

4. Definitions: Quality : “The suitability of a drug either substance or drug product for its intended use. This term includes such attributes as the identity, strength, and purity.”(ICH Q8) Quality by Design : “It is 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” 4

5. a. Development of new molecular entity · Preclinical study. · Nonclinical study. · Clinical Study. · Scale up. · Submission for market Approval b. Manufacturing · Design Space. · Process Analytical Technology. · Real time Quality Control. c. Control strategy · Risk based decision. · Continuous Improvement. · Product performance STEPS IN QBD SYSTEM 5

6. Higher level of assurance of product quality Cost saving and efficiency for industry and regulators Facilitate innovation to address unmet medical needs Increase efficiency of manufacturing process and reduce manufacturing cost and product rejects Minimize/eliminate potential compliance actions, costly penalties and recalls Enhance opportunities for first cycle approval Streamline post approval manufacturing changes and regulatory processes More focused PAI and post approval cGMP inspections Opportunities for continual improvement NEED OF QBD 6

7. Eliminate batch failures Minimize deviations and costly investigations Avoid regulatory compliance problems Empowerment of technical staff Efficient, agile, flexible system Increase manufacturing efficiency, reduce costs and project rejections and waste Build scientific knowledge base for all products Better interact with industry on science issues Ensure consistent information Incorporate risk management Reduce end-product testing Speed-up release decision BENEFITS OF QBD 7

8. To facilitate innovation and continuous improvement throughout the product lifecycle To provide regulatory flexibility for specification setting and post-approval changes To streamline the submission and review processes OBJECTIVES OF QUALITY BY DESIGN 8

9. 1. Identify  the Target Product Profile 2. Critical Quality Attributes (CQAs) 3.Perform a Risk (Assessment) Analysis 4. Link the drug and excipient attributes and the process parameters to the CQAs 5. Define the Design Space 6. Define the Control Strategy 7. Product lifecycle management & continual improvement KEY ELEMENTS OF QBD 9

10. 1. Define Target Product Quality Profile (TPQP): “Prospective and dynamic 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 realized”.   Considerations for the quality target product profile could include: Intended use in clinical setting, route of administration, dosage form, delivery systems; Dosage strength(s); Container closure system; 10

11. Therapeutic moiety release or delivery and attributes affecting pharmacokinetic characteristics (e.g., dissolution, aerodynamic performance) 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. TPQP is related to identity, assay, dosage form, purity, stability in the label . 11

12. 2. Critical Quality Attributes (CQAs): A CQA has been defined as “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”. CQAs are generally associated with ; raw materials (drug substance, excipients), intermediates (in-process materials), drug product. 12

13. For   Drug Substance (chemical) For Drug product (tablet) Appearance Particle size Morphic forms Water content Residual solvents Organic impurities Inorganic impurities Heavy metals Residue on ignition Assay Appearance Identification Hardness Uniformity of dosage Physical form Dissolution Degradation products Water content Assay Microbiological limits Example; 13

14. 3. Risk Assessment : The FDA defines a Risk Management as, a strategic safety program designed to decrease product risk by using one or more interventions or tools. It is systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecycle.   Quality Risk Management provides a structure to initiate and follow a risk management process. 14

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17. Risk Assessment Tools :- Failure mode effects analysis (FMEA): It is a systematic and proactive method to identify and mitigate the possible failure in the process. Failure Mode, Effects and Criticality Analysis (FMECA): In FMECA, each failure mode of the product is identified and then evaluated for criticality. This criticality is then translated into a risk, and if this level of risk is not acceptable, corrective action must be taken.  Fault tree analysis (FTA): This tool assumes failure of the functionality of a product or process. Hazard analysis and critical control points (HACCP): HACCP provides detailed documentation to show process or product understanding through identifying parameters to control and monitor. 17

18. 4. Critical Process Parameters(CPPs): “A critical process parameter (CPP) is defined as parameter whose variability has an impact on CQA and therefore should be monitored and controlled to ensure process produces desired quality.” 18

19. Operation During Tableting Critical Process Parameter Wet granulation 1.Mixing time , 4. Impeller speed 2.Binder fluid addition rate & time 3.Method of binder addition, 5. Temperature Drying 1.Drying time 2.Inlet air flow 3.Exhaust air temperature & flow Milling 1.Milling speed 2.Screen size 3.Feeding rate Mixing 1.Mixer type 2.Mixing time 3.Order of addition Compression 1.Pre compression force 5. Main compression force 2.Dwell time 6. Hopper design 3.Punch penetration depth 7. Roller type 4. Auger screw rate 8. Ejection force Coating 1.Inlet air flow 3. Time 2.Temperature 4. Spray pattern & rate 19

20. 5.Design Space : - ICH Q8(R2) defines design space as “ 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. X Example : TPQP % Dissolution CPP Z Y CMA Drying time Conc. Raw material 20

21. 6.Control strategy : ICH Q10 defines a control strategy as “a planned set of controls derived from current product and process understanding that assures process performance and product quality. A control strategy can include, but is not limited to, the following: 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(s); 21

22. Controls for unit operations that have an impact on downstream processing or product quality (e.g., the impact of drying on degradation, particle size distribution of the granulate on dissolution); In-process or real-time release testing in lieu of end-product testing (e.g. measurement and control of CQAs during processing); A monitoring program (e.g., full product testing at regular intervals) for verifying multivariate prediction models. 22

23. Conclusion : Quality by design is an essential part of the modern approach to pharmaceutical quality.  The goal of QbD is to reduce product variability and defects, thereby enhancing patient efficacy and safety Reduce product recalls and compliance actions, resulting in cost savings for pharmaceutical companies. QbD methodology helps in identifying and justifying target product profiles, product and process understanding. Helps in continuous improvement. There is a need for vigorous and well funded research programs to develop new pharmaceutical manufacturing platforms. 23

24. 1. Juran JM. Juran on Quality by Design :The new step for planning quality into goods and services. New York : The Free Press; 1992 pg.no 1-2 2 . Woodcock J, The concept of pharmaceutical quality, American Pharmaceutical Review, 7(6), 2004, 10-15 . 3. ICH Q8 (R1) — Guidance for Industry Pharmaceutical Development Revision 1 November 2007 4. ICH Q9- Quality risk management , 2006 5. ICH Q10: Pharmaceutical Quality System, 2007. 6. US FDA – Guidance for Industry - Nov 2009 ICH Revision 2 7. European Medicinal Agency -ICH guideline Q8 (R2) on pharmaceutical development 2004 8. Blog On QbD in pharmaceutical industry by DR Anthony Melvin Crasto, Worlddrugtracker , www.allfordrugs.com/ qbd-in-pharmaceutical-industry/ REFERENCE 24

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