Quality by design

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1. Quality By Design Presented by:- shashikant maurya M.Pharm 1 st year (Pharmaceutics )

2. Q b D QbD has been adopted by the U.S. Food and Drug Administration (FDA) for the discovery, development, and manufacture of drugs According to ICH Q 8(R1 ) QbD is defined as: A systematic approach to development that begins with predefined objectives It emphasizes on product and process understanding and process control. It is based on sound science and quality risk management . FDA PAT Guidelines define QbD as a system for designing, analyzing and controlling manufacturing through timely measurements ( i.e. during processing) of critical quality and performance attributes of new and in-process materials and processes, with the goal of ensuring final product safety.

3. SIGNIFICANCE OF QbD : Quality by Design means: designing and developing formulations and manufacturing processes to ensure a predefined quality Quality by Design requires: understanding how formulation and manufacturing process variables influence product quality Quality by Design ensures: Product quality with effective control strategy BENEFITS OF QBD: QbD is good Business Eliminate batch failures Minimize deviations and costly investigations Avoid regulatory compliance problems Organizational learning is an investment in the future QbD is good Science Better development decisions Empowerment of technical staff

4. The QbD initiative, which originated from the Office of Biotechnology Products (OBP), attempts to provide guidance on pharmaceutical development to facilitate design of products and processes that maximizes the product’s efficacy and safety profile while enhancing product manufacturability IMPROVEMENTS BY QbD : Ensure higher level of assurance of product quality for patient Improved product and process design & understanding Monitoring, tracking & trending of product & process. More efficient regulatory oversight Efficiency and cost saving for industry Increase efficiency of manufacturing process Minimize / eliminate potential compliance actions

5. STEPS INVOLVED IN QUALITY BY DESIGN PRODUCTS Development of new molecular entity Preclinical study Nonclinical study Clinical Study Scale up Submission for market Approval Manufacturing Design Space Process Analytical Technology Real time Quality Control Control Strategy Risk based decision Continuous Improvement Product performance

6. QBD DEVELOPMENT PROCESS INCLUDE: Begin with a target product profile that describes the use, safety and efficacy of the product Define a target product quality profile that will be used by formulators and process engineers as a quantitative surrogate for aspects of clinical safety and efficacy during product development Gather relevant prior knowledge about the drug substance, potential excipients and process operations into a knowledge space. Design a formulation and identify the critical material (quality) attributes of the final product that must be controlled to meet the target product quality profile . Design a manufacturing process to produce a final product having these critical material attributes. Identify the critical process parameters and input (raw) material attributes that must be controlled to achieve these critical material attributes of the final product.

7. Use risk assessment to prioritize process parameters and material attributes for experimental verification. Combine prior knowledge with experiments to establish a design space or other representation of process understanding. Establish a control strategy for the entire process that may include input material controls, process controls and monitors, design spaces around individual or multiple unit operations, and/or final product tests. The control strategy should encompass expected changes in scale and can be guided by a risk assessment. Continually monitor and update the process to assure consistent quality.

8. Traditional approach & Enhanced QbD approach ASPECTS CURRENT QbD Pharmaceutical Development Empirical, Random, Focus on optimization Systematic, Multivariate experiments, Focus on control strategy and robustness Manufacturing Process Fixed Adjustable within design space, managed by company’s quality systems Process Control Some in-process testing PAT utilized, Process operations tracked and trended Product Specification Primary means of quality control, based on batch data Part of the overall quality control strategy, based on desired product performance Control Strategy By testing and inspection Risk-based control strategy , real-time release possible

9. ICH Q8, Q9, Q10 GUIDELINES: THE FOUNDATION OF QbD ICH Guidelines Q8 for Pharmaceutical Development Q9 for Quality Risk Management, Q10 for Quality systems are foundation of QbD Quality by Design relative to ICH - Concepts aligned - Design Space - Key to understanding - Process robustness - Design of Experiments (DOE) - Quality management Quality management Critical Concept: Design Space Demonstrated to provide assurance of quality Defined by applicant and reviewed by regulator

10. Defined regulator Once design space is approved, regulatory post approval change requirements will be simplified A pproval Inside vs. outside design space Inside space Regulatory flexibility to operate within the design space Regulatory space.

11. BENEFITS OF IMPLEMENTING QbD FOR FDA Enhances scientific foundation for review Provides for better coordination across review, compliance and inspection Improves information in regulatory submissions Provides for better consistency Improves quality of review (establishing a QMS for CMC) Provides for more flexibility in decision making Ensures decisions made on science and not on empirical information Involves various disciplines in decision making Uses resources to address higher risks

12. Advantages of QbD Benefits for Industry: Better understanding of the process. Less batch failure. More efficient and effective control of change. Return on investment / cost savings . Allows for implementation of new technology to improve manufacturing without regulatory scrutiny Improves interaction with FDA –deal on a science level instead of on a process level Allows for continuous improvements in products and manufacturing process. Additional opportunities : An enhance QbD approach to pharmaceutical development provides opportunities for more flexible regulatory approaches .

13. Pharmaceutical Development :

14. THANK YOU