Dr. Parizad ElchidanaPrincipal Technical ConsultantACG
In the ever-evolving pharmaceutical landscape, Quality by Design (QbD) ensures development of genuinely robust formulations.
Underpinned by universal risk-management and scientific principles, QbD’s systematic approach enhances product quality and predictability. For pharmaceutical professionals, embracing it has become a strategic necessity.
Implementing QbD successfully in formulation development ensures products have predetermined quality attributes and much-reduced variability. It also informs a far deeper understanding of the process, and of the relationships between raw materials, process parameters, and Critical Quality Attributes (CQAs). This not only ensures regulatory compliance, but also streamlines the development process, saving time and resources.
QbD Essentials
Product Design
QbD starts with clear definition of the Target Product Profile (TPP) and the Quality Target Product Profile (QTPP). This involves specifying the desired attributes of the final product – including its safety, efficacy and quality characteristics.
Process Design
With the product attributes defined, attention shifts to developing a manufacturing process that can consistently achieve the desired prod- uct quality. This involves identifying Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs) that can affect the product.
Process Performance
QbD requires a thorough understanding of the relationships between various factors, and how they can affect the process. Design of Experiments (DoE) is often employed to explore these relationships systematically, and helps to establish a ‘Design Space’ in which proven processes combine to ensure product quality.
Product Performance: This element of QbD focuses on monitoring and assessing a product’s Critical Quality Attributes (CQAs) throughout the manufacturing process using PAT. Real-time monitoring allows for proactive adjustments, ensuring the final product consistently meets the predefined quality standards.
The importance of QbD in pharmaceutical formulation development cannot be overstated. It shifts the traditional focus from post-production testing to a proactive, design-based approach. By embedding quality into every stage of formulation development, QbD reduces variability, enhances process understanding, and provides a structured methodology for risk management. In a field where precision and predictability are paramount, QbD emerges as a strategic imperative, aligning seamlessly with the principles of pharmaceutical development excellence.
QbD Advantages: Enhancing Product and Process Design
Enhanced Process Understanding
QbD encourages a joined-up understanding of the formulation’s critical aspects, from raw materials to the manufacturing process. This depth of comprehension minimizes uncertainties and unexpected variations, resulting in a more robust and reliable process.
Reduced Variability
The systematic nature of QbD – especially in identifying and controlling critical parameters early in the development process – means far less variability. This not only ensures consistent product quality, but also minimises the risk of batch failures.
Streamlined Regulatory Compliance
Aligning QbD with regulatory expectations means a smoother regulatory approval process. The emphasis on scientific understanding and risk management resonates with current Good Manufacturing Practices (cGMP) and other regulatory guidelines.
Cost Savings
QbD minimises the need for extensive post-production testing and reworking. This reduces the number of batch failures and rejections significantly, thereby saving time and money.
Faster Time to Market
The proactive nature of QbD not only enhances process understanding, but also accelerates the development and manufacturing processes, enabling pharmaceutical companies to get high-quality products to market much faster.
QbD principles apply across all stages of pharmaceutical research and manufacturing:
• Research and Development
QbD guides the selection of formulation components, the design of manufacturing processes, establishment of in-process controls, analytical method development and design of clinical protocols. It ensures that potential issues are identified and addressed early in the development cycle, preventing delays and setbacks.
• Quality Control
QbD provides a framework for quality-control teams to monitor critical parameters during production. Real-time monitoring allows for immediate corrective actions, ensuring the production of consistently high-quality pharmaceuticals.
• Production and Operations
QbD facilitates process optimisation and scale-up in production and operations. Establishing a design space supports efficient transfer of processes from development to production, minimising the risk of unexpected variations.
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Implementing QbD in pharmaceutical formulation development demands a structured and collaborative approach. Here are the key steps for basic product design and formulation development:
Define Objectives: Clearly articulate the TPP and QTPP to align the team with the project’s goals.
Risk Assessment: Identify CMAs and CPPs through a thorough risk assessment using tools such as Failure Mode and Effects Analysis (FMEA).
Design of Experiments (DoE): Utilize DoE to systematically explore the impact of various factors on product quality and process performance.
Establish Design Space: Based on the results of DoE, define a design space that allows for flexibility in manufacturing, while maintaining product quality.
Real-Time Monitoring: Implement real-time monitoring and control strategies to ensure continuous assessment of critical parameters during production.
Control Strategy: Develop a robust control strategy that includes in-process controls, testing, and monitoring to ensure consistent product quality.
Documentation and Training: Maintain thorough documentation of the QbD process and provide ongoing training to ensure all team members are aligned with QbD principles.
Strategies for successful QbD implementation
Collaborative Cross-Functional Approach: Encourage collaboration between formulation-development scientists, R&D teams, quality-control experts, and production and operations teams. A cross- functional approach ensures diverse complementary expertise contributes to the QbD process.
Continuous Improvement Culture: Incorporate feedback from across manufacturing processes to refine and optimise the design space. This iterative approach ensures the agility to adapt to evolving challenges.
Thorough Documentation: Maintain detailed documentation of the QbD process, from initial formulation design to manufacturing. This is crucial for regulatory compliance and internal knowledge-sharing.
As we continue to explore the frontiers of pharmaceutical formulation, QbD is an essential tool for successfully navigating the complexities and uncertainties inherent in drug development. QbD isn’t just a regulatory necessity – it’s also a powerful tool for transforming pharmaceutical formulation development. In the pursuit of excellence, integrating QbD principles can achieve clear differentiation in a highly competitive pharmaceutical landscape. Pharmaceutical professionals can achieve excellence and push the boundaries of possibility in providing high-quality, super-reliable, and genuinely innovative pharmaceutical formulations.
Publication Detail
This article appeared in American Pharmaceutical Review:
Vol. 26, No. 8
Nov/Dec 2023
Pages: 60-61
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