Understanding Quality by Design

Highly regulated manufacturers must prioritize precision and quality. To do this, they must rely on rigorous processes and designs. Quality by Design is a planned approach to ensuring the delivery of high-quality products. It is a core element of safe and effective manufacturing and a crucial element to the success of your business. In this article, we explore Quality by Design approach to manufacturing and process development, the identification of critical quality attributes (CQAs) and definition of critical process parameters (CPPs), the development of a detailed process flow, and the drafting of a validation master plan.

Quality by Design: Elevating Process Design to Ensure Excellence

The concepts behind quality by design were introduced in international guidelines intended for the pharmaceutical industry between 2009 and 2012. Quality by Design is a systematic and science-based approach to pharmaceutical products and process development but is used by many life sciences manufacturers. It shifts the focus from traditional quality control to a proactive and holistic strategy, where quality is built into the product from the outset.

One of the key tenets of Quality by Design is the exploration of the design space. The design space is the multidimensional combination of input variables and process parameters that ensures the product consistently meets its defined quality attributes. It’s not just about finding a single, rigid pathway; rather, it’s about understanding the realm of possibilities and optimizing the process within those boundaries.

Quality by Design introduces a proactive approach to risk management. Through the systematic identification and assessment of potential risks to product quality, manufacturers can implement measures to mitigate these risks early in the design phase. This not only enhances the robustness of the manufacturing process but also minimizes the likelihood of unexpected deviations down the production line.

In the realm of Quality by Design, real-time monitoring and control take center stage. The ability to monitor critical parameters in real-time provides manufacturers with a continuous feedback loop, allowing for immediate adjustments and ensuring that the process stays within the predefined design space.

Quality by Design is not a standalone concept, but rather an integral part of process validation. It fundamentally changes the way manufacturers approach all three stages of process validation: process design, process qualification, and continuous process verification. Its principles are tightly woven into the fabric of process validation, influencing its entire lifecycle.

Quality by Design Approach to Manufacturing

The principles of Quality by Design can be applied to multiple areas of manufacturing in the life sciences sector:

Manufacturing of Equipment

• Design Optimization: Equipment should be designed to meet quality requirements, emphasizing factors like precision, reliability, and ease of cleaning to prevent contamination.
• Process Control: Advanced equipment can incorporate real-time monitoring and control systems, ensuring that critical process parameters are maintained within defined limits.
• Risk Mitigation: Quality by Design enables the identification of potential equipment-related risks and the implementation of strategies to mitigate those risks.
• Change Control: Quality by Design principles help in managing changes to equipment by evaluating their potential impact on product quality and making informed decisions about validation and requalification.

Computer Systems

• Data Integrity: Ensuring data integrity is essential for quality and compliance. Quality by Design principles guide the design and validation of computer systems to maintain data accuracy and security.
• Process Automation: Automated systems can help in achieving precise control over processes, reducing the potential for human error and variations.
• Risk-Based Validation: Quality by Design emphasizes a risk-based approach, which applies to computer system validation, allowing manufacturers to focus resources on areas with the highest potential risks.
• Documentation and Record-Keeping: Properly validated computer systems facilitate robust documentation and record-keeping practices, which are essential for regulatory compliance and data traceability.

Incorporating the principles into manufacturing equipment and computer systems not only enhances product quality but also supports efficiency and compliance in pharmaceutical and related industries. It encourages proactive risk management, systematic validation, and a holistic approach to quality assurance.

Pharmaceutical Products

• Designing Quality: It emphasizes the design of pharmaceutical products and processes to consistently meet predefined critical quality attributes (CQAs). Rather than relying on post-production testing and inspection to ensure quality, Quality by Design starts with a thorough understanding of product requirements and designing processes to meet those requirements.
• Identifying Critical Quality Attributes (CQAs): CQAs are the product attributes critical to its quality, safety, and efficacy. Identifying and defining these attributes is fundamental in the Quality by Design approach. For example, in a tablet formulation, CQAs may include dosage uniformity, dissolution rate, and physical stability.
• Controlling Critical Process Parameters (CPPs): Critical Process Parameters (CPPs) are the factors that significantly affect CQAs if there is variability to the parameter. In a tablet manufacturing process, these could include mixing duration, temperature, and humidity. It focuses on understanding and controlling CPPs to ensure that CQAs are consistently met.
• Risk-Based Approach: It incorporates a risk-based approach to process development and validation. It involves identifying potential risks and implementing strategies to mitigate them. This approach aligns with the principles of patient safety and product quality.

Learn More in the Digital Process Validation Guide

Process validation is complex and time consuming, but it has the potential to be a key competitive advantage. We’ve put together a Digital Process Validation Guide to show you how to get more from your process validation activities and execute faster.

In our guide, we explain the benefits of digital process validation, including how to leverage your existing data and documents to supercharge your production. You’ll gain insights from experts and learn why Kneat is the leading digital process validation solution in the industry.

The Digital Process Validation Guide

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About the Author

Olivia Calder – Process Validation SME, Kneat

Olivia is an experienced process validation expert, with years of first-hand experience running multiple validation activities in life science manufacturing.

Based in Cleveland, Ohio she works with Kneat customers to augment and streamline their process validation programs as well as lead customers in Initial Deployments of Kneat Gx for a variety of validation disciplines. She is skilled in Process Improvement, Customer Service, and Regulatory Compliance.

Olivia is a strong Quality Assurance professional with a bachelor’s degree in chemical engineering from The University of Toledo.