Organizations that implement Quality by Design (QbD) fundamentals are well-positioned to avoid disruptions in product supply rather than those who haven’t considered the implications of their potentially outdated processes. Key benefits include identifying and mitigating risks early, ensuring consistency, enabling flexibility within approved design spaces, and fostering continuous improvement that leads to reduced costs and more efficient processes. 

What is Quality by Design? 

Quality by Design (QbD) is a strategic approach to product manufacturing and development that ensures consistent delivery of high-quality products. QbD is important because it builds quality into products from the beginning rather than later in processes, thereby, leading to safer and more reliable products. The fundamentals of QbD are captured in industry regulations and are considered best practice. 

Fundamental Principles of QbD 

While the quality organization is responsible for overseeing QbD, cross-functional input from manufacturing and packaging teams leads to enhanced processes and product delivery. There are several fundamental principles of QbD that should be implemented to ensure successful products and processes: 

1. Define the Quality Target Product Profile (QTPP), which forms the basis of design for product development because it takes into account the desired quality of the finished product. The QTPP should take into consideration the quality, safety, and efficacy of the product while also examining the dosage form, route of administration, and bioavailability. 
2. Identify Critical Quality Attributes (CQAs) or product characteristics that have a direct impact on product quality so they can be controlled and measured. Consider which CQAs would be most impacted by variation (highest risk) in the process, thereby impacting product quality and subsequently patient safety. Examples include any materials based on output of processes such as product uniformity, degradation, color, and distribution. 
3. Perform a Risk Assessment to determine which product attributes or process parameters influence product CQAs. By performing a risk assessment early in the product development process, you can develop a list of parameters that can be excessive but can be modified as necessary. Consider evaluating the effectiveness of your process to determine which process steps impact your CQAs. These steps will directly affect the reproducibility of your process by identifying and controlling potential issues throughout the development and manufacturing process. 
4. Determine the Design Space to identify the relationship between product attributes and process parameters with CQAs. Performing a risk assessment can help identify attributes in addition to variables and their ranges within which consistent quality can be achieved. A description of the attribute as well as its effect on product quality should be included. In some cases, a rationale for why certain attributes were not included in the design space can be helpful to avoid monitoring excessive attributes that may not provide value. The use of historical data should also be addressed.  
5. Define a Control Strategy to ensure that a product will be produced with consistent product quality. The elements of a control strategy should describe and justify how in-process controls and controls around the input of materials, intermediates, container closure system, and drug products contribute to the final product quality. These controls should be specific to the product formulation and include, at minimum, the CQAs, and material attributes. Identifying and understanding sources of variability that can impact in-process materials, and product quality can help to refine controls upstream of your process and minimize the need for end-product testing.  
6. Management of the Product Lifecycle to monitor process performance and application of continuous improvement measures. Process performance should be monitored to ensure that the process is operating as predicted by the design space. The CQAs should be monitored continuously, allowing for adjustments to be made, as necessary. Monitoring should include trend analysis to maintain process performance and proactively identify anomalies. 

Ensuring High-Quality Products  

Implementing QbD can be challenging due to the nuances involved in manufacturing and product development. It is important to select the appropriate attributes to monitor to ensure consistent delivery of high-quality products. Clarkston has dedicated Q+C experts who can help you evaluate your processes and implement the fundamentals of QbD – reach out to us today.