What is Quality by Design (QbD): Meaning and Solutions

More than 64 deaths. 753 infections. One contaminated pharmaceutical batch. That is the very real case of the New England Compounding Center meningitis outbreak. [7] Academic research reveals that 330 drug recalls happen annually. 84% of them stem from process control failures that reactive quality testing can’t prevent. For Manufacturing IT Directors managing GMP systems, this isn’t a compliance problem – it’s proof that traditional approaches are fundamentally broken and, unfortunately, lethal. [5]

Quality by Design (QbD) cuts batch failures by 40% by embedding quality controls directly into manufacturing execution systems, not bolting on more tests. This technical deep-dive shows how leading manufacturers deploy QbD through Process Analytical Technology, real-time data architectures, and multivariate control strategies, with proven implementation frameworks. [6]

Let us dive into the realm of this new process!

What is Quality by Design?

Quality by Design is a proactive approach to product development that builds quality directly into both the product and its manufacturing process. Instead of testing for quality at the end (the traditional approach), QbD plans for quality from the very beginning.

Quality expert Joseph M. Juran first introduced this concept, arguing that most quality problems come from poor initial planning.[1] QbD addresses this by requiring a deep understanding of both the product and manufacturing process, backed by solid science and risk management.

The Evolution of QbD: from traditional quality control to proactive design

The pharmaceutical industry, known for its regulations, was initially slow to adopt these modern quality paradigms. Historically, formulation development often followed a “One Factor At a Time” (OFAT) approach. This meant testing products after manufacturing to find defects. However, this “quality by testing” (QbT) approach is inefficient and costly. The US Food and Drug Administration (FDA) began encouraging QbD in 2004. The FDA recognized that more testing alone does not improve quality. [2]

The shift towards QbD was spurred by regulatory bodies such as the FDA and the International Conference on Harmonisation (ICH). The ICH issued key guidelines (Q8, Q9, Q10, Q11) that provide a framework for QbD in drug development and manufacturing. By 2013, the FDA was strongly encouraging QbD for generic drug applications (ANDAs). The FDA was even citing ANDAs absence in deficiency letters. This reflects a move towards building quality from the design phase, rather than simply inspecting it at the end. [2]

Core principles of Quality by Design

What would including QbD in your workflow look like? The process can be broken down into several foundational principles:

• Define Quality Objectives Early. Think of this as creating a blueprint for success. Your Quality Target Product Profile (QTPP) becomes the center point for your entire project, outlining everything from how patients will use your product to what safety standards it must meet. Get this right early, and every decision downstream becomes clearer.

• Identify Critical Quality Attributes (CQAs). Here’s where you separate the “must-haves” from the “nice-to-haves.” Which properties absolutely cannot fail without compromising your product? For a vaccine, losing immunogenicity would be a complete mission failure – for others, it is not. Define those attributes and think of them as your non-negotiable quality checkpoints.

• Control Process Variabilit.y This step is like mapping the DNA of your manufacturing process. You’ll discover which raw materials and process conditions (temperature swings, pH changes) can make or break your product quality. When you understand these relationships, you create a “safe zone” for manufacturing (your design space) where quality stays consistent even when conditions vary.

• Use Risk-Based Decision Making. This is where critical analysis and deduction come in and replace guesswork. Spot potential problems before they happen, learn from every batch you make, and continuously fine-tune your process. It’s quality improvement on autopilot.

Key Components of a QbD framework

We have explored the theoretical side of how QbD works. A thorough understanding naturally requires delving into the details of the working environment of QbD and its many tools.

Design of Experiments (DoE) for process optimization

Design of Experiments (DoE) is a critical statistical tool in QbD. It involves systematically varying controlled input factors. DoE is used to determine the effects of the input factors on the process output and product quality. As a result, experts can understand the multivariate interactions between parameters. 

Statistical process control and data analytics

QbD integrates statistical analysis from the design phase itself. This helps build quality into the product. Process Analytical Technology (PAT) tools are vital for this. PAT involves real-time measurements of critical quality and performance attributes during processing.

Failure mode and effects analysis (FMEA)

Risk assessment is a cornerstone of QbD, and tools like Failure Mode and Effects Analysis (FMEA) are frequently used. FMEA helps identify potential failure modes within a process or product system. It also assesses their effects and causes. 

The Ishikawa (fishbone) diagram is another risk assessment tool recommended by ICH. [3] It is also referred to as the cause and effect diagram, as it is used to identify the potential causes for an event. In QbD, this diagram is used to determine which design choices would lead to what results.

Real-time monitoring and process automation

PAT tools are essential for real-time monitoring and control in QbD. For example, in spray drying, PAT tools can monitor particle size distribution, a Critical Quality Attribute. Experts use these tools to measure if raw materials have optimal physical characteristics or to track spray patterns during the process. Manufacturers can make immediate adjustments with the Real-time monitoring technology. This helps maintain product quality at every stage. 

Applications of QbD in healthcare and pharma

All those tools can be extremely useful if used correctly. QbD has thus found its place in a range of applications. Let’s have a look at a non-exhaustive list of them:

• Vaccines: QbD principles help stabilize vaccines through drying processes like freeze drying (FD) and spray drying (SD). It defines critical quality attributes and process parameters for vaccine stability. For example, QbD has been applied to freeze-dried vaccine production to increase robustness and efficiency. 

Spray-dried influenza virus vaccines have been developed using QbD principles to enhance stability and enable versatile delivery routes. Researchers are also exploring microwave vacuum drying as a semi-continuous technique for vaccine stabilization.

• Monoclonal Antibodies (mAbs): QbD is extensively used for developing and manufacturing these complex biological molecules. It helps define critical quality attributes (CQAs) related to safety and efficacy and establishes design spaces for purification processes. Professionals use QbD to understand how process parameters like temperature and pH affect product quality during cell culture development.
• Cell Therapies: Despite the biological complexity of cells, QbD provides a rational framework to produce high-quality, functioning cells reliably and cost-effectively. QbD helps define Quality Target Product Profiles (QTPP) for cell therapies and optimizes process parameters in bioreactor systems. For instance, QbD has been used to define critical process parameters for mesenchymal stem cell expansion.
• Small Molecule Drugs: QbD principles apply to small molecule development and manufacturing, including solid oral dosage forms, modified-release products, and sterile manufacturing. Olaparib process development, for example, successfully employed QbD for achieving excellent yields and high purities.
• Analytical Methods (AQbD): QbD principles extend to analytical method development, known as Analytical Quality by Design (AQbD). Experts use AQbD for High-Performance Liquid Chromatography (HPLC) and Ultra-High Performance Liquid Chromatography (UHPLC). These techniques help separate, identify, and quantify the components of a mixture.

Benefits of implementing QbD

These applications demonstrate QbD’s versatility, but you might be wondering: what’s the real value proposition? What would implementing QbD actually bring to you and your team?

While we could easily spend considerable time listing benefits, QbD has potential applications across virtually every field, and you may identify additional advantages specific to your industry:

Improved product quality and reliability 

Implementing QbD can guarantee that product quality and performance remain consistently high by building quality directly into the development process from day one. It directly enhances patient safety and product efficacy while also significantly reducing product variability and defects. Rather than hoping quality emerges at the end, you’re engineering it from the beginning.

Cost reduction and increased efficiency 

The financial benefits of QbD implementation can be substantial but naturally depend on the scale of your project. You can minimize costly errors and reduce rework by identifying critical parameters early in development. The result is avoiding expensive post-production investigations. 

Faster innovation and market readiness 

QbD streamlines the entire development process and paves the way for faster market entry for new products. More importantly, it creates the material conditions for deeper scientific understanding of your pharmaceutical processes – a foundational factor for sustained innovation and competitive advantage.

Challenges and limitations in adopting QbD

As with virtually every solution on the market, there is always friction with the product. Understanding those challenges is the key to reaping the benefits of QbD while not succumbing to potential pitfalls that are avoidable if tackled properly:

• High initial investment and process complexity: Adopting QbD requires a significant upfront investment in time, labor, and resources. It necessitates new equipment and training for personnel. The complexity of pharmaceutical manufacturing processes and biological products can make QbD implementation challenging.

• Need for skilled workforce and advanced tools: QbD demands a deep understanding of processes and products. This requires a highly skilled workforce and specialized expertise. Advanced analytical tools and information systems are also necessary to capture and manage documentation.

• Resistance to change in traditional industries: There can be internal unwillingness within companies to adopt new methods. This is often due to a lack of belief in the business case for QbD. Established therapeutics might still be selling with good profit, reducing incentives for change. Misalignment among international regulatory bodies also poses a challenge to global acceptance.

Thankfully, there is a solution to all of these issues. Many healthcare facilities have begun partnering with firms specialized in implementing healthcare software, such as BGO Software, to outsource the know-how of tackling these issues.

Regulatory and industry standards for QbD

We did mention that QbD helps with regulatory compliance. That is the fortunate result of the fact that QbD is deeply integrated into global regulatory and quality frameworks.

The FDA actively encourages QbD approaches. The ICH guidelines (Q8, Q9, Q10, Q11) provide the foundational principles and framework for QbD. These guidelines emphasize scientific, risk-based development and a lifecycle approach. The European Union passed the European Medicines Agency (EMA) also welcomes applications incorporating QbD aspects. It supports QbD through its process analytical technology (PAT) team.

Best practices for ensuring compliance

Compliance with QbD is fundamentally achieved through the establishment of a robust control strategy. The strategy should continuously monitor and manage critical material attributes (CMAs) and critical process parameters (CPPs) within an approved design space. Developers must include continuous process verification and improvement throughout the product lifecycle. 

Documentation is crucial in demonstrating scientific understanding and regulatory readiness. Your company must keep comprehensive records of all design decisions and risk assessments. Regular training and cross-functional collaboration between manufacturing and regulatory teams ensure that QbD principles are consistently applied across all stages of development and production.

Conclusion

Quality by Design delivers real, measurable pharmaceutical manufacturing improvements: 40% reductions in batch failures and predictive quality control through advanced PAT systems. [6] However, a successful QbD deployment demands deep regulatory knowledge combined with advanced technical capabilities – precisely the intersection where BGO Software specializes in pharmaceutical manufacturing systems.

Ready to embed quality by design into your manufacturing technology stack?

Sources

• [1] Mahapatra, A., & Meyyanathan, S. N. (2022). Analytical quality by design – A review. Indian Research Journal of Pharmacy and Science, 9(25), 2132–2140. https://www.researchgate.net/publication/342924833 
• [2] Mahapatra, A., & Meyyanathan, S. N. (2022). Analytical quality by design – A review. Indian Research Journal of Pharmacy and Science, 9(25), 2132–2140. https://www.researchgate.net/publication/342924833 
• [3] Mourtas, S., Michanetzis, G., Missirlis, D., & Antimisiaris, S. G. (2023). Quality by design approach in liposomal formulations: Robust product development. Nanomedicine, 18(3), 189–206. https://doi.org/10.2217/nnm-2022-0283 
• [4] Rathore, A. S., & Winkle, H. (Eds.). (2009). Quality by design for biopharmaceuticals: Principles and case studies. Wiley. https://doi.org/10.1002/9780470466315 
• [5] Ghijs, S., Wynendaele, E., & De Spiegeleer, B. (2024). The continuing challenge of drug recalls: Insights from a ten-year FDA data analysis. Journal of Pharmaceutical and Biomedical Analysis, 249, 116349. 
• [6] Yang, S., Hu, X., Zhu, J., Zheng, B., Bi, W., Wang, X., … & Wu, Y. (2025). Aspects and implementation of pharmaceutical quality by design from conceptual frameworks to industrial applications. Pharmaceutics, 17(5), 623. 
• [7] Abbas, K. M., Dorratoltaj, N., O’Dell, M. L., Bordwine, P., Kerkering, T. M., & Redican, K. J. (2016). Clinical response, outbreak investigation, and epidemiology of the fungal meningitis epidemic in the United States: systematic review. Disaster medicine and public health preparedness, 10(1), 145-151.

Dobrin Kolarov

Healthcare business analyst with expertise in marketing and business development, and holds an MPharm degree. He specialises in creating and executing communication strategies that make digital health solutions and pharmaceutical technologies clear, accessible, and resonation for their audiences.