Quality by Design in an Era of Advanced Technologies in Life Sciences

Introduction of Key Elements, Results and Definitions of QbD 

There are five elements of QbD: defining the Quality Target Product Profile (QTPP); identifying Critical Quality Attributes (CQAs); performing risk assessments; establishing a control strategy; and enabling continuous improvement. These elements are interconnected and form a framework for building quality into a product and process from the start, rather than testing for it later.

The QbD approach has been implemented by many organizations for quite some time. It is defined as a systematic approach to development based on predefined objectives, and aims to achieve a process control based on sound science and quality risk management.

The key results of QbD in pharma include enhanced drug quality and safety by building the process and controlling the critical points throughout the manufacturing process by defining, upfront, the desired quality characteristics of the product. QbD also can benefit from increased manufacturing efficiencies and reduce costs and time to market through a proactive, science-based approach to drug development and manufacturing. This systematic process builds quality into the product from the start, leading to better batch consistency, reduced failures, and a deeper understanding of the relationship between process parameters and product quality.

QTPP is the basis of the design of the development of the product and is defined as “a prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy.” QTPP should include at least the definition of its intended use, route of administration, dosage forms and possible delivery systems, dosage strength, container closure system, therapeutic moiety release or delivery, and attributes affecting drug product pharmacokinetic and drug product quality criteria such as purity, stability, and sterility.

CQA is defined as “a physical, chemical, biological, or microbiological property or characteristic of an output material that should stay inside a defined limit, range, or distribution to ensure the desired product quality.” CQAs are associated with drug substances, intermediates, excipients, and drug products.

Strictly connected to CQAs are the Critical Process Parameters (CPP), defined as “a parameter whose variability has an impact on a CQA and therefore should be monitored or controlled to ensure the process produces the desired quality”.

In order to monitor and control CPPs and CQAs, it will be necessary to put in place a Control Strategy defined in ICH Q10² as “a planned set of controls, derived from the current product and process understanding that ensures process performance and product quality.” Controls include parameters and attributes of the drug substance and drug product’s materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and associated methods and frequency of monitoring and control.

Another important topic to be considered is the Design Space, designated during development, defined as “the multidimensional combination of interaction of input variables and process parameters that have been demonstrated to provide assurance of quality.” This topic has an impact on possible marketing authorization submission, as working inside the design space is not considered a process/product change from a regulatory point of view.

All the above mentioned topics are part of an organized approach to product development managed by using quality risk management reported in ICH Q9 (R1)³.

PQE Group's relevance to QbD 

PQE Group helps companies implement QbD, which is a method for ensuring product quality by focusing on scientific and risk-based approaches from the design phase through manufacturing. Companies around the world frequently turn to PQE Group for strategic advice and its plethora of services, and more specifically, when it comes to QbD Strategy and Implementation.

• Quality is by Design, not testing: In a blog post titled "Connecting Two Novel Concepts: Critical Thinking & Quality by Design", PQE Group reinforces the fundamental principle of QbD—that quality must be built into a product from the start, rather than inspected at the end. The company mentions that many quality issues arise from poor product design.
• QbD for compliance: The Company suggests that QbD, along with a strong quality assurance department, can help life science companies ensure that their products conform to safety, quality, and stability standards.

The latest trends in Life Sciences Quality by Design (QbD)

Today the focus is on integrating advanced technology like AI and big data for Risk-Based Quality Management (RBQM), streamlining Regulatory compliance through digitized oversight, and leveraging QbD for more efficient and patient-centric development.  Key developments include the use of AI for anomaly detection, QMS, Manufacturing, central monitoring of Clinical Trials, and use of Digital Twins to simulate risks, all of which is supported by faster Regulatory alignment between agencies like the FDA and EMA.

PQE Group has featured multiple case studies and presentations on AI applications within the life sciences industry, focusing on compliance, innovation, and practical implementation around the world which align well with the Latest Trends in Life Sciences QbD as illustrated below:

Technological Integration:

• Artificial intelligence and big data: AI is being used to analyze data, identify cause-and-effect relationships, and optimize processes. AI-powered tools are used for anomaly detection, protocol optimization, and regulatory submissions.

• Digital twins: These are used to simulate trial risks in advance, helping companies to mitigate potential problems before they occur.

• Centralized monitoring: Regulatory bodies are pushing for centralized monitoring as a core RBQM practice to better oversee quality and risk across the development process, helping to ensure regulatory alignment and compliance.

Streamlined Risk Indicators: 

There's a move toward fewer, but more impactful Key Risk Indicators (KRIs) and Quality Tolerance Limits (QTLs) to focus on what is most critical.

• Digitized oversight: Regulations like the EU's Clinical Trials Information System (CTIS) roll-out further support risk-based and digitized oversight of drug development.

• Faster Alignment: Regulatory bodies like the FDA and EMA are aligning faster than ever on expectations for implementing digital tools and risk-based approaches for enhanced development, quality, and efficiency.

• Focus on Patient-Centricity: QbD is being used to design products that meet the specific needs of patients, ensuring both safety and efficacy. 

• Improved Efficiency: By building quality in from the start, companies can improve R&D efficiency, reduce waste, and lower costs. 

• Holistic approach: QbD is not just about risk mitigation; it is a holistic, proactive approach that helps discover insights throughout the development process and enables more efficient use of procured funding for Research and Development.

• Post-Approval Management: QbD is also being applied to improve root cause analysis and post-approval change management.

Quality by Design (QbD) in the Era of Advanced Technologies and Continuous Improvement in the Life Sciences Industry

The evolution of QbD has transformed how the Life Sciences Industry approaches product and process development, shifting from reactive testing to a proactive, science- and risk-based methodology. Introduced formally by the FDA in 2002 and reinforced through ICH guidelines (Q8–Q11), QbD focuses on embedding quality throughout the product lifecycle—from defining the Quality Target Product Profile (QTPP) to identifying Critical Quality Attributes (CQA), managing Critical Process Parameters (CPP), establishing a Control Strategy, and operating within a defined Design Space.

The adoption of QbD has been further accelerated by technological advancements, including the integration of Artificial Intelligence (AI), Machine Learning (ML), and Digital Twins, which enable deeper data-driven insights, real-time risk-based monitoring, and enhanced regulatory compliance. These innovations are aligned with global regulatory frameworks like Annex 11, Annex 22, and initiatives by both the FDA and EMA promoting harmonization and digitized oversight.

Organizations like PQE Group have been pivotal in supporting companies through this transformation. With deep expertise in compliance, digital governance, product quality, validation, and regulatory strategy, PQE Group helps clients implement effective QbD strategies that align with evolving regulatory expectations and leverage advanced technologies to drive continuous improvement and patient-centric innovation.

QbD is now seen not just as a regulatory requirement, but as a holistic, strategic enabler of improved product quality, increased manufacturing efficiency, and reduced time to market. As the life sciences industry continues to innovate, QbD—strengthened by digital transformation and regulatory convergence—remains central to ensuring consistent product performance, safety, and efficacy in a rapidly evolving global landscape.

References:

1. ICH Q8 (R2) “Pharmaceutical Development”, 2009
2. ICH Q10
3. ICH Q9 (R1)
4. P. ter Horst, S. L. Turimella, F Metsers, A. Zwiers, Therapeutic Innovation & Regulatory Science, 590 (2021)