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Quality by design

Quality by Design (QbD) is a systematic, science- and risk-based approach to pharmaceutical development that begins with predefined quality objectives and emphasizes comprehensive understanding and control of the product and manufacturing process to ensure consistent quality.^[1] This methodology shifts the focus from traditional end-product testing to proactively designing quality into the product from the outset, enabling more flexible regulatory oversight and lifecycle management.^[2] Pioneered in general quality management by Joseph M. Juran in his 1992 publication Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services, the concept was adapted for the pharmaceutical sector through international guidelines, particularly the International Council for Harmonisation (ICH) Q8(R2) Pharmaceutical Development guideline issued in 2009.^[3] At its core, QbD involves defining a Quality Target Product Profile (QTPP), which outlines the desired quality characteristics for the drug product, including dosage form, route of administration, strength, and purity to meet safety, efficacy, and performance needs.^[1] From the QTPP, developers identify Critical Quality Attributes (CQAs)—physical, chemical, biological, or microbiological properties that must be controlled within defined limits to ensure the product meets its quality standards.^[4] Risk assessment tools, such as those in ICH Q9 (Quality Risk Management), are then used to link Critical Material Attributes (CMAs) of the drug substance, excipients, and container-closure system, along with Critical Process Parameters (CPPs) of the manufacturing process, to the CQAs.^[3] This establishes a design space, a multidimensional range of input variables and process parameters where quality is assured, allowing variations without impacting product quality.^[1] The implementation of QbD is supported by a robust control strategy, which includes specifications for materials, analytical procedures for testing, in-process controls, and process monitoring to maintain operations within the design space.^[4] Integrated with ICH Q10 (Pharmaceutical Quality System), QbD facilitates continual improvement throughout the product lifecycle, from development and scale-up to commercialization and post-approval changes.^[3] Benefits include reduced product variability and defects, enhanced manufacturing efficiency, lower development costs, and greater assurance of supply chain reliability, as evidenced by its endorsement by regulatory agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).^[2] While primarily applied in pharmaceuticals, QbD principles extend to other regulated industries such as biotechnology and medical devices, promoting a proactive quality culture.^[1]

Overview and Principles

Definition and Core Concepts

Quality by Design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.^[1] This proactive quality management philosophy ensures that quality is built into products and processes from the outset, rather than depending on end-stage testing to achieve compliance.^[5] By integrating quality considerations early, QbD aims to enhance product robustness and consistency across manufacturing.^[1] The core principles of QbD include a risk-based approach that employs quality risk management to identify and prioritize factors affecting product quality early in development.^[1] Central to this is the establishment of a design space, defined as the multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality.^[1] Additionally, QbD utilizes a quality target product profile (QTPP), which serves as a prospective summary of the quality characteristics of a product that should be achieved to ensure desired quality, safety, and efficacy.^[1] A control strategy is then developed as a planned set of controls derived from product and process understanding to assure performance and quality.^[1] Key concepts foundational to QbD implementation are critical quality attributes (CQAs), which are physical, chemical, biological, or microbiological properties that must be controlled within defined limits to ensure product quality; critical process parameters (CPPs), whose variability impacts CQAs and thus require monitoring or control; and critical material attributes (CMAs), which are properties of input materials that influence CQAs.^[1] These elements enable a structured identification of variables through risk assessment, facilitating targeted development efforts.^[1] In contrast to traditional quality control, which relies on empirical methods and reactive end-product testing to detect defects, QbD shifts to preventive design by incorporating systematic science- and risk-based strategies that reduce variability and enhance process robustness from the initial stages.^[6] This fundamental change minimizes the risk of product failures and supports more flexible manufacturing operations.^[6]

Historical Development

The concept of Quality by Design (QbD) emerged in the mid-20th century from foundational work in statistical quality control, pioneered by Walter Shewhart at Bell Telephone Laboratories in the 1920s. Shewhart introduced control charts as a tool to monitor and reduce process variation, shifting quality efforts from inspection of finished products to proactive control during production.^[7] This statistical approach laid the groundwork for understanding variation as a key driver of defects, influencing subsequent quality management philosophies.^[8] Building on Shewhart's methods, W. Edwards Deming advanced quality management in the 1930s and 1940s by promoting statistical process control and emphasizing systemic improvements in organizational culture, particularly through his post-World War II consulting in Japan. Deming's 14 Points for management, which stressed reducing variation and fostering continuous improvement, further integrated statistical tools into broader quality strategies.^[8] Joseph M. Juran extended these ideas in the 1950s with his quality trilogy—planning, control, and improvement—arguing that quality must be designed into products from the outset rather than inspected in afterward.^[9] Juran formalized QbD principles in his 1992 book Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services, which outlined a structured process for incorporating customer needs and variation control during the design phase.^[3] The evolution of QbD accelerated in the 2000s within the pharmaceutical sector, driven by regulatory initiatives to enhance manufacturing efficiency and product consistency. In 2002, the U.S. Food and Drug Administration (FDA) launched the Pharmaceutical cGMPs for the 21st Century initiative, advocating a risk-based approach that incorporated QbD to build quality into processes proactively.^[10] This was followed in 2004 by the FDA's guidance on Process Analytical Technology (PAT), which positioned real-time monitoring tools as enablers for QbD implementation, allowing for better control of critical process parameters.^[11] These milestones spurred broader industry adoption, extending QbD beyond traditional manufacturing to emphasize design space and risk management. By the 2020s, QbD has integrated with Industry 4.0 technologies, including artificial intelligence (AI) and digital twins, to enable real-time monitoring and predictive optimization in pharmaceutical development. For instance, digital twins simulate processes to explore robust design spaces, accelerating sustainable medicines manufacturing while minimizing experimental trials.^[12] This integration has also facilitated QbD's expansion to non-manufacturing sectors, such as software engineering and service industries, where it supports proactive quality planning for information systems and customer-focused processes.^[13]

Juran's Quality by Design Framework

Integrated Planning

Integrated planning serves as the foundational phase in Joseph M. Juran's Quality by Design (QbD) framework, with the purpose of translating customer requirements into a comprehensive product design blueprint that embeds quality from the initial stages. This phase ensures that all aspects of the product—ranging from features to processes—are aligned with market-driven goals, systematically bridging the gap between customer expectations and practical execution. By prioritizing proactive design, integrated planning minimizes downstream quality failures and associated costs.^[13]^[14] The key steps in integrated planning begin with identifying customer needs through rigorous market research and the voice of the customer (VOC) methodologies, such as advanced surveys and statistical analysis techniques. A multidisciplinary team, comprising representatives from design, engineering, marketing, and operations, is established to oversee the process and foster concurrent engineering practices. Customer needs are then prioritized and translated into technical specifications using tools like quality function deployment (QFD), which maps requirements to functional, design, process, and control features via structured planning worksheets. Juran emphasized this phase as the "breakthrough" in quality management, where thorough planning prevents the majority of quality issues that arise from inadequate upfront design, such as those leading to costly manufacturing redesigns.^[13]^[14]^[15] The outputs of integrated planning include preliminary design specifications that outline measurable customer needs, product and process features tied to real-world benchmarks, and initial risk assessments—often conducted through failure mode and effects analysis (FMEA)—to prioritize critical quality elements. These deliverables provide a robust foundation for subsequent phases, such as customer-focused optimization, ensuring sustained alignment with quality objectives throughout the product lifecycle.^[13]^[14]

Customer-Focused Optimization

Customer-focused optimization represents the second phase in Juran's Quality by Design framework, where the initial product design is refined through systematic testing and iteration to ensure it delivers maximum value to the end-user by balancing functionality, cost, and quality attributes informed by customer inputs.^[13] This phase aims to enhance customer loyalty and minimize defects at launch by aligning design features with measurable customer needs, such as performance reliability and usability.^[13] Key methods in this phase include the application of design of experiments (DoE) for prototyping and testing, which employs statistical techniques like non-linear response surface methodology to identify optimal design parameters under varying conditions.^[13] Simulation modeling is also utilized to predict product performance and assess potential failure modes, allowing teams to evaluate outcomes without physical prototypes.^[13] Iterative feedback loops further support refinement, incorporating customer validation through design reviews and trade-off analyses to adjust features based on real-world usage data.^[13] Juran viewed optimization as a creative, multidisciplinary process essential to achieving "fitness for use," where the product not only meets but exceeds customer expectations in terms of utility and satisfaction.^[13] In consumer goods applications, such as appliance manufacturing, this approach has enabled significant quality enhancements; for instance, iterative design refinements in product features have historically led to substantial defect reductions by prioritizing user-centric attributes over initial specifications.^[13] Essential tools and metrics in customer-focused optimization encompass tolerance design, which establishes acceptable limits for variation in key quality attributes to ensure consistent performance, and cost-benefit analysis, often through value engineering, to prioritize modifications that yield the highest return on investment.^[13] These elements facilitate a data-driven evaluation, quantifying trade-offs between design enhancements and production costs to guide decisions. This phase sets the foundation for subsequent variation control in operations transfer.^[13]

Variation Control and Operations Transfer

In Juran's Quality by Design framework, the variation control and operations transfer phase ensures that the optimized product or process design translates reliably into production by systematically identifying, measuring, and mitigating sources of variability to achieve consistent, defect-free outputs. This phase builds on prior planning and optimization by focusing on process robustness, where variability—arising from materials, equipment, methods, or environmental factors—is minimized to meet quality goals without excessive costs. The ultimate aim is to create a stable operating system that maintains performance over time, preventing the need for constant corrective actions.^[13] Central techniques for variation control include statistical process control (SPC), a method for monitoring process behavior using data analysis to detect and address deviations before they impact quality. SPC enables real-time oversight by distinguishing between inherent (common cause) variation, which is predictable and manageable, and assignable (special cause) variation, which requires immediate intervention to restore stability. Within SPC, control charts are essential tools that plot process measurements over time against statistically derived upper and lower control limits, typically set at three standard deviations from the mean, allowing operators to identify out-of-control signals such as trends or shifts.^[16]^[17] Risk mitigation is further supported by failure mode and effects analysis (FMEA), a structured approach to proactively evaluate potential failure modes in the process, assess their severity, occurrence probability, and detectability, and prioritize corrective actions through a risk priority number (RPN) calculation. FMEA helps in designing safeguards that reduce the likelihood of variability-induced defects, ensuring the process remains resilient during scale-up. Process capability is quantified using indices like Cp and Cpk to evaluate how well the process variation fits within specification limits. The Cp index, which assumes the process is centered, is calculated as:

Cp = \frac{USL - LSL}{6\sigma}

where USL and LSL are the upper and lower specification limits, and \sigma is the process standard deviation; a Cp value exceeding 1.33 generally indicates sufficient capability for reliable performance. Cpk adjusts for process centering by incorporating the mean's position relative to the limits, providing a more comprehensive measure when the process is off-center.^[18]^[19] The operations transfer component institutionalizes these controls by handing off the design to production teams through rigorous validation, training, and documentation. Process validation occurs in stages: installation qualification (IQ) verifies that equipment and systems are installed correctly and meet design specifications; operational qualification (OQ) confirms that processes operate within predefined parameters under various conditions; and performance qualification (PQ) demonstrates consistent output meeting quality requirements during extended runs. Operators receive targeted training to execute control strategies effectively, fostering self-inspection and adherence to standards. Comprehensive documentation, including control plans, standard operating procedures, and audit trails, ensures traceability and facilitates ongoing compliance.^[13] From Juran's viewpoint, this transfer phase represents the "institutionalization" of quality, embedding preventive controls into routine operations to provide stability and avert performance drift, where processes might otherwise degrade due to unaddressed chronic issues. By achieving this, organizations shift from reactive firefighting to proactive management, aligning production with customer needs while minimizing waste and rework.

Applications in the Pharmaceutical Industry

Key Elements of Pharmaceutical QbD

In the pharmaceutical industry, Quality by Design (QbD) is specifically adapted to integrate the development of drug substances and drug products, applying systematic scientific approaches and risk management to prioritize patient safety and efficacy throughout the lifecycle.^[1] Central to pharmaceutical QbD is the Quality Target Product Profile (QTPP), which defines the prospective and desired summary of the quality characteristics of the drug product, including aspects such as dosage form, route of administration, strength, purity levels, and stability.^[1] From the QTPP, Critical Quality Attributes (CQAs) are identified as the physical, chemical, biological, or microbiological properties or characteristics that must be controlled within appropriate limits to ensure product quality; representative examples include dissolution rate, which impacts bioavailability, and impurity profiles, which affect safety.^[1] These CQAs are linked to manufacturing inputs through Critical Material Attributes (CMAs)—properties of raw materials influencing quality—and Critical Process Parameters (CPPs)—process variables affecting CQAs—via structured risk assessment tools like Ishikawa diagrams, which categorize potential causes of variation to prioritize impactful factors.^[1]^[20] The design space represents a multidimensional knowledge space in pharmaceutical development, encompassing the established ranges of CMAs and CPPs where variation in inputs does not significantly impact product quality, thereby providing flexibility in manufacturing without compromising efficacy or safety.^[1] This space is established and verified through Design of Experiments (DoE), a statistical methodology that systematically explores interactions among variables to map boundaries of acceptable performance.^[1] For example, in tablet formulation, the design space may define acceptable pH ranges for the granulation process to ensure consistent drug solubility and dissolution, preventing quality deviations.^[3] Process Analytical Technology (PAT) is integral to pharmaceutical QbD, facilitating the design and implementation of strategies for real-time monitoring, analysis, and control of manufacturing processes to assure quality.^[1] Tools such as near-infrared (NIR) spectroscopy enable non-destructive, in-line assessment of critical attributes like blend uniformity or moisture content during production, supporting proactive adjustments to maintain the process within the design space.^[1]^[21]

Implementation Steps and Tools

The implementation of Quality by Design (QbD) in pharmaceutical development follows a structured workflow that integrates scientific principles to ensure product quality from the outset. The process begins with defining the Quality Target Product Profile (QTPP), which outlines the desired quality characteristics of the drug product, such as dosage form, strength, and route of administration, serving as the foundation for subsequent development activities.^[20] This is followed by identifying Critical Quality Attributes (CQAs), which are physical, chemical, biological, or microbiological properties that must be controlled to ensure product quality.^[20] Risk identification is then conducted using tools like Failure Mode and Effects Analysis (FMEA), where potential failure modes in materials and processes are evaluated based on severity, occurrence, and detectability to prioritize risks with a Risk Priority Number (RPN).^[20] Next, Design of Experiments (DoE) is employed to systematically vary Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs) that impact CQAs, enabling the mapping of the design space—a multidimensional region where material and process variations yield acceptable product quality.^[20] A control strategy is subsequently developed to manage variability, incorporating Process Analytical Technology (PAT) for real-time monitoring, such as near-infrared (NIR) spectroscopy to assess blend uniformity during manufacturing.^[20] Finally, lifecycle management ensures continuous verification and improvement through ongoing process monitoring and periodic reviews to maintain quality over the product's life.^[20] Practical tools support these steps, particularly for DoE analysis and process simulation. Software platforms like JMP from SAS Institute facilitate experimental design, modeling, and visualization, allowing pharmaceutical scientists to optimize formulations and processes efficiently, as demonstrated in applications for tablet development.^[22] Similarly, MODDE software from Sartorius enables robust DoE setups, including D-optimal designs, to define design spaces in scenarios like dry particle coating for functionalised particles.^[23] For process simulation, mathematical modeling such as population balance models (PBMs) is used to predict granule size distribution in wet granulation processes, integrating nucleation, growth, and breakage mechanisms to align with QbD principles.^[24] A representative case example illustrates these steps in tablet manufacturing. In optimizing film coating uniformity, researchers applied QbD by conducting DoE to evaluate parameters like pan speed, spray rate, and fill level, using response surface methodology to identify an optimal 6% weight gain that minimized coating thickness variability; this approach reduced inter-tablet coating variability by more than 50% compared to the initial process, validated through laser-induced breakdown spectroscopy (LIBS) measurements.^[25] Despite these benefits, challenges in pharmaceutical QbD implementation include balancing innovation—such as adopting novel continuous manufacturing—with regulatory scrutiny, which demands rigorous validation of design spaces and control strategies to avoid delays in approval.^[26] This tension requires interdisciplinary collaboration to ensure scientific advancements align with compliance needs without stifling progress.^[26]

Regulatory Frameworks and Guidelines

FDA Initiatives and Activities

The U.S. Food and Drug Administration (FDA) initiated its promotion of Quality by Design (QbD) concepts through the Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach, announced on August 21, 2002, which emphasized modernizing pharmaceutical manufacturing by integrating quality systems, risk management, and science-based approaches to build quality into products from the outset.^[27] This initiative laid the groundwork for QbD by shifting from traditional end-product testing to proactive design strategies that ensure consistent quality. Building on this, the FDA issued its Guidance for Industry: PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance in September 2004, which introduced Process Analytical Technology (PAT) as a key enabler for QbD by enabling real-time monitoring and control of manufacturing processes to enhance product understanding and variability management.^[28] To facilitate practical adoption, the FDA launched the Office of New Drug Quality Assessment (ONDQA) QbD Pilot Program in 2005, targeting investigational new drug (IND) applications and new drug applications (NDA) submissions that incorporated QbD elements, allowing sponsors to demonstrate enhanced process knowledge and risk-based submissions.^[29] This was followed by the issuance of the FDA's Quality by Design for ANDAs: An Example for Immediate-Release Tablets guidance in April 2012, which provided detailed examples of QbD implementation, including the establishment and declaration of design space—a multidimensional range of process parameters ensuring product quality—to guide applicants in regulatory submissions. These efforts encouraged industry to submit robust, data-driven dossiers, with the pilot program concluding that QbD-based applications improved regulatory assessments by clarifying critical quality attributes and controls. As of 2025, the FDA continues to integrate QbD principles into its Quality Metrics Program, launched in 2015 and with guidance issued in 2016, which requires reporting of key performance indicators to monitor manufacturing quality and supports QbD by linking metrics to risk-based process verification and continuous improvement.^[30] The agency has also fostered collaborations with industry through its Emerging Technology Program, established in 2015 and expanded by 2024, to develop digital QbD tools such as predictive modeling and advanced analytics for real-time process optimization. Furthermore, FDA guidance emphasizes that post-approval changes within an established design space do not require prior approval supplements, reducing regulatory burden and enabling flexibility for manufacturers to implement improvements without extensive filings.^[31]

ICH Guidelines and International Harmonization

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) plays a pivotal role in standardizing Quality by Design (QbD) principles across global regulatory agencies, including the FDA, EMA, and others, to ensure consistent pharmaceutical development and manufacturing practices.^[32] ICH Q8 (Pharmaceutical Development), adopted in 2009, establishes the foundational principles of QbD by emphasizing a systematic approach to product and process development, including the definition of quality target product profiles, critical quality attributes, and design space to assure product quality throughout the lifecycle.^[1] Complementing this, ICH Q9 (Quality Risk Management), finalized in 2006, provides principles and tools for identifying, assessing, and mitigating risks in pharmaceutical quality systems, enabling proactive QbD implementation.^[33] ICH Q10 (Pharmaceutical Quality System), adopted in 2008, integrates QbD into a comprehensive lifecycle management framework, applying knowledge management, change control, and continual improvement to drug substances and products. Additionally, ICH Q11 (Development and Manufacture of Drug Substances), issued in 2012, extends these concepts to both chemical entities and biotechnological/biological entities, guiding the selection of starting materials and process understanding to support QbD. The harmonization process under ICH involves collaborative development of guidelines through expert working groups from regulatory authorities and industry, culminating in consensus documents that align expectations across regions. For instance, the revision to ICH Q8(R2) in 2009 explicitly incorporated the concept of design space—the multidimensional combination of input variables and process parameters that assure quality—facilitating regulatory flexibility without triggering post-approval changes when operating within it.^[1] This process ensures that agencies like the FDA and EMA apply uniform scientific standards, reducing discrepancies in approval criteria and promoting efficient global development.^[4] Globally, ICH QbD guidelines have been adopted through regional implementations, such as the EMA's reflections on pharmaceutical development, which endorse Q8 principles for marketing authorization applications to enhance product robustness and reduce variability.^[34] This harmonization has streamlined multi-regional filings by allowing shared design spaces and control strategies, as demonstrated in the FDA-EMA pilot program (extended 2014–2017), where parallel assessments of QbD elements in applications led to faster approvals and minimized redundant testing across jurisdictions.^[35] Recent updates include ICH Q12 (Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management), adopted in 2019, which builds on QbD by introducing established conditions and post-approval change protocols to enable more predictable management of manufacturing variations without extensive regulatory submissions.^[36] More recently, ICH Q14 (Analytical Procedure Development), adopted in 2022, extends QbD principles to the development of analytical procedures.^[37] Up to 2025, ICH has increasingly focused on applying QbD to biotech products, with Q11 providing tailored guidance for complex biological entities and ongoing implementations emphasizing risk-based approaches in their development to address variability in upstream and downstream processes.

Broader Industry Applications and Challenges

QbD in Manufacturing and Other Sectors

Quality by Design (QbD) principles, originally conceptualized by Joseph M. Juran for systematic product and process development, have been adapted across manufacturing sectors to embed quality from the outset, reducing variability and enhancing efficiency.^[13] In the automotive industry, QbD principles support quality improvements in product design and assembly, aligning with methodologies like statistical process control to meet reliability standards.^[38] In electronics and semiconductor manufacturing, QbD focuses on controlling process variability to achieve high yield and precision in chip fabrication. Techniques such as multivariate analysis help define design spaces that account for material inconsistencies and environmental factors, leading to improved defect rates in production lines.^[39] This approach aligns with established practices like statistical process control, which has driven quality improvements in semiconductor processes by targeting sources of variation early in the design cycle.^[40] Adaptations in the food industry leverage QbD for process optimization, integrating with safety frameworks to enhance product consistency. For shelf-life optimization, real-time monitoring via spectroscopic tools establishes critical quality attributes like moisture content and microbial stability, reducing waste through proactive variability control.^[41] Nestlé, for example, applies quality by design principles to anticipate risks in ingredient processing, ensuring nutritional integrity and extending product viability without relying solely on end-of-line testing.^[42] In software development, QbD-like strategies incorporate risk-based testing within agile frameworks, where iterative sprints prioritize high-impact features and use failure mode analysis to refine code architecture, fostering robust, scalable applications.^[13] Cross-sector tools like Design of Experiments (DoE) and Failure Mode and Effects Analysis (FMEA) underpin these applications, with adaptations to sector-specific metrics. DoE facilitates parameter optimization in automotive assembly lines to meet durability targets, while in aerospace, it supports reliability modeling for flight-critical components.^[43] FMEA, meanwhile, evaluates potential failures in electronics fabrication for yield enhancement and in food processing for contamination prevention, contrasting with purity-focused assessments in more regulated benchmarks like pharmaceuticals.^[44]

Benefits, Limitations, and Future Directions

Quality by Design (QbD) offers several key benefits across industries by embedding quality into the product lifecycle from the outset, leading to enhanced product robustness and consistency. This systematic approach minimizes variability in manufacturing processes, resulting in fewer defects and improved efficiency; for example, it reduces waste and rework in sectors like food and electronics through better process understanding.^[45] Additionally, QbD reduces risks by proactively identifying and controlling critical quality attributes, thereby improving overall product reliability.^[46] QbD also accelerates time-to-market and drives cost efficiencies via preventive design strategies. By optimizing processes early, it supports faster development and commercialization across manufacturing sectors.^[47] Furthermore, implementations often yield returns on investment through reduced rework, lower manufacturing costs, and increased output quality.^[48] Despite these advantages, QbD presents notable limitations that can hinder adoption. The approach demands high upfront investments in expertise, experimental design, and advanced tools, which may strain resources, particularly for smaller organizations.^[49] Defining the design space for novel or complex products adds further complexity due to challenges in fully characterizing multifaceted interactions and variabilities.^[40] Resistance persists in legacy industries accustomed to empirical methods, where limited knowledge of QbD's business drivers and potential returns can slow implementation. Looking ahead, QbD is poised for evolution through integration with emerging technologies, particularly artificial intelligence (AI) for predictive applications. Machine learning algorithms can enhance risk assessments by analyzing vast datasets to forecast process variabilities, enabling more precise control strategies and reducing reliance on extensive physical experiments.^[50] Sustainability is another focus, with QbD principles applied to eco-friendly process designs that minimize waste and resource use, as seen in digital twins and model-driven optimizations for greener manufacturing.^[12] Expansion into personalized medicine and advanced manufacturing like 3D printing will further leverage QbD to ensure quality in customized therapies, while scalable digital platforms are addressing adoption gaps for small-scale operations as of 2025, democratizing access to these tools.^[51]^[52]

References

[1]
[PDF] Q8(R2) - ICH
A more systematic approach to development (also defined as quality by design) can include, for example, incorporation of prior knowledge, results of studies ...
[2]
Quality by Design (QbD) | European Medicines Agency (EMA)
Quality by Design (QbD) is a scientific guideline from the EMA that helps medicine developers prepare marketing authorization applications for human medicines.
[3]
Understanding Pharmaceutical Quality by Design - PMC - NIH
This paper is intended to describe the objectives of pharmaceutical QbD, detail its concept and elements, and explain implementation tools and studies.
[4]
[PDF] Q8(R2) Pharmaceutical Development - FDA
Q8(R2) Pharmaceutical Development is a guidance from the FDA, covering drug product components, formulation, manufacturing, and container closure systems.
[5]
[PDF] Guidance for Industry - FDA
Quality by Design and Product Development. Quality by design means designing and developing a product and associated manufacturing processes that will be ...Missing: core | Show results with:core
[6]
[PDF] ICH Q8, Q9 and Q10 Questions and answers (R5)
Feb 5, 2025 · What is the difference in a control strategy for products developed using the minimal approach vs. 'quality-by-design' approach? Control ...
[7]
6.1.1. How did Statistical Quality Control Begin?
The first to apply the newly discovered statistical methods to the problem of quality control was Walter A. Shewhart of the Bell Telephone Laboratories. He ...
[8]
https://asq.org/quality-resources/history-of-quality
[9]
The History of Quality Management System - Juran Institute
Mar 4, 2020 · Quality management systems, as we now think of them, first started to be developed in the 1920s, as statistical sampling techniques were introduced into ...
[10]
[PDF] PHARMACEUTICAL CGMPS FOR THE 21 CENTURY - FDA
Sep 8, 2004 · harmonized CGMP standards and quality systems of world-wide pharmaceutical inspectorates. ... quality by design, continuous improvement and ...
[11]
[PDF] FDA Guidance for Industry PAT – A Framework for Innovative ...
The goal of PAT is to enhance understanding and control the manufacturing process, which is consistent with our current drug quality system: quality cannot be ...Missing: core | Show results with:core<|control11|><|separator|>
[12]
Quality by digital design to accelerate sustainable medicines ...
Aug 20, 2025 · QbDD can accelerate medicines development via exploration of more robust design spaces exploiting model-driven experimental approaches.
[13]
Quality by Design (QbD): An Overview - Juran Institute
Jun 24, 2019 · Quality by Design (QbD) is a structured process for designing and launching new products. Products include goods, services, information, or internal processes.<|control11|><|separator|>
[14]
https://books.google.com/books?id=KPUXbZ2Hw1EC
[15]
QFD based optimal process quality planning
Oct 1, 2005 · Juran JM (1992) Juran on quality by design: the new steps for planning quality into goods and services. Free Press, New York. Google Scholar.
[16]
Statistical Process Control and Quality Improvement - Juran Institute
Jan 18, 2019 · The control process detects and takes action on sporadic quality problems; the improvement process identifies and takes action on chronic quality problems.<|control11|><|separator|>
[17]
Guide to Statistical Control Charts - Juran Institute
Jul 1, 2018 · A statistical control chart compares process performance data to computed “statistical control limits,” drawn as limit lines on the chart.
[18]
Guide to Failure Mode and Effect Analysis - FMEA - Juran Institute
Apr 2, 2018 · Design FMEA (DFMEA) is a methodology used to analyze risks associated with a new, updated or modified product design and explores the ...
[19]
Process Capability: Formulas & Implementation - Juran Institute
Apr 1, 2018 · Most processes should have a minimum index of 1.33. If the process is not capable, identify and eliminate the root causes for excessive ...
[20]
Application of quality by design in the current drug development - PMC
In this paper, the basic knowledge of QbD, the elements of QbD, steps and tools for QbD implementation in pharmaceutics field, including risk assessment ...Missing: seminal | Show results with:seminal<|control11|><|separator|>
[21]
A Quality-by-Design (QbD) Approach to Quantitative Near-Infrared ...
Sep 1, 2011 · Near-infrared Spectroscopy (NIRS) has become established as a key technique within the Process Analytical Tool (PAT) toolbox and there are many ...
[22]
[PDF] Pharmaceutical Quality by Design Using JMP - SAS Support
This document discusses pharmaceutical quality by design using JMP to solve product development and manufacturing problems, such as overfilling and dental ...
[23]
Quality by Design (QbD) based process optimisation to develop ...
Nov 1, 2018 · DOE was statistically designed using MODDE software version 8.2 (Umetrics Inc., NJ, USA). A D-optimal design was selected to account for the ...
[24]
Towards QbD in Drug Product Pharmaceutical Manufacturing
Feb 25, 2014 · This paper focuses on the predictive model development for a pharmaceutically relevant model granulation process. A population balance ...
[25]
Improvement of Tablet Coating Uniformity Using a Quality by Design ...
A combination of analytical and statistical methods is used to improve a tablet coating process guided by quality by design (QbD) principles.
[26]
[PDF] Quality by Design (QbD) in pharmaceutical development
Jan 20, 2024 · Challenge: Balancing innovation with regulatory requirements and maintaining control within the design space can be a delicate process. 5 ...
[27]
FDA's Pharmaceutical Quality Initiatives: Implementation of a ...
On Aug. 21, 2002, FDA announced a significant new initiative: "Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century: A Risk-Based ...
[28]
PAT — A Framework for Innovative Pharmaceutical Development ...
A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance Guidance for Industry October 2004. Download ...Missing: Design | Show results with:Design
[29]
[PDF] center for drug evaluation and - accessdata.fda.gov
The CMC portion of this NDA was submitted as part of the ONDQA CMC Pilot. Program to explore science and risk based approaches to assuring product quality.
[30]
Submission of Quality Metrics Data Guidance for Industry - FDA
May 5, 2020 · Quality metrics are used throughout the drugs and biologics industry to monitor quality control systems and processes and drive continuous improvement efforts ...
[31]
Q8, Q9, & Q10 Questions and Answers -- Appendix - FDA
Using the Quality by Design (QbD) approach does not change regional regulatory requirements but can provide opportunities for more flexible approaches to meet ...Missing: core | Show results with:core
[32]
QbD: Improving Pharmaceutical Development and Manufacturing ...
Sep 1, 2017 · Implementing quality by design in product design and formulation and manufacturing workflows can help improve efficiency and shorten development times.
[33]
Quality Guidelines - ICH
A more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.
[34]
[PDF] Quality Risk Management - ICH
Nov 9, 2005 · This guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of ...
[35]
ICH Q8 (R2) Pharmaceutical development - Scientific guideline
This document describes the suggested contents for the 3.2.P.2 (Pharmaceutical Development) section of a regulatory submission in the ICH M4 Common Technical ...
[36]
Final Report from the FDA-EMA pilot program for the parallel
Jan 7, 2025 · Final report: FDA-EMA QbD Pilot Program. The pilot aimed to: share knowledge;; support consistent implementation of quality by design concepts ...
[37]
ICH Q12 Technical and regulatory considerations for ...
Dec 18, 2017 · This guideline provides a globally agreed framework to facilitate the management of such post-approval CMC changes in a predictable and efficient manner across ...
[38]
Quality by Design and Innovation - IEEE Xplore
The notion of quality by design has gained traction in business, engineering, and quality communities since the 1970s, following the Japanese automotive ...
[39]
An analysis of designing for quality in the automotive industry
The paper is based on the authors' experiences in devising and conducting continuing education courses on Designing for Quality for design, development and ...
[40]
Semiconductor Supplier Quality Best Practices | Applied SmartFactory
Supplier quality is a key contributor to enhancing Quality by Design practices. Improving quality systems for semiconductor manufacturing. by Yoram Barak and ...
[41]
An Industry Perspective on Quality By Design
Mar 1, 2012 · Here we present the results from a survey of biopharmaceutical manufacturing professionals undertaken to determine current QbD understanding in the industry.
[42]
Process Analytical Technology in the food industry - ScienceDirect
In this overview publication the principles of Process Analytical Technology (PAT) and Quality by Design (QbD) in food processing will be outlined.
[43]
Food safety and quality by design | Nestlé Global
Using science and technology, we ensure product safety and quality 'by design', while developing methods to identify, screen or anticipate potential risks.
[44]
Lean Production: Boeing Goes Full Throttle - 6Sigma.com
Feb 28, 2025 · The Boeing plan is to use newer and more standardized manufacturing techniques for its new 777X jetliner, paving the way for more significant savings.
[45]
Boeing: The Turning Point(s) - The Lean Thinker
Jul 2, 2024 · The new plane was also being designed with producibility in mind. The structural designs were far more tolerant of production variation, for ...Managing For World Class... · The Impact · Peak Boeing
[46]
Design of Experiments (DOE): Applications and Benefits in Quality ...
This chapter explores the applications and benefits of Design of Experiments (DOE) in the context of quality control and quality assurance.Missing: FMEA aerospace
[47]
The 6 Best Industries and Projects to use FMEA (Failure Mode and ...
Feb 25, 2025 · FMEA: Industries and Projects That Benefit from It · Automotive · Aerospace · Semiconductors · Food · Medical Devices · Telecommunications.How It Works · Fmea: Industries And... · Why It Matters
[48]
Aspects and Implementation of Pharmaceutical Quality by Design ...
May 8, 2025 · This review critically examines QbD's theoretical frameworks, implementation workflows, and industrial applications, aiming to bridge academic research and ...
[49]
Why is Quality by Design (QbD) important?
May 3, 2025 · Quality by Design (QbD) is a systematic approach to drug and medical ... Firstly, it reduces the risk of product recalls due to manufacturing ...
[50]
Rethinking Pharmaceutical Industry with Quality by Design
Oct 4, 2025 · Studies indicate that QbD can reduce development time by up to 40% by optimizing formulation parameters before full-scale manufacturing.
[51]
Quality-by-Design: The Good, The Bad, The Inevitable
QbD represents a schema or thought-process behind the development and manufacture of a product and adds a measure of accountability.
[52]
What Are The Advantages Of Using QbD? - LGM Pharma
Oct 1, 2021 · The QbD process is not the cheap route. It is important to factor in batch failures, which leads to another concern—upfront costs. Active ...Missing: limitations | Show results with:limitations
[53]
Integrating Artificial Intelligence with Quality by Design in the ...
Aug 8, 2023 · The aim of the current study is to explore the potential of artificial intelligence (AI) when integrated with Quality by Design (QbD) ...<|control11|><|separator|>
[54]
Revolutionizing Drug Development: The Role of Quality by Design ...
In personalized medicine and biologics, QbD ensures product consistency and quality, addressing the unique challenges posed by these complex therapies. Despite ...Missing: directions sustainability
[55]
[PDF] Building the next frontier: Artificial intelligence in 3D-printed medicines
Aug 14, 2025 · Using machine learning. (ML) and advanced data analytics, AI can rapidly predict optimal formulations, compositions, and printing parameters,.