Quality by Design
Quality by Design (QbD) is a concept first outlined by quality expert Joseph M. Juran in publications, most notably Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services. Designing for quality and innovation is one of the three universal processes of the Juran Trilogy, required to achieve breakthroughs in new products, services, and processes. Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned.
While Quality by Design principles have been used to advance product and process quality in every industry, and particularly the automotive industry, they have most recently been adopted by the U.S. Food and Drug Administration (FDA) as a vehicle for the transformation of how drugs are discovered, developed, and commercially manufactured.
Juran on Quality by Design
The Juran Trilogy  points out that the word “quality” incorporates two meanings: first, the presence of features that create customer satisfaction; second, freedom from failures of those features is also needed. In short, failures in features create dissatisfactions.
- Removing failures is the purpose of quality improvement.
- Creating features is the purpose of quality by design.
Modern design and planning seeks to create features in response to understanding customer needs. These are customer-driven features. The sum of all features is the new product, service, or process.
The Juran Quality by Design Model consists of following simple steps, primarily leading to a better understanding of the customers that will benefit from the new product. It is not a statistical design method as Design for Six Sigma is considered. It is often used to design new services and processes. The steps are as follows:
- Establish the project design targets and goals.
- Define the market and customers that will be targeted.
- Discover the market, customers, and societal needs.
- Develop the features of the new design that will meet the needs.
- Develop or redevelop the processes to produce the features.
- Develop process controls to be able to transfer the new designs to operations.
The Quality by Design model and its associated methods, tools, and techniques have been developed because in the history of modern society, organizations rather universally have demonstrated a consistent failure to produce the goods and services that unerringly delight their customers.
Integrated planning requires a team with a leader whose sole accountability is for the total success of the new product from defining the opportunity through customer purchase, use, service, and recommendation to others. This team leader reports directly to a senior executive, or the team leader can be a senior executive. Each team member’s job is to ensure the success of the new product.
- In addition to organizational integration, a successful team must begin with clearly articulated common goals for the product that are measurable and authorized by the enterprise. These goals must, at a minimum, cover such elements as:
- The customers or customer segments to be served by the new product
- The relative and absolute quality goals
- The volume of sales or revenue to be generated in an initial time period and for the long run
- Market share, penetration, or sales relative to key competitors
- The release date
The team will follow a structured process. The structure is the common framework for all participants in launching the new product and helps ensure success.
Quality by Design starts and ends with the customer. Every new product introduction always has some amount of trade-off involved. If there are multiple customers, they may have conflicting needs. Even the same customer may have needs that compete with each other. Capacity and speed compete with cost of operation. Capacity can compete with speed. Flexibility and feature-rich offerings may have reduced ease of use, and so on.
Quality by design offers a range of tools and methods to make these tradeoffs explicit and optimal for the customer. Some tools are highly mathematical, and others relate more to customer behavior.
Creativity and innovation must be highly valued, and Quality by Design sets strong expectations for creative approaches to functional design, product features and goals, and production design. Because quality by design provides strong and systematic assurances that the final design will create delighted, loyal customers, creativity will have significant payoff. The risks of innovations that will not sell, or creative designs that will not work, are much lower when companies observe the principles of quality by design. The chances of a truly magnificent innovation succeeding are greatly increased within this structured environment that ensures the defect-free delivery of that great design.
Control over variation and transfer to operations
Quality by design incorporates modern tools to dominate variation rather than merely suffer and recover from its consequences. These tools and methods always begin by measuring and understanding the variation that exists. Using historical data, testing, and modeling helps to forecast, analyze, and eliminate the deleterious effects of variation using standard statistical techniques. Process control consists of three basic activities:
- Evaluate the actual performance of the process
- Compare actual performance with goals
- Take action on the difference 
The final activity of the quality by design process is to implement the plan and validate that the transfer has occurred. A great deal of time and effort has gone into creating the product plan, and validating that it all works is well worth the effort.
Pharmaceutical Quality by Design (QbD)
The FDA imperative is outlined in its report “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach.” In the past few years, the agency has implemented the concepts of QbD into its pre-market processes. The focus of this concept is that quality should be built into a product with an understanding of the product and process by which it is developed and manufactured along with a knowledge of the risks involved in manufacturing the product and how best to mitigate those risks. This is a successor to the "quality by QC" (or "quality after design") approach that the companies have taken up until the 1990s.
The QbD initiative, which originated from the Office of Biotechnology Products (OBP), attempts to provide guidance on pharmaceutical development to facilitate design of products and processes that maximizes the product’s efficacy and safety profile while enhancing product manufacturability.
QbD activities within FDA
The following activities are guiding the implementation of QbD:
- In FDA’s Office of New Drug Quality Assessment (ONDQA), a new risk-based pharmaceutical quality assessment system (PQAS) was established based on the application of product and process understanding.
- Implementation of a pilot program to allow manufacturers in the pharmaceutical industry to submit information for a new drug application demonstrating use of QbD principles, product knowledge, and process understanding. In 2006, Merck & Co.’s Januvia became the first product approved based upon such an application.
- Implementation of a Question-based Review (QbR) Process has occurred in CDER's Office of Generic Drugs.
- CDER's Office of Compliance has played a role in complementing the QbD initiative by optimizing pre-approval inspection processes to evaluate commercial process feasibility and determining if a state of process control is maintained throughout the lifecycle, in accord with the ICH Q10 lifecycle Quality System.
- First QbD Approval - including design space - for Biologic License Application (BLA) is Gazyva (Roche) 
While QbD will provide better design predictions, there is alsoa recognition that industrial scale-up and commercial manufacturing experience provides knowledge about the process and the raw materials used therein. FDA's release of the Process Validation guidance in January 2011 notes the need for companies to continue benefiting from knowledge gained, and continually improve throughout the process lifecycle by making adaptations to assure root causes of manufacturing problems are corrected.
On the other hand - the premise that the current iteration of QbD places too much emphasis on mathematical algorithmic Design of Experiment (DoE) models unsuitable for application to complex, multifactorial, non-stochastic pharmaceutical processes has been advanced.
Working with regulators in the European Union (the European Medicines Agency) and Japan, the FDA has furthered Quality by Design objectives through the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH guidelines Q8 (on Pharmaceutical Development), Q9 (on Quality Risk Management), and Q10 (on Pharmaceutical Quality System) provide some assistance for manufacturers to implement Quality by Design into their own operations. The ICH Steering Committee meets twice a year to discuss the progress of its efforts. This practical input should help ensure that quality risk management and knowledge management are used to make lifecycle adaptations that maintain process control and product quality.
Joseph M. Juran, a perspective on past contributions and future impact, Quality and Reliability Engineering International, Vol. 23, pp. 653–663, 2007 by Godfrey, A.B. and Kenett, R.S.
Quality by Design Applications in Biosimilar Technological Products, ACQUAL, Accreditation and Quality Assurance, Springer Verlag, Vol. 13, No 12, pp. 681–690, 2008 by Kenett R.S. and Kenett D.A.
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