Quality By Design
   HOME

TheInfoList



OR:

Quality by design (QbD) is a concept first outlined by quality expert
Joseph M. Juran Joseph Moses Juran (December 24, 1904 – February 28, 2008) was a Romanian-born American engineer, management consultant and author. He was an advocate for quality and quality management and wrote several books on the topics. He was the brother ...
in publications, most notably ''Juran on Quality by Design''. Designing for quality and innovation is one of the three universal processes of the Juran Trilogy, in which Juran describes what is 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 industry, and particularly the
automotive industry The automotive industry comprises a wide range of company, companies and organizations involved in the design, Business development, development, manufacturing, marketing, selling, Maintenance, repairing, and Custom car, modification of motor ve ...
, they have also been adopted by the
U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) for the discovery, development, and manufacture of drugs.


Juran on quality by design

The Juran Trilogy defines the word "quality" as having two meanings: first, the presence of features that create customer satisfaction; second, the reliability of those features. Failures in features create dissatisfactions, so removing failures is the purpose of quality improvement, while creating features is the purpose of quality by design. Juran's process 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 quality by design model consists of the following steps: # 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 control Industrial process control (IPC) or simply process control is a system used in modern manufacturing which uses the principles of control theory and physical industrial control systems to monitor, control and optimize continuous Industrial processe ...
s to be able to transfer the new designs to operations. It is not a statistical design method like Design for Six Sigma.


Integrated planning

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.


Customer-focused optimization

Quality by design starts and ends with the customer. Every new product introduction 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 intended to make these tradeoffs explicit and optimal for the customer. Some tools are highly mathematical, and others relate more to customer behavior. Quality by design sets strong expectations for creative approaches to functional design, product features and goals, and production design.


Control over variation and transfer to operations

Quality by design incorporates modern tools to preemptively control variation. These tools and methods begin by measuring and understanding the variation that exists by using historical data, testing, and modeling to help 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.


Pharmaceutical quality by design

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 A process is a series or set of activities that interact to produce a result; it may occur once-only or be recurrent or periodic. Things called a process include: Business and management * Business process, activities that produce a specific s ...
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 The pharmaceutical industry is a medical industry that discovers, develops, produces, and markets pharmaceutical goods such as medications and medical devices. Medications are then administered to (or self-administered by) patients for curing ...
to submit information for a
new drug application The Food and Drug Administration's (FDA) New Drug Application (NDA) is the vehicle in the United States through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing. Some 30% or less of initial ...
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 The Center for Drug Evaluation and Research (CDER, pronounced "see'-der") is a division of the U.S. Food and Drug Administration (FDA) that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also le ...
'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 A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows: The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...
(BLA) is Gazyva (Roche) While QbD will provide better design predictions, there is also a 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 Process validation is the analysis of data gathered throughout the design and manufacturing of a product in order to confirm that the process can reliably output products of a determined standard. Regulatory authorities like EMA and FDA have publish ...
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.


ICH activities

Working with regulators in the
European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...
(the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
) and
Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...
, the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
has furthered quality by design objectives through the
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an initiative that brings together regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of p ...
. The ICH Guidelines Q8 through Q11 encapsulate these unified recommendations and provide some assistance for manufacturers to implement quality by design into their own operations. ICH Guideline Q8 describes QbD-based drug formulation development and was first published in 2004, being subsequently revised in 2008 (Q8(R2)). The ICH Guideline Q9 describes Quality Risk Management plans, Q10 explains Pharmaceutical Quality Systems, and Q11 refer to the development of active pharmacological substances including biologicals. In November 2017, the ICH issued Guideline Q12 for public consultation to extend the recommendations for the Product Lifecycle Management Plan that were initially defined in the Guideline Q10. According to the ICH, Guideline Q13 will extend the previous guidelines to accommodate continuous pharmaceutical manufacturing and Q2 (Analytical Validation) will be revised and extended into the guideline Q2(R2)/Q14 to include Analytical quality by design or AQbD. 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.


See also

* Laboratory quality control *
Quality control Quality control (QC) is a process by which entities review the quality of all factors involved in production. ISO 9000 defines quality control as "a part of quality management focused on fulfilling quality requirements". This approach plac ...


Further reading

* *


References


External links


Implementing Quality by Design, by Helen Winkle, FDA

Implementation of QbD Principles in CMC Review, by Chi-Wan Chen, PhD, Deputy Director, Office of New Drug Chemistry

Quality-by-Design Case Studies in Pharmaceuticals and Biologics

Juran.com
{{DEFAULTSORT:Quality By Design Quality