Quality by Design
Encyclopedia
Quality by Design is a concept first outlined by well-known quality expert Joseph M. Juran
in various publications, most notably Juran on Quality by Design.. Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned in the first place.
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.
In the past few years, the Agency has made significant progress in implementing the concepts of "Quality by Design" (QbD) into its pre-market processes. The focus of this concept is that quality should be built into a product with a thorough 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 1990s.
While QbD will provide better design predictions, there is also a strong recognition that industrial scale-up and comercial manufacturing experience provides new and very important knowledge about the process and the raw materials used therein. FDA is aware that knowledge is not static and builds throughout the manufacturing lifecycle. 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 quickly corrected. This vigilant and nimble approach is explained by FDA to be essential to best protect the consumer (patient).
(the European Medicines Agency
) and Japan
, FDA has been instrumental in furthering 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. Further details are being developed by industry organizations to assure that Quality Systems objectives are met by application of experience and innovations as process understanding builds throughout the process lifecycle. This practical input should help ensure that quality risk management and knowledge management are used to make necessary lifecycle adaptations that maintain process control and product quality, including evolved controls as well as rapid corrective and preventative action (CAPA) to assure sustainable CGMP compliance.
Joseph M. Juran
Joseph Moses Juran was a 20th century management consultant who is principally remembered as an evangelist for quality and quality management, writing several influential books on those subjects. He was the brother of Academy Award winner Nathan H...
in various publications, most notably Juran on Quality by Design.. Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned in the first place.
While Quality by Design principles have been used to advance product and process quality in every industry, and particularly the automotive industry
Automotive industry
The automotive industry designs, develops, manufactures, markets, and sells motor vehicles, and is one of the world's most important economic sectors by revenue....
, 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.
Pharmaceutical quality by design
This FDA imperative is best outlined in its report “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach.”In the past few years, the Agency has made significant progress in implementing the concepts of "Quality by Design" (QbD) into its pre-market processes. The focus of this concept is that quality should be built into a product with a thorough understanding of the product
Product (business)
In general, the product is defined as a "thing produced by labor or effort" or the "result of an act or a process", and stems from the verb produce, from the Latin prōdūce ' lead or bring forth'. Since 1575, the word "product" has referred to anything produced...
and process
Business process
A business process or business method is a collection of related, structured activities or tasks that produce a specific service or product for a particular customer or customers...
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 1990s.
QbD activities within FDA
Specifically, the following activities are guiding the overall 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 applicationNew drug applicationThe New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
demonstrating use of QbD principles, product knowledge, and process understanding. In 2006, Merck & Co.Merck & Co.Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
’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 an active role in complementing the QbD initiative by optimizing pre-approval inspectional 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.
- Implementation of QbD for a Biologic License ApplicationBiologic License ApplicationAs defined by the US FDA, a Biologic License Application is: Biological products are approved for marketing under the provisions of the Public Health Service Act. The Act requires a firm who manufactures a biologic for sale in interstate commerce to hold a license for the product...
(BLA) is progressing.
While QbD will provide better design predictions, there is also a strong recognition that industrial scale-up and comercial manufacturing experience provides new and very important knowledge about the process and the raw materials used therein. FDA is aware that knowledge is not static and builds throughout the manufacturing lifecycle. 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 quickly corrected. This vigilant and nimble approach is explained by FDA to be essential to best protect the consumer (patient).
ICH activities
Working with regulators in the European UnionEuropean Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
(the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
) and Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, FDA has been instrumental in furthering 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. Further details are being developed by industry organizations to assure that Quality Systems objectives are met by application of experience and innovations as process understanding builds throughout the process lifecycle. This practical input should help ensure that quality risk management and knowledge management are used to make necessary lifecycle adaptations that maintain process control and product quality, including evolved controls as well as rapid corrective and preventative action (CAPA) to assure sustainable CGMP compliance.
See also
- Laboratory quality controlLaboratory quality controlLaboratory quality control is designed to detect, reduce, and correct deficiencies in a laboratory's internal analytical process prior to the release of patient results and improve the quality of the results reported by the laboratory. Quality control is a measure of precision or how well the...
- Quality controlQuality controlQuality control, or QC for short, is a process by which entities review the quality of all factors involved in production. This approach places an emphasis on three aspects:...
- International Society for Quality Electronic DesignInternational Society for Quality Electronic DesignThe International Society for Quality Electronic Design was established in 1990s with the mission to promote and foster quality in design of electronic systems and circuits...
External links
- Pharmaceutical Quality by Design: Improving Emphasis on Manufacturing Science in the 21 st Century, by Ajaz Hussain, PhD (formerly of FDA)
- Engineering a Proactive Decision System for Pharmaceutical Quality, by Ajaz Hussain, PhD (formerly of FDA)
- Implementing Quality by Design, by Helen Winkle, FDA
- Role of Statistics in Pharmaceutical Development Using Quality-by-Design Approach – an FDA Perspective
- Implementation of QbD Principles in CMC Review, by Chi-Wan Chen, PhD, Deputy Director, Office of New Drug Chemistry
- ICH Q9 Briefing Pack