Quality by Design

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Quality by Design (QbD) is a concept first outlined by quality expert Joseph M. Juran in publications, most notably Juran on Quality by Design.[1] 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.[2][3][4]

Pharmaceutical Quality by Design (QbD)[edit]

The FDA imperative is outlined in its report “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach.”[5] 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.[6]

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[edit]

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.[7]
  • 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) [8]

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[6] 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.[9]

ICH activities[edit]

Working with regulators in the European Union (the European Medicines Agency) and Japan, FDA has been 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.[10] 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[edit]


8. 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.

9. 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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