A glance on the history of pharmaceutical quality by design

Introduction Quality by design is a risk management and science-based approach promoted by the United States Food and Drug Administration to enhance pharmaceutical development throughout a product’s life cycle. Risk assessment approaches, process analytical technology tools and mathematical, statistical and continuous improvement tools are important elements of quality by design continuum, which mainly focus on the identification of critical parameters and defining a design space statistically. In this article, quality by design principles were discussed on the basis of several published case studies including development of bulk powder, granules, capsules, orally dispersible tablets, botanical drug products, nanoparticles and biopharmaceutical drugs. The use of quality by design approach in development of different methods, formulations and systems such as chromatographic and dissolution methods, physiologically absorption models, in situ implant formulations and singleuse bioreactors was also considered. Conclusion Full adoption of quality by design has great long-term benefits including enhanced understanding, well-defined system and regulatory flexibility. Quality by design has a great application potential for almost every step of pharmaceutical development. Industry, academia and regulatory bodies should cooperate to increase the level of quality by design implementation in the future. Introduction Quality by design (QbD) is one arm of the quality system based on building quality in the development phase and throughout a product’s life cycle. It can be underlined with risk management and science together1. International Conference on Harmonisation (ICH) defines QbD as2 ‘... a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management’. In 2002, United States Food and Drug Administration (FDA) made the first steps towards integrating the QbD concept into current good manufacturing practices (cGMPs), and in 2004 FDA released its final report on ‘Pharmaceutical cGMPs for the 21st Century: A Risk Based Approach’ guideline, with the aim of modernising the regulation of pharmaceutical manufacturing and product quality. This pharmaceutical quality paradigm shift is highlighted in the FDA’s ‘Process Analytical Technology (PAT): Guideline for Industry – A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance’. Besides this, ICH’s current ‘Q8(R2) Pharmaceutical Development’, ‘Q9 Quality Risk Management’ and ‘Q10 Pharmaceutical Quality System Guidelines’ were released in 2009, 2005 and 2008, respectively. QbD was first introduced into the Chemistry, Manufacturing and Controls review process in 2004 as a result of the Pharmaceutical cGMPs for the 21st Century Initiative3. Despite having been seen as a new paradigm in the pharmaceutical industry, QbD is not that new. In the 1950s, the first thoughts of operation windows, which transformed today’s design space, came up. Joseph M Juran created the QbD as a term in the 1970s and popularised it in the 1990s with several publications. After aforementioned guidelines were released, global regulatory agencies and industry have been trying to understand and to implement the QbD approach to the manufacturing process, for almost a decade. The pharmaceutical industry seems behind the times, but also with the 30–40 years of field experience, learning and implementation phases can be carried out quicker than other industries4,5. QbD fundamentally means building quality in, not testing it. QbD is good business and good science, with a complete product and process understanding. Compared with traditional quality by the testing (QbT) approach (Figure 1), QbD has great opportunities to build an efficient and flexible system with increased manufacturing efficiency, reduced costs, project rejections and waste. With scientific knowledge and risk management, QbD ensures consistent information and incorporated risk management6. While everyone is aware of these benefits and opportunities, QbD has not reached its potential yet. Betterman et al. pointed out its main cause as uncertainty in regulatory flexibility and recommended the strategic use of risk assessment tools, beginning with available ones instead of using all aspects of QbD at once, to enhance product development and fulfil regulatory needs7. * Corresponding author Email: ycapan@hacettepe.edu.tr Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey DrugDesignandDelivery1.indd 1 7/4/2014 12:51:21 PM