Introduction to Quality by Design in Pharmaceutical Manufacturing and Analytical Development

Written by twenty-five authors from academia, pharmaceutical industry and Pharmacopeias worldwide, this monograph covers the fundamentals and applications of Quality by Design (QbD) and Analytical Quality by Design (AQbD) in a practical and didactic manner. The book starts by describing the motivation and the urgent need for the implementation of the QbD framework in pharmaceutical development, along with the definition of its major elements: Quality Target Product Profile (QTTP), Critical Quality Attributes (CQAs), Critical Process Parameters (CPPs), Critical Material Attributes (CMAs) and the importance of using multivariate methods of Design of Experiments (DOE). The concept of life cycle and regulatory perspectives are discussed. 

Three chapters are entirely dedicated to DOE theory from screening to optimization designs. Moreover, a comprehensive discussion on modelling and data treatment is presented. Practical aspects of QbD and DOE for pharmaceutical product and process of different dosage forms is included, as well as a practical guide of the input process variables, material attributes, intermediate, and final quality attributes for the most representative pharmaceutical processes. Analytical Quality by Design (AQbD) is also deeply explored, including risk analysis, definitions of Analytical Target Profile (ATP), Method Operable Design Region (MODR) and the life cycle approach, taking into account the compendial and regulatory perspectives. A detailed example of a new chromatographic method for the quality control of a pharmaceutical topical product based on the AQbD procedure is shown. 

Finally, advanced statistical approaches and DOE methods for extraction studies of bioactive compounds are also presented. The vast amount of information offered in this book provides a comprehensive perspective on QbD, AQbD and DOE principles, essential tools for modern pharmaceutical and analytical development.

Part 1: Quality by Design (QbD) 

Chapter 1. Pharmaceutical Quality by Design (QbD) overview and major elements. Marcia Cristina and Ana Vanessa Dutra Silva. 

Chapter 2. Fundamentals of design of experiments and optimization: designs for factor screening and data analysis in pre-response surface methodology.  Fabricio A. Chiappini, Carla M. Teglia, Silvana M. Azcarate, Hector C. Goicoechea. 

Chapter 3. Fundamentals of design of experiments and optimization: experimental designs in response surface methodology. Silvana M. Azcarate, Carla M. Teglia, Fabricio A. Chiappini and Hector C. Goicoechea 

Chapter 4. Fundamentals of design of experiments and optimization: data modeling in response surface methodology. Fabricio A. Chiappini, Silvana M. Azcarate, Carla M. Teglia and Hector C. Goicoechea. 

Chapter 5. Quality by Design in pharmaceutical product and process development. Marília Medeiros and  Márcia Cristina Breitkreitz.  

Chapter 6. A Quality by Design update on nano-drug delivery systems. Darío Leonardi,  María Celina Lamas, Claudio Javier Salomon. 

Chapter 7. Control strategies of solid dosage forms by PAT tools. Pierre-Yves Sacré, Charlotte De Bleye, Philippe Hubert, Eric Ziemons. 

Part 2: Analytical Quality by Design (AQbD) 

Chapter 8. Analytical Quality by Design Fundamentals, Compendial and Regulatory Perspectives. Amanda Guiraldelli Mahr, Felipe Rebello Lourenço, Phil Borman, Jane Weitzel, and Jean-Marc Roussel. 

Chapter 9. Analytical Target Profile (ATP) and Method Operable Design Region (MODR). Amanda Guiraldelli Mahr, Felipe Rebello Lourenço, Phil Borman, Jane Weitzel, and Jean-Marc Roussel. 

Chapter 10: Quality by Design applications to development of analytical methods for quality control of pharmaceuticals. Yamile Soledad Caro, María Silvia Cámara and María Mercedes De Zan. 

Chapter 11. Design of Experiments Applied to the Extraction of Active Compounds. Ieda Spacino carminio1 and Roy Edward Bruns. 

Márcia Cristina Breitkreitz has worked since 2014 as Professor in the Chemistry Institute of the University of Campinas (UNICAMP), coordinating the Laboratory of Pharmaceutical Research and Chemometrics (LabFarQui). She was a researcher in Chemometrics from 2006-2007 at the International Institute of Pharmaceutical Research (IIPF, Brazil) and coordinator of Research and Development (R&D) from 2007 to 2009, where she started the implementation of chemometrics methods for pharmaceutical development.  She received her PhD (2013) degree from UNICAMP, with a project aimed at using hyperspectral imaging  (NIR/Raman) and multivariate analysis to develop stable pharmaceutical formulations.  Her major research interests are related to Chemometrics applied to the development of pharmaceutical products and processes according to the strategy of Quality by Design (QbD); development of analytical methods based Analytical Quality by Design (AQbD) and the use of vibrational spectroscopy (IR, NIR and Raman, point and imaging) for pharmaceutical development and troubleshooting. In addition to her research work and teaching (graduate and undergraduate levels), Prof. Marcia is dedicated to courses and consultancy on relevant topics to the pharmaceutical industry, especially related to Chemometrics within the context of Quality by Design.

Héctor C. Goicoechea was born in Santa Fe, Argentina, on May 15, 1961. He received his Ph.D. (2000) from the National University of Rosario. After a postdoctoral research at North Dakota State University, USA, he joined the University of Litoral, Santa Fe (2004), where he is Full Professor of Analytical Chemistry/Chemometrics. He is fellow (Senior Researcher) of the National Research Council of Argentina (CONICET), and has founded a research group (LADAQ). His works in the development of analytical methods based on spectroscopy, separations and electrochemistry coupled to chemometrics. He published more than 220 papers in well-known international journals, two books, 8 book chapters and has supervised thirteen Ph.D. Theses.