Pharmaceutical Quality by Design

Principles and Applications

Sarwar Beg, Md Saquib Hasnain, Sarwar Beg, Md Saquib Hasnain

• Publisher: Academic Press
• Year: 2019
• ISBN:
  9780128163726
• Topic: Medicine
• Subtopic: Pharmacology

Pharmaceutical Quality by Design: Principles and Applications discusses the Quality by Design (QbD) concept implemented by regulatory agencies to ensure the development of a consistent and high-quality pharmaceutical product that safely provides the maximum therapeutic benefit to patients. The book walks readers through the QbD framework by covering the fundamental principles of QbD, the current regulatory requirements, and the applications of QbD at various stages of pharmaceutical product development, including drug substance and excipient development, analytical development, formulation development, dissolution testing, manufacturing, stability studies, bioequivalence testing, risk and assessment, and clinical trials.

Contributions from global leaders in QbD provide specific insight in its application in a diversity of pharmaceutical products, including nanopharmaceuticals, biopharmaceuticals, and vaccines. The inclusion of illustrations, practical examples, and case studies makes this book a useful reference guide to pharmaceutical scientists and researchers who are engaged in the formulation of various delivery systems and the analysis of pharmaceutical product development and drug manufacturing process.

• Discusses vital QbD precepts and fundamental aspects of QbD implementation in the pharma, biopharma and biotechnology industries
• Provides helpful illustrations, practical examples and research case studies to explain QbD concepts to readers
• Includes contributions from global leaders and experts from academia, industry and regulatory agencies

Chapter 1

Introduction to Quality by Design (QbD): Fundamentals, Principles, and Applications

Sarwar Beg*; Md Saquib Hasnain^†; Mahfoozur Rahman^‡; Suryakanta Swain^§ * Department of Pharmaceutics, School of Pharmaceutical Education and Research (SPER), Jamia Hamdard (Hamdard University), New Delhi, India
^† Department of Pharmacy, Shri Venkateshwara University, Gajraula, India
^‡ Department of Pharmaceutical Sciences, Shalom Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad, India
^§ Southern Institute of Medical Sciences, College of Pharmacy, Department of Pharmaceutics, SIMS Group of Institutions, Guntur, India

Abstract

Pharmaceutical quality has been under long debate for decades. In the current scenario of regulatory environments, the pharmaceutical industry is continuously facing challenges with respect to achieving the desired quality of drug products. The two major issues highlighted over the years include poor cGMP compliance and lack of understanding regarding the product and process parameters. This has ultimately generated consumer skepticism regarding the quality of pharmaceutical products, especially the generic medicines. Hence, the global regulatory agencies such as ICH and USFDA took initiatives by implementing the culture of quality for improving manufacturing standards. In this context, the pharmaceutical industry has undergone a paradigm shift from traditional quality by testing (QbT) to the systematic quality by design (QbD) approach for attaining efficient development of drug products with enhanced quality and resource economics. Recently, QbD has been considered as a lifecycle approach, as it is omnipresent at all stages of the product development. The present book chapter, in this regard, endeavors to provide an overview account on various facets of QbD in pharmaceutical development for ultimately attaining manufacturing excellence and regulatory compliance.

Keywords

Optimization; Risk assessment; Quality by design (QbD); Design space; Control strategy

1 Introduction

The pharmaceutical market has been considered as one of the highly regulated sectors, which has been continuously providing quality drug products for human use to provide desired pharmacotherapeutic effects for the treatment of diverse ailments. From the past few decades, however, the pharmaceutical industry has been continuously facing challenges in delivering quality drug products. As per the news article published in The Wall Street Journal on September 2002, it was reported that “although pharmaceutical industry has a little secret as it invents futuristic new drugs, yet its manufacturing standards are lag far behind the potato chips and laundry soap makers.” The major issues pertaining to the poor quality of drug products could be attributed to more than one reasons such as variable starting materials, lack of manufacturing process automation and control, and improper understanding on the product and process parameters.¹ Fig. 1 shows the key sources of variability associated with the development of pharmaceutical products, which are responsible for product recall in a major manner.

Fig. 1 Sources of variability in drug product quality.

Due to the poor pharmaceutical product quality, the first initiative was a step forward by the United States Food and Drug Administration (USFDA) for inculcation of quality paradigms into pharmaceutical development and regulatory practice. In this regard, a concept paper was published in 2004, which highlighted the vision of agency for revolutionizing the quality paradigm in the form of “Pharmaceutical cGMP for 21st Century”.² After this initiative, the International Conference on Harmonization (ICH) instituted various regulatory guidances (Q8, Q9, and Q10) and set forth the concept of quality by design (QbD) as a holistic approach, which delivers high-quality robust drug products.

2 Evolution of QbD concept

QbD is not a new concept for the world. The concept was formulated by J.M. Juran, an American Engineer, in the early 1970s through his famous book “Juran on Quality by Design”,³ which was later adopted by several technology-driven areas like, telecommunication, automobile, and aviation industries engaged in the development of high-quality products and services. The concept was later adopted by health-care industries, and especially utilized by medical device manufacturers in the 1990s. QbD into the pharmaceutical industry entered quite late in 2004, when USFDA took initiative for improving the standards of pharmaceutical manufacturing.²

3 Pharmaceutical Quality System: A Newer Quality Trend

In 2005, USFDA built up the culture of quality through guidance for industry published in the form of “Quality Systems Approach to Pharmaceutical CGMP Regulations.”⁴ This newer system was exclusively focused on critical attributes related to the chemistry, manufacturing, and control, and their relevance to safety and effectiveness of the drug product. It also emphasized the scientific basis of the submission, ultimately demonstrating product and process understanding. Later, it enabled the FDA to provide flexibility in regulatory oversight for revolutionizing product development efficiency in prior submission and after submission during post-approval phases. Moreover, this system also endeavored to facilitate scientific innovation and continuous improvement throughout the product lifecycle. Fig. 2 illustrates in detail pharmaceutical quality systems, which contain multiple systems marked with control on the production process, facilities and equipment maintenance, laboratory control monitoring, material management, packaging, and labeling control.

Fig. 2 Quality system indicating various cross-functional systems involved during pharmaceutical product development. (Adapted from USFDA Guidance for Industry Quality Systems Approach to Pharmaceutical CGMP Regulations.)

4 ICH Guidelines on QbD and Related Paradigms

ICH instituted three different guidelines for implementation of the culture of quality into pharmaceutical development practice. These include ICH Q8, Q9, and Q10 guidelines, which act in tandem with each other to potentiate quality development. ICH Q8 primarily aims for Pharmaceutical Development to design a quality product and its manufacturing process to consistently deliver the intended product performance.⁵ ICH Q9 primarily aims for Quality Risk Management principles, which as a part of effective quality system, help in identifying the probability of occurrence and severity of risk.⁶ ICH Q10 describes the Pharmaceutical Quality System, which is based on the International Standards Organization (ISO) principle related to Good Manufacturing Practice (GMP) regulations, and also complements ICH Q8 and Q9 guidelines for holistic improvement in the quality.⁷

5 Philosophy and Principles of QbD

Based on the heels of Juran's philosophy and culture of quality, pharmaceutical QbD also relies on development of drug product(s) and process(es) using systematic approaches and rational scientific principles for achieving target quality in the end product.⁸ With QbD around, the predefined objectives of the target quality enable zero quality defects and avoid quality crisis. Many scientists consider quality as a matter of conscious intent and meaningful execution of the operations involved in the manufacturing of the drug products.⁹ QbD also facilitates improvement in quality by thoughtful planning and meaningful execution. Hence, QbD is also called quality by planning, but not by chance. Use of sound scientific principles and quality risk management (QRM) are the two key enablers of QbD philosophy, which provides enhanced p...