Biomedical Engineering Reference
In-Depth Information
9
APPLICATION OF QUALITY
BY DESIGN AND RISK
ASSESSMENT PRINCIPLES
FOR THE DEVELOPMENT OF
FORMULATION DESIGN SPACE
Kingman Ng and Natarajan Rajagopalan
9.1 INTRODUCTION
The goal of pharmaceutical development is to design and establish a formulation
composition and its manufacturing process to consistently meet all the appropriate
quality attributes required for its intended therapeutic performance and safety profile. In
the past, unacceptable product quality due to either component or process variability was
only detected from laboratory testing of the finished product. Recently, FDA has
challenged the pharmaceutical industry to embrace the concept of Quality by Design
(QbD), where the appropriate level of quality must be designed into the product and
the process based on scientific understanding and quality risk management approach.
In particular, the information and knowledge gained from pharmaceutical development
studies and manufacturing experience provide scientific understanding to support the
establishment of the design space, specifications, and manufacturing controls [1].
Development of an acceptable dosage form for biotechnology-derived products is
extremely challenging because protein molecules require a unique three-dimensional
structure for biological activity. In addition, proteins are composed of numerous reactive
groups that can be subject to various types of degradation chemistry such as covalent and
noncovalent aggregation, deamidation, cleavages, oxidation, and denaturation, all of
