ICH set as their task to develop a new quality paradigm of which QbD is part of, by developing a harmonised pharmaceutical quality system, applicable across the lifecycle of the product, emphasizing an integrated approach to quality risk management and science.
The concept and definition of Quality by Design (QbD) is first and foremost described in ICH Q8:
- A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management
Quality by Design is described as a more systematic approach to pharmaceutical development. There are certain activities, which are required, as a minimum, to assure the process and the product are fully under control, compliant and meet the patients’ needs.
These basic activities include:
- Defining the quality target product profile (QTPP), which is a prospective summary of the quality characteristics of a drug product, as it relates to quality, safety and efficacy, considering e.g., the route of administration, dosage form, bioavailability, strength, and stability
- Identifying potential critical quality attributes (CQAs), which are a physical, chemical, biological or microbiological property or characteristic of the drug product, so that those product characteristics having an impact on product quality can be studied and controlled
- Determining the critical quality attributes of the drug substance, excipients etc., and selecting the type and amount of excipients to deliver drug product of the desired quality, where quality is defined as the suitability of either a drug substance or a drug product for its intended use. This term includes such attributes as the identity, strength, and purity
- Selecting an appropriate manufacturing process
- Defining a control strategy, which is a planned set of controls, derived from current product and process understanding that ensures process performance and product quality
Clearly, more information is needed to understand what is different between traditional (i.e. current) approaches versus the QbD way of developing a product along the drug lifecycle, also referred to as the enhanced approach.
Figure 16.G-3 is the comparison table as developed by ICH and published in ICH Q8(R2) (see chapter E.8).
Figure 16.G-3 The Enhanced Quality by Design Approach
The enhanced approach supports and emphasises:
- Quality must be built into the process as testing and inspection alone will not provide sufficient assurance that the product meets its quality target product profile (QTPP).
- Over the past two decades enormous scientific and technical progress has been made. The QbD approach calls for better utilisation of modern science throughout the product lifecycle.
- Limited resources and the need for speed (time to market) require risk-based decisions all the time. Quality Risk Management is seen as a key enabler to achieving the necessary controls and measures throughout product lifecycle.
- Existing Quality Management Systems (QMS) are focussed on meeting regulatory requirements, rather than focus on product quality in the first place. A robust Pharmaceutical Quality System assures quality throughout product life cycle.
- Whereas in the past companies could build up know-how about process and product throughout the lifecycle in-house, this model hardly exists these days. Many Contract Manufacturing Organisations (CMOs) and other service suppliers are involved in the generation of process and product understanding. Therefore, an appropriate approach to Knowledge Management is essential for the enhanced approach.
- The new paradigm is a challenge for all parties involved, the pharmaceutical industry, the regulatory agencies, standards bodies1, suppliers and teaching institutions2. Industry and regulators have to co-operate in delivering an integrated approach to development, manufacturing and quality.
About the Author
Dr. Siegfried Schmitt
PAREXEL Consulting, Uxbridge, Middlesex, England
Publications at Maas & Peither GMP Publishing:
(Author of chapter 16.G Quality by design - release in April 2012)
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