Quality by Design (QbD) involves switching from an empirical approach to one based on knowledge, understanding and sound science. Arguably its most significant impact will be at the development stage when more information will be required to thoroughly map product and process behavior. A better understanding of material properties will be essential and the industry is keen to find tools that will help. For powders, modern universal testers that measure shear, bulk and dynamic properties are a great choice, since they give the fullest material characterization, making it easier to detect which variables impact performance. 

For the pharmaceutical industry the conventional approach to manufacture involves very close specification of all aspects of the process, with testing at every stage to verify success. If a batch fails then it is discarded, often without really understanding the underlying causes of failure. The impact of variability, in a feed material or process parameter, is generally not well understood, and so a great deal of effort is made to avoid it; irrelevant specification setting is quite common. Since all process details form part of the regulatory submission there is a significant barrier to ongoing optimization.

The starting point for QbD is the identification of ‘critical to quality’ attributes, parameters that directly impact the performance of the final product. Process development focuses on the monitoring and control of these variables as a route to consistent production. An important step is development of the ‘design space’, a multivariate operating window within which manufacture is successful. It is important to recognize that the QbD approach defines acceptable boundaries for variability, based on a thorough understanding of the impact on product performance, rather than avoiding it completely (which is almost impossible in practical terms). From a regulatory point-of-view changes within the design space are not treated as process changes in the conventional sense, giving the manufacturer greater operational flexibility. Optimal definition of the design space is therefore vital.

The implementation of QbD clearly demands in depth understanding of the factors influencing product and process performance. For powders, this information can be gained by correlating aspects of behaviour – measured product properties or processing experience, for example - with specific powder properties. Since powders can be characterized in many different ways, and numerical models of their behaviour are beyond our current capabilities, multivariate characterization provides an optimal approach. With a universal powder tester, behaviour can be quantified rapidly and accurately in a range of different ways. These tools are therefore extremely valuable for the additional, more open-ended investigative research and development work encouraged by QbD.

Author Biography

Tim Freeman, Managing Director, Freeman Technology

Tim Freeman is Managing Director of powder characterisation company Freeman Technology for whom he has worked since the late 1990s. He was instrumental in the design and continuing development of the FT4 Powder Rheometer? and the Uniaxial Powder Tester. Through his work with various professional bodies, and involvement in industry initiatives, Tim is an established contributor to wider developments in powder processing.

Tim has a degree in Mechatronics from the University of Sussex in the UK. He is a mentor on a number of project groups for the Engineering Research Center for Structured Organic Particulate Systems in the US and a frequent contributor to industry conferences in the area of powder characterisation and processing. A past Chair of the American Association of Pharmaceutical Scientists (AAPS) Process Analytical Technology Focus Group Tim is a member of the Editorial Advisory Board of Pharmaceutical Technology and features on the Industry Expert Panel in European Pharmaceutical Review magazine.  Tim is also a committee member of the Particle Technology Special Interest Group at the Institute of Chemical Engineers, Vice-Chair of the D18.24 sub-committee on the Characterisation and Handling of Powders and Bulk Solids at ASTM and a member of the United States Pharmacopeial (USP) General Chapters Physical Analysis Expert Committee (GC-PA EC).

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