Department of Pharmaceutical Analysis

Fanny Stauffer

Laboratory of Pharmaceutical Process Analytical TechnologyFanny Stauffer

Ottergemsesteenweg 460
B-9000 Gent (Belgium)
Tel.: +32-9-264.80.39
Fax: +32-9-222.82.36
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Managing raw material variability in continuous manufacturing based on twin-screw granulation

Currently, pharmaceutical processes are mainly performed batch wise, implying a time-consuming a posteriori quality control of randomly-collected samples of intermediate and final products. Recently, the interest of the pharmaceutical industry for continuous processing has arisen in order to ensure more efficient production and a better control of the final product quality. This mind shift presents the advantage of reducing the development and production costs by limiting or avoiding scale-up and by improving the stability and flexibility of production processes.

The development of continuous processes was greatly accelerated by the publication of the FDA guidance for industry process analytical technology (PAT) [1]. This guidance states that “quality cannot be tested into products; it should be built-in or should be by design”. From this moment, developers and manufacturers were encouraged to understand the relationship between raw material physico-chemical characteristics, process parameters and the final product critical quality attributes (CQA’s).

This study focuses on the influence of raw material variability in continuous twin-screw granulation. In a first step, raw materials are characterized physically and technologically to determine their critical attributes for processability and the final product quality. In a second step, these data will be included in the process transfer from batch high-shear granulation to continuous twin-screw granulation. Furthermore, mechanistic models will be developed and process analytics will be implemented to develop a statistical process monitoring and ensure a consistent product quality.

[1]    Food and Drug Administration. Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. (2004).