This thesis discusses the potential applications of process analytical techniques (PAT) and associated benefits of exploiting such in-line and at-line measurement tools during process development of solid dosage forms using case studies of two different development projects.
The most critical unit operations of the manufacturing process affecting downstream processability and Critical Quality Attributes of the final drug product to a great extent were fluid bed granulation for the first project (Project A) and active coating of tablets for the second project (Project B).
In Project A, fluid bed granulation processes were investigated by in-line particle size measurements using spatial filtering velocimetry and in-line moisture determination by near infrared spectroscopy (NIRS).
Implementation of these in-line tools significantly enhanced process understanding during development.
In addition, the candidate will present findings at conferences, in scientific publications, and enable industry-wide adaptation of technological advances.
IMA Active and VIAVI Solutions have the pleasure of inviting you to the symposium “PAT and Qb D in the solid dosage manufacturing: NIR integration from an engineering perspective”. (Founder at Optimal) Martin graduated in engineering with an honours degree from the University of Bath in the late 1970’s, when still we wrote with quill pens and electricity was a new novelty.The effect of varying process parameters on resulting granulate particle size was systematically investigated by means of a Design of Experiments (Do E) study, performed as several fractional factorial designs.The developed statistical model obtained from this study could accurately predict the median granulate size (D50) in dependence on the process parameters inlet air temperature and product temperature in the investigated ranges.Finally, in-line moisture monitoring by NIRS turned out to effectively support the scale-up activities to commercial scale.The added value of application of PAT during process development in this project did not save development time, but increased the required understanding of the (inter-) relationships between process parameters and attributes of the produced granulates.The candidate will partner with process and manufacturing scientists to identify, prioritize, and develop innovative PAT solutions within each of Biogen's four therapeutic modalities Job Category Technical Development Requisition Number36340BRThe candidate will partner with process and manufacturing scientists to identify, prioritize, and develop innovative PAT solutions within each of Biogen's four therapeutic modalities.Responsibilities include evaluation of existing and emerging analytical technologies, design of laboratory/pilot scale-based implementations of process monitoring advances, and a strong partnership with manufacturing scientists to ensure the development and eventual commercial implementation of fit-for-purpose technologies.In-line particle sizing provided insight into the dynamics of particle growth during different phases of fluid bed granulation process: wetting and nucleation, agglomeration and finally a steady-state phase, when agglomeration and attrition are at par.Furthermore, different technologies for particle sizing were compared.Two distinct models were developed: one focusing on measurements of individual tablets and one using a rotating sample cup as a measuring device, which allows the simultaneous measurement of a larger surface area of several tablets.Principal Component Analysis proves the specificity of both final models for the API.