Dr. Stephen Sheenan
Abstract
The overall objective of this industry-led project was to establish a platform approach to direct compression (DC) tablet formulation/process development. A platform approach is the application of common processes to develop a family of similar products, in this study DC tablet DC. Platform processing approaches are commonly reported to accelerate product development in the biopharmaceutical sector. The advantages of platform approaches during development include a decrease in development time and cost, increase time to market. and simplification of scale up and process transfer. To date platform processes have not been reported for tablet manufacture or development of other small molecule drug products. However, it is commonplace for formulation developers to build on knowledge from similar products developed within their portfolio. To facilitate a structured methodology to implement a platform process approach to DC formulation development, an empirical modelling approach was employed.
The DC process can be divided into three stages; die filling, blend compaction and tablet ejection. The platform process was developed using 2 models; one for die filling and one for compaction. Eighteen DoEs were completed (6 formulations x 3 presses (1 R&D and 2 Production)) at the Alkermes sites at Athlone and Wilmington, and GEA Belgium. To generate the process models, 900 kg of blends were compressed and 20,000 tablets tested. The placebo formulations used for model development were designed with input from Alkermes scientists in Ireland and the US to cover the range of flow and compaction behaviour of commercial DC formulations.
The developed models currently inform formulation and process design plus scale-up to production tablet press models at the Alkermes site. For example, this model can predict how formulation flow behaviour can influence production capacity at commercial scale, Figure 1. Improving formulation flow during development can enable production capacity to be doubled. The models developed can identify formulations which are unable to achieve tablet specifications on pilot tablet presses due, to equipment limitations, but achieve these specifications on production scale models.
Figure 1. Implications of blend flow for production volumes and press usage
Dr. Stephen Sheehan is the Director of External Development and Manufacturing at Alkermes Pharma Ireland Ltd. Stephen has fifteen years’ experience in process engineering, technology transfers, project engineering and R&D in pharmaceutical, medical device and semiconductor industries. Whilst working in Alkermes Stephen successfully developed, registered and scaled numerous unit operations across three different oral solid dosage (OSD) drug product (DP) projects and one drug substance biological program. In his current role Stephen is responsible for the management of CDMOs involved with development activities and manufacturing of Alkermes drug development candidates through to the end of Stage 1, Process Design.
Stephen has a BE Eng in Chemical Engineering, an M Eng in Energy Systems, and a PhD in Chemical Engineering all from University College Dublin. Stephen also completed his MBA from the Micheal Smurfit Business School in Dublin.
You must be logged in to post a comment.