-
Implementation of a fully integrated CM direct compression and coating process at a commercial pharmaceutical facility - Part 2: PAT and RTD results for normal operational conditions batches.
Contributor(s):: Rosas, JG, Brush, P, Thompson, B, Miller, C, Overton, P, Tugby, N, Stoliarskaia, D, Hurley, S, Ramasamy, M, Conway, SL
This is the second of two articles detailing the continuous manufacturing (CM) development and implementation activities for an marketed product which have been realized in novel, qualified equipment, using validated control strategy elements to enable manufacture of batches under current good...
-
Implementation of a fully integrated continuous manufacturing line for direct compression and coating at a commercial pharmaceutical facility – Part 1: Operational considerations and control strategy
Contributor(s):: Conway, Stephen L., Rosas, Juan G., Overton, Paul, Tugby, Neil, Cryan, Phillip, Witulski, Frank, Hurley, Samantha, Wareham, Laura, Tantuccio, Anthony, Ramasamy, Manoharan, Lalloo, Anita, Gibbs, Mason, Meyer, Robert F.
We implement a fully integrated continuous manufacturing (CM) line for direct compression and coating of a pharmaceutical oral solid dosage form in a commercial production facility. In this first paper of a two-part series, we describe process design and operational choices made to introduce CM...
-
Real-time assessment of critical quality attributes of a continuous granulation process
Contributor(s):: Fonteyne, Margot, Vercruysse, Jurgen, Díaz, Damián Córdoba, Gildemyn, Delphine, Vervaet, Chris, Remon, Jean Paul, De Beer, Thomas
There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories,...
-
Prediction of quality attributes of continuously produced granules using complementary PAT tools
Contributor(s):: Fonteyne, Margot, Soares, Sandra, Vercruysse, Jurgen, Peeters, Elisabeth, Burggraeve, Anneleen, Vervaet, Chris, Remon, Jean Paul, Sandler, Niklas, De Beer, Thomas
Manufacturers of pharmaceutical solid dosage forms aim for a reduced production time and a shorter‘‘time-to-market.’’ Therefore, continuous manufacturing gains increasing interest in the pharmaceutical industry. For continuous manufacturing, the quality of produced pharmaceuticals should be...
-
Orthogonal Redundant Monitoring of a New Continuous Fluid-Bed Dryer for Pharmaceutical Processing by Means of Mass and Energy Balance Calculations and Spectroscopic Techniques
Contributor(s):: Pauli, Victoria, Elbaz, Frantz, Kleinebudde, Peter, Krumme, Markus
In line with the ongoing shift from batch to continuous pharmaceutical production of solid oral dosage forms, a novel continuous fluid-bed dryer was developed. The forced feed nature of the Glatt GPCG2 CM fluid-bed dryer allows continuous, first-in-first-out drying of wet granulate materials...
-
Modelling the primary drying step for the determination of the optimal dynamic heating pad temperature in a continuous pharmaceutical freeze-drying process for unit doses
Contributor(s):: De Meyer, Laurens, Lammens, Joris, Mortier, Severine Therese F. C., Vanbillemont, Brecht, Van Bockstal, Pieter Jan, Corver, Jos, Nopens, Ingmar, Vervaet, Chris, De Beer, Thomas
In the pharmaceutical industry, traditional freeze-drying of unit doses is a batch-wise process associated with many disadvantages. To overcome these disadvantages and to guarantee a uniform product quality and high process efficiency, a continuous freeze-drying process is developed and...
-
Monitoring ibuprofen–nicotinamide cocrystal formation during solvent free continuous cocrystallization (SFCC) using near infrared spectroscopy as a PAT tool
Contributor(s):: Kelly, A.L., Gough, T., Dhumal, R.S., Halsey, S.A., Paradkar, A.
The purpose of this work was to explore NIR spectroscopy as a PAT tool to monitor the formation of ibuprofen and nicotinamide cocrystals during extrusion based solvent free continuous cocrystallization (SFCC). Drug and co-former were gravimetrically fed into a heated co-rotating twin screw...
-
Flexible automation with compact NMR spectroscopy for continuous production of pharmaceuticals
Contributor(s):: Kern, Simon, Wander, Lukas, Meyer, Klas, Guhl, Svetlana, Gottu Mukkula, Anwesh, Holtkamp, Manuel, Salge, Malte, Fleischer, Christoph, Weber, Nils, King, Rudibert, Engell, Sebastian, Paul, Andrea, Pereira Remelhe, Manuel, Maiwald, Michael
Modular plants using intensified continuous processes represent an appealing concept for the production of pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes; besides, it enables plug-and-produce / reconfiguration for fast product...
-
Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses
Contributor(s):: De Meyer, L., Van Bockstal, P. -J., Corver, J., Vervaet, C., Remon, J. P., De Beer, T.
Spin-freezing as alternative freezing approach was evaluated as part of an innovative continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials in a batch freeze-dryer, and its...
-
Concentration monitoring with near infrared chemical imaging in a tableting press
Contributor(s):: Dalvi, Himmat, Fauteux-Lefebvre, Clémence, Guay, Jean-Maxime, Abatzoglou, Nicolas, Gosselin, Ryan
Monitoring powder potency and homogeneity is important in achieving real-time release testing in a continuous tablet manufacturing operation. If quality related issues are encountered, monitoring powder potency inside a feed frame offers a last opportunity to intervene in the process before...
-
Application of FT-NIR Analysis for In-line and Real-Time Monitoring of Pharmaceutical Hot Melt Extrusion: a Technical Note
Contributor(s):: Vo, Anh Q., He, Herman, Zhang, Jiaxiang, Martin, Scott, Chen, Rui, Repka, Michael A.
Continuous manufacturing, a gaining interest paradigm in the pharmaceutical industry, requires in-process monitoring of critical process parameters to ensure product consistency. This study demonstrated the application of Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with...
-
A Framework for Representative Sampling for NIR Analysis – Theory of Sampling (TOS)
Contributor(s):: Esbensen, Kim H, Ciurczak, Emil W., Igne, Benoît, Workman, Jr.,Jerome, Burns, Donald A., Romañach, Rodolfo J.
This chapter deals with all critical steps before near-infrared spectroscopy (NIR) analysis, irrespective of whether the total sampling error contribution is large, intermediate, or small – all cases can be treated identically, including the widespread sensor-based solutions from the...