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Process Analytical Technology (process + analytical_technology)
Selected AbstractsDisposable bioprocessing: The future has arrivedBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Govind Rao Abstract Increasing cost pressures are driving the rapid adoption of disposables in bioprocessing. While well ensconced in lab-scale operations, the lower operating/ validation costs at larger scale and relative ease of use are leading to these systems entering all stages and operations of a typical biopharmaceutical manufacturing process. Here, we focus on progress made in the incorporation of disposable equipment with sensor technology in bioprocessing throughout the development cycle. We note that sensor patch technology is mostly being adapted to disposable cell culture devices, but future adaptation to downstream steps is conceivable. Lastly, regulatory requirements are also briefly assessed in the context of disposables and the Process Analytical Technologies (PAT) and Quality by Design (QbD) initiatives. Biotechnol. Bioeng. 2009;102: 348,356. © 2008 Wiley Periodicals, Inc. [source] Noncontact photo-acoustic defect detection in drug tabletsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2007Ivin Varghese Abstract Quality assurance monitoring is of great importance in the pharmaceutical industry for the reason that if defects such as coating layer irregularities, internal cracks, and delamination are present in a drug tablet, the desired dose delivery and bioavailability can be compromised. The U.S. Food and Drug Administration (FDA) established the Process Analytical Technology (PAT) initiative, in order to ensure efficient quality monitoring at each stage of the manufacturing process by the integration of analysis systems into the evaluation procedure. Improving consistency and predictability of tablet action by improving quality and uniformity of tablet coatings as well as ensuring core integrity is required. An ideal technique for quality monitoring would be noninvasive, nondestructive, have a short measurement time, intrinsically safe, and relatively inexpensive. In the proposed acoustic system, a pulsed laser is utilized to generate noncontact mechanical excitations and interferometric detection of transient vibrations of the drug tablets is employed for sensing. Two novel methods to excite vibrational modes in drug tablets are developed and employed: (i) a vibration plate excited by a pulsed-laser and (ii) pulsed laser-induced plasma generated shockwave expansion. Damage in coat and/or core of a tablet weakens its mechanical stiffness and, consequently, affects its acoustic response to an external dynamic force field. From the analysis of frequency spectra and the time,frequency spectrograms obtained under both mechanisms, it can be concluded that defective tablets can be effectively differentiated from the defect-free ones and the proposed proof-of-concept techniques have potential to provide a technology platform to be used in the greater PAT effort. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:2125,2133, 2007 [source] A Process Analytical Technology approach to near-infrared process control of pharmaceutical powder blending.JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006Part I: D-optimal design for characterization of powder mixing, preliminary spectral data evaluation Abstract Experimental design, multivariate data acquisition, and analysis in addition to real time monitoring and control through process analyzers, represent an integrated approach for implementation of Process Analytical Technology (PAT) in the pharmaceutical industry. This study, which is the first in a series of three parts, uses an experimental design approach to identify critical factors affecting powder blending. Powder mixtures composed of salicylic acid and lactose were mixed in an 8 qt. V-blender. D-optimal design was employed to characterize the blending process, by studying the effect of humidity, component concentration, and blender speed on mixing end point. Additionally, changes in particle size and density of powder mixtures were examined. A near-infrared (NIR) fiber-optic probe was used to monitor mixing, through multiple optical ports on the blender. Humidity, component concentration, and blender speed were shown to have a significant impact on the blending process. Furthermore, humidity and concentration had a significant effect on particle size and density of powder mixtures. NIRS was sensitive to changes in physicochemical properties of the mixtures, resulting from process variables. Proper selection of NIR spectral preprocessing is of ultimate importance for successful implementation of this technology in the monitoring and control of powder blending and is discussed. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:392,406, 2006 [source] Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for real-time monitoring and mapping the state of a pharmaceutical coprecipitation process,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2010Huiquan Wu Abstract In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen) and a polymer (eudragit) coprecipitation process: real-time in-line near-infrared (NIR) absorbance monitoring, real-time on-line turbidity monitoring, and in situ crystal size monitoring. The data and information obtained through these three monitoring techniques confirmed the observation of the onsets of three distinct stages: incubation, nucleation, and crystal growth. The process trajectory constructed based on results of applying principal component analysis (PCA) to either process NIR spectra data or process turbidity profile, clearly demonstrated that various distinguishable process events, including incubation, nucleation, and crystal growth, could be accurately tracked and differentiated. These findings were further supported by process knowledge and information, such as process design, process sequence, thermodynamic and mass-transfer analysis. Therefore, this work provides a case study that illustrated a rational approach to develop a science-based and knowledge-based process monitoring strategy, which is essential for establishing both a suitable process control strategy and an operational process space for a pharmaceutical unit operation. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1516,1534, 2010 [source] Biomanufacturing process analytical technology (PAT) application for downstream processing: Using dissolved oxygen as an indicator of product quality for a protein refolding reactionBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Shelly A. Pizarro Abstract Process analytical technology (PAT) is an initiative from the US FDA combining analytical and statistical tools to improve manufacturing operations and ensure regulatory compliance. This work describes the use of a continuous monitoring system for a protein refolding reaction to provide consistency in product quality and process performance across batches. A small-scale bioreactor (3,L) is used to understand the impact of aeration for refolding recombinant human vascular endothelial growth factor (rhVEGF) in a reducing environment. A reverse-phase HPLC assay is used to assess product quality. The goal in understanding the oxygen needs of the reaction and its impact to quality, is to make a product that is efficiently refolded to its native and active form with minimum oxidative degradation from batch to batch. Because this refolding process is heavily dependent on oxygen, the % dissolved oxygen (DO) profile is explored as a PAT tool to regulate process performance at commercial manufacturing scale. A dynamic gassing out approach using constant mass transfer (kLa) is used for scale-up of the aeration parameters to manufacturing scale tanks (2,000,L, 15,000,L). The resulting DO profiles of the refolding reaction show similar trends across scales and these are analyzed using rpHPLC. The desired product quality attributes are then achieved through alternating air and nitrogen sparging triggered by changes in the monitored DO profile. This approach mitigates the impact of differences in equipment or feedstock components between runs, and is directly inline with the key goal of PAT to "actively manage process variability using a knowledge-based approach." Biotechnol. Bioeng. 2009; 104: 340,351 © 2009 Wiley Periodicals, Inc. [source] Case study and application of process analytical technology (PAT) towards bioprocessing: Use of tryptophan fluorescence as at-line tool for making pooling decisions for process chromatographyBIOTECHNOLOGY PROGRESS, Issue 5 2009Anurag S. Rathore Abstract Process analytical technology (PAT) has been gaining momentum in the biopharmaceutical community due to the potential for continuous real time quality assurance resulting in improved operational control and compliance. Two imperatives for implementing any PAT tool are that "variability is managed by the process" and "product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions." Recently, we have been examining the feasibility of applying different analytical tools to bioprocessing unit operations. We have previously demonstarted that commercially available online-high performance liquid chromatography and ultra performance liquid chromatography systems can be used for analysis that can facilitate real-time decisions for column pooling based on product quality attributes (Rathore et al., 2008a,b). In this article, we review an at-line tool that can be used for pooling of process chromatography columns. We have demonstrated that our tryptophan fluorescence method offers a feasible approach and meets the requirements of a PAT application. It is significantly faster than the alternative of fractionation, offline analysis followed by pooling. Although the method as presented here is not an online method, this technique may offer better resolution for certain applications and may be a more optimal approach as it is very conducive to implementation in a manufacturing environment. This technique is also amenable to be used as an online tool via front face fluorescence measurements done concurrently with product concentration determination by UV. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Bioprocess optimization using design-of-experiments methodologyBIOTECHNOLOGY PROGRESS, Issue 6 2008Carl-Fredrik Mandenius Abstract This review surveys recent applications of design-of-experiments (DoE) methodology in the development of biotechnological processes. Methods such as factorial design, response surface methodology, and (DoE) provide powerful and efficient ways to optimize cultivations and other unit operations and procedures using a reduced number of experiments. The multitude of interdependent parameters involved within a unit operation or between units in a bioprocess sequence may be substantially refined and improved by the use of such methods. Other bioprocess-related applications include strain screening evaluation and cultivation media balancing. In view of the emerging regulatory demands on pharmaceutical manufacturing processes, exemplified by the process analytical technology (PAT) initiative of the United States Food and Drug Administration, the use of experimental design approaches to improve process development for safer and more reproducible production is becoming increasingly important. Here, these options are highlighted and discussed with a few selected examples from antibiotic fermentation, expanded bed optimization, virus vector transfection of insect cell cultivation, feed profile adaptation, embryonic stem cell expansion protocols, and mammalian cell harvesting. [source] | ||||||||||