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Analytical Technology (analytical + technology)
Kinds of 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] Applications of PAT-Process Analytical Technology in Recombinant Protein Processes with Escherichia coliENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 2 2008C. Kaiser Abstract Monitoring of bioprocesses and thus observation and identification of such processes is one of the main aims of bioprocess engineering. It is of vital importance in bioprocess development to improve the overall productivity by avoiding unintentional limitations to ensure not only optimal process conditions but also the observation of established production processes. Furthermore, reproducibility needs to be improved and final product quality and quantity be guaranteed. Therefore, an advanced monitoring and control system has been developed, which is based on different in-line, on-line and at-line measurements for substrates and products. Observation of cell viability applying in-line radio frequency impedance measurement and on-line determination of intracellular recombinant target protein using the reporter protein T-Sapphire GFP based on in-line fluorescence measurement show the ability for the detection of critical process states. In this way, the possibility for the on-line recognition of optimal harvest times arises and disturbances in the scheduled process route can be perceived. [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] Large scale demonstration of a process analytical technology application in bioprocessing: Use of on-line high performance liquid chromatography for making real time pooling decisions for process chromatographyBIOTECHNOLOGY PROGRESS, Issue 2 2010Anurag S. Rathore Abstract Process Analytical Technology (PAT) has been gaining a lot of momentum in the biopharmaceutical community because of the potential for continuous real time quality assurance resulting in improved operational control and compliance. In previous publications, we have demonstrated feasibility of applications involving use of high performance liquid chromatography (HPLC) and ultra performance liquid chromatography (UPLC) for real-time pooling of process chromatography column. In this article we follow a similar approach to perform lab studies and create a model for a chromatography step of a different modality (hydrophobic interaction chromatography). It is seen that the predictions of the model compare well to actual experimental data, demonstrating the usefulness of the approach across the different modes of chromatography. Also, use of online HPLC when the step is scaled up to pilot scale (a 2294 fold scale-up from a 3.4 mL column in the lab to a 7.8 L column in the pilot plant) and eventually to manufacturing scale (a 45930 fold scale-up from a 3.4 mL column in the lab to a 158 L column in the manufacturing plant) is examined. Overall, the results confirm that for the application under consideration, online-HPLC offers a feasible approach for analysis that can facilitate real-time decisions for column pooling based on product quality attributes. The observations demonstrate that the proposed analytical scheme allows us to meet two of the key goals that have been outlined for PAT, i.e., "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". The application presented here can be extended to other modes of process chromatography and/or HPLC analysis. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Integrated process design for single-cell analytical technologiesAICHE JOURNAL, Issue 10 2010J. Christopher Love First page of article [source] Application of mass spectrometry in the analysis of polybrominated diphenyl ethersMASS SPECTROMETRY REVIEWS, Issue 5 2010Dongli Wang Abstract This review summarized the applications of mass spectrometric techniques for the analysis of the important flame retardants polybrominated diphenyl ethers (PBDEs) to understand the environmental sources, fate and toxicity of PBDEs that were briefly discussed to give a general idea for the need of analytical methodologies. Specific performance of various mass spectrometers hyphenated with, for example, gas chromatograph, liquid chromatograph, and inductively coupled plasma (GC/MS, LC/MS, and ICP/MS, respectively) for the analysis of PBDEs was compared with an objective to present the information on the evolution of MS techniques for determining PBDEs in environmental and human samples. GC/electron capture negative ionization quadrupole MS (GC/NCI qMS), GC/high resolution MS (GC/HRMS) and GC ion trap MS (GC/ITMS) are most commonly used MS techniques for the determination of PBDEs. New analytical technologies such as fast tandem GC/MS and LC/MS become available to improve analyses of higher PBDEs. The development and application of the tandem MS techniques have helped to understand environmental fate and transformations of PBDEs of which abiotic and biotic degradation of decaBDE is thought to be one major source of Br1-9BDEs present in the environment in addition to direct loading from commercial mixtures. MS-based proteomics will offer an insight into the molecular mechanisms of toxicity and potential developmental and neurotoxicity of PBDEs. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:737,775, 2010 [source] Quality specifications for peptide drugs: a regulatory-pharmaceutical approachJOURNAL OF PEPTIDE SCIENCE, Issue 11 2009Valentijn Vergote Abstract Peptide drugs, as all types of pharmaceuticals, require adequate specifications (i.e. quality attributes, procedures and acceptance criteria) as part of their quality assurance to ensure the safety and efficacy of drug substances (i.e. active pharmaceutical ingredients) and drug products (i.e. finished pharmaceutical dosage forms). Compendial monographs are updated regularly to keep up with the most recent advances in peptide synthesis (e.g. reduced by-products) and analytical technology. Nevertheless, currently applied pharmacopoeial peptide specifications are barely harmonized yet (e.g. large differences between the European Pharmacopoeia and the United States Pharmacopeia), increasing the manufacturers' burden of performing analytical procedures in different ways, using different acceptance criteria. Additionally, the peptide monographs are not always consistent within a single pharmacopoeia. In this review, we highlight the main differences and similarities in compendial peptide specifications (including identification, purity and assay). Based on comparison, and together with additional information from peptide drug substance manufacturers and public evaluation reports on registration files of non-pharmacopoeial peptide drugs, a consistent monograph structure is proposed. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [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] Assessment of diffuse transmission mode in near-infrared quantification,part I: The press effect on low-dose pharmaceutical tabletsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009M. Saeed Abstract Quantitative applications for pharmaceutical solid dosage forms using near-infrared (NIR) spectroscopy are central to process analytical technology (PAT) manufacturing designs. A series of studies were conducted to evaluate the use of NIR transmission mode under various pharmaceutical settings. The spectral variability in relation to tablet physical parameters were investigated using placebo tablets with different thickness and porosity steps and both variables showed an exponential relationship with the detected transmittance signal drop. The drug content of 2.5% m/m folic acid tablets produced under extremely different compaction conditions was predicted and found to agree with UV assay results after inclusion of extreme physical outliers to the training sets. NIR transmission was also shown to traverse a wide section of the tablet by comparing relative blocking intensities from different regions of the tablet surface and >90% of the signal was detected through a central area of 7 mm diameters of the tablet surface. NIR Quantification of both film thickness and active ingredient for film-coated tablets are examined in part II of this study. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4877,4886, 2009 [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] Process analytical technology and compensating for nonlinear effects in process spectroscopic data for improved process monitoring and controlBIOTECHNOLOGY JOURNAL, Issue 5 2009Zengping Chen First page of article [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] | |||||||||||||