Production Runs (production + run)

Distribution by Scientific Domains

Selected Abstracts

Toxic gas release caused by the thermal decomposition of a bulk powder blend containing sodium dichloroisocyanurate

Andrew R. Carpenter P.E.
A thermal runaway reaction occurred during the mixing of a batch of a bulk powder that resulted in the production and release of toxic gases. The mixture consisted of an oxidizer (sodium dichloroisocyanurate), some organic compounds, and inert compounds. This toxic release led to the evacuation of the building and resulted in extensive damage to the facility. This was only the fourth time an 1,100-pound batch of this material had been mixed in this equipment. Prior to this production run, the material had been prepared in small batches of 2 to 50 kilograms. Accelerated Rate Calorimetry (ARC) testing had been performed prior to the scale-up to production batches. This paper looks into the root causes of this particular accident and demonstrates how proper analysis of the testing data and other warning signs observed during the bench testing could have revealed the likelihood of this accident. Further, this paper will consider how simple design changes to the manufacturing process resulted in an inherently safer design. [source]

On the design of ultrafast shutters for time-resolved synchrotron experiments

Milan Gembicky
A comprehensive treatment of the limitations and possibilities for single-pulse selection in synchrotron operating modes with ,150,ns bunch separation, as occurs in the standard operating mode at the Advanced Photon Source, is presented. It is shown that the strength of available materials and allowable kinetic energy build-up limit single-bunch selection for this separation to sample sizes of ,100,m, and that for minimization of kinetic energy build-up it is preferable to increase the r.p.m. within physically acceptable limits rather than increase the disc radius to obtain a desirable peripheral speed. A slight modification of the equal-bunch spacing standard fill patterns is proposed that allows use of samples as large as 500,m. The corresponding peripheral speed of the chopper wheel is ,600,m,s,1, which is within the limits of high-strength titanium alloys. For smaller samples, peripheral speeds are proportionally lower. Versatility can be achieved with interchangeable chopper wheels and the use of different orientations of the rotation axis relative to the X-ray beam, which opens the possibility of larger, rather than one-of-a-kind, production runs. [source]

The Influence of Knowledge Accumulation on Buyer-Supplier Codevelopment Projects

Melissa M. Appleyard
This article investigates innovation across a supply chain and considers how knowledge accumulation as a consequence of buyer-supplier codevelopment projects can influence the projects' specifications. The setting is the semiconductor industry, and the players are chip producers who cooperate with their suppliers to modify their manufacturing equipment used to produce new semiconductor devices. Two detailed case studies were undertaken to determine the tradeoffs encountered by the buyer and supplier when setting the parameters that govern codevelopment projects. The findings from the case studies inform a conceptual framework that outlines the net payoffs to buyers when deciding whether to "make" or "buy" their production equipment. If buyers pursue the "make" option, they then have to decide the degree to which they sponsor modifications tailored to their production processes or modifications more generally applicable across the industry. More generally applicable modifications likely would prompt suppliers to invest relatively more in follow-on knowledge creation for upgrades and field support while leading to lower equipment costs due to economies of scale from larger production runs of the new equipment. The framework suggests that when making this sequence of decisions, an innovative buyer also weighs the importance of codevelopment for securing intellectual property rights, guaranteeing early access to new equipment enabling early product launch, and achieving high production yields quickly due to "previewing" the equipment. The conceptual framework leads to a multi-period model that focuses on the importance of knowledge accumulation for project parameterization. As captured by the model, buyers may prefer generally applicable modifications to customized ones, because generally applicable modifications may lead to greater knowledge accumulation at the supplier. This knowledge accumulation may be either "embodied" in equipment upgrades or "unembodied" in improved field support. In addition to shaping the nature of particular codevelopment projects, knowledge accumulation also may have profound implications for long-run industry structure. As seen in the semiconductor industry, knowledge accumulation at equipment suppliers has contributed to the rise of contract manufacturers, because these manufacturers can outfit their production facilities with equipment that embodies the accumulated knowledge. These findings suggest that for both short-run and long-run reasons, the dynamics of knowledge accumulation merit thorough attention when members of a supply chain cooperate during the course of new product development. [source]

Multivariate data analysis on historical IPV production data for better process understanding and future improvements

Yvonne E. Thomassen
Abstract Historical manufacturing data can potentially harbor a wealth of information for process optimization and enhancement of efficiency and robustness. To extract useful data multivariate data analysis (MVDA) using projection methods is often applied. In this contribution, the results obtained from applying MVDA on data from inactivated polio vaccine (IPV) production runs are described. Data from over 50 batches at two different production scales (700-L and 1,500-L) were available. The explorative analysis performed on single unit operations indicated consistent manufacturing. Known outliers (e.g., rejected batches) were identified using principal component analysis (PCA). The source of operational variation was pinpointed to variation of input such as media. Other relevant process parameters were in control and, using this manufacturing data, could not be correlated to product quality attributes. The gained knowledge of the IPV production process, not only from the MVDA, but also from digitalizing the available historical data, has proven to be useful for troubleshooting, understanding limitations of available data and seeing the opportunity for improvements. Biotechnol. Bioeng. 2010;107: 96,104. 2010 Wiley Periodicals, Inc. [source]

Theoretical analysis of excipient concentrations during the final ultrafiltration/diafiltration step of therapeutic antibody

Fudu Miao
Abstract Diafiltration of a protein solution into a new buffer is a common final step in biopharmaceutical manufacturing. However, the excipient concentrations in the retentate are not always equal to their corresponding concentrations in the new buffer (diafiltration buffer). This phenomenon was observed repeatedly during diafiltration of different therapeutic monoclonal antibodies in which the concentrations of histidine and either sorbitol or sucrose (depending on which was chosen for the diafiltration buffer) in the retentate were lower than in the diafiltration buffer. Experimental studies and theoretical analyses of the ultrafiltration/diafiltration (UF/DF) step were carried out to determine the primary causes of the phenomenon and to develop a mathematical model capable of predicting retentate excipient concentrations. The analyses showed that retentate histidine concentration was low primarily because of repulsive charge interactions between positively-charged histidine molecules and positively-charged protein molecules, and that volume exclusion effects were secondary for like-charged molecules. The positively-charged protein molecules generate an electrical potential that cause an uneven distribution of charged histidine molecules. This interaction was used to construct a mathematical model based on the Poisson-Boltzmann equation. The model successfully predicted the final histidine concentration in the diafiltered product (retentate) from the UF/DF development and production runs, with good agreement across a wide range of protein and histidine concentrations for four therapeutic monoclonal antibodies. The concentrations of uncharged excipients (sorbitol or sucrose) were also successfully predicted using previously established models, with volume exclusion identified as the primary cause of differences in uncharged excipient concentrations in the retentate and diafiltration buffer. 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]