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The appearance of an extrudate formulation was monitored during hot-melt extrusion (HME) continuous manufacturing over 3 days. The formulation matrix consisted of a polymeric component, copovidone, and a low molecular weight surfactant, polysorbate 80. Based on studies prior to the continuous manufacturing, the desired appearance of the target extrudate is translucent. Although process parameters such as feed rate and screw speed were fixed during the continuous manufacturing, the extrudate appearance changed over time from turbid to translucent. For root-cause investigation, the extrudates were analyzed offline by differential scanning calorimetry (DSC) and advanced polymer chromatography (APC™). Although the polysorbate 80 content of both turbid and translucent extrudates was within target, the glass transition temperature of the turbid extrudate was 2 °C above expected value. The observed turbidity was traced to lot-to-lot variability of the polysorbate 80 used in the continuous manufacturing, where APC™ analysis revealed that the relative content of the low molecular weight component varied from 23% to 27% in correlation with the evolution from turbid to translucent extrudates. This work stresses the importance of taking feeding material variability into account during continuous manufacturing. [ABSTRACT FROM AUTHOR]

A critical step of radiation hardness assurance (RHA) for space systems is given by the parts selection in accordance with the observed (or estimated) radiation effects. Although radiation testing is the most decisive way of studying the radiation degradation of electronic components, the increasing use of commercial off-the-shelf (COTS) devices and the challenges posed by NewSpace are pushing the need of finding new approaches to assess the risk associated with radiation environments. This work tries to evaluate if valuable information might be extracted from archival data to carry out this assessment despite the well-known and dramatic lot-to-lot, or even part-to-part, variability for some technologies and the impact of the different test conditions, such as the bias conditions and the dose rate in enhanced low dose rate sensitivity (ELDRS). These factors are briefly analyzed for some examples. A new radiation database is briefly introduced, and some statistical approaches are cited, apart from the analysis herein followed. To finish, a first analysis on three families of bipolar transistors is presented together with the independent results from three external reports, with a good agreement between the experimental results and the expected ones. [ABSTRACT FROM AUTHOR]

During a recent manufacturing campaign for a monoclonal antibody using a fed-batch process, poor cell culture performance was observed across two manufacturing sites with similar scales and equipment. Root cause analysis indicated that the poor cell culture performance was linked to the production basal media. Genealogy of the precursor raw materials used in the media revealed that a particular lot of Poloxamer 188 (P188) was the common link to the poor-performing media lots. P188 serves a critical role in protecting cells against shear in cell culture bioprocesses. However, the small-scale studies suggested that the poor cell culture performance was cytostatic in nature rather than being caused due to lack of shear protection. Several P188 lots were tested analytically using SEC-MS and RP-LC-MS methods and a unique low molecular weight species was identified in the suspect lot of poloxamer. The impurity was identified to be polypropylene oxide (PPO), a reaction intermediate in P188 synthesis. Spiking studies with PPO further confirmed its cytostatic nature. This case study highlights yet another scenario where lot-to-lot variability continues to impact bioprocesses and re-emphasizes the need for robust analytical and cell-culture raw material screening methods. • A specific lot of Poloxamer 188 in the basal media was linked to poor cell culture performance for mAb production runs. • Investigational studies suggested that the poor cell culture performance was cytostatic in nature. • Analytical methods such as SEC-LC-MS and RP-LC-MS were used to identify the impurity, polypropylene oxide (PPO). • This case study highlights a scenario where lot-to-lot variability in raw materials continue to impact bioprocesses. [ABSTRACT FROM AUTHOR]

Objectives Anti-Müllerian hormone (AMH) measurement is useful as an aid in the evaluation of ovarian reserve. In the past, its conventional use was restricted by the low-throughput and variability of existing manual AMH assays. We developed the automated Access AMH assay for the quantitative determination of AMH levels on the Access family of immunoassay systems. The analytical performance of this new assay was evaluated. Design and methods Sensitivity, dilution linearity, assay imprecision, AMH sample stability, lot-to-lot comparison and correlation with AMH Gen II assay (Beckman Coulter, Inc.) were evaluated. Reference intervals for Access AMH were established in healthy females, males, newborns (≤ 60 days) and pediatric males classified by Tanner stages. Results The limit of blank and limit of detection were below 0.0077 and 0.0098 ng/mL, respectively. The limit of quantitation was 0.010 ng/mL. The total imprecision ranged from 2.4 to 5.2%. Linearity was observed up to 24 ng/mL. Sample storage at room temperature up to 48 h, at 2–8 °C up to 7 days and at − 20 °C up to 15 months had no impact on measured AMH. The correlation study gave a coefficient between 0.99 and 1 and a regression slope between 0.89 and 0.92. Excellent lot-to-lot comparability was observed on controls and patient samples with a maximum bias of 3.7% between 2.81 and 15.03 ng/mL. Conclusions The fully automated Access AMH immunoassay demonstrates excellent analytical performance. As a consequence, the availability of this assay will represent a robust, fast and precise alternative to manual AMH assay testing. [ABSTRACT FROM AUTHOR]

This article addresses the problem of estimating the shelf-life of a drug through a standard stability study that is routinely performed in the pharmaceutical industry. Based upon a dataset of the degradation of the drug efficacy over time, the objective is to estimate at what time point the drug efficacy falls below a minimally acceptable level. In this article, attention is directed toward the different roles played by lot-to-lot variability and measurement error in the performances of various estimation methodologies. The standard estimation method, as proposed by the United States Food and Drug Administration, for example, in accordance with current international guidelines, is compared with some new approaches. Simulation results are presented, which illustrate the advantages and disadvantages of the different estimation methodologies, and some recommendations and suggestions are made for shelf-life estimations. [ABSTRACT FROM PUBLISHER]

Background: Both accurate measurement of HbA1c and minimal reagent lot-to-lot variability are essential for point-of-care HbA1c assays. The accuracy of three different cartridge lots of the Samsung LABGEO PT HbA1c Test was investigated to determine whether the results can be used for follow-up and screening of patients with diabetes., Methods: The LABGEO PT10 device and three different lots of the LABGEO PT HbA1c Test cartridge were used. Seven levels of reference materials were measured using each cartridge in a duplicate manner for 3 days. The bias, within-laboratory precision, and total error were calculated. The medical decision point analysis was performed., Results: The mean absolute bias, within-laboratory precision, and total error of each cartridge were 3.3%, 2.5%, and 8.1% for Lot1; 1.9%, 2.6%, and 7.1% for Lot2; and 2.7%, 2.8%, and 8.1% for Lot3. The predicted value (95% confidence interval) of each cartridge at an HbA1c of 6.5% was 6.74% (6.66, 6.83) for Lot1, 6.60 (6.51, 6.70) for Lot2, and 6.51 (6.39, 6.63) for Lot3., Conclusions: Our data suggest that the LABGEO PT HbA1c Test can be used to monitor patients with diabetes and perform diabetes screening when false-positive results are obtained in the doctor's office., (© 2016 by the Association of Clinical Scientists, Inc.)