Measurement of impurities to support process development and manufacture of biopharmaceuticals

The biopharmaceutical industry is a growing market relying on analytical methods to bring safe and efficacious drugs from conception to market. Analytical methods are required during the entire drug life cycle as it plays a vital role during decision making. Impurities influence product quality, stability and efficacy, so their levels need to be minimised. There are regulatory guidelines that set out principles for consideration in meeting product quality specifications. Analytical methods have limits in their sensitivity and accuracy of measurement, their sample throughput and/or range of detection. This highlights the need to have orthogonal assays that can confidently quantify critical impurities to the appropriate levels. In this review, we discuss three major analytically challenging critical quality attributes – two product related impurities (aggregates and incorrect glycosylation) and one process related impurity (host cell proteins) – and the analytical assays that are commonly used to measure their quantity and quality

Sinter formation during directed energy deposition of titanium alloy powders

During directed energy deposition (DED) additive manufacturing, powder agglomeration and sintering can occur outside of the melt pool when using titanium alloy powders. Using in situ synchrotron radiography we investigate the mechanisms by which sintering of Ti6242 powder occurs around the pool, performing a parametric study to determine the influence of laser power and stage traverse speed on sinter build-up. The results reveal that detrimental sinter can be reduced using a high laser power or increased stage traverse speed, although the latter also reduces deposition layer thickness. The mechanism of sinter formation during DED was determined to be in-flight heating of the powder particles in the laser beam. Calculations of particle heating under the processing conditions explored in this study confirm that powder particles can reasonably exceed 700 °C, the threshold for Ti surface oxide dissolution, and thus the powder is prone to sintering if not incorporated into the melt pool. The build-up of sinter powder layer on deposit surfaces led to lack of fusion pores. To mitigate sinter formation and its detrimental effects on DED component quality, it is essential that the powder delivery spot area is smaller than the melt pool, ensuring most powder lands in the melt pool

Optimal design of multi-channel microreactor for uniform residence time distribution

Multi-channel microreactors can be used for various applications that require chemical or electrochemical reactions in either liquid, gaseous or multi phase. For an optimal control of the chemical reactions, one key parameter for the design of such microreactors is the residence time distribution of the fluid, which should be as uniform as possible in the series of microchannels that make up the core of the reactor. Based on simplifying assumptions, an analytical model is proposed for optimizing the design of the collecting and distributing channels which supply the series of rectangular microchannels of the reactor, in the case of liquid flows. The accuracy of this analytical approach is discussed after comparison with CFD simulations and hybrid analytical-CFD calculations that allow an improved refinement of the meshing in the most complex zones of the flow. The analytical model is then extended to the case of microchannels with other cross-sections (trapezoidal or circular segment) and to gaseous flows, in the continuum and slip flow regimes. In the latter case, the model is based on second-order slip flow boundary conditions, and takes into account the compressibility as well as the rarefaction of the gas flow

Examining the impact of health research facilitated by small peer-reviewed research operating grants in a women's and children's health centre

Abstract Background There has been limited research on the impact of research funding for small, institutional grants. The IWK Health Centre, a children and women's hospital in Maritime Canada, provides small amounts (up to $15,000) of research funding for staff and trainees at all levels of experience through its Research Operating Grants. These grants are rigorously peer-reviewed. To evaluate the impact of these grants, an assessment was completed of several different areas of impact. Findings An online questionnaire was sent to 64 Principal Investigators and Co-Investigators from Research Operating Grants awarded from 2004 to 2006. The questionnaire was designed to assess five areas of potential impact: (1) research, (2) policy, (3) practice, (4) society and (5) personal. Research impact reported by participants included publications (72%), presentations (82%) and knowledge transfer beyond the traditional formats (51%). Practice impact was reported by 67% of participants, policy impact by 15% and societal impact by 18%. All participants reported personal impact. Conclusions Small research grants yield similar impacts to relatively large research grants. Regardless of the total amount of research funds awarded, rigorously peer-reviewed research projects have the potential for significant impact at the level of knowledge transfer and changes in clinical practice and policy. Additional findings in the present research indicate that small awards have the potential to have significant impact on the individual grant holder across a variety of capacity building variables. These personal impacts are particularly noteworthy in the context of developing the research programs of novice researchers.</p

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

A synbiotic-containing amino acid-based formula improves gut microbiota in non-IgE-mediated allergic infants

BACKGROUND: Prebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino acid-based formula (AAF) for infants with cow's milk allergy (CMA). METHODS: This multicenter, double-blind, randomized controlled trial investigated the effects of an AAF including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age matched healthy breastfed infants were used as reference (HBR) for primary outcomes. CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics. RESULTS: Thirty-five (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, median percentage of bifidobacteria was higher in test group vs control group (35.4 vs. 9.7%, respectively P&lt;0.001), whereas ER/CC was lower (9.5 vs. 24.2%, respectively; P&lt;0.001). HBR levels of bifidobacteria and ER/CC were 55 and 6.5%, respectively. CONCLUSION: AAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy