Assessing the Impact of Different Light Sources on Product Quality During Pharmaceutical Drug Product Manufacture - Fluorescent Versus Light-Emitting Diode Light.

Pharmaceutical scientists are often asked to assess the impact of modifications to the illumination in the manufacturing and product packaging environment on product quality. To assess the impact of switching light sources, four model compounds were exposed to standard fluorescent light, LED, and "yellow light" and the extent of drug photodegradation was determined. Photodegradation under LED light is generally reduced compared to fluorescent light and is often predictable if the UV-Vis absorption spectrum of the active pharmaceutical ingredient (API) and the spectral power distribution emitted by the various light sources overlap. However, lack of noticeable spectral overlap does not ensure absence of API photodegradation and may require additional assessment for selection of appropriate lighting conditions. A detailed evaluation of the API and solid formulation absorbance was performed to assess degradation risk for Compound A and Vitamin D3 when exposed to LED light. The light budget was established for Compound A, spanning all stages of the manufacturing process, under different illumination conditions to enable a complex supply chain. The results also demonstrate that while LEDs used in manufacturing areas are generally "better" compared to fluorescent lights, they are not replacing yellow lights for compounds sensitive to visible light.

In-Use Photostability Practice and Regulatory Evaluation for Pharmaceutical Products in an Age of Light-Emitting Diode Light Sources.

This article describes how the increased use of energy-efficient solid-state light sources (e.g., light-emitting diode [LED]-based illumination) in hospitals, pharmacies, and at home can help alleviate concerns of photodegradation for pharmaceuticals. LED light sources, unlike fluorescent ones, do not have spurious spectral contributions <400 nm. Because photostability is primarily evaluated in the International Council of Harmonization Q1B tests with older fluorescent bulb standards (International Organization for Standardization 10977), the amount of photodegradation observed can over-predict what happens in reality, as products are increasingly being stored and used in environments fitted with LED bulbs. Because photodegradation is premised on light absorption by a compound of interest (or a photosensitizer), one can use the overlap between the spectral distribution of a light source and the absorption spectra of a given compound to estimate if photodegradation is a possibility. Based on the absorption spectra of a sample of 150 pharmaceutical compounds in development, only 15% would meet the required overlap to be a candidate to undergo direct photodegradation in the presence of LED lights, against a baseline of 55% of compounds that would, when considering regular fluorescent lights. Biological drug products such as peptides and monoclonal antibodies are also expected to benefit from the use of more efficient solid-state lighting.

Effect of Home Visiting with Pregnant Teens on Maternal Health.

PURPOSE: Determine the extent that participation in Resource Mothers Program (RMP) home visiting improves maternal health at 3 months postpartum. STUDY DESIGN AND METHODS: A randomized controlled trial using RMPs in two urban and one rural location in a mid-Atlantic state. Community health workers from these RMPs enrolled teens into the study and the research team assigned participants to either the intervention group or telephone support control group using computerized randomization assignments. Data collection from baseline and 3 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS) and the Prenatal Psychosocial Profile (PPP) is reported. RESULTS: The sample included 150 pregnant teens with a mean age of 17 years. Mean self-esteem scores between groups were not significantly different at baseline, but the RMP group self-esteem scores improved significantly at the 3 months postpartum interview (36.40 ± 5.63 for RMP vs. 34.10 ± 4.29 telephone control group, p = 0.049). Neither group was at risk for depression at baseline or 3 months postpartum. Because 60% of the total sample identified as Hispanic, post hoc analysis revealed significantly different baseline stress mean scores between Hispanic and non-Hispanic teens (p = 0.038); however, these differences were no longer significant by 3 months postpartum (p = 0.073). The EPDS scores by ethnicity were not different at baseline (p = 0.875) but were significantly different at 3 months (p = 0.007). CLINICAL IMPLICATIONS: The RMP home-visiting intervention can lead to improved self-esteem scores in teens, particularly in Hispanic teens. Improved self-esteem has been shown to lead to better parenting.

The Xylella fastidiosa PD1063 protein is secreted in association with outer membrane vesicles.

Xylella fastidiosa is a gram-negative, xylem-limited plant pathogenic bacterium that causes disease in a variety of economically important agricultural crops including Pierce's disease of grapevines. Xylella fastidiosa biofilms formed in the xylem vessels of plants play a key role in early colonization and pathogenicity by providing a protected niche and enhanced cell survival. Here we investigate the role of Xylella fastidiosa PD1063, the predicted ortholog of Xanthomonas oryzae pv. oryzae PXO_03968, which encodes an outer membrane protein. To assess the function of the Xylella fastidiosa ortholog, we created Xylella fastidiosa mutants deleted for PD1063 and then assessed biofilm formation, cell-cell aggregation and cell growth in vitro. We also assessed disease severity and pathogen titers in grapevines mechanically inoculated with the Xylella fastidiosa PD1063 mutant. We found a significant decrease in cell-cell aggregation among PD1063 mutants but no differences in cell growth, biofilm formation, disease severity or titers in planta. Based on the demonstration that Xanthomonas oryzae pv. oryzae PXO_03968 encodes an outer membrane protein, secreted in association with outer membrane vesicles, we predicted that PD1063 would also be secreted in a similar manner. Using anti-PD1063 antibodies, we found PD1063 in the supernatant and secreted in association with outer membrane vesicles. PD1063 purified from the supernatant, outer membrane fractions and outer membrane vesicles was 19.2 kD, corresponding to the predicted size of the processed protein. Our findings suggest Xylella fastidiosa PD1063 is not essential for development of Pierce's disease in Vitis vinifera grapevines although further research is required to determine the function of the PD1063 outer membrane protein in Xylella fastidiosa.

Role of dissolved organic matter in ice photochemistry.

In this study, we provide evidence that dissolved organic matter (DOM) plays an important role in indirect photolysis processes in ice, producing reactive oxygen species (ROS) and leading to the efficient photodegradation of a probe hydrophobic organic pollutant, aldrin. Rates of DOM-mediated aldrin loss are between 2 and 56 times faster in ice than in liquid water (depending on DOM source and concentration), likely due to a freeze-concentration effect that occurs when the water freezes, providing a mechanism to concentrate reactive components into smaller, liquid-like regions within or on the ice. Rates of DOM-mediated aldrin loss are also temperature dependent, with higher rates of loss as temperature decreases. This also illustrates the importance of the freeze-concentration effect in altering reaction kinetics for processes occurring in environmental ices. All DOM source types studied were able to mediate aldrin loss, including commercially available fulvic and humic acids and an authentic Arctic snow DOM sample isolated by solid phase extraction, indicating the ubiquity of DOM in indirect photochemistry in environmental ices.