Late stage process development for a commercial streptococcus pneumoniae fermentation bioprocess

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Challenges in the development and scale-up of a purification process for an attenuated live virus vaccine candidate

Prophylactic live attenuated vaccines (LAV) have been successfully developed for multiple viral disease targets, offering an advantage over subunit vaccine approaches by simultaneously stimulating innate, humoral and cellular immune responses. However, the development of manufacturing processes for robust production of LAVs at commercially viable scales can be challenging, particularly because of the need to use novel and/or adherent cell lines, the inefficient performance of conventional chromatography for processing large viral particles, and the complexity of product characterization. Further adding to these challenges, closed-system aseptic processes are required for those viruses too large for terminal sterile filtration, thereby limiting processing options and complicating process logistics at commercial scale. Highlighting these challenges, we present here on the development of a scalable, fully sterile, purification process for a large, enveloped, live attenuated virus having multiple glycoprotein complexes. During the development of this vaccine the process was changed from a static cell culture process to one that is amenable to scaling in a stirred tank single-use bioreactor. This change presented challenges for the purification process, requiring modifications of the process separation techniques including evaluation of new unit operations of various separation modes such as membrane and monolith absorbers, resin chromatography, selective precipitation, large pore tangential flow filtration, and centrifugation. Critical to this evaluation was the understanding of the adaptability of these unit operations to closed sterile processing, with a premium placed on industry ready, single-use technologies. Through this process development effort, a scalable, sterile, purification process was defined that met targets for purity and yield

Method development, validation, and implementation of Raman spectroscopy as an in-situ process analytical technology for fermentation process development and commercial manufacturing

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The effect of black cohosh extract and risedronate coadministration on bone health in an ovariectomized rat model

Preparations of black cohosh extract are sold as dietary supplements marketed to relieve the vasomotor symptoms of menopause, and some studies suggest it may protect against postmenopausal bone loss. Postmenopausal women are also frequently prescribed bisphosphonates, such as risedronate, to prevent osteoporotic bone loss. However, the pharmacodynamic interactions between these compounds when taken together is not known. To investigate possible interactions, 6-month-old, female Sprague-Dawley rats underwent bilateral ovariectomy or sham surgery and were treated for 24 weeks with either vehicle, ethinyl estradiol, risedronate, black cohosh extract or coadministration of risedronate and black cohosh extract, at low or high doses. Bone mineral density (BMD) of the femur, tibia, and lumbar vertebrae was then measured by dual-energy X-ray absorptiometry (DEXA) at weeks 0, 8, 16, and 24. A high dose of risedronate significantly increased BMD of the femur and vertebrae, while black cohosh extract had no significant effect on BMD individually and minimal effects upon coadministration with risedronate. Under these experimental conditions, black cohosh extract alone had no effect on BMD, nor did it negatively impact the BMD-enhancing properties of risedronate