Recent advances to accelerate purification process development: A review with a focus on vaccines.

The safety requirements for vaccines are extremely high since they are administered to healthy people. For that reason, vaccine development is time-consuming and very expensive. Reducing time-to-market is key for pharmaceutical companies, saving lives and money. Therefore the need is raised for systematic, general and efficient process development strategies to shorten development times and enhance process understanding. High throughput technologies tremendously increased the volume of process-related data available and, combined with statistical and mechanistic modeling, new high throughput process development (HTPD) approaches evolved. The introduction of model-based HTPD enabled faster and broader screening of conditions, and furthermore increased knowledge. Model-based HTPD has particularly been important for chromatography, which is a crucial separation technique to attain high purities. This review provides an overview of downstream process development strategies and tools used within the (bio)pharmaceutical industry, focusing attention on (protein subunit) vaccine purification processes. Subsequently high throughput process development and other combinatorial approaches are discussed and compared according to their experimental effort and understanding. Within a growing sea of information, novel modeling tools and artificial intelligence (AI) gain importance for finding patterns behind the data and thereby acquiring a deeper process understanding.

F-Specific RNA Bacteriophages Model the Behavior of Human Noroviruses during Purification of Oysters: the Main Mechanism Is Probably Inactivation Rather than Release.

Noroviruses (NoV) are responsible for many shellfish outbreaks. Purification processes may be applied to oysters before marketing to decrease potential fecal pollution. This step is rapidly highly effective in reducing Escherichia coli; nevertheless, the elimination of virus genomes has been described to be much slower. It is therefore important to identify (i) the purification conditions that optimize virus removal and (ii) the mechanism involved. To this end, the effects of oyster stress, nutrients, and the presence of a potential competitor to NoV adhesion during purification were investigated using naturally contaminated oysters. Concentrations of NoV (genomes) and of the viral indicator F-specific RNA bacteriophage (FRNAPH; genomes and infectious particles) were regularly monitored. No significant differences were observed under the test conditions. The decrease kinetics of both virus genomes were similar, again showing the potential of FRNAPH as an indicator of NoV behavior during purification. The T90 (time to reduce 90% of the initial titer) values were 47.8 days for the genogroup I NoV genome, 26.7 days for the genogroup II NoV genome, and 43.9 days for the FRNAPH-II genome. Conversely, monitoring of the viral genomes could not be used to determine the behavior of infectious viruses because the T90 values were more than two times lower for infectious FRNAPH (20.6 days) compared to their genomes (43.9 days). Finally, this study highlighted that viruses are primarily inactivated in oysters rather than released in the water during purification processes.IMPORTANCE This study provides new data about the behavior of viruses in oysters under purification processes and about their elimination mechanism. First, a high correlation has been observed between F-specific RNA bacteriophages of subgroup II (FRNAPH-II) and norovirus (NoV) in oysters impacted by fecal contamination when both are detected using molecular approaches. Second, when using reverse transcription-quantitative PCR and culture to detect FRNAPH-II genomes and infectious FRNAPH in oysters, respectively, it appears that genome detection provides limited information about the presence of infectious particles. The comparison of both genomes and infectious particles highlights that the main mechanism of virus elimination in oysters is inactivation. Finally, this study shows that none of the conditions tested modify virus removal.

Safe and Effective Delivery of Amphotericin B: A Survey of Patents.

BACKGROUND: Amphotericin B, designated as the gold standard among antifungal drugs is the only fungicidal effective against systemic fungal infections. But this drug has various pitfalls associated with it, to bypass which various techniques have been employed and resulted in a variety of lipid based commercially available formulations, which demolished only few of the shortcomings associated with this drug. Further, improvement in the delivery systems of Amphotericin B is advancing at increasingly frenetic pace, to surmount its research and to exploit its therapeutic potency with least toxicities. METHOD: The patent search on "Amphotericin B for its safe and effective delivery" has been carried out to present assimilated information on the patents of the universally accepted Amphotericin B formulations and technologies. Also, the area of focus was the physicochemical properties of Amphotericin B, their role in formulation development and also nanotechnology based formulations of Amphotericin B. RESULTS: Amphotericin B possesses poor aqueous solubility and systemic toxicity rendering obstacle in its formulation development. The interest of scientists and pharmaceutical industries to make further investments in the development of Amphotericin B formulations is due to rare occurrence of resistance to this drug. To bypass these drawbacks, various techniques have been patented which resulted in a variety of commercially available formulations to overcome the limitations of high cost, limited availability, poor storage stability and poor patient compliance. In lieu to this, scientists have developed and patented many novel drug delivery system based formulations and technologies such as use of novel carriers, modification in process for production and purification of Amphotericin B, formation of salts and complexes etc. to bring in limelight the benefits of this wonder drug. CONCLUSION: The purpose of the article is to present assimilated information regarding patents on Amphotericin B formulations and technologies.

Optimization of Chitosan Flocculation Purification Process of Zhigancao Decoction by Orthogonal Test / 中国药师

Objective:To optimize the chitosan flocculation purification process of Zhigancao decoction. Methods:With the total content of ginsenoside Rg1 , Re and Rb1 and the impurity removal rate as the evaluation indices, an orthogonal test was used to investi-gate the effects of concentration of solution, amount of chitosan and standing temperature on the purification process. Results:The op-timum conditions of chitosan flocculation clarification process of Zhigancao decoction were as follows:the concentration of extraction so-lution was 0. 25 g·ml-1 , the standing temperature was 25℃, and the amount of chitosan was 12% . Conclusion:The optimum con-ditions of purification process are promising with high impurity removal rate and active ingredients retention rate, which provide refer-ence for the dosage form reformation of Zhigancao decoction.