Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Monterrey, Nuevo León, Mexico.
Departamento de Ciencias Biológicas, Universidad de los Andes, Bogotá, Colombia.
Biotechnol Prog. 2019 Sep;35(5):e2852. doi: 10.1002/btpr.2852. Epub 2019 Jun 14.
Poultry products are one of the major transmission media of Salmonella enteritidis to humans. A promising alternative to reduce the load of Salmonella in poultry are bacteriophages. Elsewhere, a mixture of six bacteriophages has been used successfully, but large-scale production would be necessary to supply potential poultry market and costs analyses have not been calculated yet. For this, a powerful tool to predict production costs is bioprocess modeling coupled with economic analyses. This work aims to model the scaled-up production of a six bacteriophages mixture based on a laboratory/pilot-scale production using Biosolve Process. For the model construction, a combination of experimental and reported data was applied, in which different production alternatives and the range of 1-100% of the Colombian poultry market (at broiler's farm and slaughterhouse) were analyzed. Results indicate that the best cost-effective process configuration/scale is to use one bioreactor (156 L) for the six bacteriophages, then a 0.45 μm filtration for removal of biomass, and a 0.22 μm filtration for sterility; this to supply the 35% of the market size for broiler farms (equivalent to 210 million chickens). This configuration gives a production cost per chicken of US$ 0.02. Additionally, a sensitivity analysis and a theoretical contrast for understanding the impact that titer and recovery have on production scale determined that titer affects the most the cost and requires optimization. The present works serves as a first, and required, approach for the development of phage therapy products that are alternatives to present-day pathogens control strategies.
家禽产品是肠炎沙门氏菌传播给人类的主要媒介之一。噬菌体是减少家禽中沙门氏菌负荷的一种很有前途的替代方法。在其他地方,已经成功使用了六种噬菌体的混合物,但需要大规模生产才能供应潜在的家禽市场,而且尚未计算成本分析。为此,一种强大的工具可以预测生产成本,即生物过程建模与经济分析相结合。这项工作旨在基于使用 Biosolve Process 的实验室/中试规模生产来模拟六种噬菌体混合物的放大生产。在模型构建中,应用了实验和报告数据的组合,其中分析了不同的生产方案和哥伦比亚家禽市场的 1-100%范围(在肉鸡养殖场和屠宰场)。结果表明,最具成本效益的工艺配置/规模是使用一个生物反应器(156L)来生产六种噬菌体,然后进行 0.45μm 过滤以去除生物质,再进行 0.22μm 过滤以达到无菌;这将为肉鸡养殖场(相当于 2.1 亿只鸡)的 35%市场规模提供供应。这种配置使每只鸡的生产成本为 0.02 美元。此外,敏感性分析和理论对比有助于了解效价和回收率对生产规模的影响,结果表明效价对成本的影响最大,需要进行优化。这项工作是开发噬菌体疗法产品的第一步,也是当前病原体控制策略的替代方法所必需的。