[Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine].

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Diagnosing and characterizing the mechanisms of biological phosphorus removal at the Great Lakes Water Authority (GLWA) water resource recovery facility (WRRF).

Previous research has demonstrated that biological phosphorus removal (bio-P) occurs in the Great Lakes Water Authority (GLWA) water resource recovery facility (WRRF) high purity oxygen activated sludge (HPO-AS) process, suggesting that sludge fermentation in the secondary clarifier sludge blanket is key to bio-P occurrence. This study, combining batch reactor testing, the development of a process model for the HPO-AS process using Sumo21 (Dynamita), and the analysis of eight and a half years of plant operating data, showed that bio-P consistently occurs at the GLWA WRRF. This occurrence is attributed to the unique configuration of the HPO-AS process, which has a relatively large secondary clarifier compared to the bioreactor, and the characteristics of the influent wastewater, primarily particulate matter with limited concentrations of dissolved biodegradable organic matter. The volatile fatty acids (VFAs) needed for polyphosphate accumulating organisms (PAOs) growth are produced in the secondary clarifier sludge blanket, which provides more than four times the anaerobic biomass inventory compared to the anaerobic zones in the bioreactor, thus facilitating bio-P in the current system. Opportunities exist to further optimize the phosphorus removal performance of the HPO-AS process and reduce the amount of ferric chloride used. These findings may be of interest to researchers investigating biological phosphorus removal in similar systems. PRACTITIONER POINTS: Fermentation in the clarifier sludge blanket an essential component of bio-P process at this facility. Results suggest simple adjustments to the system could lead to further improvements in bio-P. It is possible to decrease the use of chemical phosphorus removal methods (i.e., ferric chloride) while simultaneously increasing bio-P. Determining the phosphorus mass balance from sludge streams provides insight into evaluating the effectiveness of the phosphorus recovery system.

[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review / 中国中药杂志

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

[Application of multivariate models in whole process control of solid preparations].

The production of solid preparations is a multi-unit and multi-step system and is a whole process chain. Its quality is affected by many factors such as material properties and process parameters. As an important analysis tool, multivariate models play an important role in pharmaceutical monitoring. Besides, multivariate models can comprehensively understand the multi-factor relationship between material properties, process parameters, and quality attributes of products, thereby promoting the whole process optimization and controlling the drug production quality. This paper summarized the application of commonly used multivariate models in the process of solid preparations, which provides a certain reference for the process modeling of Chinese medicinal preparations.

Research progress on the ethanol precipitation process of traditional Chinese medicine.

Ethanol precipitation is a purification process widely used in the purification of Chinese medicine concentrates. This article reviews the research progress on the process mechanism of ethanol precipitation, ethanol precipitation process application for bioactive component purification, ethanol precipitation and traditional Chinese medicine quality, ethanol precipitation equipment, critical parameters, parameter research methods, process modeling and calculation methods, and process monitoring technology. This review proposes that ethanol precipitation technology should be further developed in terms of five aspects, namely, an in-depth study of the mechanism, further study of the effects on traditional Chinese medicine quality, improvement of the quality control of concentrates, development of new process detection methods, and development of a complete intelligent set of equipment.

Formulation and characterization of an optimized functional beverage from hibiscus (Hibiscus sabdariffa L.) and green tea (Camellia sinensis L.).

Hibiscus sabdariffa and Camellia sinensis are traditionally consumed as beverages and are good sources of health-promoting phenolic compounds. The objective of this work was to use response surface methodology to develop an optimized functional beverage with high total phenolic content, antioxidant capacity, and acceptable for potential consumers. Optimum infusion conditions were 4.9 g of hibiscus calyces or C. sinensis leaves/100 ml of water at 26 ℃ for 291 min. These conditions yielded a total phenolic content of 14.80 ± 1.4 and 33.02 ± 0.34 mg gallic acid equivalents/100 ml for hibiscus and green tea, respectively. The optimized beverages were combined in a 7:3 (hibiscus:green tea, v/v) ratio; a consumer preference test showed that this combination had an acceptable taste according to untrained panelists. A chromatographic analysis showed that this formulation contained flavonoids, phenolic acids, and anthocyanins as its main components. Our data suggested that hibiscus and green tea phenolic compounds were efficiently extracted using near-ambient temperature water for prolonged times, contrary to routine methods (high temperature, short time). Our method also preserved antioxidant capacity, possibly by avoiding chemical changes/degradation due to high temperatures. This process can be used to produce organoleptically acceptable functional beverages that deliver a varied phenolic compound profile to the consumer.

Role of Knowledge Management in Development and Lifecycle Management of Biopharmaceuticals.

Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the interface between KM and QbD-driven biopharmaceutical production systems as perceived by academic as well as industrial viewpoints. A comprehensive set of 356 publications addressing the applications of KM tools to QbD-related tasks were screened and a query to gather industrial inputs from 17 major biopharmaceutical organizations was performed. Three KM tool classes were identified as having high relevance for biopharmaceutical production systems and have been further explored: knowledge indicators, ontologies, and process modeling. A proposed categorization of 16 distinct KM tool classes allowed for the identification of holistic technologies supporting QbD. In addition, the classification allowed for addressing the disparity between industrial and academic expectations regarding the application of KM methodologies. This is a first of a kind attempt and thus we think that this paper would be of considerable interest to those in academia and industry that are engaged in accelerating development and commercialization of biopharmaceuticals.

Manufacturing and device options for the delivery of biotherapeutics.

Biotherapeutic aerosol formulations are an intense area of interest for systemic and local drug delivery. This article provides a short overview of typical factors required specifically for biotherapeutic aerosol formulation design, the processing options open for consideration, and the issue of inhalation device selection. Focusing on spray drying, four case studies are used to highlight the relevant issues, describing investigations into: (1) the mechanical stresses occurring in bacteriophage formulations during spray-dryer atomization; (2) modeling of the spray-dryer process and droplet drying kinetics, to assist process design and predictions of formulation stability; (3) a predictive approach to the design and processing of a five-component dry powder aerosol formulation; and (4) the survival of bacteriophages after pressurized metered dose inhaler atomization.