Optimization of production process of Aeromonas veronii CA07 strain inactivated vaccine / 中国生物制品学杂志

@#Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review / 中国中药杂志

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

Sustentabilidad asociada al traspaso generacional en un tambo / Sustainability associated with generational transfer in dairy farm

Resumen El enfoque de un sistema productivo tanto en la dinámica económica-productiva, socio-cultural y ambiental de la sustentabilidad brinda una mirada integral de las problemáticas estableciendo las limitantes y potencialidades con las que cuenta el sistema, las cuales tienen un impacto directo sobre la productividad. La continuidad de un emprendimiento a lo largo de las generaciones presenta dificultades desde el punto de vista empresarial y sistémico. Los desafíos humanos y técnicos traen aparejados conflictos de difícil resolución que en muchas ocasiones terminan con la disolución de la empresa o una fuerte modificación en su dirección para mejorar los resultados en los pilares mencionados.

Abstract The focus of a production system on the economic, productive, socio-cultural and environmental dynamics of sustaina-bility offers a comprehensive perspective of common issues, establishing the limitations and potentialities of said system, which will impact productivity directly. Continuity of an enterprise over generations proves difficult from an entrepreneurial and systemic point of view. Human and technical challenges bring about complex conflicts which end in the dissolution of the enterprise in many instances or a considerable shift in direction in order to improve the results of the mentioned pillars.

Management system and development strategy of quality Chinese medicine / 中国中药杂志

The development of quality Chinese medicine is an important way to improve the quality of Chinese medicine, and ensure the safety and effectiveness of Chinese medicine. This article systematically elaborates the definition, classification, standard and mana-gement certification strategy of quality Chinese medicine. We present the quality Chinese medicine which is higher quality than that of eligible Chinese medicine based on quality control standards. Quality Chinese medicine is strictly in accordance with management procedures, likely GAP and GMP et al, during the productive process, which quality indicators is higher than that of the current relevant national quality standards, such as Chinese Pharmacopoeia(ChP) et al; its limited indicators such as exogenous pollutants and endogenous toxic substances are lower than that of the current relevant national quality standards, likely ChP et al; meanwhile these Chinese herbal medicine, medicinal pieces, patent medicines, and health products and foods with Chinese medicine raw materials are been certificated by quality Chinese medicine. At the same time, this article systematically expounds the five major management systems of quality Chinese medicine, including technical training management for practitioners, productive process management, standard mana-gement, quality inspection and certification management, and product traceability management. And we put forward strategies to improve the supervision and management system, and promote the standardization and development of quality Chinese medicine by improving the technical management system of quality Chinese medicine, strengthening the quality management system and six sigma(6σ) management in the company. These strategies will provide a reliable basis and effective way to improve the quality of Chinese medicine.

Research progress of continuous manufacturing and process knowledge system of traditional Chinese medicine / 中国中药杂志

In the past few years, continuous manufacturing(CM) has been put forward by the FDA. Pharmaceutical enterprises are encouraged to promote the implementation of CM, which has become a hot research direction of pharmaceutical technology. In February 2019, the FDA issued a draft guideline for the implementation of CM, which greatly promoted the development of CM and provided reference for continuous manufacturing of traditional Chinese medicine(TCM). The production process of TCM is a complex system. With the innovation of production equipment and the promotion of automation and informatization of TCM production, the exis-ting policies, regulations and traditional production control capacity are difficult to meet the market demand for high-quality TCM pro-ducts. In this paper, we reviewed the new technologies and methods of quality control in accordance with the characteristics of TCM production by referring to modern manufacturing technology, information technology and quality control technology. Based on the "QbD" theory and "PAT" technology, process knowledge system(PKS), an advanced control strategy, was proposed to provide a reference for the implementation of CM in TCM production.

Research Strategies for Quality Standards of Famous Classical Formula Based on Standard Decoction (Material Reference) / 中国实验方剂学杂志

The inheritance of traditional clinical value of famous classical formulae is an important direction for the development of traditional Chinese medicine industry.Compared with the previous research and development of new drugs, the management requirement of " material reference" was introduced into the famous classical formulae research, which is used as the reference of process optimization and quality control.The characteristics of compound preparation of famous classical formulae are also reflected in the core concept of " quality inheritance of classics" in the road of industrial development.How to implement the above requirements and concepts into product development and industrial production? There are many specific common problems to be solved in practical research.How to effectively establish the " material reference" of famous classical formulae of different dosage forms? How to use " material reference" to guide the process optimization of compound preparation of famous classical formulae? How to determine the daily dose of famous classical formulae? How to take effective measures in the selection of raw material to reduce quality fluctuation range? This paper discusses the key issues such as production process and quality evaluation from the following aspects.Firstly, the management regulations and research and development guidelines are analyzed, and the specific implementation methods are given.Then, the possible problems in the Requirements for Declaration Documents (Draft for Opinions) are pointed out, and relevant suggestions are given.Finally, based on the research experience of standard decoction and famous classical formulae in the laboratory, an example is given to provide reference for the development of compound preparation of famous classical formulae.

Identification of key process parameters of Chinese materia medica production process based on grey relation analysis / 中草药

Objective: To identify the key process parameters of the Chinese materia medica (CMM) production process by using grey relation analysis (GRA) method. Methods: Taking Lonicerae Japonicae Flos and Artemisiae Annuae Herba extraction section of Reduning Injection as an example, GRA was adopted to calculate and compare the influence of the process parameters on the quality index. Meanwhile, analytic hierarchy process (AHP) combined with Spearman rank correlation analysis was used to validate mutually. Results: According to GRA Results:, the relative importance of process parameters was ranked as follows: average volume flow rate of extraction (X4) > pH after acid adjustment (X2) > the paste temperature of extracting concentration (X7) > alcohol precipitation concentrated extract weight (X1) > hydrochloric acid weight (X3) > extraction time (X6) > relative standard deviation of flow rate (X5). The correlation coefficient between the order by GRA and that by AHP was 0.893. According to the importance of process parameters, the average volume flow rate of extraction, the pH after acid adjustment, and the paste temperature of extracting concentration were identified as the key process parameters. Conclusion: The Results: obtained in this study show the feasibility of GRA in selecting key process parameters, which can provide theoretical reference for the establishment of prediction model as well as online feedback regulation.

History, research status, and thinking on management of production process changes of Chinese materia medica preparations / 中草药

To analyze the characteristics and reasons of production process changes of Chinese materia medica (CMM) preparations, study the history and research status on production process changes of CMM preparations, and provide reference for the management of production process changes of CMM preparations. It is considered that there is no effective solution for the management of production process changes of CMM preparations in the current status, so manufacturing companies take a wait-and-see attitude toward these changes. It is suggested that we should apply the risk-based approach and more flexible regulation pattern on production process changes to substitute the present regulatory method, at the same time, improve the technical requirements of production process changes according with the preparations characteristics and development of CMM preparations, and encourage marketing authorization holder to carry out research on the quality uniformity of products to manage the production process changes of CMM preparations, thereby promoting more scientific and rational on production process changes and ensuring the uniformity and stability of CMM preparations.

Trabalho, saúde e formação política na enquete operária de marx / Work, health, and political training in marx's worker's inquiry / Trabajo, salud y formación política en la encuesta obrera de marx

Resumo Em 1880, Marx redigiu e publicou a Enquete operária para investigar as condições de vida e saúde da classe trabalhadora francesa. Além da investigação em si, tratava-se de politizar e fortalecer as organizações de luta dos trabalhadores franceses. A Enquete é, portanto, um mecanismo de investigação e politização da classe trabalhadora. O objetivo deste ensaio foi analisar a atualidade da Enquete de 1880. Quatro aspectos dela foram discutidos: desenvolvimento e utilização, acidentes de trabalho, jornadas e intensidade do trabalho, salários e condições de vida. A consistência da Enquete se deve à teoria marxista que a sustenta. Afirma-se, neste ensaio, que o questionário de Marx e a forma enquete operária - entendida como mecanismo de investigação e politização - permanecem válidos.

Abstract In 1880, Marx wrote and published A Worker's Inquiry to investigate the living and health conditions of the French working class. In addition to the research itself, it had to do with politicizing and strengthening the French workers' struggle organizations. A Worker's Inquiry is, therefore, an investigation and politicization mechanism of the working class. The purpose of this assay was to analyze how current the 1880 A Worker's Inquiry is today. Four aspects of it were discussed: Development and use, labor accidents, working hours and intensity of the work, wages, and living conditions. The consistency of A Worker's is due to the Marxist theory that supports it. This essay states that Marx' questionnaire and the form of "worker's inquiry" - understood as a mechanism for research and politicization - remain valid.

Resumen En 1880, Marx redactó y publicó la Encuesta obrera para investigar sobre las condiciones de vida y salud de la clase trabajadora francesa. Además de la investigación en sí, se trataba de politizar y fortalecer las organizaciones de lucha de los trabajadores franceses. La Encuesta es, por lo tanto, un mecanismo de investigación y politización de la clase trabajadora. El objetivo de este ensayo fue analizar la actualizada de la Encuesta de 1880. Se discutieron cuatro aspectos de la misma: desarrollo y utilización, accidentes de trabajo, jornadas e intensidad del trabajo, salarios y condiciones de vida. La consistencia de la Encuesta se debe a la teoría marxista que la sostiene. En este ensayo, se afirma que el cuestionario de Marx y la forma encuesta obrera - entendida como mecanismo de investigación y politización - continúan siendo válidos.

Application of Interactive Integration Marketing System in Informatization Management in Drug Produc-tion Process / 中国药房

OBJECTIVE:To establish an effective technical system to achieve the informatization management in drug produc-tion process,and provide reference for the drug informatization management during production process in China. METHODS:Through analyzing the common problems existing in informatization management in drug production process,above problems were solved by interactive integration marketing system(IIMS)based on mobile internet. Informatization supervision was conducted for the production progress of a batch of drugs in a pharmaceutical production enterprise,and feasibility of the technical system was in-vestigated. RESULTS:There were problems commonly existed in the production process,such as supervision and data collection out of touch,no advanced means,delayed and closed informatization transmission,high cost of informatization collection,hard to develop,etc. IIMS consisted of transit label,informatization collection terminal and monitoring management platform had achieved batch production records paperless data interaction and solved informatization interaction and supervision issues in process of drug quality. In the actual study,IIMS totally supervised 15 links from raw materials purchasing to finished products,and all data were successfully collected. IIMS achieved the real-time remote control of data to make the government easy to regulate,without chang-ing the operational processes,and did not cause economic burden to the enterprises. CONCLUSIONS:The technical system is suit-able for the informatization management in drug production process in pharmaceutical production enterprise,and it can be extended to the scientific research institutes and drug supervision departments in the further.

Determination of Phase-transition Temperature of White Vaseline Produced by Different Processes by DSC / 中国药师

Objective:To determine the phase-transition temperature of white vaseline produced by different processes by differen-tial scanning calorimetry ( DSC) in order to analyze the relevance between the melting point and the phase-transition temperature and the relevance between different production processes and the phase-transition temperature. Methods: Hermertic aluminum pans were used to encapsulate the samples, and the testing conditions were optimized. The sample weight was about 10 mg, and the range of measuring temperature was -20-100℃. The heating rate was 5℃·min-1 and the flow rate of nitrogen was 30 ml·min-1 . Results:The phase-transition temperature and the melting point were significantly different. The phase-transition temperature of white vaseline samples produced by different processes was quite different. Conclusion:Melting point determination in the current standard method of white vaseline exists defects, and the composition of white vaseline produced by various processes is quite different.

Research on Change of Constituents of Bear Bile Powder During Production Process of Tanreqing Capsules by HPLC-MS/MS / 中国药学杂志

OBJECTIVE: To identify the chemical components of bile acids from bear bile powder, the intermediate of bear bile powder and Tanreqing capsules by HPLC-MS/MS. METHODS: All samples were extracted with 70% methanol(V/V), and an Ultimate XB C18 column (4.6 mm×250 mm, 5 μm) was employed for separation with acetonitrile-0.1% formic acid as mobile phase in gradient elution. The MS spectrum was acquired in both positive and negative ion mode using ESI ion source. The chemical components were identified by the second mass spectrometric pyrolysis fragments, chromatographic peak retention time and fragmentation regularity summarized from the reference standards and the available literature. RESULTS: A total of 33 compounds were successfully identified or tentatively predicted, and six chemical compounds including tauroursodeoxycholic acid, taurochenodeoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid, 7α-hydroxy-3-oxo-5β-cholanic acid and one unknown constituent were finally transferred to Tanreqing capsules through the intermediate of bear bile powder. Moreover, 21 new chemical compounds (major ingredients of free bile acids) were generated during the production process of the intermediate, and 19 components were also detected in Tanreqing capsules. CONCLUSION: The investigation of the change of constituents in bear bile powder during Tanreqing capsules production provides a basis for the quality control and evaluation of Tanreqing capsules during production process.

Evaluation of Heavy Metal Chromium Pollution Problems and Results in the Production Process of Tradi-tional Chinese Medicines / 中国药师

Objective:To prove the production process( pulverzation processing) by stainless steel pharmaceutical machines of tra-ditional Chinese medicines, including various batches of raw materials, decoction pieces, patent drugs and medicinal subsidiary materi-als, lead to heavy metal chromium exceed the standard. Methods:According to ChP 2010 version Vol 1 appendixⅨB“lead, cad-mium, arsenic, mercury, copper determination method”, referring to ChP 2010 version Vol 2 gelatin capsules “chrome check stand-ard”. Results:Most of the test data showed that the chromium content of the sample exceeded the standard in varying degrees. Con-clusion:Pharmaceutical machinery and equipment using stainless steel lead to chromium exceed the standard in Chinese medicine pro-duction process, bring hidden trouble to the quality of the products.

Review on process analytical technology application in production process of Chinese medicine injection / 中草药

Based on "Quality by Design" concept, this study summarized that quality control of Chinese materia medica (CMM) injection should introduce the process analytical technology during the processes of herbs cultivation, processing, casting herbs, extraction, concentration, macroporous resin purification, column chromatography, extraction, alcohol precipitation, crystallization, and final examination of product. The control proposal of how to control the production of CMM injection by process analytical technology was also suggested, aimed at a thorough understanding and control of the production process of injection, thereby ensuring uniformity of inter-batch quality and stability of process of CMM injections.

Study on alcohol precipitation technology of Liuwei Dihuang Prescription / 中草药

Objective: Through studying the rationalization of alcohol precipitation process of Liuwei Dihuang Prescription to obtain the stability alcohol precipitation process which could be used to promote industrialization. Methods: It screens the most reasonable alcohol precipitation process taking the contents, the relative molecular weight distribution, and the extract of loganin, peoniflorin, morroniside, manninotriose, and polysaccharide as the evaluation index to investigate the way of adding ethanol, centrifugation,, and whether to carry out the ethanol washing process. Results: The alcohol precipitation process is reasonable by calculating the alcohol volume method. The polysaccharides and alcohol precipitation supernatant could be efficiently separated by ethanol washing method. The polysaccharide extract and the contents of glycosides and manninotriose were up to the standard after the process improved. Conclusion: The optimized alcohol precipitation process is easy operation with good controllability and repeatability. It is worthy of popularization and application of industrialization.

Process Diversity Comparison of Artemisinin and Artemisinin Production between China and Abroad / 世界科学技术-中医药现代化

Artemisinin is the antidote to malaria, and has made hundreds of millions patients get rid of the disease since application in clinic. At present, the main accesses to artemisinin are directly extracted from Artemisia annua,chemical synthesis and biosynthesis. By comparing the differences of artemisinin production process between China and abroad, this research analyzes the reasons of the problem, and put forward their views and suggestions, so as to provide references for Artemisia annua further research.

Management of drug production process changes based on pharmaceutical quality system / 中国药学杂志

OBJECTIVE: To analyze the key problems in the management of drug production process changes during the drug life cycle, thus to improve the management of pharmaceutical production process changes. METHODS: Taking the change of injection sterilization process as an example, the issues in the study and management of process change were analyzed by employing empirical a-nalysis methods and introducing the concept of equilibrium analysis of the pharmaceutical quality system. RESULTS AND CONCLUSION: The pharmaceutical quality system is the equilibrium system of five aspects, including prescription composition, raw material control, production process, packaging and quality control. Process change research should follow the concept that quality comes from design, use process analytical technologies, and give full consideration to the quality system equilibrium. Process change management needs a systematic management of drugs.

Avaliação do processo produtivo de polpas de frutas congeladas / Evaluation of the produtive quality for processing the frozen fruit pulps

No estado de Roraima, os fabricantes de polpas de frutas empregam processos artesanais de produção, os quais não asseguram a qualidade do produto; apesar disso, esse segmento da agroindústria tem se expandido principalmente entre as microempresas. O procedimento de produção de polpas de frutas congeladas empregado em Boa Vista/RR foi avaliado por meio de visitas técnicas e aplicação de check list em quatro fabricantes selecionados que produzem polpa de fruta in natura. Constatou-se que o processo produtivo das indústrias locais é insatisfatório, sendo necessária a sua adequação às exigências da legislação em vigor.

In Roraima State, the local frozen fruit pulps producers employ artesanal procedures which do not ensure the quality of the final products; even so, this agroindustry segment has been increasing and predominalty among the small companies. The quality of frozen fruit pulps production in Boa Vista/RR was assessed by a technical visit and applying a check list at four selected companies proccessing in natura fruit pulps. Inadequate frozen fruit pulps productive processing at local industries was evidenced, thus being innoncompliace with the legislation in force.

Evaluation of production process and quality of large-volume intravenous solutions locally produced.

During 1997-1998, this project was carried out to evaluate the production process of local manufacturers and the quality of their products. The chosen manufacturers were those that had GMP certificates from Thai FDA. The chosen provincial hospitals were those whose criteria of Pharmaceutical Standard Performance under the Health Service System Development Project (HSSD), 1996 were met regarding the production area and clean room facility in producing sterile products. The expected outcome of the project was to provide information for proper manufacturing and to upgrade production to meet international standard requirements. The assessment of the manufacturing site was completed and all types of large-volume injection products from 4 manufacturers and 6 hospitals were collected and analyzed. It was found that 4 manufacturers met the requirements of GMP and HSSD on production process and quality control, only 3 of which having a perfect autoclaving validation. The cleaning process of reused glass containers in all 6 hospitals did not conform to standard criteria. In addition, lack of a sterilization process validation and no facilities in basic quality control for products such as particulate matter, pyrogen test or LAL test, etc. was also found. The quality of all collected products was analyzed and all conformed to the standard requirement. Finally, the author would like to suggest that the cleaning procedure of re-used glass containers and some production steps in the hospitals should be corrected, improved and verified. We also recommend unequiped hospitals to purchase these products from a qualified manufacturer.