Large-scale synthesis of peptides

Recent advances in the areas of formulation and delivery have rekindled the interest of the pharmaceutical community in peptides as drug candidates, which, in turn, has provided a challenge to the peptide industry to develop efficient methods for the manufacture of relatively complex peptides on scales of up to metric tons per year. This article focuses on chemical synthesis approaches for peptides, and presents an overview of the methods available and in use currently, together with a discussion of scale-up strategies. Examples of the different methods are discussed, together with solutions to some specific problems encountered during scale-up development. Finally, an overview is presented of issues common to all manufacturing methods, i.e., methods used for the large-scale purification and isolation of final bulk products and regulatory considerations to be addressed during scale-up of processes to commercial levels.     

Sterilization of Allograft Bone: is 25 kGy the Gold Standard for Gamma Irradiation?

For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10⁻⁶. The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks.     

The application of biotechnological methods in authenticity testing

By counterfeiting brand names in the food and drink industry as well as fraudulently labelling and selling low quality products as premium products, this sector of the industry has lost significant amounts of money and the consumer has been deceived. While it was difficult to establish certain types of fraud before the advent of modern biotechnology, DNA-based methods make an important contribution to protect high-quality brand names and protect the consumer. Several years ago, DNA technologies were considered as methods used in universities, primarily for research purpose, not so much for 'real-life' applications. However, this has changed and a number of laboratories have specialised in offering such services to the industry. This article will review DNA-based techniques commonly used for authenticity testing.     

Integrated System of Phytodepuration for Agroindustrial Wastewater: Three Different Case Studies

The effluents deriving from agricultural industries are sources of wastewater sensibly different from common civil wastewater treatment plants effluents, because they are characterized by significant amounts of nutrients and organic load. Agricultural industries require considerable water volumes for processing the farm products, in doing so generating huge volumes of wastewater, with high concentration of chemical oxygen demand (COD), nitrogen (N) and phosphorus (P). Advanced and low cost techniques for water depuration are required in such circumstances, as the use of Integrated System of Phytodepuration (ISP). In the present work, three different case studies (a dairy, a pig feedlot and a vinegar industry) are investigated: the performances of the ISPs were evaluated analyzing raw wastewaters and final effluents over a period ranging from 2 to 4 years. The results obtained show that the designed ISPs are characterized by a mean efficiency value higher than 85% for COD removal, 73% for N and 85% for P. Moreover, for the pig feedlot the ISP final effluent is characterized by a quality level not only suited for the release into surface waters but also for irrigation, while for the other two case studies is possible to release the final effluent in surface water.     

Precaution in Practice

Voluntary initiatives by industry have been frequently proposed as one of the most promising ways to reduce potential negative impacts on human health and the environment from nanomaterials. In this study, we examined the industrial perceptions, internal procedures, and performance of the nanomaterial industry. We conducted a written survey of 40 companies in Switzerland and Germany. Most companies replied that nanoparticulate materials (NPMs) should be subject to some kind of regulation, but industry did not convey a clear opinion as to who should be responsible for managing the potential environmental health impacts or how to regulate NPMs throughout their life cycle. If NPM risks were to be identified, most of the companies surveyed do not have standardized procedures for changing production technology, substituting inputs, redesigning processes, or reformulating final products to reduce or eliminate risks of NPMs. However, a majority of the survey respondents found their existing routines regarding these procedures to be sufficient.     

Structural Path Analysis of Fossil Fuel Based CO2 Emissions: A Case Study for China

Environmentally extended input-output analysis (EEIOA) has long been used to quantify global and regional environmental impacts and to clarify emission transfers. Structural path analysis (SPA), a technique based on EEIOA, is especially useful for measuring significant flows in this environmental-economic system. This paper constructs an imports-adjusted single-region input-output (SRIO) model considering only domestic final use elements, and it uses the SPA technique to highlight crucial routes along the production chain in both final use and sectoral perspectives. The results indicate that future mitigation policies on household consumption should change direct energy use structures in rural areas, cut unreasonable demand for power and chemical products, and focus on urban areas due to their consistently higher magnitudes than rural areas in the structural routes. Impacts originating from government spending should be tackled by managing onsite energy use in 3 major service sectors and promoting cleaner fuels and energy-saving techniques in the transport sector. Policies on investment should concentrate on sectoral interrelationships along the production chain by setting up standards to regulate upstream industries, especially for the services, construction and equipment manufacturing sectors, which have high demand pulling effects. Apart from the similar methods above, mitigating policies in exports should also consider improving embodied technology and quality in manufactured products to achieve sustainable development. Additionally, detailed sectoral results in the coal extraction industry highlight the onsite energy use management in large domestic companies, emphasize energy structure rearrangement, and indicate resources and energy safety issues. Conclusions based on the construction and public administration sectors reveal that future mitigation in secondary and tertiary industries should be combined with upstream emission intensive industries in a systematic viewpoint to achieve sustainable development. Overall, SPA is a useful tool in empirical studies, and it can be used to analyze national environmental impacts and guide future mitigation policies.     

Useful products from human placenta

Human placenta is a viable source of many useful products. Some of the products obtained are of use in health care industry. This review article deals with cosmetics, pharmaceuticals, blood products and hormone like substances obtained from human placenta. Various methods of their extraction, purification, characterization and their method of preparation have been discussed in detail.     

The production of fine chemicals by biotransformations

Today, biocatalysis is a standard technology for the production of chemicals. An analysis of 134 industrial biotransformations reveals that hydrolases (44%) and redox biocatalysts (30%) are the most prominent categories. Most products are chiral (89%) and are used as fine chemicals. In the chemical industry, successful product developments involve on average a yield of 78%, a volumetric productivity of 15.5 g/(L.h) and a final product concentration of 108 g/L. By contrast, the pharmaceutical industry focuses on time-to-market. The implications of this for future research and development on biocatalysis are discussed.     

Generation of an Industry-specific Physico-chemical Allocation Matrix. Application in the Dairy Industry and Implications for Systems Analysis (9 pp)

Background, Aims and Scope Allocation is required when quantifying environmental impacts of individual products from multi-product manufacturing plants. The International Organization for Standardization (ISO) recommends in ISO 14041 that allocation should reflect underlying physical relationships between inputs and outputs, or in the absence of such knowledge, allocation should reflect other relationships (e.g. economic value). Economic allocation is generally recommended if process specific information on the manufacturing process is lacking. In this paper, a physico-chemical allocation matrix, based on industry-specific data from the dairy industry, is developed and discussed as an alternative allocation method. Methods Operational data from 17 dairy manufacturing plants was used to develop an industry specific physico-chemical allocation matrix. Through an extensive process of substraction/substitution, it is possible to determine average resource use (e.g. electricity, thermal energy, water, etc) and wastewater emissions for individual dairy products within multi-product manufacturing plants. The average operational data for individual products were normalised to maintain industry confidentiality and then used as an industry specific allocation matrix. The quantity of raw milk required per product is based on the milk solids basis to account for dairy by-products that would otherwise be neglected. Results and Discussion Applying fixed type allocation methods (e.g. economic) for all input and outputs based on the quantity of product introduces order of magnitude sized deviations from physico-chemical allocation in some cases. The error associated with the quality of the whole of factory plant data or truncation error associated with setting system boundaries is insignificant in comparison. The profound effects of the results on systems analysis are discussed. The results raise concerns about using economic allocation as a default when allocating intra-industry sectoral flows (i.e. mass and process energy) in the absence of detailed technical information. It is recommended that economic allocation is better suited as a default for reflecting inter-industry sectoral flows. Conclusion The study highlights the importance of accurate causal allocation procedures that reflect industry-specific production methods. Generation of industry-specific allocation matrices is possible through a process of substitution/subtraction and optimisation. Allocation using such matrices overcomes the inherit bias of mass, process energy or price allocations for a multi-product manufacturing plant and gives a more realistic indication of resource use or emissions per product. The approach appears to be advantageous for resource use or emissions allocation if data is only available on a whole of factory basis for several plants with a similar level of technology. Recommendation and Perspective The industry specific allocation matrix approach will assist with allocation in multi-product LCAs where the level of technology in an industry is similar. The matrix will also benefit dairy manufacturing companies and help them more accurately allocate resources and impacts (i.e. costs) to different products within the one plant. It is recommended that similar physico-chemical allocation matrices be developed for other industry sectors with a view of ultimately coupling them with input-output analysis.     

Valorization of Dairy Wastes: Integrative Approaches for Value Added Products

The era of rapid industrialization succeeded by a shift in organizational focus on research and technology development which has fueled many industries along with the dairy industry to grow at an exponential rate. The dairy industry has achieved remarkable growth in the last decade in India. Waste produced by dairy industry consists of a high organic load thus cannot be discharged untreated. Even though treatment and management of waste are well documented, but the main problem is concerned with sludge produced after treatment. There is a gap in the application of various methods for effective treatment of the waste, hence there is a need for technology-oriented research in this area because of a paradigm shift in perspectives towards sustainable management of waste to recover value added products including energy as energy demand is also rising. Sludge which is generally land spread can also be used for energy generation. This paper discusses the environmental effects of waste generated due to dairy industrial activities; various methods used for the advanced treatment of dairy waste. This review article aims to present and discuss the state-of-art information for recovery of value-added products (single cell protein, biofertilizers, biopolymers and biosurfactants) from dairy waste with emphasis on integration of technologies for environmental sustainability. This paper also includes challenges and future perspectives in this field.     

Enantioselective Polymeric Transporters for Tryptophan, Phenylalanine, and Histidine Prepared Using Molecular Imprinting Techniques

Developing new methods for the separation of enantiomers is of great current interest because of the importance, challenge, and high cost associated with such separations. This is particularly true in the pharmaceutical industry because of the requirement for the high purity, including enantiopurity, of the final drug products. In this study, polymeric molecular transporters were prepared using molecular imprinting techniques with -tryptophan, -phenylalanine, and -histidine as the templates, respectively. It was found that the transporters thus prepared were able to transport the template amino acids across a hydrophobic chloroform layer in a U-tube at rates that were 1.34- to 3.8-fold higher than the transport of their -enantiomers. The magnitude of discrimination depends on the conditions of polymerization and the templates used. Molecular “receptors” prepared using molecular imprinting techniques could potentially be used for the separation of enantiomers through serial enantioselective transports.     

Acrylamide in processed potato products: progress made and present status

Concerns related to higher levels of acrylamide in processed carbohydrate-rich foods, especially in fried potato products, are well known. This article provides updates on various aspects of acrylamide in processed potato products including mechanisms of acrylamide formation and health risks due to its intake. Levels of reducing sugars in potatoes are considered as a main factor contributing towards the formation of acrylamide in processed potato products. Useful approaches in lowering the levels of reducing sugars such as use of suitable varieties, storage methods, storage temperature and duration of storage are described and discussed. Importance and practical utility of various steps before and during the processing that can contribute in reducing the final concentration of acrylamide are highlighted. Progress made and present status of potato processing industry in India are part of this article. The article describes varietal improvement and spread of short-term and long-term storage technologies in India and their contribution towards round the year availability of processing-grade potatoes to the processing industries and how all this has helped in achieving reduced levels of acrylamide in chips and French fries. Outcome and implications of cold-induced sweetening tolerance in potatoes are presented along with other management practices and strategies that can lower the acrylamide levels in processed potato products. Future lines of work have been suggested to make the consumption of fried potato products safer.     

Determination of antibiotic impurities in good manufacturing practices-grade cell therapy medicinal products

Abstract

Backrounds: According to the regulations of the health autorities, cell-based therapy products must be manufactured in good manufacturing production (GMP) facilities, fulfilling the required GMP standards. Products developed under the high quality control (QC) necessarity need to be approved for some QC tests. One of the main residual test is antibiotic test and this test should be validated. The aim of this study is to validate and determine the methods of detection of the antibiotic residue in the final product.

Methods: Liquid Chromatography Tandem-Mass Spectrometry (LC-MS/MS) methods were used for the main steps of the production procedure, as well as the final products. Pharmaceutical Grade penicillin G and streptomycin sulfate were used as positive controls.

Results: The results suggest that penicillin is broken down during cell culture and streptomycin is eliminated at the first washing step of the final product manufacture. It is shown in this study that LC-MS/MS method is one of the convenient method to test residual anibiotics and can be used to detect the antibiotic residues in cellular therapy products.

Discussion: Since the antibiotic residues are eliminated in the final product and also it could be suggested that the methodology we followed is sufficiently safe and final product is pure.     

Transporter Engineering for Microbial Manufacturing

Microbes play an important role in biotransformation and biosynthesis of biofuels, natural products, and polymers. Therefore, microbial manufacturing has been widely used in medicine, industry, and agriculture. However, common strategies including enzyme engineering, pathway optimization, and host engineering are generally inadequate to obtain an efficient microbial production system. Transporter engineering provides an alternative strategy to promote the transmembrane transfer of substrates, intermediates, and final products in microbial cells and thus enhances production by alleviating feedback inhibition and cytotoxicity caused by final products. According to the current studies in transport engineering, native transporters usually have low expression and poor transportation ability, resulting in inefficient transport processes and microbial production. In this review, current approaches for transporter mining, characterization, and verification are comprehensively summarized. Practical approaches to enhance the transport system in engineered cells, such as balancing transporter overexpression and cell growth, and evolution of native transporters are discussed. Furthermore, the applications of transporter engineering in microbial manufacturing, including enhancement of substrate utilization, concentration of metabolic flux to the target pathway, and acceleration of efflux and recovery of products, demonstrate its outstanding advantages and promising prospects.     

Facile production of mono-substituted urea side chains in solid phase peptide synthesis

A method is reported for the straightforward generation of urea-containing peptides during Boc solid phase peptide synthesis. Primary amine side chains are converted to mono-alkyl ureas in two steps via an intermediate p-nitrophenyl carbamate. Use of p-methoxybenzyl amine as an ammonia equivalent affords mono-alkyl final products from standard resin cleavage methods, without the need for additional steps. The reaction is highly efficient and applicable to variable length side chains and peptides.     

Greenhouse gas emissions of the production chain behind consumption of products in Austria: Development and application of a product‐ and technology‐specific approach

Globalization has been one main driver affecting our whole economy. Thus, greenhouse gas emissions (GHGs) associated with imports and exports should get addressed in addition to the national emission inventory according to the United Nations Framework Convention on Climate Change (UNFCCC), which is focused on territorial emissions only. To enable a correct calculation for imports and exports and to find the most emission‐intensive products and their origin, a product‐ and technology‐specific approach would be favorable which has not been applied up to now. This article addresses this research gap in developing and applying such an approach to calculate the GHGs behind consumption of products in Austria. It is based on physical flows combined with life‐cycle‐based emission factors and emission intensities derived from sector‐ and country‐specific energy mix, for calculating all emissions behind the production chain (resources to final products) of products consumed in Austria. The results have shown that consumption of products in Austria leads to about 60% more emissions than those of the national inventory and that the main part of these emissions comes from the provision of products. The most emission‐intensive products are coming from the chemical and the metal industry. In particular, imports are the main driver of these emissions and are more emission intensive than those produced in Austria. As a result, it is necessary to look at practical measures to reduce emissions along the production chain not only in Austria, but especially abroad as well.     

Reducing the Risk of Contamination of Sterile Parenteral Products via Ready-to-Use Closure Components

The preparation of sterile parenteral products requires careful control of all ingredients, materials, and processes to ensure the final product has the identity and strength, and meets the quality and purity characteristics that it purports to possess. Contamination affecting these critical properties of parenteral products can occur in many ways and from many sources. The use of closures supplied by manufacturers in a ready-to-use state can be an effective method for reducing the risk of contamination and improving the quality of the drug product. This article will address contamination attributable to elastomeric container closure components and the regulatory requirements associated with container closure systems. Possible contaminants, including microorganisms, endotoxins, and chemicals, along with the methods by which these contaminants can enter the product will be reviewed. Such methods include inappropriate material selection, improper closure preparation processes, compromised container closure integrity, degradation of closures, and leaching of compounds from the closures.     

烟草中茄尼醇分离纯化研究进展

茄尼醇是一种重要的药物中间体,广泛用于合成辅酶Q10,因其在药物、保健品、化妆品等方面巨大的应用前景和市场需求而备受关注。本文综述了烟叶中茄尼醇提取、分离纯化与快速检测的研究进展,为高纯度茄尼醇的生产提供参考。     

Sugar levels in Charmat sparkling wines can affect the quality and resveratrol levels

Sparkling wines contain CO(2) obtained through a second fermentation by natural processes (Charmat method); they may be prepared with variable final sugar concentrations, resulting in physicochemical compositions and phenolic profiles different to those obtained with other natural methods. The purpose of this study was to verify the influence of sweetness on enological parameters, trans-resveratrol and trans-piceid levels, antioxidant capacity (power of scavenger the radical DPPH(?) (1,1-diphenyl-2-picrylhydrazyl) and mimetic enzymatic activities of superoxide dismutase (SOD-like) and catalase (CAT-like) assays, and β-glucosidase activities on Charmat sparkling wines. The interaction of polyphenol levels and sweetness was observed. Levels of trans-piceid and trans-resveratrol showed a decrease in function of glucose concentration up to 40 g/l. All samples showed antioxidant capacity and β-glucosidase activity was stable even in the presence of sugar. A positive correlation between SOD-like and DPPH(?) was observed. This work shows an approach able to clarify important aspects for the wine industry with regard to world-wide consumer demand for sweetened products.