Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

Improvement of the Assay Method for Steviol Glycosides in the JECFA Specifications

Steviol glycosides are natural sweetener constituents found in the leaves of Stevia rebaudiana Bertoni (Asteraceae). The specifications for steviol glycosides were established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2008, although there was a call in the following year for the modification of this assay method to enable the determination of nine steviol glycosides rather than just seven. In response, based on a proposed method by the Japan Stevia Association, we developed an improved method by changing the HPLC conditions and including the use of an octadecylsilyl column instead of an amino-bonded column to enable the rapid and reliable determination of the nine steviol glycosides by an isocratic HPLC-UV method. With the developed method, the nine steviol glycosides can be separately determined, and identified using individual reference chemicals as standards, unlike the previous identification method, which was based on the relative retention times. In addition, the single stevioside quantification standard was replaced with both stevioside and rebaudioside A quantification standards. Importantly, the validation of the developed method was successful. The limits of quantification for the nine steviol glycosides were between 0.2% and 0.6%. The developed assay method for the nine steviol glycosides was proposed to JECFA and adopted as the revised assay method for the steviol glycosides specifications at its 73rd meeting in 2010.

Technical Specifications for Seed Breeding of Gentiana macrophylla Pall.

This paper elaborates on the seedling technology,field cultivation technology,field management technology,seed harvesting and seed processing technology in the propagation process of Gentiana macrophylla to provide technical support for artificial breeding of G. macrophylla.

Research Status of Technical Specifications for Bioremediation of Shorelines Polluted by Spilling Oil

Bioremediation of shorelines polluted by spilling oil has no secondary pollution and saves manpower and material resources, so it has a wide market. Standardizing the operation methods and materials used of the technology can improve its efficiency. Therefore, the research process of technical specifications for bioremediation of shorelines polluted by spilling oil at home and abroad was expounded in this study.

CONVEX CONTROLLER DESIGN APPLIED TO AC INDUCTION MOTOR TO SATISFY MULTIPLE SIMULTANEOUS SPECIFICATIONS

The application of a closed-loop specification oriented feedback control design method, which addresses the design of controllers to satisfy multiple simultaneous conflicting closed-loop performance specifications is presented. The proposed approach is well suited to the design of controllers which must meet a set of conflicting performance specifications. Gain tuning is central to the design process, however, the tuning process is greatly simplified over that presented by the problem of tuning a PID controller for example. The proposed control method is applied to an AC induction motor, with an inner-loop flux vector controller applied to design a position control system. Experimental results verify the effectiveness of this method.

Development of Product Design Projects Applying Specifications and Factors Matrix (SFM) as a Support Tool in Higher Education

The application of work strategies taking into account, from the initial stages, all the factors involved in the product design process is considered essential by the researches to generate higher quality products, assess users’ needs and anticipate design problems. This paper presents two approaches of design project development, denominated respectively: projects with imposed specifications and projects with derived specifications and proposes the use of the matrix that integrates specifications and design factors (SFM). This design support tool complements others already used in the development of product concepts by higher education students, increasing the capacity of synthesis and structuring of information in order to facilitate decision-making into the design process. Its elaboration implies understanding of objectives, identifying of factors and establishing of specifications. At the same time, it aims to foster the reflection process and an integrated information analysis. The application of SFM and its contribution to different project approaches are shown in this paper.

Specifications of nanosecond laser ablation with solid targets,aluminum,silicon rubber,and polymethylmethacrylate(PMMA)

The ablation parameters such as threshold fluence, etch depth, ablation rate and the effect of material targets were investigated under the interaction of laser pulse with low intensity. The parameters of the laser system are： laser pulse energy in the range of 110–140 m J, wavelength1064 nm and pulse duration 20 ns. By macroscopic estimation of the outward images of the ablation and data obtained, we can conclude that the photothermal and photoionization processes have more influence for aluminum ablation. In contrast, for polymer samples, from the macroscopic observation of the border pattern at the irradiated spot, and also the data obtained from the experiment results, we deduce that both chemical change due to heating and photochemical dissociation were effective mechanisms of ablation. However, concerning the two polymer samples, apart from considering the same theoretical ablation model, it is conceived that the photomehanical specifications of PMMA are involved in the ablation parameters. The threshold fluence for an ablation rate of 30 laser shots were obtained as 12.4, 24.64, and 11.71 J cm^（-2）, for aluminum, silicon rubber and polymethylmethacrylate（PMMA） respectively.The ablation rate is exponentially decreased by the laser-shot number, especially for aluminum.Furthermore, the etch depth after 30 laser shots was measured as 180, 630 and 870 μm, for aluminum, silicon rubber and PMMA, respectively.

National Verification Regulations and Calibration Specifications of Measuring Instruments of P.R.China in 2010(2010 No.131)

General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 8 national measuring verification regulations in 2010 and publicize now.

National Verification Regulations and Calibration Specifications of Measuring Instruments of P.R.China in 2008 2008 NO.35

General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 11 national measuring verification regulations in 2008 and publicize now.

National Verification Regulations and Calibration Specifications of Measuring Instruments of P.R.China in 2008

General Administration of Quality Supervision,Inspection and Quarantine of P.R.China hasapproved the following 24 national measuring verification regulations in 2008 and publicize now.

National Verification Regulations and Calibration Specifications of Measuring Instruments of P.R.China in 2008 2008 No.22

General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 10 national measuring verification regulations in 2008 and publicize now.

A FORMAL MODEL FOR ANALYZING THE SCR-STYLE REQUIREMENTS SPECIFICATIONS

Based on SCR(Software Cost Reduction), this paper presents a formal mOdel analyzingSCR-style requirements- This model mainly apply state trans1ation rules, semantic computing rules and attributes to define formal sementics of a tabular notation in the SCR requirements method, and may automatically analyze requirements specifications to be specified by the SCR method. Combining with a simp1eexample, this paper introduces how to analyze consistency and completeness of requirements specifica-tlons.

The Quality Specifications of Mischmetal Wire and Rod and the Method of Adding Rare Earth in Steel

The quality of mischmetal wire and rod and the method of adding rare earth into steel are quite important for making high quality steel. This paper proposes a quality specification of wire and rod as well as related adding method. The paper also provides principles for selecting raw material and adding method.

A Comparative Study of the Hydroxyl and Saponification Values of Polysorbate 60 in International Food Additive Specifications

We investigated the hydroxyl and saponification values of 27 samples of Polysorbate 60 products that were commercially available worldwide. We observed that the values of most of the studied samples were not within the range established at the Joint FAO/WHO Expert Committee on Food Additives (JECFA), while they did agree with the specifications described in the USA, the EU and Japan. We believe that purities of the new commercial Polysorbate 60 samples are higher than those of the older products which were available when the JECFA specifications were discussed (around 1973). The present study suggests that the hydroxyl and saponification values of the current JECFA specifications for Polysorbate 60 should be re-evaluated.

Preparation of Technical Specifications on the Cultivation of Sweet Sorghums for Forage( Excerpt)

The aim of this study is to standardize the planting technology of sweet sorghums for forage,to prepare? technical specifications for planting sweet sorghums for forage. Based on years of experiment,it is prepared according to the requirements of GB/1. 1 Standardization Guide Rule Part I: Standard Structure and Compilation. The results show that it defines the application scope,basic requirements,preparation before sowing,planting requirements,field management,harvesting requirements of the technical specifications for planting sweet sorghums for forages,and determines the specific measures and technical indicators of the technical specifications. This paper provides technical support for the standardization,industrialization and marketization of planting sweet sorghums for forage.

Technical Specifications for Integrated Prevention and Control of Yellow Aphids

[Objectives]The purpose was to standardize the scientific prevention and control of yellow aphids and effectively control their occurrence and spread.[Methods]On the basis of consulting domestic and foreign data and standards extensively,a series of related trials were carried out.[Results]Technical specifications for integrated prevention and control of yellow aphids were formulated.[Conclusions]It is of great significance to the healthy and sustainable development of the fruit trees’industry,the implementation of standardized management,the reduction of pesticide uses,and the reduction of damage caused by yellow aphids to fruit trees,and also provides urgent-needed technical support and guarantee for the prevention and control of yellow aphids.

Specifications and control of spatial frequency errors of components in two-beam laser static holographic exposure for pulse compression grating fabrication

The large-aperture pulse compression grating(PCG) is a critical component in generating an ultra-high-intensity, ultra-short-pulse laser;however, the size of the PCG manufactured by transmission holographic exposure is limited to large-scale high-quality materials. The reflective method is a potential way for solving the size limitation, but there is still no successful precedent due to the lack of scientific specifications and advanced processing technology of exposure mirrors. In this paper, an analytical model is developed to clarify the specifications of components, and advanced processing technology is adopted to control the spatial frequency errors. Hereafter, we have successfully fabricated a multilayer dielectric grating of 200 mm × 150 mm by using an off-axis reflective exposure system with Φ300 mm. This demonstration proves that PCGs can be manufactured by using the reflection holographic exposure method and shows the potential for manufacturing the meter-level gratings used in 100 petawatt class high-power lasers.

Design of Fully Automatic Specification Selection System for Resistance Welding Equipment

A system for fully automatic selection of welding specifications in resistance welding equipment has been developed to address the problem of workers frequently choosing the wrong specifications during manual welding of multiple parts on a single machine in automobile factories. The system incorporates an automatic recognition system for different workpiece materials using the added machine fixture,visual detection system for nuts and bolts,and secondary graphical confirmation to ensure the correctness of specification calling. This system achieves reliable,fully automatic selection of welding specifications in resistance welding equipment and has shown significant effects in improving welding quality for massproduced workpieces,while solving the problem of specification calling errors that can occur with traditional methods involving process charts and code adjustments. This system is particularly suitable for promoting applications in manual welding of multiple parts on a single machine in automobile factories,ensuring correct specification calling and welding quality.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.