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.

Study on specifications of farmland shelterbelt net in Northeastern Plain of China

s: The farmland shelterbelts in Northeastern Plain of China have formed relatively complete net system. The func-tions of shelterbelt net in omnibearing wind check and prevention of frostbite as well as the field of integrated climate effect within shelterbelt net were analyzed, through located observation of meteorological factors. Within the shelterbelt net, the area with more than 10% efficiency of omnibearing wind check was determined as benefited area. The analysis of yield and quality of crops indicated that the sheltering range of shelterbelt net was 25 times tree height. The mature heights of the various varieties of poplar composed the shelterbelts were determined according to their height growth. Based on the comprehensive analysis above, the suitable size of farmland shelterbelt net in Northeastern Plain of China was decided to be 400 m×400 m.

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.

Specifications and Quality of Lube Oil Base Stocks in China

The Chinese standard Q/SHR001-95 for base stocks is compared with the APIspecifications. The viscosity-temperature characteristics of base stock required by lube oil in useand market demand on oil quality are analyzed. The quality indicators of base stocks in China andother countries are compared. A new classification of base stocks in response to the requirements ofmodern lube oil is proposed and the research on new technology to produce premium base stocksmeeting API specification is recommended on the basis of current base stock processing technology.

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.

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.

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.

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.

Dynamic Output Feedback Control Synthesis with Mixed Frequency Small Gain Specifications

这篇论文与混合频率为线性连续时间的系统经由动态输出反馈涉及控制合成问题小获得说明。为设计动态产量反馈控制器的一个新方法被介绍以便结果靠近环的系统是 asymptotically 稳定的并且在两个有限频率范围和全部频率范围满足小获得说明的要求。设计条件以一套线性矩阵不平等(LMI ) 的答案被给。最后，一个数字例子被给与存在那个比较说明设计过程和建议方法的优点。

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.

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.

Study on Design Specifications and Wear Behavior of MCC

Main design parameters of MCC （metallic card clothing） which include front angle, base width, tooth pitch, and tooth point dimensions are discussed to investigate the carding effect of MCC. Experimental results show that type C machine has the best carding effect, which is not ascribed to single factor control but the integrated design optimization and good performance of wire teeth. In comparison with the teeth design, the wire performance is another important factor that influences the perfommnce of modem high efficient production carding machine.

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.

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.

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.

The Effect of Infestation by the Confused Flour Beetle （Tribolium Confusum Duv.） on Specifications of Wheat Flour

The objective of this research is to investigate the impact of infestation by the confused flour beetle Tribolium confusum on the specification of flour and its product. The results of this work showed that infestation by the confused flour beetle with 5 pairs of adult stage and its progeny within 3 months period may cause high deterioration and damaged of the flour specification. The people in lraq get their flour from some official and non-official mills which they produce not so good quality of this flour in addition to which it contains some times an infestation with the two species of the flour beetles T. castaneum and T. confusum, when people do not use this quantity as quickly as possible during this period of storage, the beetles will be increased in numbers and make the flour unacceptable for any kind of pastes or bread. The infestation by this beetle causes great pollution to the flour by the ecdysial of larvae and a bad smell that it leaves on the flour and all its products.

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.

Efficacy of a Diabetes Specific Nutrition Supplement on Glycemic, Anthropometric, Dietary and Gut Health Markers in Adults with Type 2 Diabetes: An RCT

With increasing incidence of diabetes, use of diabetes specific nutrition supplements (DSNS) is common for better management of the disease. To study effect of 12-week DSNS supplementation on glycemic markers, anthropometry, lipid profile, SCFAs, and gut microbiome in individuals with diabetes. Markers studied were glycemic [Fasting Blood Glucose (FBG), Post Prandial Glucose (PPG), HbA1c, Incremental Area under curve (iAUC), Mean Amplitude of Glycemic Excursions (MAGE), Time in/above Range (TIR/TAR)], anthropometry [weight, Body Mass Index (BMI), waist circumference (WC)], lipid profile, diet and gut health [plasma short chain fatty acids (SCFAs)]. N = 210 adults were randomized to receive either DSNS with standard care (DSNS + SC;n = 105) or standard care alone (SC alone;n = 105). After 12 weeks, significant differences between DSNS + SC versus SC alone was observed in FBG [−3 ± 6 vs 14 ± 6 mg/dl;p = 0.03], PPG [−35 ± 9 vs −3 ± 9 mg/dl;p = 0.01], weight [−0.6 ± 0.1 vs 0.2 ± 0.1 kg;p = 0.0001], BMI [−0.3 ± 0.1 vs 0.1 ± 0.1 kg/m2;p = 0.0001] and WC [−0.3 ± 0.2 vs 0.2 ± 0.2 cm;p = 0.01]. HbA1C and low-density lipoprotein (LDL) were significantly reduced in DSNS + SC [−0.2 ± 0.9;p = 0.04 and −5 mg/dl;p = 0.03] respectively with no change in control. Continuous Glucose Monitoring (CGM) reported significant differences between DSNS + SC versus SC alone for mean glucose [−12 ± 65 vs 28 ± 93 mg/dl;p < 0.01], TAR 180 [−9 ± 42 vs 7 ± 45 mg/dl;p = 0.04], TAR 250 [−3 ± 27 vs 9 ± 38 mg/dl;p = 0.05], iAUC [−192 (1.1) vs −48 (1.1) mg/dl;p = 0.03]. MAGE was significantly reduced for both DSNS + SC (−19 ± 67;p < 0.001) and SC alone (−8 ± 70;p = 0.04), with reduction being more pronounced for DSNS + SC. DSNS + SC reported a decrease in carbohydrate energy % [−9.4 (−11.3, −7.6) %;p < 0.0001] and amount [−47.4 (−67.1, −27.7) g;p < 0.0001], increased dietary fiber [9.5 (7.2, 11.8) g;p < 0.0001] and protein energy % [0.9 (0.5, 1.3) %;p < 0.0001] versus SC alone. DSNS + SC reported significant increases versus SC alone in total (0.3 ng/ml;p = 0.03) and individual plasma SCFAs. The consumption of DSNS significantly improves the glycemic, anthropometric, dietary, and gut health markers in diabetes.

Efficacy of a Diabetes Specific Nutritional Supplement (DSNS) on Glycemic Response in Prediabetic Adults: A Two-Armed, Open-Labelled Randomized Controlled Study

It is well known that Diabetes Specific Nutritional Supplements (DSNSs) are linked to improved glycemic control in individuals with diabetes. However, data on efficacy of DSNSs in prediabetics is limited. This was a two-armed, open-labelled, randomized controlled six-week study on 199 prediabetics [30 - 65 years;Glycosylated Hemoglobin (HbA1c) 5.7% - 6.4% and/or Fasting Blood Glucose (FBG) 100-125 mg/dl]. Two parallel phases were conducted: Acute Blood Glucose Response (ABGR) and Intervention phase. Prediabetic participants were randomized into test (n = 100) and control (n = 99). The primary objective was to assess the ABGR of DSNS versus an isocaloric snack, measured by incremental Area under the Curve (iAUC). Test and control received 60 g of DSNS and 56 g of isocaloric snack (cornflakes) respectively, both in 250 ml double-toned milk on visit days 1, 15, 29 and 43. Postprandial Blood Glucose (PPG) was estimated at 30, 60, 90, 120, 150 and 180 minutes. During the 4 weeks intervention phase, the test group received DSNS with lifestyle counselling (DSNS + LC) and was compared with the control receiving lifestyle counselling alone (LC alone). Impact was studied on FBG, HbA1C, anthropometry, body composition, blood pressure, nutrient intake, and physical activity. The impact of DSNS was also studied using CGM between two 14-day phases: CGM1 baseline (days 1 - 14) and CGM2 endline (days 28 - 42). DSNS showed significantly lower PPG versus isocaloric snack at 30 (p 12, and chromium were reported by DSNS + LC versus LC alone. No other significant changes were reported between groups. It may be concluded that DSNS may be considered as a snack for prediabetic or hyperglycemic individuals requiring nutritional support for improved glycemic control.