Product Quality Attributes Research Articles

Integration and digitalization in the manufacturing of therapeutic proteins

The biopharmaceutical market has experienced a tremendous growth in the last years. However, this growth should be balanced considering the difficulty in bioproduct development and the associated high manufacturing costs. These limitations are pushing towards process intensification, stimulated by the Quality by Design (QbD) initiative. Integrated continuous biomanufacturing has emerged as a promising approach towards high throughputs and reliable product quality attributes. At the same time, to face the increased management complexity and compensate fluctuations at the level of the different unit operations, model-based digitalization stands as a fundamental element. In this review, we discuss the state of the art in integrated biomanufacturing and digitalization to highlight their potential towards process intensification. The continuous technologies adopted in the upstream and downstream processing are first reviewed, with a focus on perfusion bioreactors and continuous chromatography. Then, model-based digitalization and its potential in the monitoring and control of integrated bioprocesses are discussed.

A high cell density perfusion process for Modified Vaccinia virus Ankara production: Process integration with inline DNA digestion and cost analysis.

By integrating continuous cell cultures with continuous purification methods, process yields and product quality attributes have beenimproved over the last 10 years for recombinant protein production. However, for the production of viral vectors such as Modified Vaccinia virus Ankara (MVA), no such studies have been reported although there is an increasing need to meet the requirements for a rising number of clinical trials against infectious or neoplastic diseases. Here, we present for the first time a scalable suspension cell (AGE1.CR.pIX cells) culture-based perfusion process in bioreactors integrating continuous virus harvesting through an acoustic settler with semi-continuous chromatographic purification. This allowed obtaining purified MVA particles with a space-time yield more than 600% higher for the integrated perfusion process (1.05 × 1011 TCID50 /Lbioreactor /day) compared to the integrated batch process. Without further optimization, purification by membrane-based steric exclusion chromatography resulted in an overall product recovery of 50.5%. To decrease the level of host cell DNA before chromatography, a novel inline continuous DNA digestion step was integrated into the process train. A detailed cost analysis comparing integrated production in batch versus production in perfusion mode showed that the cost per dose for MVA was reduced by nearly one-third using this intensified small-scale process.

Effects of Fructose and Oligofructose Addition on Milk Fermentation Using Novel Lactobacillus Cultures to Obtain High-Quality Yogurt-like Products.

The incorporation of prebiotics in fermented milk products is one of the best ways to promote health benefits while improving their sensory characteristics at the same time. The aim of this study was to evaluate the effects of the addition of fructose and oligofructose (1% and 2%) on the physicochemical, rheological, sensory, and microbiological quality attributes of fermented milk products inoculated with indigenous probiotic starter cultures of Lactobacillus isolated from Polish traditional fermented foods. The samples were evaluated during 35 days of refrigerated storage. The oligofructose and fructose caused increases in the populations of bacteria in comparison to the control fermented milk products without the addition of saccharides. The degrees of acidification in different fermented milk samples, as well as their viscosity, firmness, syneresis, and color attributes, changed during storage. The highest overall sensory quality levels were observed for the samples supplemented with L. brevis B1 and oligofructose. This study is the first attempt to compare the influences of different sugar sources on the physicochemical, rheological, sensory, and microbiological quality attributes of fermented milk products.

Syringe Filling of High-Concentration mAb Products Using Peristaltic Pump-Based Mechanism: Challenges and Mitigation Strategies

Syringe filling of high-concentration mAb formulation during manufacturing of large-scale drug product batches may present challenges such as product deposition onto the area of the syringe barrel where the stopper is inserted, product splashing or dripping, droplets left after the fill cycle, filling needle clogging, product build-up inside the needle during line stoppages, variation in fill weight/volume, and potential impact on product quality attributes. In this article, a summary of these issues and approaches to overcome them are summarized. Potential failure modes of the syringe filling process and appropriate in-process controls are provided. In addition to developing the filling process or resolving manufacturing issues, the pharmaceutical company developing the product and associated drug product manufacturing process may want to implement long-term strategic approaches to support the portfolio progression. Potential long-term approaches such as use of a viscosity reducing formulation development approach, improving peristaltic filling technology performance, building small-scale filling capability and establishing a streamlined filling process management cycle are also summarized. The aspects summarized in this article may be used to develop a robust filling process and control strategy for high-concentration mAb products and implement long-term strategic approaches to support the portfolio progression.

Customer Perceived Service Quality, Product Quality, Satisfaction and Loyalty in Beauty Business

In the hyper competitive and low entry barrier in beauty industry, customer loyalty is critical factor for gaining success for the company. The customer loyalty and satisfaction are key of success factor for strengthen bussiness performance. By creating and preserving customer loyalty, business entities can develop a long term relationship with the customers. The purpose of the research is to know further the determinant of customer satisfaction and loyalty from service quality and product quality. This study is designed by qualitative research by using theoretical review based and supporting by previously research. The basic concepts underlyed this theoretical review are dimensions of service quality, product quality, customer satisfaction, and customer loyalty. By critical review and classifying the result of previous research, this research found some propositions: (1) Service quality have significant effect on customer satisfaction (2) Product quality have significant effect on customer satisfaction (3) Service quality have significant effect on customer loyalty (4) Product quality have significant effect on customer loyalty (5) customer satisfaction have significant effect on customer loyalty.

Evaluation of a gluten-free sourdough bakery product

AbstractThe population of gluten sensitive people has been gradually rising in the last decades. The food industry, especially the bakery industry has to develop more gluten-free products to satisfy the consumer's demand. However, the quality of these products differs from the quality attributes of a standard glutenious bakery product. Therefore, the aim of our research was to develop a good quality gluten-free sourdough product with 3 different gluten-free flours: millet, brown rice and a commercially available mixture (Belbake). We investigated the differences in moisture content, the baking loss, the texture and the sensory properties of the products. According to our results in the case of the moisture content the brown rice sample had the highest, while the millet gave the lowest value. The baking loss measurement gave reverse results. In the texture analysis the brown rice sample was the softest, but the millet and the Belbake had better results in resilience and in springiness. Also, in the sensory analyses the Belbake product was found to be the best by the judges, however, there were no significant differences between them. In conclusion, the product development of a gluten-free sourdough bakery product was successful. Further research is needed to investigate the shelf life of the products.

Imaging Spectroscopy and Machine Learning for Intelligent Determination of Potato and Sweet Potato Quality.

Imaging spectroscopy has emerged as a reliable analytical method for effectively characterizing and quantifying quality attributes of agricultural products. By providing spectral information relevant to food quality properties, imaging spectroscopy has been demonstrated to be a potential method for rapid and non-destructive classification, authentication, and prediction of quality parameters of various categories of tubers, including potato and sweet potato. The imaging technique has demonstrated great capacities for gaining rapid information about tuber physical properties (such as texture, water binding capacity, and specific gravity), chemical components (such as protein, starch, and total anthocyanin), varietal authentication, and defect aspects. This paper emphasizes how recent developments in spectral imaging with machine learning have enhanced overall capabilities to evaluate tubers. The machine learning algorithms coupled with feature variable identification approaches have obtained acceptable results. This review briefly introduces imaging spectroscopy and machine learning, then provides examples and discussions of these techniques in tuber quality determinations, and presents the challenges and future prospects of the technology. This review will be of great significance to the study of tubers using spectral imaging technology.

CRISPR/Cas9 technology for improving agronomic traits and future prospective in agriculture.

In this review, we have focused on the CRISPR/Cas9 technology for improving the agronomic traits in plants through point mutations, knockout, and single base editing, and we highlighted the recent progress in plant metabolic engineering. CRISPR/Cas9 technology has immense power to reproduce plants with desired characters and revolutionizing the field of genome engineering by erasing the barriers in targeted genome editing. Agriculture fields are using this advance genome editing tool to get the desired traits in the crops plants such as increase yield, improve product quality attributes, and enhance resistance against biotic and abiotic stresses by identifying and editing genes of interest. This review focuses on CRISPR/Cas-based gene knockout for trait improvement and single base editing to boost yield, quality, stress tolerance, and disease resistance traits in crops. Use of CRISPR/Cas9 system to facilitate crop domestication and hybrid breeding are also touched. We summarize recent developments and up-gradation of delivery mechanism (nanotechnology and virus particle-based delivery system) and progress in multiplex gene editing. We also shed lights in advances and challenges of engineering the important metabolic pathways that contain a variety of dietary metabolites and phytochemicals. In addition, we endorsed substantial technical hurdles and possible ways to overcome the unpredictability of CRISPR/Cas technology for broader application across various crop species. We speculated that by making a strong interconnection among all genomic fields will give a gigantic bunt of knowledge to develop crop expressing desired traits.

Evaluation of ultrasound‐assisted microwave hot air convective drying Chinese hickory—Drying kinetics and product's quality properties

AbstractThe fresh Chinese hickory nuts (Carya cathayensis sarg.) were exposed to airborne ultrasound‐assisted convective drying and microwave‐assisted convective drying, as well as their combination. We investigated the effect of different drying schemes on process kinetics and quality characteristics. The global model of drying kinetics based on coupled ordinary differential equations was used to describe the moisture and material temperature profiles during drying. Application of ultrasound and microwave in convective drying reduced drying time in the range of 14.0–56.6%, but the maximum savings was found for simultaneous exposure of convection, ultrasound, and microwave with the range of 73.6–84.2%. The globally mathematical model was successfully used to simulate the real drying kinetics processes. The quality properties about the content of heat‐sensitive bioactive substances such as phenolic, flavonoid, proanthocyanidin, individual phenolic compounds, as well as antioxidant capacity in convective drying assisted with microwave (100 W) and ultrasound (200 W; CU2M1) are found to be significantly higher than the other groups. The results allow stating ultrasound increase drying efficiency, as expected by reducing the drying time there is less damage to the product.Practical ApplicationIn this work, we designed an experimental scale hybrid dryer that equipped with hot‐air convective drying, ultrasound generator and microwave drying system to dehydrate Chinese hickory nut and the effect of different drying schemes on the drying kinetics and product characteristics were investigated. This is an innovative technology of microwave and ultrasound hybrid drying to produce dried hickory products. Application of ultrasound and microwave in convective drying reduced drying time in the range of 14–56.6%, but the shortest drying time was observed for simultaneous action of convection, ultrasound, and microwave. The results of qualitative analysis showed a product improvement due to ultrasound as compared to convective drying and microwave‐convective drying.

Continuous mixing technology: Validation of a DEM model

Continuous powder mixing is an important technology used in the development and manufacturing of solid oral dosage forms. Since critical quality attributes of the final product greatly depend on the performance of the mixing step, an analysis of such a process using the Discrete Element Method (DEM) is of crucial importance. On one hand, the number of expensive experimental runs can be reduced dramatically. On the other hand, numerical simulations can provide information that is very difficult to obtain experimentally. In order to apply such a simulation technology in product development and to replace experimental runs, an intensive model validation step is required. This paper presents a DEM model of the vertical continuous mixing device termed CMT (continuous mixing technology) and an extensive validation workflow. First, a cohesive contact model was calibrated in two small-scale characterization experiments: a compression test with spring-back and a shear cell test. An improved, quicker calibration procedure utilizing the previously calibrated contact models is presented. The calibration procedure is able to differentiate between the blend properties caused by different API particle sizes in the same formulation. Second, DEM simulations of the CMT were carried out to determine the residence time distribution (RTD) of the material inside the mixer. After that, the predicted RTDs were compared with the results of tracer spike experiments conducted with two blend material properties at two mass throughputs of 15 kg/h and 30 kg/h. Additionally, three hold-up masses (500, 730 and 850 g) and three impeller speeds (400, 440 and 650 rpms) were considered. Finally, both RTD datasets from DEM and tracer experiments were used to predict the damping behavior of incoming feeder fluctuations and the funnel of maximum duration and magnitude of incoming deviations that do not require a control action. The results for both tools in terms of enabling a control strategy (the fluctuation damping and the funnel plot) are in excellent agreement, indicating that DEM simulations are well suited to replace process-scale tracer spike experiments to determine the RTD.

Why Does the Precautionary Principle Suffice for Blood Regulation?

Traditional approaches to blood regulation emphasise the precautionary principle and pursue zero-risk for viral transmission; these traditional approaches have usually followed tragedy, such as the HIV and hepatitis C infections that followed the use of factor VIII concentrates. However, a much more haphazard haemovigilance system operates for general adverse events. Such imprecise assessment of hazards prevents sound benefit-risk assessment, and for blood products this is further confounded by the fact that their efficacy has attracted little systematic study. The ongoing COVID-19 pandemic has now prompted the proposal of a convalescent plasma (CP) blood product. Clearly, mere freedom from infectious agents will not suffice in assessing CP, and an objective measure of efficacy, so as to permit formal benefit-risk analysis, is essential. This is both a scientific and an ethical demand, as has been the case for other experimental COVID-19 treatments. With special reference to COVID-19 CP, the well-recognized adverse events of transfusion-associated lung injury (TRALI) and transfusion-associated circulatory overload (TACO) will be important. Furthermore, not only efficacy but also product quality attributes (e.g., antibody titre) will have to be defined. Both of these are outside the traditional regulatory philosophy for blood products and are needed to truly assess the benefit-risk of this putative therapeutic product.

Physicochemical, nutritional, and sensory attributes of Minas frescal cheese from grazing cows fed a supplement containing different levels of babassu coconut (Orbignyaspeciosa)

Alternative feeds can reduce milk production costs, but quality attributes of dairy products may also be affected. The physicochemical, sensory, and fatty acid (FA) profiles of Minas frescal cheese produced from grazing cows fed different levels of cracked babassu coconut (CBC) were investigated in the present study. Actual and adjusted cheese yields in kg cow−1 d−1 decreased as CBC levels increased in the supplement. Physicochemical composition was unaltered, whereas proportions of trans-11 18:1 and cis-9, trans-11 CLA linearly increased in cheese from cows fed increasing CBC levels. Conversely, the n-6:n-3 FA ratio showed a linear decreasing pattern. Yellow intensity decreased linearly, whereas a quadratic response was observed for aroma and appearance scores. In conclusion, feeding CBC to grazing cows induces beneficial changes in FA composition and other quality attributes of Minas frescal cheese, but cheese yield in kg cow−1 d−1 is strongly reduced, limiting the use of CBC in dairy cow diets.

CARCASS AND MEAT QUALITY CHARACTERISTICS OF WILD BOAR CROSSBREDS

Due to the growing interest in the production and consumption of wild boar meat, the quality attributes of meat products should be well established. To characterize the quality of wild boar cross meat, two males and two females reared in the same environment were slaughtered at an average of one year of age, and meat samples were was collected and analyzed for different parameters such as for moisture, pH value, protein, fat, iron, phosphorous, calcium, water holding capacity through the measure of cooking loss. Data obtained for live body weight, carcass biochemical characteristics, and meat quality traits were submitted to one-way analysis of variance (ANOVA) using a general linear model (uni-variate) in Statistical Package for Social Sciences (SPSS) computer program and the level of significance was determined observing the probability value (p) obtained through ANOVA of respective traits. To study the association among nutritive values and body parts, Pearson’s correlation coefficients were determined using in Statistical Package for Social Sciences (SPSS) computer program. The pH values were found to be in the range of 5.78 to 5.90. Moisture, total ash, fat, and protein contents were observed to be in the range of 71.38 to 73.57 %, 0.89 to 1.10 %, 4.34 to 5.54 %, and 16.73 to 18.84 % respectively. Iron, phosphorous, and calcium content were found to be in the range of 1.94 to 2.94 mg/100g, 20.17 to 37.57 mg/100g, and 170.68 to 190.88 mg/100g respectively whereas cooking loss was in the range of 31.59 to 26.88 %. Sensory evaluation of meat samples was examined by a group of panelists according to the hedonic rating test. The consumer preference was similar to both types of meat samples (male and female). The overall acceptance; however, were higher in female samples than in male samples due to boar taint evident during the cooking or eating of pork derived from non-castrated male pigs once they reach puberty. The comparison of wild crosses among available commercial pigs and indigenous pigs is warranted for further studies with an appropriate and defined production system to obtain lean meat as per the consumer preferences which could be extensively used in commercial pig production to provide high-quality pork.

Interpretable biomanufacturing process risk and sensitivity analyses for quality‐by‐design and stability control

AbstractWhile biomanufacturing plays a significant role in supporting the economy and ensuring public health, it faces critical challenges, including complexity, high variability, lengthy lead time, and very limited process data, especially for personalized new cell and gene biotherapeutics. Driven by these challenges, we propose an interpretable semantic bioprocess probabilistic knowledge graph and develop a game theory based risk and sensitivity analyses for production process to facilitate quality‐by‐design and stability control. Specifically, by exploring the causal relationships and interactions of critical process parameters and product quality attributes, we create a Bayesian network based probabilistic knowledge graph characterizing the complex causal interdependencies of all factors. Then, we introduce a Shapley value based sensitivity analysis, which can correctly quantify the variation contribution from each input factor on the outputs (i.e., productivity, product quality). Since the bioprocess model coefficients are learned from limited process observations, we derive the Bayesian posterior distribution to quantify model uncertainty and further develop the Shapley value based sensitivity analysis to evaluate the impact of estimation uncertainty from each set of model coefficients. Therefore, the proposed bioprocess risk and sensitivity analyses can identify the bottlenecks, guide the reliable process specifications and the most informative data collection, and improve production stability.

Multi-attribute method performance profile for quality control of monoclonal antibody therapeutics

Multi-attribute method (MAM) using peptide map analysis with high resolution mass spectrometry is increasingly common in product characterization and the identification of critical quality attributes (CQAs) of biotherapeutic proteins. Capable of providing structural information specific to amino acid residues, quantifying relative abundance of product variants or degradants, and detecting profile changes between product lots, a robust MAM can replace multiple traditional methods that generate profile-based information for product release and stability testing. In an effort to provide informative and efficient analytical monitoring for monoclonal antibody (mAb) products, from early development to manufacturing quality control, we describe the desired MAM performance profile and address the major scientific challenges in MAM method validation. Furthermore, to support fast speed investigational product development, we describe a platform method validation strategy and results of an optimized MAM workflow. This strategy is applied to support the use of MAM for multiple mAb products with similar structures and physicochemical properties, requiring minimal product-specific method validation activities. Three mAb products were used to demonstrate MAM performance for common and representative product quality attributes. Method validation design and acceptance criteria were guided by the Analytical Target Profile concept, as well as relevant regulatory guidelines to ensure the method is fit-for-purpose. A comprehensive system suitability control strategy was developed, and reported here, to ensure adequate performance of the method including sample preparation, instrument operation, and data analysis. Our results demonstrated sufficient method performance for the characteristics required for quantitative measurement of product variants and degradants.

Measuring teamwork quality in large‐scale agile organisations evaluation and integration of the aTWQ approach

The maturity of organisations is measured using process assessment models like the International Organization for Standardization (ISO)/IEC 33001. Product quality is refined with internal and external product quality characteristics based on models like the ISO/IEC 25010. With the shift from the Tailorism-driven process orientation to a more people-centric organization, the process and product quality dimensions have to be extended by the teamwork quality (TWQ) dimension. For the sake of systematic organization development, this new third quality dimension needs to be integrated into existing quality frameworks to achieve a holistic quality approach. This article introduces agile TWQ as the method of choice. It explains its design, implementation and evaluation in the large enterprise context of the Volkswagen AG. It provides insights into the effectivity of this approach in heterogeneous multi-team settings, as well as into its strengths, weaknesses, and limitations.

STRATEGI PENINGKATAN KUALITAS PRODUK DALAM RANTAI PASOK KOMODITI PISANG DI PROVINSI BENGKULU

A well-being supply chain system will affect on the sustainability of the production and consumer’s satisfaction. Consumer’s need will be fulfilled if the served quality is in the accordance with consumer’s expectations. This study aimed to identify banana supply chains, determine product quality attributes, and strategies for improving the quality of banana products. The methods used were Van der Vorst supply chain management framework, Quality Function Deployment (QFD), and Analytical Hierarchy Process (AHP). The research results exposed that banana supply chain consisted farmers, traders, industries, retailers, and consumers. The dominant quality factors on thise supply chain were the harvest planning (0.24) and harvesting technique (0.19) for fresh bananas; the frying (0.28) and the packaging (0.20) for sale banana; the frying (0.28) and the packaging (0.17) for banana chips. Meanwhile, the quality attributes for fresh bananas were fruit maturity and damage level, for sale bananas were taste and texture, and for banana chips were taste and level of cracked chips. The proposed strategies to improve product quality in the banana comodity supply chain were an increase ability or skill in the production process for each actor (0.25), using standards in the product production process (0.22), make a explicit contractual agreements between actors regarding product quality (0.21), establish a structur farmer group institutions (0.13), optimizing local wisdom (0.10) and the government’s role in assisting farmer and industrial development (0.08). Keywords: banana products,quality improvement, supply chain

ANALISIS KEPUASAN KONSUMEN MADU LOKAL DI KOTA PONTIANAK

Honey is a natural substance that bees produce from flower-neutral raw materials. Honey is one of the commodities of non-timber forest products that provide many benefits. The purpose of this research was to analyze the satisfaction of the honey consumers to Syaiful in Pontianak city. In this study there were 100 key respondents to answer questionnaires. Through five dimensions namely product quality dimensions, service quality dimensions, price dimensions, emotional dimensions, and ease dimensions will be known attributes - what attributes need to be maintained, performance, improved or reduced and determine the top priority, maintain achievements, low priority and excessive priority into cartesian diagrams. Respondents with accidental sampling who happened to meet with researchers to be analyzed using Importance Performance Analysis (IPA) and Customer Satisfaction Index (CSI). IPA results showed that the dimensions of consumer satisfaction that became the main priority in improving the performance of its implementation are honey color, honey aroma, neat-looking employees, affordable prices, prices according to product quality, proud to consume local honey. CSI results showed that the contingency satisfaction level in Syaiful honey shop fell into the category of satisfied with avalue of 71.20%.

Physiologically‐Based Pharmacokinetic Modeling to Support Determination of Bioequivalence for Dermatological Drug Products: Scientific and Regulatory Considerations

Physiologically-based pharmacokinetic (PBPK) modeling and simulation provides mechanism-based predictions of the pharmacokinetics of an active ingredient following its administration in humans. Dermal PBPK models describe the skin permeation and disposition of the active ingredient following the application of a dermatological product on the skin of virtual healthy and diseased human subjects. These models take into account information on product quality attributes, physicochemical properties of the active ingredient and skin (patho)physiology, and their interplay with each other. Regulatory and product development decision makers can leverage these quantitative tools to identify factors impacting local and systemic exposure. In the realm of generic drug products, the number of US Food and Drug Administratioin (FDA) interactions that use dermal PBPK modeling to support alternative bioequivalence (BE) approaches is increasing. In this report, we share scientific considerations on the development, verification and validation (V&V), and application of PBPK models within the context of a virtual BE assessment for dermatological drug products. We discuss the challenges associated with model V&V for these drug products stemming from the fact that target-site active ingredient concentrations are typically not measurable. Additionally, there are no established relationships between local and systemic PK profiles, when the latter are quantifiable. To that end, we detail a multilevel model V&V approach involving validation for the model of the drug product of interest coupled with the overall assessment of the modeling platform in use while leveraging in vitro and in vivo data related to local and systemic bioavailability.

Honeybee and Plant Products as Natural Antimicrobials in Enhancement of Poultry Health and Production

The quality and safety attributes of poultry products have attracted increasing widespread attention and interest from scholarly groups and the general population. As natural and safe alternatives to synthetic and artificial chemical drugs (e.g., antibiotics), botanical products are recently being used in poultry farms more than 60% of the time for producing organic products. Medicinal plants, and honeybee products, are natural substances, and they were added to poultry diets in a small amount (between 1% and 3%) as a source of nutrition and to provide health benefits for poultry. In addition, they have several biological functions in the poultry body and may help to enhance their welfare. These supplements can increase the bodyweight of broilers and the egg production of laying hens by approximately 7% and 10% and enhance meat and egg quality by more than 25%. Moreover, they can improve rooster semen quality by an average of 20%. Previous research on the main biological activities performed by biotics has shown that most research only concentrated on the notion of using botanical products as growth promoters, anti-inflammatory, and antibacterial agents. In the current review, the critical effects and functions of bee products and botanicals are explored as natural and safe alternative feed additives in poultry production, such as antioxidants, sexual-stimulants, immuno-stimulants, and for producing healthy products.