Online/at‐line measurement, analysis and control of product titer and critical product quality attributes (CQAs) during process development

2020 ◽  
Vol 117 (12) ◽  
pp. 3757-3765 ◽  
Author(s):  
Letha Chemmalil ◽  
Tanushree Prabhakar ◽  
June Kuang ◽  
Jay West ◽  
Zhijun Tan ◽  
...  
Authorea ◽  
2020 ◽  
Author(s):  
Letha Chemmalil ◽  
Tanushree Prabhakar ◽  
June Kuang ◽  
Jay West ◽  
Zhijun Tan ◽  
...  

Author(s):  
Alison Lee ◽  
Yee Jiun Kok ◽  
Meiyappan Lakshmanan ◽  
Dawn Leong ◽  
Lu Zheng ◽  
...  

A robust monoclonal antibody (mAb) bioprocess requires physiological parameters such as temperature, pH, or dissolved oxygen (DO) to be well-controlled as even small variations in them could potentially impact the final product quality. For instance, pH substantially affects N-glycosylation, protein aggregation and charge variant profiles, as well as mAb productivity. However, relatively less is known about how pH jointly influences product quality and titer. In this study, we investigated the effect of pH on culture performance, product titer and quality profiles by applying longitudinal multi-omics profiling, including transcriptomics, proteomics, metabolomics and glycomics, at three different culture pH set points. The subsequent systematic analysis of multi-omics data showed that pH set points differentially regulated various intracellular pathways including intracellular vesicular trafficking, cell cycle, and apoptosis, thereby resulting in differences in specific productivity, product titer and quality profiles. In addition, a time-dependent variation in mAb N-glycosylation profiles, independent of pH was identified to be mainly due to the accumulation of mAb proteins in the endoplasmic reticulum (ER) over culture time, disrupting cellular homeostasis. Overall, this multi-omics-based study provides an in-depth understanding of the intracellular processes in mAb-producing CHO cell line under varied pH conditions and could serve as a baseline for enabling the quality optimization and control of mAb production.


2008 ◽  
Vol 3 (1) ◽  
Author(s):  
Balazs Balasko ◽  
Sandor Nemeth ◽  
Gabor Nagy ◽  
Janos Abonyi

In the near future of chemical industry, communication between design, manufacturing, marketing and management should be centered on modeling and simulation, which could integrate the whole product and process development chains, process units and subdivisions of the company. Solutions to this topic often set aside one or more components from product, process and control models, hence, as a novel know-how, an information system methodology was developed. Its structure integrates models of these components with a process data warehouse where integration includes information, location, application and time integrity. It supports complex engineering tasks related to analysis of system performance, process optimization, operator training systems (OTS), decision support systems (DSS), reverse engineering or software sensors (soft-sensors). The case study in this article presents the application of the proposed methodology for product quality soft-sensor application by on-line melt index prediction of an operating polymerization technology.


2019 ◽  
Vol 1 (1) ◽  
pp. 44
Author(s):  
Rony Trizudha ◽  
Sri Rahayuningsih ◽  
Ana Komari

As technology advances at this time, players in business are aware of the importance of product quality in the increasingly fierce competition in the industrial world due to the emergence of many similar companies. Therefore, companies must be able to compete to meet customer desires and try to retain customers. To maintain customers and their marketing areas, companies must have high competitiveness in order to survive by prioritizing quality improvement, increasing efficiency and increasing productivity to improve quality because by increasing quality, products can be accepted among consumers so that company goals can be fulfilled. Therefore, the company must carry out effective quality control which will result in high productivity, lower overall cost of making goods and the factors that cause production failure to be minimized. To improve quality, use the six sigma method, DMAIC and seven tools so that it can be known the cause of the damage and what actions are taken so that there needs to be a controversy to stabilize the processes of the production process so that we can know what percentage of damage and what factors cause damage, therefore there must be measurements and recommendations for improvement and control to reduce the causes From the analysis, it was found that the dent cup was 20.36%, the lid was 21.36% less dense, the lid was damaged in the finished product 18.72%, the cup was 19.28% less thick, the packaging was flexible 20.55%Seiring kemajuan teknologi pada saat ini pelaku di bisnis menyadari akan pentingnya kualitas produk dalam persaingan dunia industri yang semakin ketat karena banyak bermunculan perusahaan-perusahaan sejenis. Oleh sebab itu perusahaan harus dapat bersaing untuk memenuhi keinginan  pelanggan dan berusaha dapat mempertahankan pelanggan. Untuk mempertahankan pelangan dan wilayah pemasaranya perusahaan-perusahaan harus mempunyai daya saing yang tinggi untuk dapat bertahan dengan mengutamakan peningkatan mutu, peningkatan efisiensi dan peningkatan produktivitas untuk meningkatkan kualitas karena dengan peningkatan kualitas, produk dapat diterima di kalangan konsumen sehingga tujuan perusahaan dapat terpenuhi. Maka dari itu perusahaan harus melakukan pengendalian kualitas yang efektif akan menghasilkan produktivitas yang tinggi, biaya pembuatan barang keseluruhan yang lebih  rendah serta  faktor-faktor yang menyebabkan kegagalan produksi akan dapat ditekan sekecil mungkin. Untuk meningkatkan kualitas mengunakan metode six sigma, DMAIC dan seven tools agar dapat diketahui penyebab  kerusakan  dan  tindakan  apa  saja  yang dilakukan sehingga perlu ada kontror untuk menstabilkan  peoses proses produksi sehinga dapat di ketahui berapa persen  kerusakan dan faktor-faktor apa saja yang menyebabkan  kerusakan maka dari itu harus ada pengukuran dan  rekomendasi perbaikan serta melakukan kontrol untuk mengurangi penyebab kerusakan. Dari hasil analisis  di ketahui cup  penyok 20,36%, lid kurang  rapat  21,36%, lid  rusak  pada produk jadi 18,72%,cup kurang tebal 19,28 %kemasan lentur 20,55%


2007 ◽  
Vol 3 (2) ◽  
pp. 1-9 ◽  
Author(s):  
Wenzhong Hu and Yueming Jiang

2012 ◽  
Vol 59 (1) ◽  
Author(s):  
Mohd Helmi Sani ◽  
Frank Baganz

At present, there are a number of commercial small scale shaken systems available on the market with instrumented controllable microbioreactors such as Micro–24 Microreactor System (Pall Corporation, Port Washington, NY) and M2P Biolector, (M2P Labs GmbH, Aachen, Germany). The Micro–24 system is basically an orbital shaken 24–well plate that operates at working volume 3 – 7 mL with 24 independent reactors (deep wells, shaken and sparged) running simultaneously. Each reactor is designed as single use reactor that has the ability to continuously monitor and control the pH, DO and temperature. The reactor aeration is supplied by sparging air from gas feeds that can be controlled individually. Furthermore, pH can be controlled by gas sparging using either dilute ammonia or carbon dioxide directly into the culture medium through a membrane at the bottom of each reactor. Chen et al., (2009) evaluated the Micro–24 system for the mammalian cell culture process development and found the Micro–24 system is suitable as scaledown tool for cell culture application. The result showed that intra-well reproducibility, cell growth, metabolites profiles and protein titres were scalable with 2 L bioreactors.


Crystals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 68
Author(s):  
Mingtang Tan ◽  
Jun Mei ◽  
Jing Xie

Although freezing has been used to delay the deterioration of product quality and extend its shelf life, the formation of ice crystals inevitably destroys product quality. This comprehensive review describes detailed information on the effects of ice crystals on aquatic products during freezing storage. The affecting factors (including nucleation temperature, freezing point, freezing rate, and temperature fluctuation) on the size, number, distribution, and shape of ice crystals are also elaborated in detail. Meanwhile, the corresponding technologies to control ice crystals have been developed based on these affecting factors to control the formation of ice crystals by inhibiting or inducing ice crystallization. In addition, the effects of ice crystals on the water, texture, and protein of aquatic products are comprehensively discussed, and the paper tries to describe their underlying mechanisms. This review can provide an understanding of ice crystallization in the aquatic products during freezing and contribute more clues for maintaining frozen food quality.


Sign in / Sign up

Export Citation Format

Share Document