Review
Polymer Science
S. Farid Mohseni-Motlagh, Roshanak Dolatabadi, Majid Baniassadi, Mostafa Baghani, Slawomir Wilczynski, Aneta Ostrozka-Cieslik
Summary: Hydrogel-based drug delivery systems have advantages but also challenges, and the quality by design approach can help develop better products with fewer errors.
Article
Pharmacology & Pharmacy
Cecilia de Barros, Norberto Aranha, Patricia Severino, Eliana B. Souto, Aleksandra Zielinska, Andre Lopes, Alessandra Rios, Fernando Batain, Kessi Crescencio, Marco Chaud, Thais Alves
Summary: The aim of this study was to develop a liposomal formulation as a carrier of ghrelin, using a quality by design (QbD) approach and chitosan coating for improvement. The optimized liposomes showed small size, high encapsulation efficiency, and improved performance in ex vivo permeation and mucoadhesion analyses, suggesting a potential innovative opportunity for the treatment of cachexia.
Article
Biotechnology & Applied Microbiology
Lalintip Hocharoen, Sarawuth Noppiboon, Panit Kitsubun
Summary: DNA vaccines, as the third generation of vaccines, show potential for customizability and stability in protection and treatment. The main challenge lies in producing active DNA conforming to regulations. By understanding the purification step, process parameters impacting critical quality attributes and performance attributes can be analyzed for Quality by Design application.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kondasingh Charankumar, Deepkumar Bagasariya, Naitik Jain, Paras Famta, Saurabh Shah, Ganesh Vambhurkar, Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh, Saurabh Srivastava
Summary: We have developed Pioglitazone-loaded liposomes embedded within the hyaluronic acid gel, which demonstrated sustained release of the drug from the gel matrix. Cellular internalization studies confirmed the successful internalization of Pio-Lipo in SK-MEL-28 cells and nuclear staining study revealed cell apoptosis. Thus, Pioglitazone-based liposomal gel could be an effective alternative for melanoma management.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Chemistry, Applied
Yasunori Abe, Kosuke Emori
Summary: This article describes a novel experimental design and statistical analysis method for identifying the critical process parameters (CPPs) of impurities in futibatinib. Through failure mode and effects analysis, 11 potential CPPs were identified for investigation. Orthogonal experiments and statistical analysis were used to analyze the factors influencing each impurity, and the details of the process parameters to be examined in commercial production were clarified.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Applied
Yasunori Abe, Kosuke Emori
Summary: This study aims to construct a design space for impurities based on the quality-by-design concept, using experiment design and statistical analysis for risk assessment. Regression equations were identified for critical process parameters of impurities using a face-centered composite design, and a prediction model was constructed for analyzing the risk. The risk was evaluated through process understanding and control ranges in the construction of a control strategy.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Applied
Yasunori Abe, Kosuke Emori
Summary: This study constructs a control strategy for futibatinib by designing a space for particle size distribution, and demonstrates that stable production of the drug can be achieved without additional milling process.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Review
Biochemistry & Molecular Biology
Walhan Alshaer, Hamdi Nsairat, Zainab Lafi, Omar M. Hourani, Abdulfattah Al-Kadash, Ezaldeen Esawi, Alaaldin M. Alkilany
Summary: Nanomedicine is a growing field and liposomal formulations are a major platform in this field. Quality by design (QbD) is a powerful approach that can be applied to develop liposomal-based nano-pharmaceuticals, ensuring efficient and safe therapeutics. This review discusses the current practices of employing QbD in this area.
Review
Pharmacology & Pharmacy
Maram Suresh Gupta, Tegginamath Pramod Kumar, Devegowda Vishkante Gowda, Jessica M. Rosenholm
Summary: Orodispersible films (ODFs) are a unique pharmaceutical dosage form that can improve patient compliance and convenience, particularly for pediatric and geriatric populations. They have the potential to serve as carriers for drugs, herbal extracts, probiotics, and vaccines, while also aiding in drug loading, taste masking, and stability enhancement.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Biotechnology & Applied Microbiology
Anurag S. Rathore, Andrew L. Zydney, Anupa Anupa, Saxena Nikita, Neelesh Gangwar
Summary: Continuous processing is widely acknowledged in the biopharmaceutical industry for its higher productivity and greater consistency in product quality compared to batch manufacturing. Technology enablers play a crucial role in the transition from batch to continuous processing, including new bioreactors, cell retention devices, continuous flow refolding, continuous chromatography, and single-pass filtration systems.
TRENDS IN BIOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jonas Pielenhofer, Sophie Luise Meiser, Karsten Gogoll, Anna-Maria Ciciliani, Mark Denny, Michael Klak, Berenice M. M. Lang, Petra Staubach, Stephan Grabbe, Hansjoerg Schild, Markus P. P. Radsak, Hilde Spahn-Langguth, Peter Langguth
Summary: This article demonstrates the application of quality by design (QbD) in the development of a nanoparticulate imiquimod emulsion gel formulation. The critical quality attributes (CQAs) and critical process parameters (CPPs) were identified and optimized, leading to consistent quality and minimal batch-to-batch variability. The model validation showed good correlation between predicted and observed values.
Article
Engineering, Chemical
Alex Juckers, Petra Knerr, Frank Harms, Jochen Strube
Summary: Lyophilization is commonly used for preserving thermolabile products, with the main drawback being the long processing time. By implementing the quality by design (QbD) approach and process analytical technology (PAT), the process duration can be optimized for increased productivity while maintaining product safety.
Article
Chemistry, Applied
Mahender Madaraboina, Bhimavarapu Srinivasa Reddy, Venkata Siva Kumar Boddupalli, Pavani Sankar Reddy, Jaya Shree Anireddy, Rajeev Rehani Budhdev, Rakeshwar Bandichhor, Srinivas Achanta
Summary: A practical and scalable manufacturing process for the anti-inflammatory drug lifitegrast was developed, ensuring compliance with quality guidelines. The process features protecting-group-free synthesis, inhibition of racemization, and removal of impurities and undesired optical isomer.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Engineering, Chemical
Axel Schmidt, Heribert Helgers, Florian Lukas Vetter, Steffen Zobel-Roos, Alina Hengelbrock, Jochen Strube
Summary: Vaccine supply faces manufacturing capacity issues due to operation personnel and chemical demands. Continuous manufacturing processes, enabled by strict application of regulatory quality by design process based on digital twins, process analytical technology, and control automation strategies, can help improve manufacturing capacity, reduce batch failures, optimize personnel training and utilization of buffers and chemicals, and speed up product release.
Article
Biotechnology & Applied Microbiology
Christopher Taylor, Lukas Marschall, Marco Kunzelmann, Michael Richter, Frederik Rudolph, Judith Vajda, Beate Presser, Thomas Zahel, Joey Studts, Christoph Herwig
Summary: The study introduces a novel integrated process model procedure to optimize the process validation workflow by maximizing the use of development data. The evaluation in a case study for a candidate monoclonal antibody bioprocess demonstrated the potential to reduce investigated parameters by up to 24%.
BIOENGINEERING-BASEL
(2021)
Article
Endocrinology & Metabolism
Gayatri Vishwakarma, Neh Nupur, Anurag S. Rathore
Summary: In this study, the structural and functional similarity of biosimilars of insulin glargine were evaluated. The results showed that some biosimilars had higher levels of high molecular weight species and related substances, as well as higher rates of impurity generation. The aggregation at 14 days was found to be correlated with the aggregation at 0 day and the number of months from expiry. Overall, insulin glargine biosimilars demonstrated similarity to the innovator product, but certain biosimilars exhibited low amounts of product-related variants that impacted product stability. The order of biosimilarity was Lantus((R)) > Biosimilar 2 > Biosimilar 4 > Biosimilar 1 > Biosimilar 3.
JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Anurag S. Rathore, Yuexia Li, Hemlata Chhabra, Akshat Lohiya
Summary: This study examines the reasons for warning letters issued by the FDA to pharmaceutical companies after post-approval inspections. The most common reasons for the warning letters are poor compliance to CGMP and misbranding. Detailed analysis of CGMP warning letters reveals three major types of violations: deficiencies in process validation, documentation practices (data integrity), and quality control. The study emphasizes the importance of improving CGMP compliance and implementing effective quality management systems to avoid warning letters.
JOURNAL OF PHARMACEUTICAL INNOVATION
(2023)
Review
Biotechnology & Applied Microbiology
Anurag S. Rathore, Garima Thakur, Nikhil Kateja
Summary: Continuous integrated bioprocessing has gained significant attention from the biopharma industry, but its implementation in the biologics industry faces challenges due to legacy infrastructure, regulatory guidelines, and a focus on novel therapies. This article provides a review and perspective on the status and hurdles of continuous integrated bioprocessing. It suggests that the real impact of this technology may be seen when manufacturing costs become a significant portion of product development costs.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Review
Biotechnology & Applied Microbiology
Anurag S. Rathore, Saxena Nikita, Garima Thakur, Somesh Mishra
Summary: Artificial intelligence and machine learning have vast potential in optimizing the design, monitoring, and control of biopharmaceutical manufacturing. The driving forces for adopting these techniques include the increasing global demand for biotherapeutics and the rise of Industry 4.0, which require intelligent, automated supervision. This review summarizes the applications of artificial intelligence and machine learning in biopharmaceutical manufacturing, focusing on commonly used algorithms such as multivariate data analysis, artificial neural networks, and reinforcement learning. Perspectives on the future growth of these applications and the challenges in implementing them at manufacturing scale are also discussed.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Rajinder Kaur, Ritu Jain, Niharika Budholiya, Anurag S. Rathore
Summary: The study investigates the impact of long term culturing on cell morphology and altered cellular functions, which may lead to phenotypic drift and affect product yield and quality. The study highlights the use of cellular and analytical assay toolbox to define cell line stability and optimize culture performance and product quality.
BIOTECHNOLOGY LETTERS
(2023)
Article
Biochemical Research Methods
Ramesh Kumar, Deepika Sarin, Anurag S. S. Rathore
Summary: The complexity of biotherapeutic products requires monitoring and characterization of numerous product quality attributes. Capillary electrophoresis (CE) has been used in biopharmaceutical analysis but is considered low-throughput. In this study, the dead time of CE was utilized to analyze three monoclonal antibody samples, resulting in a significant reduction in analysis time and increased productivity without compromising resolution. Good method reproducibility was observed, suggesting that sequential injections can be applied for fast and robust CE analysis of biopharmaceuticals.
Review
Pharmacology & Pharmacy
Ritu Jain, Janakiraman Subramanian, Anurag S. Rathore
Summary: The drug approval process involves extensive and expensive preclinical and clinical examination. Most drugs fail in late-stage clinical trials due to inability to achieve primary endpoints or intolerable adverse effects. Only one-tenth of the drugs that enter clinical trials progress to FDA regulatory submission.
EXPERT OPINION ON PHARMACOTHERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Rajinder Kaur, Anurag S. Rathore
Summary: This study demonstrates that the addition of antioxidants in cell culture can reduce ROS levels, increase mitochondrial membrane potential, improve cell viability, reduce apoptosis and lysosome activity. Furthermore, antioxidants can enhance antibody production and improve its quality.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2023)
Article
Chemistry, Analytical
Anuj Shrivastava, Shyamapada Mandal, Sudip K. Pattanayek, Anurag S. Rathore
Summary: Aggregation of monoclonal antibody therapeutics is a serious concern. A new approach using dynamic light scattering (DLS) and machine learning (ML) algorithm is proposed to quantify the relative percentage of multimers in a monoclonal antibody therapeutic product.
ANALYTICAL CHEMISTRY
(2023)
Review
Biotechnology & Applied Microbiology
Saxena Nikita, Somesh Mishra, Keshari Gupta, Venkataramana Runkana, James Gomes, Anurag S. Rathore
Summary: Advanced control strategies have been widely implemented in chemical, pharmaceutical, and food processing industries. Recently, there has been exploration of applying these strategies to bioreactor control for the production of biotherapeutics. The development of a robust and advanced process control system, aided by advancements in sensors, machinery, and industrial internet of things, can greatly improve bioreactor process performance, productivity, and reproducibility. This review discusses the advancements, challenges, and future prospects for control strategies in industrial-scale production of biotherapeutic products.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Medicine, Research & Experimental
Shravan Sreenivasan, Anurag S. Rathore
Summary: This study investigated the aggregation of mAb in the presence of Fe2+ and H2O2 in saline and in vitro models. The results showed that the combined presence of Fe2+ and H2O2 increased mAb aggregation and altered protein structure and hydrophobicity. Increasing the time, temperature, and Fe2+ and H2O2 concentration further enhanced mAb aggregation. Additionally, mAb samples with copper and cobalt chlorides also resulted in degradation.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Akshay Chenna, Wajihul Hasan Khan, Rozaleen Dash, Saurabh Saraswat, Archana Chugh, Anurag S. Rathore, Gaurav Goel
Summary: This study used a structural bioinformatics protocol to design peptides that can inhibit the complexation of SARS-CoV-2 RdRp. Two designed peptides with high geometric complementarity and interaction specificity for the binding interface of nsp7 were identified. These peptides showed better binding affinity than nsp12 and effectively inhibited the complexation of nsp7-nsp12.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Chemistry, Analytical
Geetanjali Basavaraj Hubli, Shantanu Banerjee, Anurag S. Rathore
Summary: In this study, a robust FT-NIR based quantification method has been developed for the measurement of all 20 amino acids, glucose, lactate, and trastuzumab in CHO cell culture. The method achieved good calibration statistics and demonstrated the ability to accurately predict the concentrations of these components. The proposed tool has the potential to play a critical role in biopharmaceutical manufacturing and process control.
Article
Public, Environmental & Occupational Health
Sonia Gandhi, Smita Kashiramka, Anurag S. Rathore
Summary: The high prices of biotherapeutics are a concern for agencies working on strategies to manage medicine prices and promote equitable access. This study identifies factors influencing the price of biotherapeutics, highlighting the importance of considering innovation capability, development costs, and regulatory environment. Policymakers need to implement innovative pricing frameworks that align with national policies, regulations, and market dynamics.
WORLD MEDICAL & HEALTH POLICY
(2023)
Article
Biotechnology & Applied Microbiology
Anupa Anupa, Vikrant Bansode, Nikhil Kateja, Anurag S. Rathore
Summary: This article presents a novel approach for the separation of charge variants during continuous CEX chromatography. By combining displacement mode chromatography and salt-based step elution, the content of acidic and basic variants is effectively controlled. Compared to traditional methods, this approach increases resin productivity and utilization, while achieving high recovery rates.
BIOTECHNOLOGY PROGRESS
(2023)
