qbd vaccine

In recent years, Generalized Modules for Membrane Antigens (GMMA) have received increased attention as an innovative vaccine platform against bacterial pathogens, particularly attractive for low- and middle-income countries because of manufacturing simplicity. The assessment of critical quality attributes (CQAs), product-process interactions, identification of appropriate in process analytical methods, and process modeling is part of a robust quality by design (QbD) framework to support further development and control of manufacturing processes...

Vaccines are integral to human life to protect them from life-threatening diseases. However, conventional vaccines often suffer limitations like inefficiency, safety concerns, unavailability for non-culturable microbes, and genetic variability among pathogens. Chimeric vaccines combine multiple antigen-encoding genes of similar or different microbial strains to protect against hyper-evolving drug-resistant pathogens. The outbreaks of dreadful diseases have led researchers to develop economical chimeric vaccines that can cater to a large population in a shorter time...

Messenger RNA (mRNA) technologies have shown great potential in prophylactic vaccines and therapeutic medicines due to their adaptability, rapidity, efficacy, and safety. The purity of mRNA determines the efficacy and safety of mRNA drugs. Though chromatographic technologies are currently employed in mRNA purification, they are facing challenges, mainly arising from the large size, relatively simple chemical composition, instability, and high resemblance of by-products to the target mRNA. In this review, we will first make a comprehensive analysis of physiochemical properties differences between mRNA and proteins, then the major challenges facing in mRNA purification and general considerations are highlighted...

The continuous emergence of new pathogens and the evolution of microbial drug resistance make it absolutely necessary to develop innovative, effective vaccination strategies. Use of nasal vaccination can increase convenience, safety, cause both local and systemic immune reactions. Intranasal administration nevertheless has a number of shortcomings that can be overcome by using the latest achievements of pharmaceutical science. One of the aspects of such solution may be the use of systems for the production of intranasal vaccines in situ polymer compositions that provide a directed sol-gel transition controlled by the physiological conditions of the nasal cavity...

Serology assays are essential tools to mitigate the effect of COVID-19, help to identify previous SARS-CoV-2 infections or vaccination, and provide data for surveillance and epidemiologic studies. In this study, we report the production and purification process of the receptor-binding domain (RBD) of SARS-CoV-2 in HEK293 cells, which allowed the design, optimization, and validation of an indirect ELISA (iELISA) for the detection of human anti-RBD antibodies. To find the optimal conditions of this iELISA, a multivariate strategy was performed throughout design of experiments (DoE) and response surface methodology (RSM), one of the main tools of quality by design (QbD) approach...

Immunoengineering technologies harness the power of immune system modulators such as monoclonal antibodies, cytokines, and vaccines to treat myriad diseases. Immunoengineering innovations have showed great promise in various practices including oncology, infectious disease, autoimmune diseases, and transplantation. Despite the countless successes, the majority of immunoengineering products contain active moieties that are prone to instability. The current review aims to feature freeze-drying as a robust and scalable solution to the inherent stability challenges in immunoengineering products by preventing the active moiety from degradation...

The mRNA-based vaccines are quality-by-design (QbD) immunotherapies that provide safe, tunable, scalable, streamlined and potent treatment possibilities against different types of diseases. The self-amplifying mRNA (saRNA) vaccines, as a highly advantageous class of mRNA vaccines, are inspired by the intracellular self-multiplication nature of some positive-sense RNA viruses. Such vaccine platforms provide a relatively increased expression level of vaccine antigen(s) together with self-adjuvanticity properties...

Pandemics and epidemics are continually challenging human beings' health and imposing major stresses on the societies particularly over the last few decades, when their frequency has increased significantly. Protecting humans from multiple diseases is best achieved through vaccination. However, vaccines thermal instability has always been a hurdle in their widespread application, especially in less developed countries. Furthermore, insufficient vaccine processing capacity is also a major challenge for global vaccination programs...

RNA-based products have emerged as one of the most promising and strategic technologies for global vaccination, infectious disease control, and future therapy development. The assessment of critical quality attributes (CQAs), product-process interactions, relevant process analytical technologies, and process modeling capabilities can feed into a robust Quality by Design (QbD) framework for future development, design, and control of manufacturing processes. QbD implementation will help the RNA technology reach its full potential and will be central to the development, pre-qualification, and regulatory approval of rapid response, disease-agnostic RNA platform production processes...

Process Analytical Technology (PAT) instruments include analyzers capable of measuring physical and chemical process parameters and key attributes with the goal of optimizing process controls. PAT in the form of a probe or sensor is designed to integrate within the pharmaceutical manufacturing line and is coupled with computing equipment to perform chemometric modeling for result interpretation and multilayer statistical control of processes. PAT solutions are intended for understanding bioprocesses with a goal to control quality at all stages of product manufacturing and achieve quality by design (QbD)...

Orodispersible films (ODFs) are ultra-thin, stamp-sized, elegant, portable and patient-centric pharmaceutical dosage forms that do not need water to be ingested. They are particularly useful for paediatric and geriatric patient populations with special needs such as dysphagia, Parkinson's disease, and oral cancer. Accordingly, they hold tremendous potential in gaining patient compliance, convenience and pharmacotherapy. In the present review, conception and evolution of ODFs as a product and its technology are discussed...

DNA vaccines, the third generation of vaccines, are a promising therapeutic option for many diseases as they offer the customization of their ability on protection and treatment with high stability. The production of DNA vaccines is considered rapid and less complicated compared to others such as mRNA vaccines, viral vaccines, or subunit protein vaccines. However, the main issue for DNA vaccines is how to produce the active DNA, a supercoiled isoform, to comply with the regulations. Our work therefore focuses on gaining a process understanding of the purification step which processes parameters that have impacts on the critical quality attribute (CQA), supercoiled DNA and performance attribute (PA), and step yield...

Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model...

Due to the biological activity of the vaccine, the complicated production process, sterility and uniformity of the product, the producing process of the vaccine is complicated and the product quality hard to control. In recent years, with the development of basic science such as cell biology, molecular biology, and metabolic engineering, bioprocess engineering research has developed rapidly. Therefore, FDA and EMA conduct stringent control over the development of biomedical process engineering and product quality...

The anticipated increasing demand for inactivated foot-and-mouth (FMD) disease vaccine calls for its larger production capacity, while development of a large-scale process typically requires high running cost and has very limited experimental throughput at manufacturing scale. Thus, an economic scale-down model of representing a large-scale process becomes necessary and essential. In this study, we used a systematic approach to establish a scale-down model representing a 4000-L culture process for FMD vaccine production by suspension BHK-21 cells...

There is always a need for alternative and efficient methods of drug delivery. The nasal cavity can be considered as a non-invasive and efficient route of administration. It has been used for local, systemic, brain targeting, and vaccination delivery. Although, many intranasal products are currently available on the market, the majority is used for local delivery with fewer products available for the other targets. As nanotechnology utilization in the drug delivery has rapidly spread out, the nasal delivery has become attractive as a promising approach...

Quality by design (QbD) principle has been established as a guideline to emphasize the understanding of the relationship of product quality with process control. Vaccine product have characteristics of security and high efficiency, but it also has features such as complexity and rigorous regulatory for production. This case study describes an example of QbD-driven process development for manufacturing a veterinary vaccine produced with baby hamster kidney-21 cells. The study revealed that cell culture duration was the most significant factor affecting 50% tissue culture infectious doses (TCID50 ) and antigenic titer, and the factors of culture temperature and pH at infection phase exhibited less effect...

Quality by design (ICH-Topic Q8) requires a prospective summary of the desired quality characteristics of a drug product. This is known as the Quality Target Product Profile (QTPP), which forms the basis for the design and development of the product. An analogous term has been established for analytical procedures called the Analytical Target Profile (ATP). The ATP, in a similar fashion to the QTPP, prospectively summarizes the requirements associated with a measurement on a quality attribute which needs to be met by an analytical procedure...

Traditional parenteral recombinant hepatitis B virus (HBV) vaccines have effectively reduced the disease burden despite being able to induce seroprotective antibody titers in 5-10% vaccinated individuals (non-responders). Moreover, an estimated 340 million chronic HBV cases are in need of treatment. Development of safe, stable, and more effective hepatitis B vaccine formulation would address these challenges. Recombinant hepatitis B surface antigen (rHBsAg) entrapped solid fat nanoemulsions (SFNs) containing monophosphoryl lipid A (MPLA) that was prepared and optimized by quality by design (QbD) using response surface methodology (RSM), i...

Bexsero is the first approved vaccine for active immunization of individuals from 2 months of age and older to prevent invasive disease caused by Neisseria meningitidis serogroup B. The active components of the vaccine are Neisseria Heparin Binding Antigen, factor H binding protein, Neisseria adhesin A, produced in Escherichia coli cells by recombinant DNA technology, and Outer Membrane Vesicles (expressing Porin A and Porin B), produced by fermentation of Neisseria meningitidis strain NZ98/254. All the Bexsero active components are adsorbed on aluminum hydroxide and the unadsorbed antigens content is a product critical quality attribute...