scholarly journals In-Line Monitoring of Downstream Purification Processes for VSV Based SARS-CoV-2 Vaccine Using a Novel Technique

BioTech ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 25
Author(s):  
Arik Makovitzki ◽  
Avital Jayson ◽  
Ziv Oren ◽  
Elad Lerer ◽  
Yaron Kafri ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Product Quality ◽  
Rapid Development ◽  
Pharmaceutical Products ◽  
Cell Protein ◽  
Biological Research ◽  
Purification Process ◽  
Israel Institute ◽  
Process Yield ◽  
Critical Information

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases the need for a rapid development of efficient vaccines. Among other vaccines in clinical trials, a recombinant VSV-∆G-spike vaccine was developed by the Israel Institute for Biological Research (IIBR) and is being evaluated. The development of an efficient downstream purification process (DSP) enables the vaccine to be advanced to clinical trials. The DSP must eliminate impurities, either process- or product-related, to yield a sufficient product with high purity, potency and quality. To acquire critical information on process restrictions and qualities, the application of in-line monitoring is vital and should significantly impact the process yield, product quality and economy of the entire process. Here, we describe an in-line monitoring technique that was applied in the DSP of the VSV-∆G-spike vaccine. The technique is based on determining the concentrations of metabolites, nutrients and a host cell protein using the automatic chemistry analyzer, Cobas Integra 400 Plus. The analysis revealed critical information on process parameters and significantly impacted purification processes. The technique is rapid, easy and efficient. Adopting this technique during the purification process improves the process yield and the product quality and enhances the economy of the entire downstream process for biotechnology and bio pharmaceutical products.

scholarly journals On-line monitoring of downstream purification processes for VSV based SARS-CoV-2 vaccine by a novel technique

2021 ◽  
Author(s):  
Arik Makovitzki ◽  
Avital Jayson ◽  
Ziv Oren ◽  
Elad Lerer ◽  
Yaron Kafri ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Product Quality ◽  
Rapid Development ◽  
Pharmaceutical Products ◽  
Cell Protein ◽  
Purification Process ◽  
Israel Institute ◽  
Process Yield ◽  
Critical Information ◽  
On Line

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases the need for rapid development of efficient vaccines. Among other vaccines in clinical trials, a recombinant VSV-∆G-spike vaccine was developed by the Israel Institute for Biological, Chemical and Environmental sciences (IIBR) and is being evaluated. Development of an efficient downstream purification process (DSP) enables advancing the vaccine to clinical trials. The DSP must eliminate impurities, either process- or product -related, to yield sufficient product with high purity, potency, and quality. To acquire critical information on process restrictions and qualities, incorporation of on-line monitoring is vital. Application of on-line monitoring should significantly impact process yield, product quality and economy of the entire process. Here, we describe an on-line monitoring technique that was applied in the DSP of the VSV-∆G-spike vaccine. The technique is based on determining concentrations of metabolites, nutrients and a host cell protein (HCP) by the automatic chemistry analyzer Cobas Integra 400 Plus. The analysis revealed critical information on process parameters and significantly impacted purification processes. The technique is rapid, easy and efficient. Adaptation of this technique during the purification process improves process yield, product quality and enhances the economy of the entire downstream process of biotechnology and bio pharmaceutical products.

scholarly journals Highly Efficient Purification of Recombinant VSV-∆G-Spike Vaccine against SARS-CoV-2 by Flow-through Chromatography

BioTech ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 22
Author(s):  
Elad Lerer ◽  
Ziv Oren ◽  
Yaron Kafri ◽  
Yaakov Adar ◽  
Einat Toister ◽  
...  
Keyword(s):  
Surface Area ◽  
High Surface ◽  
High Surface Area ◽  
Packed Bed ◽  
Exchange Chromatography ◽  
Biological Research ◽  
Purification Process ◽  
Israel Institute ◽  
Highly Efficient ◽  
Flow Through

This study reports a highly efficient, rapid one-step purification process for the production of the recombinant vesicular stomatitis virus-based vaccine, rVSV-∆G-spike (rVSV-S), recently developed by the Israel Institute for Biological Research (IIBR) for the prevention of COVID-19. Several purification strategies are evaluated using a variety of chromatography methods, including membrane adsorbers and packed-bed ion-exchange chromatography. Cell harvest is initially treated with endonuclease, clarified, and further concentrated by ultrafiltration before chromatography purification. The use of anion-exchange chromatography in all forms results in strong binding of the virus to the media, necessitating a high salt concentration for elution. The large virus and spike protein binds very strongly to the high surface area of the membrane adsorbents, resulting in poor virus recovery (<15%), while the use of packed-bed chromatography, where the surface area is smaller, achieves better recovery (up to 33%). Finally, a highly efficient chromatography purification process with CaptoTM Core 700 resin, which does not require binding and the elution of the virus, is described. rVSV-S cannot enter the inner pores of the resin and is collected in the flow-through eluent. Purification of the rVSV-S virus with CaptoTM Core 700 resulted in viral infectivity above 85% for this step, with the efficient removal of host cell proteins, consistent with regulatory requirements. Similar results were obtained without an initial ultrafiltration step.

Current RNA-based Therapeutics in Clinical Trials

2019 ◽  
Vol 19 (3) ◽  
pp. 172-196 ◽  
Author(s):  
Ling-Yan Zhou ◽  
Zhou Qin ◽  
Yang-Hui Zhu ◽  
Zhi-Yao He ◽  
Ting Xu
Keyword(s):  
Clinical Trials ◽  
Rapid Development ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
Therapeutic Effects ◽  
Messenger Rnas ◽  
Small Interfering Rnas ◽  
Rna Modifications ◽  
Guide Rna ◽  
Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

Efficacy and Safety of AZD1222, BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2

2021 ◽  
Vol 5 (1) ◽  
pp. 791-796
Author(s):  
Ilir Alimehmeti
Keyword(s):  
Clinical Trials ◽  
Diagnostic Tests ◽  
Web Of Science ◽  
Rapid Development ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Vaccine Candidates ◽  
Genetic Sequence ◽  
Phase Iii Clinical Trials ◽  
Clinical Trial Results

SARS-CoV-2, the beta coronavirus causing COVID-19, was isolated and categorizes as a novel one on January 7th, 2020 in China.[1] To date, official reports depict that SARS-CoV-2 has already infected 88.828.387 persons and caused 1.926.625 deaths worldwide.[2] On January 12th, 2020, China officials made public its genetic sequence, thus paving the way towards the research and development of diagnostic tests and vaccines. With regard to vaccination, e large number of clinical trials were designed and are currently undergoing, of which 189 are listed in ClinicalTrials.gov. [3] However, up to date, only three vaccines have published their respective phase III clinical trial results in peer-reviewed medical journals. [4-6] Vaccines are needed to reduce the morbidity and mortality associated with Covid-19, and multiple vaccine platforms as AZD1222 (AstraZeneca) [4], BNT162b2 (Pfizer/BioNTech) [5] and mRNA-1273 (Moderna) have been involved in the rapid development of vaccine candidates. Methodology: In this review, PubMed, Embase, Web of Science, Scopus, medRxiv, and bioRxiv were systematically scrutinized for peer-reviewed and preprint articles on phase III clinical trials of vaccines against SARS-CoV-2. In total, only three peer-reviewed papers fulfilling the search criteria were identified. Conclusions; All vaccine candidates should publish in peer-reviewed journals their efficacy and safety well before requesting approval to the national or international authorities…

scholarly journals Web Based Data Capture for Clinical Research

10.28945/3201 ◽  
2008 ◽  
Author(s):  
Stephen Smith ◽  
Samuel Sambasivam
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Medical Device ◽  
Rapid Development ◽  
Research Data ◽  
Data Capture ◽  
Electronic Data Capture ◽  
Proof Of Concept ◽  
Web Based ◽  
Tools And Techniques

Electronic Data Capture (EDC) is increasingly being used in the pharmaceutical, biotech and medical device industries to gather research data worldwide from doctors, hospitals and universities participating in clinical trials. In this highly regulated environment, all systems and software must be thoroughly tested and validated, a task that is burdensome in terms of time and cost. Starting with database structures that are designed to be copied easily, this paper proposes a simple framework that allows for rapid development and minimal testing. The framework includes tools for building modules, for copying modules from one trial to the next, and tools to validate that the modules are the same as modules that have been fully tested previously. A proof-of-concept prototype has been built to demonstrate certain tools and techniques that can be used when designing and building a simplified EDC interface.

scholarly journals PERBANDINGAN KUALITAS PRODUK DAN MINAT MENABUNG PADA LPD DESA ADAT TAJUN DENGAN DESA ADAT TEGAL

2020 ◽  
Vol 4 (1) ◽  
pp. 59-67
Author(s):  
Eka Swarnadi Luh ◽  
Ketut Budi Susrusa ◽  
Ida Ayu Listia Dewi
Keyword(s):  
Product Quality ◽  
Financial Institutions ◽  
Rapid Development ◽  
Research Data ◽  
The Other ◽  
Physical Evidence ◽  
Significant Difference ◽  
The Difference ◽  
Better Than

LPDs are non-bank financial institutions that are regulated and approved by the Regional Regulations of the Province of Bali. The management of LPD is fully handed over to the relevant Pakraman village. In line with the rapid development of LPDs, it turns out that on the other hand it shows diverse performance, so that LPDs need to pay attention to the level of product quality and customer interest in the products offered.            The purpose of the study was to determine the comparison of product quality and interest in saving at the Tajun Traditional Village LPD with the Traditional Village of Tegal. The number of samples from Tajun Adat Village LPD was 98 people and the LPD of Tegal Traditional Village was 84 people. The research data were analyzed by the Mann-Whitney Test. The results showed that there was a significant difference between the quality of the products of the Adat Village of Tajun LPD and the Traditional Village of Tegal. This difference is indicated by indicators of physical evidence, reliability, responsiveness and empathy. The product quality of Tajun Adat Village's LPD is better than the traditional village of Tegal. There is a significant difference between the interest in saving the traditional village of Tajun LPD and the traditional village of Tegal. The difference is in the indicator of confidence. Interest in Saving Tajun Indigenous Village LPD is higher than the Traditional Village of Tegal.

Safety and Evidence of Off-Label Use of Approved Drugs at the National Cancer Center Hospital in Japan

2020 ◽  
pp. OP.20.00131
Author(s):  
Seiko Bun ◽  
Kan Yonemori ◽  
Hiroko Sunadoi ◽  
Rena Nishigaki ◽  
Emi Noguchi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pharmaceutical Products ◽  
National Cancer Center Hospital ◽  
Phase Iii ◽  
Cancer Center ◽  
Off Label Use ◽  
Pharmaceutical Development ◽  
Off Label ◽  
Center Hospital ◽  
Label Use

PURPOSE: In Japan, for pharmaceutical products to be covered by public medical insurance, their efficacy and safety must first be confirmed in clinical trials. To our knowledge, this study is the first investigation into the off-label use of pharmaceutical products at a high-volume cancer treatment center in Japan. The objective of this study is to explore the framework necessary for future pharmaceutical development and regulatory approval in the field of oncology by surveying the frequency of and indications for off-label use of pharmaceutical products at the National Cancer Center Hospital in Tokyo, Japan. MATERIALS AND METHODS: The pharmaceutical products used off-label in daily practice from 2003 to 2015 at the National Cancer Center Hospital were retrospectively examined based on applications that had been submitted to an internal review committee requesting off-label use. RESULTS: A total of 1,390 applications were submitted during the study period. The most frequently used supporting documents were the results of phase II trials, followed by case series and phase III trials. The cancer most frequently treated with off-label drugs was sarcoma (15.1%), followed by urologic cancer (9.2%) and GI cancer (7.6%). CONCLUSION: As reported in previous studies, pharmaceutical products were generally used off-label for the treatment of rare cancers, for which large-scale clinical trials are difficult to conduct. Continued discussion of the types of frameworks that are needed to guide pharmaceutical development is necessary.

scholarly journals Economic impact of industry-sponsored clinical trials of pharmaceutical products in Austria

2020 ◽  
Vol 23 (6) ◽  
pp. 566-574 ◽  
Author(s):  
Evelyn Walter ◽  
Gerald Eichhober ◽  
Marco Voit ◽  
Christian Baumgartner ◽  
Alexander Celedin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Economic Impact ◽  
Pharmaceutical Products

scholarly journals Marine natural products

2015 ◽  
Vol 32 (2) ◽  
pp. 116-211 ◽  
Author(s):  
John W. Blunt ◽  
Brent R. Copp ◽  
Robert A. Keyzers ◽  
Murray H. G. Munro ◽  
Michèle R. Prinsep
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Phase I ◽  
Marine Natural Products ◽  
Rapid Development ◽  
Phase I Clinical Trials ◽  
New Compounds

This review of marine natural products for 2013 describes 1137 new compounds and reports structural revisions and assignments of absolute configurations for previously described compounds. Included is a report of the anticancer sponge metabolite PM060184 that has undergone a remarkably rapid development from discovery in 2005 to the commencement of phase I clinical trials in 2011.

scholarly journals Targeting Apoptotic Pathways in Acute Myeloid Leukaemia

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1660 ◽  
Author(s):  
Jonathan R. Sillar ◽  
Anoop K. Enjeti
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
B Cell Lymphoma ◽  
Clinical Work ◽  
Biological Research ◽  
Apoptotic Pathways ◽  
Molecular Landscape ◽  
Early Phase Clinical Trials ◽  
Acute Myeloid

Acute Myeloid Leukaemia is a devastating disease that continues to have a poor outcome for the majority of patients. In recent years, however, a number of drugs have received FDA approval, following on from successful clinical trial results. This parallels the characterization of the molecular landscape of Acute Myeloid Leukaemia (AML) over the last decade, which has led to the development of drugs targeting newly identified recurring mutations. In addition, basic biological research into the pathobiology of AML has identified aberrant programmed cell death pathways in AML. Following on from successful outcomes in lymphoid malignancies, drugs targeting the B Cell Lymphoma 2 (BCL-2) family of anti-apoptotic proteins have been explored in AML. In this review, we will outline the preclinical and clinical work to date supporting the role of drugs targeting BCL-2, with Venetoclax being the most advanced to date. We will also highlight rationale combinations using Venetoclax, ongoing clinical trials and biomarkers of response identified from the early phase clinical trials performed.

Sign in / Sign up

Export Citation Format

Share Document