scholarly journals Biosimilars: development and investigation using achievements in modern biotechnology

2021 ◽  
Vol 23 (6) ◽  
pp. 548-560
Author(s):  
R. R. Niyazov ◽  
M. A. Dranitsyna ◽  
A. N. Vasiliev ◽  
E. V. Gavrishina
Keyword(s):  
Animal Studies ◽  
Human Subjects ◽  
Clinical Profile ◽  
Impurity Profile ◽  
Regulatory Requirements ◽  
Phase 3 ◽  
Drug Products ◽  
Modern Biotechnology ◽  
Scientific Standards

Biosimilars are biological drug products that have an equivalent clinical profile with innovator biotherapeutics but are developed under a reduced program. To this end, specific comparability approaches are followed based on reverse engineering that involves a thorough analysis of the innovator biotherapeutics and the development of the version of the latter, which should be as much as possible similar with respect to structural and functional characteristics with the innovator. This approach includes the evaluation and comparison between the biosimilar and innovator biologic with respect to the molecular structure and impurity profile and of biological activity in in vitro settings as well as pharmacokinetic, pharmacodynamic, and immunogenicity characteristics on human subjects. Where considered necessary, animal studies or phase 3 clinical studies might be performed when residual uncertainties remain in terms of biosimilarity, that could not have been resolved in the previous tests and trials. Any potentially inevitable differences should be insignificant for safety and efficacy. The state-of-the-art methods of biotechnology and analytics, when applied in line with the appropriate scientific and regulatory requirements, can allow developing similar biologics where no difference in the clinical profile exists with the respective innovator product. Available experience demonstrates the lack of major problems due to the incomparability between the biosimilar and corresponding reference biologics when applicable scientific standards and regulatory recommendations are met.

Recent Progress in the Eye Irritation Test

1993 ◽  
Vol 9 (6) ◽  
pp. 1017-1025 ◽  
Author(s):  
Ih Chu ◽  
Peter Toft
Keyword(s):  
Animal Studies ◽  
In Vitro Tests ◽  
Animal Testing ◽  
Regulatory Requirements ◽  
Eye Irritation ◽  
Significant Development ◽  
In Vivo Test ◽  
Irritation Test

The rabbit eye irritation test based on the Draize method is required for the hazard assessment of chemicals and products that may come into contact with the eye. Due to the potential for the suffering of animals and subjectivity of the test, many modifications of the method have been made that involved a reduction in the number of animals and a refinement of techniques. Additionally, there has been significant development of in vitro alternatives. This paper reviews recent advances in the in vivo test and in vitro alternatives, as well as regulatory requirements. While the refinement of in vivo protocols has resulted in a reduction in the number and discomfort on animals, the development of in vitro alternatives could lead to an eventual replacement of animal studies. In view of the inherent simplicity of many in vitro methods, some of which comprise cell cultures, further research into the relevance/mechanism of effects is required. Batteries of in vitro tests, when properly validated, may be considered as replacements for animal testing.

scholarly journals 5 Final Report on the Safety Assessment of 2-Nitro-p-Phenylenediamine and 4-Nitro-o-Phenylenediamine

1985 ◽  
Vol 4 (3) ◽  
pp. 161-202 ◽  
Keyword(s):  
Animal Studies ◽  
Human Subjects ◽  
Epidemiological Data ◽  
Final Report ◽  
Hair Dyes ◽  
Carcinogenic Effect ◽  
Hair Dye ◽  
Patch Tests ◽  
Pure Compounds

Animal data on 2NPPD and 4NOPD and cosmetic hair dyes containing these ingredients suggest that both compounds were nonirritating to rabbit skin and eyes, but were sensitizers on guinea pig skin. The results of repeated insult patch tests with hair dye products containing these ingredients indicated that neither was an irritant or a sensitizer to human subjects as normally used. In the absence of human data on the pure compounds, however, 2NPPD and 4NOPD are considered to be potential human sensitizers. Topically applied 2NPPD and 4NOPD are absorbed by experimental animals. Neither embryotoxicity nor teratogenicity was observed in animal studies when hair dyes containing 2NPPD and 4NOPD were applied to the skin. Both ingredients were mutagenic in some bacterial and in vitro mammalian systems; both compounds had some genotoxic activity. In feeding studies in mice and rats, only 2NPPD induced hepatocellular tumors in female mice. Both compounds were noncarcinogenic in male mice and in rats of either sex. Epidemiological data have not demonstrated a carcinogenic effect in man for hair dyes. For those persons not sensitized, it is concluded that 2NPPD and 4NOPD are safe as hair dye ingredients at the current concentration of use.

Anti-inflammatory Properties of Macrolide Antibiotics

2006 ◽  
Vol 19 (5) ◽  
pp. 326-329 ◽  
Author(s):  
Helen Kourlas
Keyword(s):  
Clinical Trials ◽  
Animal Studies ◽  
Respiratory Diseases ◽  
Human Subjects ◽  
Macrolide Antibiotics ◽  
Controlled Trials ◽  
Show Evidence ◽  
Anti Inflammatory ◽  
Small Clinical Trials

The use of macrolide antibiotics for other clinical uses outside of their antimicrobial capabilities has been questioned and theorized in both in vitro and animal studies. Several small clinical trials have shown that erythromycin, clarithromycin, and azithromycin possess anti-inflammatory characteristics in patients with respiratory diseases. To determine whether macrolide antibiotics possess this unique characteristic, data from controlled trials involving human subjects were extracted and analyzed. Conclusions from trials suggest that select macrolide antibiotics possess anti-inflammatory properties in patients with respiratory diseases who do not show evidence of a bacterial infection.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

’Animal Studies‘, Disziplinarität und die (Post-)Humanities

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Cary Wolfe
Keyword(s):  
Social Communication ◽  
Animal Studies ◽  
Human Subjects

Der Text von Cary Wolfe ist eine gekürzte Übersetzung des Kapitels »Animal Studies«, Disciplinarity, and the (Post)Humanities aus der Monographie What is Posthumanism? (Minnesota 2009). Wolfe diskutiert die Beziehung zwischen (Trans-)Disziplinarität und Posthumanismus im Rückgriff auf Konzepte von Derrida, Foucault und Luhmann, die eine Form von gesellschaftlicher Kommunikation zu denken erlauben, an der menschliche Subjekte zwar noch teilhaben, aber deren souveräne Urheber sie nicht mehr sind </br></br>The paper by Cary Wolfe is an abridged translation of the chapter »Animal Studies«, Disciplinarity, and the (Post)Humanities from the monograph (Minnesota 2009). Wolfe discusses the relation between (trans-)disciplinarity and posthumanism with reference to concepts by Derrida, Foucault and Luhmann, allowing to consider a form of social communication in which human subjects still may participate, but no longer are their sovereign initiators.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

Protective Effect of Isothiocyanates from Cruciferous Vegetables on Breast Cancer: Epidemiological and Preclinical Perspectives

2020 ◽  
Vol 20 ◽  
Author(s):  
Suong N.T. Ngo ◽  
Desmond B. Williams
Keyword(s):  
Breast Cancer ◽  
Protective Effect ◽  
Animal Studies ◽  
Cancer Survival ◽  
Breast Cancer Survival ◽  
Human Studies ◽  
In Vitro Studies ◽  
Cochrane Library ◽  
Cruciferous Vegetables

Background: The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their antibreast cancer effects. Objective: The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer. Methods: A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peerreviewed studies of all types (in vitro studies, animal studies, and human studies) were selected. Results: The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways which promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemoresistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively smallest inhibitory concentration IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article. Conclusion: Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane appeared to display the greatest potential.

A Comprehensive Review of Regulatory Requirements and Registration Process of Pharmaceutical Drug Products in CIS Countries

2020 ◽  
Vol 7 (3) ◽  
pp. 162-176
Author(s):  
Kapil Pihwal ◽  
Neelam Pawar ◽  
Sheikh Aamir ◽  
Mohammad Shahbaz Alam ◽  
Vikas Rathee
Keyword(s):  
Regulatory Requirements ◽  
Health Value ◽  
Drug Products ◽  
Registration Process ◽  
Potential Market ◽  
Regulatory Guidelines ◽  
Cis Countries ◽  
In Cis ◽  
Regulatory Organization ◽  
Country Specific

Background: The CIS region has a potential market for India. The registration of the drug products in CIS regions is a challenging task because these countries have no harmonized regulatory organization. The CIS region includes 12 countries such as Russia, Kyrgyzstan, Ukraine, Uzbekistan, Kazakhstan, Tajikistan, Turkmenistan, Armenia, Azerbaijan, Belarus, Georgia and Moldova, which require different regulatory guidelines for medicinal product registration as per their FDA guidelines. The different guidelines for the same region become a challenging task for the manufacturer and exporter. The registration of the same product for different countries of CIS is not possible with the same dossier due to the lack of their regulatory harmonization. These countries obey their country-specific dossier format, so to target these market manufacturers and exporters needs to submit different dossier documents for different countries. But Ukraine and Kazakhstan have harmonization and it varies in Uzbekistan and Tajikistan. Ukraine and Kazakhstan are also imposing strict rules and expecting USFDA level documents for approval. Conclusion: The overall conclusion is that harmonization in CIS is highly imbalanced, which affects both time and cost for product registration. Harmonization is the need of the era for easy product registration, and it will be beneficial for the manufacturer, regulator, importer, exporter, and to access medicines of high public health value.

scholarly journals Optimal Initial Positioning of Chest Tubes to Prevent Retained Hemothorax Using a Novel Steerable Chest Tube With Extendable Infusion Cannula

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 324-330
Author(s):  
John B Fortune ◽  
Serena Murphy ◽  
Kimberley Tiller
Keyword(s):  
Chest Tube ◽  
Animal Studies ◽  
Training Session ◽  
Penetrating Trauma ◽  
Pleural Space ◽  
Tube Placement ◽  
Clot Lysis ◽  
Retained Hemothorax ◽  
Tip Position

ABSTRACT Introduction With blunt and penetrating trauma to the chest, warfighters and civilians frequently suffer from punctured lung (pneumothorax) and/or bleeding into the pleural space (hemothorax). Optimal management of this condition requires the rapid placement of a chest tube to evacuate as much of the blood and air as possible. Incomplete drainage of blood leading to retained hemothorax may be the result of the final tube tip position not being in contact with the blood collections. To address this problem, we sought to develop a “steerable” chest tube that could be accurately placed or repositioned into a specific desired position in the pleural space to assure optimal drainage. An integrated infusion cannula was added for the instillation of anticoagulants to maintain tube patency, thrombolytics for clot lysis, and analgesics for pain control if required. Materials and Methods A triple-lumen tube was designed to provide a channel for a pull-wire which was wound around an axle integrated into a small proximal handle and controlled by a ratcheted thumbwheel. Tension on the wire creates an arc on the tube that allows for positioning. In vitro testing focused on the relationship between the tension on the pull-wire and the resultant arc. Two adult cadavers and two anesthetized pigs were used to study the feasibility of accurate tube placement. After a brief training session, providers were asked to place tubes inferiorly along the diaphragm where blood was anticipated to accumulate or at the apex of the lung for pneumothorax. Success was determined with fluoroscopic images and was judged as a tube tip lying in the targeted position. Results The design was prototyped with an extruded polyvinyl chloride multilumen tube and a 3D printed tensioning handle. In vitro studies showed that one turn of the thumbwheel created 70° to 90° of arc of the tube. Cadaver and animal studies showed consistent success in the desired placement of the tube at or near the lateral diaphragm or in the apex. Attempts were also successful by surgical residents with minimal training. Conclusions Initial preliminary studies on a novel steerable chest tube have demonstrated the ability to appropriately position the tube in a desired location. The addition of an extendable cannula will allow for safe clot lysis or maintained tube patency. Additional studies are planned to confirm the benefit of this device in preventing retained hemothorax.

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