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Biotechnology and Bioengineering Aug 2020Endotoxins are the major contributors to the pyrogenic response caused by contaminated pharmaceutical products, formulation ingredients, and medical devices. Recombinant... (Review)
Review
Endotoxins are the major contributors to the pyrogenic response caused by contaminated pharmaceutical products, formulation ingredients, and medical devices. Recombinant biopharmaceutical products are manufactured using living organisms, including Gram-negative bacteria. Upon the death of a Gram-negative bacterium, endotoxins (also known as lipopolysaccharides) in the outer cell membrane are released into the lysate where they can interact with and form bonds with biomolecules, including target therapeutic compounds. Endotoxin contamination of biologic products may also occur through water, raw materials such as excipients, media, additives, sera, equipment, containers closure systems, and expression systems used in manufacturing. The manufacturing process is, therefore, in critical need of methods to reduce and remove endotoxins by monitoring raw materials and in-process intermediates at critical steps, in addition to final drug product release testing. This review paper highlights a discussion on three major topics about endotoxin detection techniques, upstream processes for the production of therapeutic molecules, and downstream processes to eliminate endotoxins during product purification. Finally, we have evaluated the effectiveness of endotoxin removal processes from a perspective of high purity and low cost.
Topics: Animals; Biological Products; Biosensing Techniques; Biotechnology; Cattle; Chromatography; Drug Contamination; Endotoxins; Limulus Test; Rabbits
PubMed: 32333387
DOI: 10.1002/bit.27362 -
American Journal of Health-system... Jul 2022The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions... (Review)
Review
PURPOSE
The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions while maintaining stability and potency.
METHODS
During a 12-month period ending in June 2021, the prescribing information and published monographs from multiple pharmacy compendia were reviewed for all medications and biologic products approved by the US Food and Drug Administration (FDA) for human use since January 2000. Products that were subsequently withdrawn from the US market were excluded. When temperature excursion data was unavailable in published form, product manufacturers were surveyed via telephone and/or email. Acceptable storage information for all products for which storage is recommended at temperatures below room temperature (20-25 °C [68-77 °F]) was compiled and arranged in tabular format.
RESULTS
Of the 705 products or formulations approved by FDA during the predefined time period, 246 were identified as requiring storage at temperatures below room temperature. After review of available prescribing information and manufacturer communications, if applicable, acceptable periods of excursion to temperatures at room temperature or higher were identified for 214 products (87%).
CONCLUSION
Information related to acceptable periods of room temperature excursion was compiled for a total of 214 products approved for US distribution since 2000. The included tables may increase patient safety and decrease medication loss or related expenditures.
Topics: Drug Stability; Drug Storage; Humans; Pharmaceutical Preparations; Pharmaceutical Services; Temperature; United States; United States Food and Drug Administration
PubMed: 35451022
DOI: 10.1093/ajhp/zxac118 -
Journal of Esthetic and Restorative... Jul 2022To characterize the mechanical and biological properties of three commercially available resins, which are currently used for provisional restorations and to compare...
OBJECTIVES
To characterize the mechanical and biological properties of three commercially available resins, which are currently used for provisional restorations and to compare them to an experimental resin intended for definitive fixed dental prostheses.
MATERIALS AND METHODS
Three commercially available resins: Crowntec (CT, Saremco), Temporary C&B (FL, Formlabs), C&B MFH (ND, Nextdent), and the experimental resin: Permanent Bridge (PB, Saremco) were printed and subjected to biaxial flexural strength test, finite element analysis, Weibull analysis, scanning electron microscopy, cell proliferation, immunohistochemistry and cytotoxicity assays. Samples from CT, PB, and ND were provided directly from the manufacturers ensuring ideal workflow. FL was printed using the workflow as recommended by the manufacturer, using a Formlabs 2 printer and their post-processing units Form Wash and Form Cure.
RESULTS
From the tested resins, PB yielded the best overall results in terms of mechanical properties. Cell proliferation and cytotoxicity did not show any significant differences among materials. PB showed higher values for probability of survival predictions (35%) when subjected to 250 MPa loads, whereas the other materials did not reach 10%.
SIGNIFICANCE
Despite mechanical differences between the evaluated materials, the outcomes suggest that 3D printed provisional resins may be used in clinical settings, following the manufacturers indications. New materials intended for long-term use, such as the PB resin, yielded higher mechanical properties compared to the other materials. Alternative printing and post-processing methods have not yet been evaluated and should be avoided until further literature is available.
CLINICAL SIGNIFICANCE
3D printed resins for provisional restorations have become popular with the emergence of new technologies. In this study, we evaluated three different commercially available resins for provisional restorations and one new experimental resin. The results from this study indicate that commercially available resins could be used in clinical settings under certain conditions and limited periods of time. Following the manufacturers protocols is of paramount importance to not compromise these properties.
Topics: Composite Resins; Flexural Strength; Materials Testing; Printing, Three-Dimensional; Surface Properties
PubMed: 35187786
DOI: 10.1111/jerd.12888 -
Frontiers in Psychiatry 2022In 2021, the manufacturer of diamorphine reported a possible impending shortage for Switzerland and Germany. This led us to investigate this controlled medicine's... (Review)
Review
In 2021, the manufacturer of diamorphine reported a possible impending shortage for Switzerland and Germany. This led us to investigate this controlled medicine's manufacture, market, and regulatory constraints. Based on our analysis of legal texts and gray literature in the form of reports and documents, we propose recommendations to prevent and address diamorphine shortages in Switzerland. Diamorphine, also known as pharmaceutical "heroin," is used medically to treat persons with severe opioid use disorder in a handful of countries. The controlled medicine is manufactured from morphine, which, in turn, is extracted from opium poppies. Studying data from the International Narcotics Control Board for 2019, we find that Switzerland accounts for almost half of the worldwide medical consumption of diamorphine. It manufactures more than half of the worldwide total and keeps the largest stocks. Moreover, Switzerland is dependent on a sole supplier of diamorphine (monopoly). As a niche product, diamorphine has an increased risk of shortage. Such a shortage would immediately threaten a valuable public health program for around 1,660 Swiss patients. We believe it is urgent to curtail the monopoly and ensure a stable supply for the future.
PubMed: 35615450
DOI: 10.3389/fpsyt.2022.882299 -
Frontiers in Bioengineering and... 2021Current cutting-edge strategies in biomaterials science are focused on mimicking the design of natural systems which, over millions of years, have evolved to exhibit... (Review)
Review
Current cutting-edge strategies in biomaterials science are focused on mimicking the design of natural systems which, over millions of years, have evolved to exhibit extraordinary properties. Based on this premise, one of the most challenging tasks is to imitate the natural extracellular matrix (ECM), due to its ubiquitous character and its crucial role in tissue integrity. The anisotropic fibrillar architecture of the ECM has been reported to have a significant influence on cell behaviour and function. A new paradigm that pivots around the idea of incorporating biomechanical and biomolecular cues into the design of biomaterials and systems for biomedical applications has emerged in recent years. Indeed, current trends in materials science address the development of innovative biomaterials that include the dynamics, biochemistry and structural features of the native ECM. In this context, one of the most actively studied biomaterials for tissue engineering and regenerative medicine applications are nanofiber-based scaffolds. Herein we provide a broad overview of the current status, challenges, manufacturing methods and applications of nanofibers based on elastin-based materials. Starting from an introduction to elastin as an inspiring fibrous protein, as well as to the natural and synthetic elastin-based biomaterials employed to meet the challenge of developing ECM-mimicking nanofibrous-based scaffolds, this review will follow with a description of the leading strategies currently employed in nanofibrous systems production, which in the case of elastin-based materials are mainly focused on supramolecular self-assembly mechanisms and the use of advanced manufacturing technologies. Thus, we will explore the tendency of elastin-based materials to form intrinsic fibers, and the self-assembly mechanisms involved. We will describe the function and self-assembly mechanisms of silk-like motifs, antimicrobial peptides and leucine zippers when incorporated into the backbone of the elastin-based biomaterial. Advanced polymer-processing technologies, such as electrospinning and additive manufacturing, as well as their specific features, will be presented and reviewed for the specific case of elastin-based nanofiber manufacture. Finally, we will present our perspectives and outlook on the current challenges facing the development of nanofibrous ECM-mimicking scaffolds based on elastin and elastin-like biomaterials, as well as future trends in nanofabrication and applications.
PubMed: 34336798
DOI: 10.3389/fbioe.2021.652384 -
Pharmaceutics Sep 2022Nanoparticulate technologies have revolutionized drug delivery allowing for passive and active targeting, altered biodistribution, controlled drug release... (Review)
Review
Nanoparticulate technologies have revolutionized drug delivery allowing for passive and active targeting, altered biodistribution, controlled drug release (temporospatial or triggered), enhanced stability, improved solubilization capacity, and a reduction in dose and adverse effects. However, their manufacture remains immature, and challenges exist on an industrial scale due to high batch-to-batch variability hindering their clinical translation. Lipid-based nanomedicines remain the most widely approved nanomedicines, and their current manufacturing methods remain discontinuous and face several problems such as high batch-to-batch variability affecting the critical quality attributes (CQAs) of the product, laborious multistep processes, need for an expert workforce, and not being easily amenable to industrial scale-up involving typically a complex process control. Several techniques have emerged in recent years for nanomedicine manufacture, but a paradigm shift occurred when microfluidic strategies able to mix fluids in channels with dimensions of tens of micrometers and small volumes of liquid reagents in a highly controlled manner to form nanoparticles with tunable and reproducible structure were employed. In this review, we summarize the recent advancements in the manufacturing of lipid-based nanomedicines using microfluidics with particular emphasis on the parameters that govern the control of CQAs of final nanomedicines. The impact of microfluidic environments on formation dynamics of nanomaterials, and the application of microdevices as platforms for nanomaterial screening are also discussed.
PubMed: 36145688
DOI: 10.3390/pharmaceutics14091940 -
Micromachines Mar 2022Electropolishing (EP) is most widely used as a metal finishing process. It is a non-contact electrochemical process that can clean, passivate, deburr, brighten, and... (Review)
Review
Electropolishing (EP) is most widely used as a metal finishing process. It is a non-contact electrochemical process that can clean, passivate, deburr, brighten, and improve the biocompatibility of surfaces. However, there is clear potential for it to be used to shape and form the topology of micro-scale surface features, such as those found on the micro-applications of additively manufactured (AM) parts, transmission electron microscopy (TEM) samples, micro-electromechanical systems (MEMs), biomedical stents, and artificial implants. This review focuses on the fundamental principles of electrochemical polishing, the associated process parameters (voltage, current density, electrolytes, electrode gap, and time), and the increasing demand for using environmentally sustainable electrolytes and micro-scale applications. A summary of other micro-fabrication processes, including micro-milling, micro-electric discharge machining (EDM), laser polishing/ablation, lithography (LIGA), electrochemical etching (MacEtch), and reactive ion etching (RIE), are discussed and compared with EP. However, those processes have tool size, stress, wear, and structural integrity limitations for micro-structures. Hence, electropolishing offers two-fold benefits of material removal from the metal, resulting in a smooth and bright surface, along with the ability to shape/form micro-scale features, which makes the process particularly attractive for precision engineering applications.zx3.
PubMed: 35334760
DOI: 10.3390/mi13030468 -
Clinical & Experimental Optometry Jan 2020Ophthalmic lens design concerns the control of spectacle lens aberrations which occur when the eye rotates away from the optical centre of the lens. The most significant... (Review)
Review
Ophthalmic lens design concerns the control of spectacle lens aberrations which occur when the eye rotates away from the optical centre of the lens. The most significant aberrations are oblique astigmatism and mean oblique error (power error). A brief review of these aberrations is given, explaining how the lens designer can control them using just the bending of the lens, and what results can be achieved using simple spherical and toroidal surfaces. Before 1985, aspherical surfaces were used only for post-cataract spectacle lenses and high-power magnifiers. Today, aspherical surfaces are used by all major lens manufacturers to produce thinner, lighter and more attractive best-form lenses in the normal power range. Aspherical surfaces are employed because the surface itself is astigmatic and the surface astigmatism is used to combat aberrational astigmatism due to oblique incidence. The various types of aspherical surface and how the surface astigmatism arises is described, before considering how this feature is used to produce flatter, thinner lenses. In the case of astigmatic prescriptions, the surface requires different asphericities along its principal meridians and the geometry of these atoroidal surfaces is also described. The advent of free-form manufacturing techniques requires the lens designer to convert the surface description to the (x,y,z) co-ordinates needed to generate the surface. Examples of how these co-ordinates can be obtained from the equation to the surface are given for toroidal and aspherical surfaces. In the case of free-form progressive surfaces, the pre-determined z-co-ordinates must be added to the z-co-ordinates of the prescription surface to obtain the final free-form surface. In the case of optimised prescription surfaces, on-board software will analyse the result by ray tracing to obtain the final z-co-ordinates.
Topics: Equipment Design; Eyeglasses; Humans; Optics and Photonics; Refraction, Ocular; Visual Acuity
PubMed: 31222837
DOI: 10.1111/cxo.12930 -
Annual Review of Biomedical Engineering Jul 2021Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D... (Review)
Review
Additive manufacturing's attributes include print customization, low per-unit cost for small- to mid-batch production, seamless interfacing with mainstream medical 3D imaging techniques, and feasibility to create free-form objects in materials that are biocompatible and biodegradable. Consequently, additive manufacturing is apposite for a wide range of biomedical applications including custom biocompatible implants that mimic the mechanical response of bone, biodegradable scaffolds with engineered degradation rate, medical surgical tools, and biomedical instrumentation. This review surveys the materials, 3D printing methods and technologies, and biomedical applications of metal 3D printing, providing a historical perspective while focusing on the state of the art. It then identifies a number of exciting directions of future growth: () the improvement of mainstream additive manufacturing methods and associated feedstock; () the exploration of mature, less utilized metal 3D printing techniques; () the optimization of additively manufactured load-bearing structures via artificial intelligence; and () the creation of monolithic, multimaterial, finely featured, multifunctional implants.
Topics: Artificial Intelligence; Humans; Printing, Three-Dimensional; Prostheses and Implants
PubMed: 34255995
DOI: 10.1146/annurev-bioeng-082020-032402