Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen

We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.     

Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production

Control and prevention of rapid influenza spread among humans depend on the availability of efficient and safe seasonal and pandemic vaccines, made primarily from inactivated influenza virus particles. Current influenza virus production processes rely heavily on embryonated chicken eggs or on cell culture as substrate for virus propagation. Today’s efforts towards process intensification in animal cell culture could innovate viral vaccine manufacturing using high-yield suspension cells in high cell density perfusion processes. In this work, we present a MDCK cell line adapted to grow as single cell suspension with a doubling time of less than 20 h, achieving cell concentrations over 1 × 10⁷ cells/mL in batch mode. Influenza A virus titer obtained in batch infections were 3.6 log₁₀(HAU/100 µL) for total- and 10⁹ virions/mL for infectious virus particles (TCID₅₀), respectively. In semi-perfusion mode concentrations up to 6 × 10⁷ cells/mL, accumulated virus titer of 4.5 log₁₀(HAU/100 µL) and infectious titer of almost 10¹⁰ virions/mL (TCID₅₀) were possible. This exceeds results reported previously for cell culture-based influenza virus propagation by far and suggests perfusion cultures as the preferred method in viral vaccine manufacturing.     

Current status and perspective of CAD/CAM-produced resin composite crowns: a review of clinical effectiveness

The purpose of the present review was to survey the available literature on computer-aided design/computer-aided manufacturing (CAD/CAM)-produced resin composite materials to provide clinicians with a current overview of the key components necessary for daily clinical use. An electronic search was conducted in the PubMed database. Peer-reviewed articles in English language on the use of resin composites in CAD/CAM dental crowns were included. A total of 122 full-text articles were identified, 15 of which were selected during the initial review. Two additional articles were also discovered through a manual search, to obtain a final total of 17 articles included in the present review. Of these, 16 were to in vitro studies, and one was an in vivo study. Findings from the in vitro studies indicate that resin composite block materials for CAD/CAM applications demonstrate excellent physical properties and are appropriate for the clinical restoration of premolars and molars. However, the in vivo study reported a low 3-year success rate, but high survival rate for resin composite CAD/CAM crowns placed in the premolar region. The key to ensuring the successful prognosis of a resin composite CAD/CAM crown is to ensure that all steps—such as proper case selection, abutment tooth preparation, occlusal adjustment, and bonding—are accurately performed.     

Internal porosities,retentive force,and survival of cobalt–chromium alloy clasps fabricated by selective laser-sintering

PurposeThe purpose of this study was to evaluate internal porosities, retentive force values and survival of cobalt–chromium (Co–Cr) alloy clasps fabricated by direct metal laser-sintering (DMLS) and compare them to conventionally cast clasps.MethodsEmbrasure clasps were digitally designed fitting teeth 35 and 36 on identical metal models (N = 32). Sixteen clasps were fabricated using DMLS (group DMLS) and another sixteen clasps were additively manufactured from wax and then cast from a Co–Cr alloy (group CAST). Internal porosities were examined using micro-focus X-ray (micro-CT) and analyzed applying Kolmogorov–Smirnov test, Mann–Whitney test, and T test (significance level: p < 0.050). A universal testing machine was used to determine the retentive force values at baseline and after 1095, 5475, 10,950 and 65,000 cycles of simulated aging. Data were analyzed employing Kolmogorov–Smirnov test, one-way ANOVA, and Scheffé’s post-hoc test (significance level: p < 0.050). Survival was estimated for 65,000 cycles of artificial aging using Kaplan–Meier analysis.ResultsMicro-CT analysis revealed a higher prevalence (p < 0.001), but a more homogeneous size and a significantly smaller mean (p = 0.009) and total volume (p < 0.001) of internal porosities for group DMLS. The groups showed mean initial retentive force values of 13.57 N (CAST) and 15.74 N (DMLS), which significantly declined over aging for group CAST (p = 0.003), but not for group DMLS (p = 0.107). Survival was considerably higher for group DMLS (93.8%) than for group CAST (43.8%) after 65,000 cycles of aging.ConclusionsClasps made by laser-sintering could be an alternative to conventional cast clasps for the fabrication of removable partial denture frameworks.     

医院药库药房智能管理系统设计及应用的分析

在信息技术不断改进和优化的背景下,医院应用智能化管理系统是首要的趋势,医院药库药房作为医院管理期间十分重要的一部分,其对于医院管理效率的提升和后期运行有着直接性的影响。该文逐一分析了医院药库药房智能管理系统的设计和应用情况,希望在此基础上实现各个环节的规范性和信息化管理目标。     

Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration.To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.     

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

Introduction: Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, taste masking, and modifying release in drug delivery systems. Additionally, its other novel opportunities or pharmaceutical applications, and capability for continuous manufacturing are being investigated. This efficient, industrially scalable, solvent-free, continuous process can be easily automated and coupled with other novel platforms for continuous manufacturing of pharmaceutical products.

Areas covered: This review focuses on updates on solubility enhancement of poorly water-soluble drugs and process analytical tools such as UV/visible spectrophotometry; near-infrared spectroscopy; Raman spectroscopy; and rheometry for continuous manufacturing, with a special emphasis on fused deposition modeling 3D printing.

Expert opinion: The strengths, weakness, opportunities, threats (SWOT) and availability of commercial products confirmed wide HME applicability in pharmaceutical research. Increased interest in continuous manufacturing processes makes HME a promising strategy for this application. However, there is a need for extensive research using process analytical tools to establish HME as a dependable continuous manufacturing process.     

Current status and challenges of Additive manufacturing in orthopaedics: An overview

Additive manufacturing is a rapidly emerging technology which is being successfully implemented in the various field of medicine as well as in orthopaedics, where it has applications in reducing cartilage defects and treatments of bones. The technology helps through systematic collection of information about the shape of the "defects" and precise fabrication of complex 3D constructs such as cartilage, heart valve, trachea, myocardial bone tissue and blood vessels. In this paper, a large number of the relevant research papers on the additive manufacturing and its application in medical specifically orthopaedics are identified through Scopus had been studied using Bibliometric analysis and application analysis is undertaken. The bibliometric analysis shows that there is an increasing trend in the research reports on additive manufacturing applications in the field of orthopaedics. Discussions are on using technological advancement like scanning techniques and various challenges of the orthopaedic being met by additive manufacturing technology. For patient-specific orthopaedic applications, these techniques incorporate clinical practice and use for effective planning. 3D printed models printed by this technology are accepted for orthopaedic surgery such as revision of lumbar discectomy, pelvic surgery and large scapular osteochondroma. The applications of additive manufacturing in orthopaedics will experience a rapid translation in future. An orthopaedic surgeon can convert need/idea into a reality by using computer-aided design (CAD) software, analysis software to facilitate the manufacturing. Thus, AM provides a comprehensive opportunity to manufacture orthopaedic implantable medical devices.