Manufacturing Considerations Research Articles

Regulatory Considerations for Fecal Microbiota Transplantation Products

Fecal microbiota for transplantation (FMT) is being studied as a potential intervention for numerous conditions. The regulation of FMT by the FDA is discussed along with FMT donor screening and manufacturing considerations. The FDA is committed to ensuring that FMT products can be safely tested in clinical trials.

Quality, buyback and technology licensing considerations in a two-period manufacturing–remanufacturing system: a closed-loop and sustainable supply chain

Technology licensing affects both welfare and financial concepts. In the literature, while the effects of different licensing mechanisms on the decision variables of a manufacturing system are thoroughly investigated, relationships between licensing scenarios and production quantities on a closed-loop supply chain (CLSC) have not been examined completely. To fill out this gap we study three most common types of licensing mechanisms; fixed-fee, royalty cost and two-part tariff licensing scenarios with the quality level of collected second-hand items in a two-period CLSC. The proposed model consists of one manufacturer and one remanufacturer who is permitted to engage in the remanufacturing process just in the second period of the planning horizon. Our main assumption is that a constant demand is to be satisfied within a two-period CLSC. Consumer demand is satisfied in the first period by manufacturing the raw materials and in the second period, both manufacturing and remanufacturing processes are possible due to the demand quantities and quality level of the collected second-hand items. A numerical example and sensitivity analysis are presented along with analytical conclusions to provide insights into the performance of the CLSC parties in each licensing scenario. The findings prove the applicability of the proposed model.

Design and implementation of evanescent mode waveguide filters using dielectrics and additive manufacturing techniques

In this contribution, we describe the design of bandpass filters using evanescent mode waveguides and dielectric resonators implemented with additive manufacturing techniques. Two C-band Chebyshev evanescent mode waveguide filters of order five have been designed using a low cost commercial dielectric material (ABSplus), widely used by Fused Deposition Modeling (FDM) 3D printers. The housings of the filters have been manufactured using traditional computer numerical control (CNC) machining techniques. Practical manufacturing considerations are also discussed, including the integration of dielectric and metallic parts. We first discuss two breadboards using two different resonator geometries. We then demonstrate how different transfer functions can be easily implemented by changing the 3D printed parts in the same metallic housing. Breadboards show fractional bandwidths between 3% and 4.6% with return losses better than RL=18 dB, and spurious free ranges of SFR=1 GHz. Insertion losses are better than IL=4.3 dB. Even though dielectric losses from the plastic material are shown to be high, the measured results are quite satisfactory, thereby clearly showing that this strategy maybe useful for the fast production of low cost microwave filters implementing complex geometries.

Challenges and Considerations in Development and Manufacturing of High Concentration Biologics Drug Products

With the advent of novel biotherapeutics in indications such as oncology, the attention has moved to making these therapies patient centric, potentially available for self-administration. Given the volume limitations of the other convenient routes of administration such a subcutaneous, intramuscular, there is a need for high concentration drug products. Along with the concerns of inherent protein instability at high concentration, there are other practical challenges during the development of these drug products. This review focuses on the considerations in formulation screening, process development, manufacturing, analytical methods and stability for high concentration liquid drug product. For the scenarios where, high concentration liquid drug product is not feasible, alternate approaches can be undertaken to obtain high concentration drug product during administration. The discussion on the current available alternate technologies with an overview of their advantages and disadvantages are covered here. The scope of the overall discussions is introductory and limited to cautionary notes and experiences as opposed to prescriptive recommendations and detailed literature reviews: our primary goal is to provide a compiled set of considerations that can guide a detailed literature research and a to-do list for high concentration development and manufacturing activities. This manuscript aims to highlight the motivations to develop high concentration parenteral protein drug products, a wide range of -commonly known or sometimes overlooked- challenges associated with their development and manufacturing, as well as some approaches towards mitigation of said challenges.

Estimation of Energy Savings When Adopting Ultrasonic Vibration-Assisted Magnetic Compound Fluid Polishing

Reducing energy use is a major consideration in green manufacturing. Ultrasonic vibration has the advantage of improving machining performance. This work presents an experimental investigation on magnetic compound fluid (MCF) polishing with and without ultrasonic vibration and estimates reductions in polishing energy consumption and surface roughness due to ultrasonic vibration during the machining process. A series of ultrasonic vibration-assisted MCF polishing (UVAMP) tests was carried out for brass H62, and the normal and tangential polishing forces, surface roughness and material removal rate of the traditional MCF polishing (MP) and UVAMP of brass were investigated for various machining parameters. The polishing energy consumptions during traditional MCF polishing and UVAMP were calculated and analyzed from the perspective of the energy of the polishing process. Results indicate that the use of UVAMP considerably reduces energy consumption and surface roughness during the polishing of brass. The adoption of UVAMP therefore has the potential to improve the efficiency and quality of polishing processes and offers a practical solution for the greener manufacturing of brass.

Optimal production lot sizing for an imperfect manufacturing system with machine breakdown and emergency maintenance policy

Purpose The purpose of this paper is to study a production lot sizing problem with consideration of imperfect manufacturing and emergency maintenance policy, providing managerial implication for practitioners. Design/methodology/approach In this study, the authors introduce two models, where in Model I, shortages are not allowed and repair times are negligible. In Model II, shortages are allowed and are partially backlogged, and repair times are assumed to be exponentially distributed, algorithm is developed to solve the models, numerical examples were demonstrated the applications. Findings Results show that in the Model I, demand rate is the most significant parameter affecting the average expected cost, whereas the time needed to breakdown after machine shift is the most significant factor affecting the production lot size. Therefore, reduction in the time needed to breakdown after machine shift would be helpful for determining an appropriate production lot size in Model I. In Model II, repair time parameter is the most significant factor affecting the average expected cost. Reducing the value of machine shift parameter would be helpful for determining an adequate production lot size and reducing decision risk. Practical implications This paper can provide important reference value for practitioners with managerial implication of how to effectively maintain equipment, i.e. how to make product lot size considering the influence of the maintenance policy. Originality/value From the aspect of academia, this paper provides a solution to the optimal production lot sizing decision for an imperfect manufacturing system with consideration of machine breakdown and emergency maintenance, which is a supplement to imperfect EMQ model.

Isogeometric shape optimization of smoothed petal auxetics with prescribed nonlinear deformation

Auxetic materials with negative Poisson’s ratio have potential applications across a broad range of engineering fields. Several FE based design techniques have been developed to achieve auxetic materials with targeted effective properties, mostly in linear deformation regime. In this paper, an isogeometric shape optimization framework for designing 2D auxetic materials with prescribed deformation over large strain intervals is presented. Taking into account practical manufacturing considerations, a minimum thickness for each member is imposed via a spline-based geometric constraint. The capability of the framework is demonstrated through two examples. First, the paper considers shape optimization of smoothed hexa-petals in plane strain condition to achieve constant Poisson’s ratios ranging from a null value to -0.5 to an effective tensile strain of 50%. The second example showcases the shape optimization of smoothed tri- and hexa-petals in plane stress condition for targeted nonlinear deformation behaviour of cat’s skin up to 90% tensile strain.

Design Considerations for Robust Manufacturing and High Yield of 1.2 kV 4H-SiC VDMOS Transistors

Production yield is a major factor for semiconductor device manufacturing. To produce high performance devices cost efficiently, it is important to know the process windows of the implemented production technology. This can influence the yield in different ways. One of the critical steps is the photolithography. In this work the impact of misalignment within the technological limits is analyzed and discussed. 4H-SiC VDMOS Transistors were produced and the electrical characteristics were compared with the overlay accuracy of the devices. Small change in channel length can lead to large impact on the electrical characteristic. Especially when the channel length reaches values near to the critical length for short channel effects (SCEs), small overlay inaccuracies influence the electrical characteristic of the devices in an increasing manner. Different cell designs were analyzed regarding their robustness to misalignment.

Systematic design of microscope objectives. Part II: Lens modules and design principles

Abstract Based on the microscope objective database and systematic classification introduced in Part I, the Zones 1–4 objective lenses are systematically analysed in this paper to extract the building blocks. All the definitions and terms are based on the preceding paper. The lens modules utilised in the front, middle and rear groups are investigated by reliable aberration evaluation tools with robust and accurate raytracing. Thereby, the aberration correction principles are summarised, from which 29 lens modules are well sorted with respect to their decoupled aberration correction functionalities. Furthermore, some intrinsic relations between the aberration-related lens modules and the impact of applications or the consideration of manufacturing and technology are also discussed. Utilising the lens modules, system modification and synthesis examples shall be given in Part III.

Zeroing in on Sustainability

Energy usage is a key business consideration for manufacturers – but many require the support of a trusted partner to maximise their sustainability potential

Systematic design of microscope objectives. Part I: System review and analysis

Abstract In the three connected papers, a systematic analysis and synthesis approach for microscope objectives is introduced. To subtract off the hidden assumptions in the historical development of the microscope objective lenses and extract the intrinsic lens modules, a large objective database is implemented including most of the patented systems for standardised applications. Based on the systematic analysis of the database, in Part I, a general review of the development history is given. A systematic classification method is proposed with respect to the five most significant parameters. According to the review and classification, the impacts of applications, manufacture and technology considerations are systematically analysed and summarised. Details of the lens modules will be discussed in Part II, and the synthesis approach utilising the lens modules will be introduced in Part III.

Simultaneous separation of small interfering RNA and lipids using ion-pair reversed-phase liquid chromatography

RNA interference offers a novel approach for the development of new therapeutics for targets that are otherwise “undruggable” using traditional modalities. The safety and efficacy of siRNA-based therapy mainly rely on lipid or polymer-based nanocarriers to overcome inherent barriers to a systemic delivery of siRNA. A multicomponent lipid nanoparticle (LNP) system is a promising delivery platform, typically consisting of a cationic lipid, phospholipid, PEG-containing short-chain lipid, and cholesterol. Characterization and chemical analysis of the LNP formulation is important to assure drug product stability, a key consideration for chemistry, manufacturing and control strategy. Here we report an ion-pair reversed phase UHPLC method capable of simultaneously separating both siRNA and functional lipids in LNPs with a minimal retention gap for two classes of biologically essential yet chemically distinct molecules. Key chromatographic parameters critical to the separation are discussed, including the structure of the ion-pair agent, stationary phase chemistry, column temperature and an organic additive. The results showed that the retention time of siRNA is tunable by using various ion-pair reagents. The retention factor of the siRNA exhibited a first order relationship with the number of carbons in the alkyl chain of the ion-pair reagents. In contrast, the type of ion-pair reagent has no significant impact on the separation of phospholipids. Separations using a BEH phenyl column and dibutylammonium acetate as the ion-pair reagent showed satisfactory selectivity for a range of double-stranded siRNAs and phospholipids, key components for lipid nanoparticle formulations. Furthermore, the method was applied to the separation of an experimental LNP formulation, demonstrating good selectivity for siRNA, functional lipids and their potential degradation products.

DEVELOPMENTS IN LIGHTWEIGHT COMPOSITE BALLISTIC HELMET MANUFACTURE


 
 The design and manufacturing considerations for modern
 lightweight military helmets are discussed by an original equipment
 manufacturer (OEM.). The core functional requirements of contemporary military
 helmets are outlined, describing the performance measures that are routinely
 requested to quantify these requirements within specifications. The challenges
 for OEM and end-user are highlighted, as there are many ways of measuring this
 performance and many different levels of performance desired by different end
 users.  
 
 The OEM states the compromises that are made in order
 to maximise helmet performance whilst balancing the complex and competing
 requirements of military helmets. The use of lightweight fibre-reinforced
 composite structures in modern military helmets is described. The composite
 materials commonly used in these helmets are discussed, highlighting the key
 properties of the materials used and the use of hybridised shell constructions
 using many different materials in order to achieve optimum helmet shell
 performance. The challenges faced when hybridising helmet constructions in this
 way, using often incompatible materials is considered.
 
 The two most common helmet manufacturing processes are
 also outlined, and the paper discusses how careful selection of processing
 parameters is key to realise the full potential of the materials used: how the
 increased use of ultra-high molecular weight polyethylene in ballistic helmets
 has led to the use of new manufacturing processes, such as deep draw, for the
 manufacture of fibre reinforced composite helmets rather than the traditional
 compression moulding. 
 
 These preferences and the experience gained during the
 development initiatives are considered to provide insight and guidance to those
 specifying requirements for their own helmets, such as the technical
 representatives of international Ministries of Defence.
 

WeldANA: Welding decision support tool for conceptual design

This paper describes a methodology and reference implementation created to aid design engineers in the early phases of design for a new discrete product. The decision support tool is used to understand design decisions and their relation to manufacturability considerations, in particular, the weldability of a design. As such, we have defined four metrics (partability, setup/orientation, accessibility, and preparation) that encapsulate good structural weldment design. Those metrics have been codified in a software tool that interacts directly with a commercial CAD package as part of a manufacturability analysis decision support tool suite that also includes machining and casting assessment capabilities. This paper focuses on weldment manufacturability analysis, WeldANA. Several common use cases are used to demonstrate the efficacy and efficiency of the approach for use in the early stages of the design process.

Important Considerations in Manufacturing of Natural Fiber Composites: A Review

The paper overviews the essential considerations in the manufacturing process of natural fiber composites which influence the performance of biocomposites. The evaluation of thermal properties of composites matrix and natural fiber chemical composition and physical properties appears to be necessary as the initial screening factors before the manufacturing process of biocomposites. On the other hand, considerations on fiber composition, type of manufacturing process and parameter used are seen as other crucial significant factors that need to be focused during the manufacturing of biocomposites. Moreover, the treatment used in the manufacturing process such as alkali treatment and coupling agent utilization should also be highlighted as additional important measures for better performance of biocomposites. In this review, all significant factors that influence the performance outcome of natural fiber composites are highlighted to provide the base-line source of literature for the manufacturing and production of composites sample. It is expected that the findings from the present study could further enhance the performance of natural fiber composites and able to become the preferred alternative or replacement for petroleum-based polymer in various industrial and commercial applications in the future.

Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C10).

Salcaprozate sodium (SNAC) and sodium caprate (C10) are two of the most advanced intestinal permeation enhancers (PEs) that have been tested in clinical trials for oral delivery of macromolecules. Their effects on intestinal epithelia were studied for over 30 years, yet there is still debate over their mechanisms of action. C10 acts via openings of epithelial tight junctions and/or membrane perturbation, while for decades SNAC was thought to increase passive transcellular permeation across small intestinal epithelia based on increased lipophilicity arising from non-covalent macromolecule complexation. More recently, an additional mechanism for SNAC associated with a pH-elevating, monomer-inducing, and pepsin-inhibiting effect in the stomach for oral delivery of semaglutide was advocated. Comparing the two surfactants, we found equivocal evidence for discrete mechanisms at the level of epithelial interactions in the small intestine, especially at the high doses used in vivo. Evidence that one agent is more efficacious compared to the other is not convincing, with tablets containing these PEs inducing single-digit highly variable increases in oral bioavailability of payloads in human trials, although this may be adequate for potent macromolecules. Regarding safety, SNAC has generally regarded as safe (GRAS) status and is Food and Drug Administration (FDA)-approved as a medical food (Eligen®-Vitamin B12, Emisphere, Roseland, NJ, USA), whereas C10 has a long history of use in man, and has food additive status. Evidence for co-absorption of microorganisms in the presence of either SNAC or C10 has not emerged from clinical trials to date, and long-term effects from repeat dosing beyond six months have yet to be assessed. Since there are no obvious scientific reasons to prefer SNAC over C10 in orally delivering a poorly permeable macromolecule, then formulation, manufacturing, and commercial considerations are the key drivers in decision-making.

Lightweighting of Automobile Hood Using Multistep Optimization for Composite Material

<div class="section abstract"><div class="htmlview paragraph">Emission norms across the world are getting more and more stringent day by day, in pursuit of saving the mother Earth. Automotive industry is quick to respond to this huge challenge. One solution lies in making the vehicles lighter. That's why scope of the lightweight materials is more and more realized and explored during the last decade. One of the front runners in the lightweight material is Carbon Fiber Reinforced Polymer (CFRP). CFRP comes with own challenges in its understanding, designing and engineering. For effective use of the CFRP material, from a design and mass point of view, it has to be optimized in such a way that every section and layup is utilized to its maximum potential. Current paper demonstrates the multi-step optimization approach used in a design and development of car hood. Initial assessment of the hood showed that few attributes were falling short of the requirement targets, and could only be achieved with a mass penalty. After interaction with respective teams, scope for the optimization is realized. Topology optimization is utilized to derive the right structure from available design space, the reinforcer patterns and sections are worked out accordingly. Next step followed is the free-size optimization. Basic composite learnings are implemented in the development process. Results are used to decide the ply layups in different hood frame regions. Finally, hood model with the derived sections and ply information is updated for the manufacturing considerations and assessed for multiple domain performance.</div></div>

Concurrent design and manufacture of a thermoplastic composite stiffener

Fibre reinforced composite materials are finding increasing application in aerospace structures due to their superior specific properties. Aerospace structures make widespread use of stiffening elements, such as stringers, for example in wingboxes and fuselage structures. Sizing of stiffeners to fulfil strength, stiffness and manufacturing considerations is a significant challenge. Herein, a novel manufacturing approach using winding in combination with laser-assisted tape placement is used to manufacture an omega-shaped stiffener made from carbon fibre thermoplastic material. This paper discusses the integrated approach taken by considering material choice, manufacturing constraints and structural design on the performance of a closed-section omega stiffener. The sizing is based on the buckling response of the wingbox, with manufacturing constraints taken into consideration. In the collapsible mould, a low-melt aluminium alloy is used as a spacer, which can be removed post-process by exposing the mould to the alloy melt temperature, which is below the glass transition temperature of the thermoplastic composite material. Manufacturing tests show that repeatable stiffeners of the appropriate dimensions are manufactured. Characterisation tests show that both the bond strength, measured using an interlaminar shear strength test, and the corner strength, assessed using a four-point bend test, are satisfactory.

Development and validation of a CFD based optimization procedure for the design of torque converter cascade

ABSTRACTTraditional one-dimensional (1D) design theory no longer satisfies modern torque converter design requirements due to the lack of accuracy and long trial-and-error process. A computational fluid dynamics (CFD) based optimization approach was brought forward. This study is devoted to two key processes in bringing CFD into torque converter design – blade parameterization/evaluation and optimization. A six-parameter blade camber line design method was employed to represent the blade shape. The blade profile was evaluated based on manufacturability considerations. A low-fidelity CFD model was developed for parameter study and optimization, and a high-fidelity CFD model considering the transient and cavitation effects was employed to evaluate the optimization outcome. The parameter sensitivity study was performed using design of experiment (DOE) technique and the variables were categorized into primary design variable, effective design variable and insignificant design variable groups. Optimization on the primary variables was carried out using the genetic algorithm. Two optimum solutions were evaluated with the transient full 3D CFD model and then tested. The optimum torque converters’ test results indicated significant performance improvement. The proposed design procedure can improve the design efficiency & accuracy and shorten the design cycle by the application of different CFD models in conjunction with an optimization algorithm.

Improving sustainability and cost efficiency for spare part allocation strategies by utilisation of additive manufacturing technologies

Abstract Currently, no proper cost models are available to assist managers in selecting part-specific allocation strategies for spare parts under consideration of metal additive manufacturing (AM). Therefore, sustainability aspects and cost efficiency over a product lifecycle show potential for optimisation. The aim of this paper is to propose a two-stage model as a basis for decision support in spare part allocation. The first stage introduces a multi-criteria part classification regarding classical criteria as well as criteria referring to AM. The impacts on different spare part allocation strategies like final stockpiling, conventional spare part production or AM on demand will be focused. Based on the first stage, a conceptual model for a comprehensive activity-based cost assessment will be adopted to assess the arising costs that occur for each of the compared allocation strategies. Evaluating the relevant factors for the specific product, process, warehousing and capital issues, the basis for choosing the best suitable spare part allocation strategy will be presented. The present document is a working paper, where the interim results of the intended concept model are introduced.