Chapter 12 - Continuous processing

Continuous Improvement Processes: Why They do not Work and How to Fix Them

The fragility of the transponders was beforehand thought as a limitation when considering various RFID applications. However, the described applications in continuous processes have shown that transponders can be designed to survive blasting, crushing, extreme temperatures and large shear forces. Therefore, we argue that the transponder fragility should not be seen as a limitation for most uses. However, designing transponders that survive in high temperature processes are still thought to be problematic or even impossible. In some continuous processes, for example the paper industry, the transponder may be a contaminating factor in subsequent process stages. However, if the whole process is kept in mind when choosing and developing the transponder the contamination can be avoided like in, for example, the sawmill process. The selection and development of a suitable transponder may be expensive and time consuming. When transponders are dropped directly in the product flow the orientation between the reader antenna and the transponder antenna cannot be controlled. For some application all orientation may not be readable and some transponders may pass the reader without being read. By serially mount readers at different orientations in relation to the passage of the product flow, like in the pellets distribution chain, a higher fraction of transponders can be read. A low read rate implies more costs either in an increased demand of transponders or number of readers to be mounted. However, a low read rate does not imply that RFID has to be abandon as an application. Installing a reader in some continuous process may demand that the process is stopped during the installation or that the installation must be done during a maintenance stop. Therefore, the installation may be costly or limited to a specific time and making changes to an installed reader may be both difficult and costly. Simulations may provide information that can be used to reduce the risk for the need to modify an installation and thereby the cost of an installation. The production process in continuous processes is often highly automated and richly instrumented. An RFID application may affect or be affected by an existing instrument, and unexpected problems may occur similar to the problems with the metal detection equipment in the sawmill process. Hence, before an RFID application is installed it is recommended to perform a risk evaluation in an attempt to identify potential risks with the installation. To predict all potential risks for problems connected to an RFID application is complicated. Therefore, it could be wise to be cautious and initiate the application stepwise in an attempt to minimize the consequences of unexpected problems. One factor limiting the use of RFID is the physical size of the transponders. Today the size of the transponders may limit the use of RFID to trace the movement to particles 10 millimetres. Another factor limiting the use is the read range, with longer read range the transponder position could be more thoroughly followed and new applications would be

The authors have developed the continuous kneading process for lithium ion battery (LIB) slurry to prepare for future mass production and cost reduction. It is very important operation in a battery manufacturing process to disperse electrode materials because battery performance is decided by the dispersion states of electrode materials. A batch operation is generally used as a conventional method, and it needs long operation time to make dispersion slurry. Getting dispersion slurry using some of the next generation active materials having modified-surface and fine grain size is difficult for the conventional method. To provide a dispersing device capable of efficiently obtaining dispersion force is required. We use twin screw type continuous kneading machine. This continuous kneader can disperse a wide range of viscosity. The continuous kneader is also applied in various industries such as food and chemical in order to have excellent dispersing ability. Due to continuous process, automation and cost reduction become possible, and production speed is improved. The continuous kneader is closed horizontal twin screw type. The twin screws are constructed of many paddles which are mounted on the twin shafts. Each paddle is separate piece that can be arranged to suit various mixing characteristics. The shafts rotate in the same direction. The paddles are arranged in pairs along the mixing circuit, and have a constant clearance between the tip of the paddle and the inner barrel wall, as well as the tip of the paddle to the surface of the opposite piece. This gives the benefit of mixing efficiency. Volume of material is changed in compression and expansion according to paddle's rotation. Shearing actions between the barrel and paddle, and between paddles increases efficiency of kneading and dispersion. The continuous kneader was applied to the tape for manufacturing magnetic recording medium, because dispersion plays important role. The magnetic powder became finer according to enhance data capacity, the continuous kneader could manufacture good dispersion magnetic coating material in response to this change. Manufacturing of lithium ion battery electrode slurry is kneading powder materials in binder resin in the similar way of making the magnetic tape. The authors included the know-how obtained by improving manufacturing of the magnetic tape in continuous kneading process of lithium ion battery electrode slurry. The authors have performed examination of suitable kneading conditions of dispersion slurry production by using Li(Ni1/3Mn1/3Co1/3)O2 (NMC) and LiFePO4(LFP) as cathode active materials. The dispersion state of the slurry using the continuous kneader is controlled by the paddle arrangement, the rotary speed of the shaft and the supply conditions of raw materials. Several elements of kneading conditions have beneficial effect on slurry viscosity and battery performance. After changing some of kneading conditions, excellent dispersion slurries were obtained. The slurry from optimized continuous process showed high battery performance. Cyclic performance of laminated pouch type cell showed a stable characteristic about 2,000 cycles at the charge-discharge rate of 3C. The battery performance was comparison with the slurry made by using batch operation. Rate characteristics and cyclic performance of the slurry made by continuous kneading process showed better than made by batch operation. The paddle arrangement and the supply conditions of raw materials influence the dispersion state of slurry. The solid content concentration in the continuous kneader changes when supply conditions of raw materials was changes, it was considered that the dispersion of raw materials advanced by adjusting the solid content concentration appropriately. This high speed continuous kneading process greatly improves not only the battery performance but also productivity of the electrode slurry. Our high speed continuous kneading process can manufacture about 60 times faster than the conventional batch operation according to our estimates. Therefore the cost reduction may be practiced in LIB mass production. The above-mentioned results indicate that the high speed process of high performance electrode slurry made by the continuous kneader is effective method. Figure 1

The purpose of this study is to investigate the potential of using a pelletized pitch in a continuous process for the economical preparation of large-scale pitch-based carbon fibers. The pitch was pelletized before spinning because the pitch powder can agglomerate in the feed throat of a screw extruder, which can render uniform heating difficult. Using the pelletized pitch in a single-screw extruder spinning apparatus, the pitch fiber can be spun to a great length as long as the amount of pitch pellets is sufficient. To evaluate the benefits of using pitch pellets in the continuous carbon fiber spinning process, isotropic and mesophase pitch fibers were prepared by both the conventional batch process using pitch powder and continuous process using pitch pellets. Even with a huge difference in the thermal energy used, the carbon fibers prepared using the pelletized-pitch-based continuous process had better tensile properties than those prepared using the conventional process. This suggests that the continuous process using pitch pellets has the potential to be an economical large-scale process for carbon fiber preparation.

A general review of stochastic processes is given in the introduction; definitions, properties and a rough classification are presented together with the position and scope of the author's work as it fits into the general scheme. The first section presents a brief summary of the pertinent analytical properties of continuous stochastic processes and their probability-theoretic foundations which are used in the sequel. The remaining two sections (II and III), comprising the body of the work, are the author's contribution to the theory. It turns out that a very inclusive class of continuous stochastic processes are characterized by a fundamental partial differential equation and its adjoint (the Fokker-Planck equations). The coefficients appearing in those equations assimilate, in a most concise way, all the salient properties of the process, freed from boundary value considerations. The writer’s work consists in characterizing the processes through these coefficients without recourse to solving the partial differential equations. First, a class of coefficients leading to a unique, continuous process is presented, and several facts are proven to show why this class is restricted. Then, in terms of the coefficients, the unconditional statistics are deduced, these being the mean, variance and covariance. The most general class of coefficients leading to the Gaussian distribution is deduced, and a complete characterization of these processes is presented. By specializing the coefficients, all the known stochastic processes may be readily studied, and some examples of these are presented; viz. the Einstein process, Bachelier process, Ornstein-Uhlenbeck process, etc. The calculations are effectively reduced down to ordinary first order differential equations, and in addition to giving a comprehensive characterization, the derivations are materially simplified over the solution to the original partial differential equations. In the last section the properties of the integral process are presented. After an expository section on the definition, meaning, and importance of the integral process, a particular example is carried through starting from basic definition. This illustrates the fundamental properties, and an inherent paradox. Next the basic coefficients of the integral process are studied in terms of the original coefficients, and the integral process is uniquely characterized. It is shown that the integral process, with a slight modification, is a continuous Markoff process. The elementary statistics of the integral process are deduced: means, variances, and covariances, in terms of the original coefficients. It is shown that an integral process is never temporally homogeneous in a non-degenerate process. Finally, in terms of the original class of admissible coefficients, the statistics of the integral process are explicitly presented, and the integral process of all known continuous processes are specified.

With the applications of more advanced manufacturing technologies being applied to the pharmaceutical industry, continuous processes are at the forefront of innovation. One area that is highly desired to be systematically investigated is material traceability in continuous manufacturing systems. By following federal guidelines already in place, the goal was to address the issue of material traceability in a continuous direct compression tablet manufacturing process. The residence time distribution (RTD) method has been used for material traceability in continuous pharmaceutical tablet manufacturing process. Utilizing the minimum and maximum residence times for the continuous line pre-production, raw material batch changes that occur during feeder refill can be traced at the outlet of the process. MATLAB programing was used to develop software prototype to trace material components. Developed framework for implementation of material traceability into continuous manufacturing pilot-plant. To demonstrate the application of this framework, a software prototype was developed, which allows the operator to input residence time attributes for each component in the formulation. Using the minimum and maximum residence time values for that component, the lot number is incremented when the change in material batch is predicted to be present in the tablets at the outlet. The tablet lot number is recorded by the control system in real-time. Developed framework and corresponding software allows the material traceability to be fully accounted for during a continuous drug product manufacturing process. A proof of concept was created to demonstrate feasibility of such a system, which has a wide range of applications.

Model-assisted process design for better evaluation and scaling up of continuous downstream bioprocessing

Cellulose contained in peanut shells which are agricultural waste is considered to be potential as an adsorbent for removing heavy metals. Therefore, it is necessary to analyze the capacity of absorbance or the ability of meshes in the continuous adsorption process in removing heavy metal Fe in well water. The feasibility of an agricultural waste related to its use as an adsorbent has also been studied in this study through characterization by FTIR test which aims to determine the presence of cellulose organic compounds that play a role in the process of heavy metal adsorption. While the study of adsorption capacity in this study uses a continuous process that is generally carried out by Thomas modeling. Where in this study a continuous adsorption process was carried out to obtain saturation time from the adsorption of peanut shells in absorbing Fe metal. So that the absorbance capacity obtained from the once used activated carbon peanut shell has been made. In this study, a continuous adsorption process was carried out with a mass variation of 250 gr and 500 gr. This continuous adsorption process is obtained. The highest price of Constant Thomas (Kth) and the price of absorbance capacity (qo) is using activated carbon peanut shells with the use of 500 grams following the Thomas equation model y = -0.1701x + 3.3142 with a correlation coefficient (R²) = 0.4767 while the breakthrough point was reached in the 60th minute after well water through the bed

Introduction The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of the raw materials. Existing knowledge on the role of raw material properties in batch processing is however not directly transferable to continuous processes, due to the inherent differences between batch and continuous processes. Areas covered A review is performed to evaluate the role of excipient properties for different unit operations used in continuous manufacturing processes. Unit operations that will be discussed include feeding, blending, granulation, final blending, and compression. Expert opinion Although the potency of continuous manufacturing is widely recognized, full utilization still requires a number of challenges to be addressed effectively. An expert opinion will be provided that discusses those challenges and potential solutions to overcome those challenges. The provided overview can serve as a framework for the pharmaceutical industry to push ahead process optimization and formulation development for continuous manufacturing processes.

Industry 4.0 (I4.0) brings together new disruptive technologies, increasing future factories’ productivity. Indeed, the control of production processes is fast becoming a key driver for manufacturing operations. Manufacturing control systems have recently been developed for distributed or semi-heterarchical architectures, e.g., holonic systems improving global efficiency and manufacturing operations’ reactiveness. So far, previous studies and applications have not dealt with continuous production processes, such as applications for Water Supply System (WSS), oil refining, or electric power plants. The complexity of continuous production is that a single fault can degrade extensively and even cause service disruption. Therefore, this paper proposes the Holonic Production Unit (HPU) architecture as a solution to control continuous production processes. An HPU is created as a holon unit depicting resources in a continuous process. This unit can detect events within the environment, evaluate several courses of action, and change the parameters aligned to a mission. The proposed approach was tested using a simulated model of WSS. The experiments described in this paper were conducted using a traditional WSS, where the communication and decision-making features allow the application of HPU. The results suggest that constructing a holarchy with different holons can fulfill I4.0 requirements for continuous production processes.

Pollution burdens associated with load/assemble/pack of an ap based MK-66 PIP motor by continuous and batch processing

PurposeNovel process windows allow the development of faster, flexible, and greener processes. Therefore, novel process windows were applied to develop a greener process for the synthesis of vitamin D3. In this study the environmental impacts of several batch pathways to obtain vitamin D3 are benchmarked against the continuous microflow process, where novel process windows such as high temperature and pressure were applied. To evaluate the environmental impact of these processes, life cycle assessments were conducted.MethodsA new process concept was developed to optimize and simplify the synthesis of crystalline vitamin D3. This process was conducted in microflow by combining UV photoirradiation and high-p,T (photo-high-p,T) processing. Microreactors allow a high photon flux and enable the harsh conditions, respectively. The process was coupled with an integrated continuous crystallization, and its feasibility has been proven and reported before. The potential environmental impacts were assessed from a cradle-to-gate perspective. Both processes, continuous and batch, were modeled in Aspen Plus using foreground data from the experimental continuous setup, and background data from different patents. The assessment was performed in the software Umberto NXL LCA using the ReCiPe Midpoint 2008 method.Results and discussionThe continuous process has a significantly lower environmental impact than the batch processes. This lower impact is largely due to the fact that fewer amounts of material, particularly solvents, are used. Moreover, the continuous process is faster and has fewer steps, i.e., process-simplified. Among the industrial processes, the synthesis conducted in isopropanol has the lowest environmental impact, although, even in this case, the impact is between 20 and 30 times higher—depending on the conditions—compared with the continuous process. When the batch process is conducted in benzene, the worst environmental impact is obtained. Finally, recycle of the solvent for the best batch case was assessed. This improved the batch process to make it comparable with the continuous process.ConclusionsThe continuous production of vitamin D3 leads to an interesting alternative to the industrial process. Continuous manufacturing of vitamin D3 is faster, requires fewer steps, and uses less solvents compared with the industrial synthesis. However, although the environmental impact of this continuous process is already lower than that of the batch processes, the continuous process can still benefit from further optimization, particularly the introduction of a recycle loops for the solvents methyl tert-butyl ether and acetonitrile.

A continuous purification process can be beneficial to the purification of biologics due to its higher productivity and efficiency than a conventional batch purification process. However, regulatory issues and lack of established cases render deployment of the continuous process difficult in industrial settings. Here we report a case study for design and optimization of an advanced continuous process for purifying a low-titer enzyme as a model biologic. To convert a conventional batch process to an advanced continuous one in purification of biologics, conventional unit operations (UOs), including ultrafiltration/diafiltration (UF/DF) and batch chromatography, were replaced by advanced ones such as in-line dilution conditioning (IDC) and periodic counter-current chromatography (PCC). The UF/DF UO was changed to IDC UO to adjust pH and conductivity. The mixing ratio of the sample and the conditioning buffer in IDC was determined by experiments with three buffers. PCC was optimized with two variables, column height and sample loading residence time, as the delta pressure in the columns was less than 1.0 bar. A graph indicating the operating area was plotted to efficiently control the PCC. Although the sample volume increased in IDC, PCC had a complementary advantage in that purification was performed faster than batch chromatography. We observed at least 25% increase in economic advantage when the advanced continuous process was applied to purify a low-titer enzyme. We propose not only a continuous process with the substitution of UF/DF and batch chromatography with IDC and PCC but also a method to optimize PCC by plotting operating areas.

Comparison of process mass intensity (PMI) of continuous and batch manufacturing processes for biologics

Development of a novel continuous dense gas process for the production of residual solvent-free self-assembled nano-carriers