dry process milling

dry milling - an overview | sciencedirect topics

the yield of dry mills decreases very quickly when the outputs moisture exceeds 1%. Wet output agglomerates, balls and granules are covered in a layer of adhesive and plastic fines that cushions and lowers the force exerted on the output. In addition, the product circulates poorly in the mill. For these reasons, a hot air scan is often performed which requires an efficient dust removal facility;

wet, the concentration of solid pulp must be such that the pulps viscosity reaches 0.2Pa.s. A surfactant allows for a higher solid content without increasing the fracture limit of the pseudo-plastic pulp. Production is hence increased;

with a wet path, grains circulate well and do not re-agglomerate. In addition, it seems that resistance to fragmentation decreases in water. The result is that the energy consumption is greater with dry milling than with wet milling. It is on average 30% greater;

Corn dry milling operations are specially designed to manufacture fuel-grade ethanol in a one-shot process directly from the whole corn kernels. For this purpose, shelled corn arrives at the dry-mill processing facility and through processing via a hammer mill the entire corn kernel is ground into a medium-coarse to fine flour, which is referred to in the industry as meal and processed without separating out the various component parts of the grain. The meal is slurried with water in cookers to form a mash. In the cooking system, the action of heat liquefies the starch in the corn and sacccharifying enzymes are added to the mash to convert the starch to fermentable sugars. Dry milling is the most common process used today for bioethanol production because of low capital costs required to build and operate these plants. Besides ethanol, the major by-products of the corn dry milling process are dried distillers grains with solubles (DDGS) and carbon dioxide.39

Dry milling (Fig. 7.1) involves grinding the incoming grain, then processing it through a series of steps to liquefy the flour and generate fermentable sugars. Amylases are added at two points in the processthe initial slurry step, and the liquefaction step, which follows a jet cooking operation that uses high-temperature steam to swell the starch. Following liquefaction, the slurry is fed to a batch fermentation system, where glucoamylase and yeast are also added. The typical fermentation time is 4255h. Multiple fermenters are used to facilitate batch operation of this step, with the fermentation cycle time including a clean-in-place step prior to the addition of fresh mash that commences the start of the fermentation process. Final ethanol titers between 14 and 18wt% are typical. Once the fermentation is complete, the ethanol-laden mash is transferred to a beer well that ultimately feeds the first stage of a two-stage distillation system. The first distillation stage includes all of the unconverted solids, which are recovered at the bottom of the column, while the overhead, typically containing about 3040% ethanol, is fed to a second distillation column that purifies the ethanol to a concentration near its azeotrope (about 190 proof). The hydrous ethanol is then dehydrated using a set of molecular sieves, producing a 99.5% ethanol product. This product is then denatured to meet government regulations.

The wet solids recovered at the bottom of the first distillation column are centrifuged, with the liquid sent to a set of multiple effect evaporators to recover water for reuse in the process (typically added to the first slurry reactor), while the solubles (mainly sugars) are typically blended with the wet distillers grains to produce wet distillers grains with solubles (WDGS). The WDGS may be sold as is to nearby feedlots due to the limited shelf life of the wet product, or optionally dried to produce DDGS, a stable, protein-rich product that can be shipped worldwide as animal feed.

Beer is produced mainly from barley, and the annual beer production in the European Union in 2014 was about 42.5 million tonnes (FAO). Brewing (Fig. 9.2) can be divided into the stages detailed in Sections 9.2.2.19.2.2.5 (Bamforth, 2007):

illing is crucial as it should achieve optimal material extraction and endosperm grinding with minimal husk damage. Dry milling is carried out using a roller, disk, or hammer mills. Roller mills are used when wort separation is carried out with a lauter tun, while hammer (or disk) mills are used when mash filtration is applied. Wet milling may also be applied as it has been established by the corn starch industry.

Mashing aims to produce wort with the optimal composition, leading to the production of the desired beer quality during fermentation. The milled grist is suspended in hot water to facilitate the gelatinization of starch achieved at 55C65C. The action of the indigenous amylolytic enzymes on the production of fermentable sugars can be manipulated at different temperatures during mashing. For instance, dry beers are produced at low temperatures (63C) and sweet and more full-bodied beers are produced at higher temperatures (77C).

The produced wort should be rich in nutrients and relatively free of insoluble particles. The permeability of the bed of solids (e.g., sand, clay, etc.,) used in the process, the fineness of the original milling and the husks integrity, and the temperature used affect the process efficiency and wort quality characteristics. Wort separation is achieved by lauter tuns or mash filters. A lauter tun consists of a straight-sided round vessel with a slotted or wedged wire base and run-off pipes, through which wort recovery is achieved. Arms bearing vertical knives rotating around a central axis are found within the vessel. Mash filters contain plates of polypropylene for filtering the liquid wort from the residual grains. This system allows the use of high pressures for grain crashing, overcoming the reduced permeability due to smaller particle sizes. Mass filters are used by modern breweries.

Wort boiling is subsequently applied for wort sterilization, the initiation of chemical reactions (e.g., isomerization of hop resins), wort concentration, the removal of unwanted volatile compounds, and the precipitation of protein/polyphenol complexes. The wort is finally cooled before fermentation using water or glycerol as a cooling agent, leading to the precipitation of solids, which is called cold break.

The fermentation process can be divided into the primary fermentation where the wort is fermented into alcohol and various flavors, and the secondary fermentation that involves beer conditioning, considering carbon dioxide concentration, and the removal of undesirable flavors. Subsequently, the temperature is reduced to 1C or 2C, promoting the precipitation of compounds that cause a haze in the beer.

After a minimum of 3 days in cold conditioning, plate and frame filters are mainly used for beer filtration with porous materials as filter aids (e.g., kieselguhr, perlite, etc.). The shelf life of beers is increased via the removal of certain proteins and polyphenols by the precipitation of such complexes. The level of gases in the beer is also regulated. Pasteurization (e.g., tunnel pasteurization of beer cans or bottles) or sterile filtration (with pores of 0.450.8m) is finally applied.

Corn ethanol is produced by dry or wet milling [13,14]. Ethanol is the main product of the dry milling process while wet milling is more efficiently designed to separate various products and parts of corn for food and industrial uses including corn starch and corn oil, as well as ethanol. In the dry milling process the kernel is ground into flour (meal) and water is added together with enzymes to convert the starch to dextrose. Ammonia is added, the mixture is heated for sterilisation and yeast is added to ferment. After (40 to 50)h, the mixture is distilled to purify the ethanol from the stillage and the ethanol is dehydrated to about 99.3vol.% using a molecular sieve system. The remaining stillage is converted to livestock feed. The process of wet milling involves adding sulphuric acid and water to the corn grain, and after treatment for (24 to 48)h, the components are separated. Grinders separate the corn germ from the mixture. Corn oil is extracted in a process that also separates the fibre, gluten and starch using screen, hydroclonic and centrifugal separators. The gluten protein and the liquor dried with the fibre co-products are feed ingredients for the poultry and livestock industry. The corn starch is converted into ethanol through fermentation as described for dry milling.

For sucrose feedstock, biomass is crushed to extract sugar juice. The corn (65%76% starch) is processed through dry milling in which the powder form of grains is heated with water at 358K. Starch is then liquefied using -amylase that converts starch into short-chain dextrins. Saccharification (pH 4.5 and 338K) is carried out using the gluco-amylase enzyme. In contrast, the rigid lignin cell wall protects carbohydrates in lignocellulose biomass. The cellulosic biomass is thus processed through milling, followed by pretreatment. The pretreatment breaks the lignin barrier, reduces cellulose crystallinity, and enhances the accessibility of carbohydrates for hydrolysis. The pretreatment is, however, very expensive, and has an enormous influence on the overall yield of ethanol. For example, pretreatment improves the hydrolysis yield to 90% from merely 20% (without pretreatment) [25]. The polysaccharides are then hydrolyzed to fermentable sugar. Hydrolysis is accomplished using either enzyme or dilute acid. The enzymatic hydrolysis is, however, commonly used (pH 4.8 and 318K323K) [26]. Cellulase and hemicellulase enzymes are used for hydrolysis of cellulose and hemicellulose, respectively.

The sugar, starch, and cellulose are composed of hexose sugars, while both hexose and pentose sugars exist in hemicellulose. The hexose sugars are traditionally fermented by Bakers yeast. Saccharomyces cereviseae is the most common organism (at 306K and pH 44.8). The maximum yield of ethanol is 0.48g per g glucose [25]. Pichia stipitis, P. segobiensis, Candida shehatae, Pachysolen tannophilus, and Hansenula polymorpha are some of the organisms for fermentation of pentose sugars. These organisms, however, suffer from the drawback of the slow fermentation rate. The genetic modification of the microorganisms is thus done to ferment both hexose and pentose sugars. Metabolically engineered strain recombinant Escherichia coli (KO11), Saccharomyces cerevisiae 1400 (pLNH33), Zymomonas mobilis are some examples of these. The high sugar and ethanol concentration and inhibitory fermentation products are toxic to the organism. Less than 10% ethanol concentration (typically 4%4.5%) is thus maintained in fermentation broth to reduce the stress on the enzyme.

The fermentation broth is sent to the beer stripper and rectification column to obtain 95% ethanolwater azeotrope mixture. The ethanol is further purified to fuel-grade ethanol by azeotropic distillation using benzene or ethylene glycol as entrainer followed by dehydration using the molecular sieve [27]. There are several process alternatives for bio-ethanol production: (1) simultaneous saccharification and fermentation that perform enzymatic hydrolysis and fermentation in the same reactor; (2) cofermentation, in which hexose and pentose sugars are fermented by single microorganism; (3) simultaneous saccharification and co-fermentation; and (4) consolidated bioprocessing, in which cellulose production, cellulose hydrolysis, and fermentation happens in a single step [28]. These process variations aim to reduce the investment cost and have a lower risk of inhibition and contamination [25].

First generation bioethanol uses feedstock containing sugar (sugarcane, sugar beet, sweet sorghum) and containing starch (corn, wheat, cassava). Wet and dry milling routes are used to produce bioethanol from corn. Dry milling requires less investment and produces dried distillers grain with solubles (DDGS) beside bioethanol, while the wet milling produces oil and animal feed beside the bioethanol. Corn-grain is used to coproduce bioethanol and wet or DDGS as animal feed. Fig. 5 shows the basic steps of converting starch into bioethanol by biochemical process using 6-carbon sugar sources. Most corn is ground to a meal, and then the starch from the grain is hydrolyzed by enzymes to glucose (dry mill). The 6-carbon sugars are then fermented to ethanol by natural yeast and bacteria. The fermented mash is separated into ethanol and residue by distillation. Hydrated ethanol forms an azeotropic mixture; fuel grade ethanol (0.4 vol% water) can be achieved by azeotropic distillation, by means of molecular sieves, or by extractive distillation [34].

The average yield of converting corn starch to ethanol is around 100 gallons bioethanol per dry ton corn [35]. About one-third of every kilogram of corn grain is converted to ethanol, one-third to DDGS, and one-third to CO2. Ethanol is produced at ASTM D4806 standards and shipped to the refiner or distributor for blending with conventional fossil gasoline into finished gasoline.

Surplus corn in the United States and sugarcane in Brazil are used to produce bioethanol. Fermentation of a bushel of corn (approximately 25.4 kg) using the dry-mill process yields about 10.2 l of ethanol and approximately 7.9 kg of DDGS that contains 10% moisture. This coproduct is richer in protein, fat, minerals, and fiber relative to corn and hence is a valuable feed [14]. Bioethanol producers have adopted various technologies such as high-tolerance yeasts, continuous ethanol fermentation, cogeneration of steam and electricity, and molecular sieve driers to reduce ethanol production costs [35,36].

Various studies have been published of the food industry from an economic and consumer point of view (McCorkle, 1988; Connor, 1988). While these references are old, they are still accurate in an industry that does not change very quickly. The food industry is the largest by economic impact in the USA, with annual sales of over $500 billion. The industry is very diverse, but major segments include those that process raw commodities into ingredients and foods; those that preserve and modify ingredients into foods and ingredients; and those that produce consumer food products.

Corresponding to the wide range of products are the many processes involved, ranging from the relatively simple size reduction and physical separation of flour milling to the sophisticated biochemical process of fermentation and aging involved in making wine. In between are combinations of culinary and engineering art and science to reproduce on a large, commercial scale the flavor, texture and nutrition of home-prepared dishes and meals.

Food companies can be very large, with sales approaching $25 billion per year, and relatively small, with sales that might not exceed $1 million per year. (See the August issue of Food Processing (Putnam Media, Itasca, IL) each year for a list of the top 100 food companies.) In the list for 2007, the top five companies, by food sales in 2006 were:

Consolidation among large companies has made the largest multinational firms very large indeed, with operations all over the world. In the context of designing and operating facilities, one consequence is that such firms need to be cognizant of customs, regulations and cultures very different from those of their home country. As one small example, it is common in many countries to provide one or more hot meals each day to the workforce. Sometimes, dormitories are also provided for a work force that may have moved a long distance to get a job. This means that a food facility may need to have a full kitchen and extensive living quarters on site. These are not commonly found in US food facilities.

Religious and cultural practices often affect what foods are popular. Muslim and Jewish adherents do not eat pork; Hindus do not eat beef; Muslims avoid alcohol; and Chinese apparently like corn chowder, among other preferences. Such cultural practices affect what food products are likely to sell well in a given market and thus what a given facility is intended to do.

The distribution systems in developing countries may be relatively primitive due to poor roads, lack of refrigeration in homes and stores, and the lack of a commercial infrastructure. These conditions mean that the scale of operation may need to be smaller than it would be in the USA. Products that are shelf stable, as compared with frozen or refrigerated, are better suited for developing countries. Food manufacturers may need to establish their own system of distribution centers and wholesalers, whereas third parties in the USA often handle these functions.

Some facilities may be located to take advantage of local raw materials. Thus, for example, sugar mills are in tropical areas because sugar cane is a tropical crop. Sugar mills produce raw sugar, which is about 97% pure sucrose, and is shipped closer to markets in temperate areas for further refining. Tropical oils, such as palm oil and palm nut oil are harvested and the raw oil produced close to the palm plantations, with refining taking place closer to shipping points on the coasts of Southeast Asia.

Another factor in facility location is the relative density of the raw material and finished product. For instance, potato chip snacks, which have a low bulk density, are commonly made near population centers, while frozen and dehydrated potato products are usually made near potato producing areas.

Wheat flour mills in the USA tend to be located near wheat producing areas and near water ports on rivers, lakes or oceans. Flour users, such as bread bakers are closer to markets. Cookie and cracker bakers may have larger and fewer plants because cookies and crackers are denser than bread and have a longer shelf life.

The customers of food manufacturers are not usually consumers but the stores and food service institutions that serve consumers. About 50% of food consumed in the USA is consumed outside of the home, so the manufacture and distribution of products for food service are increasingly important. These products are different in many ways from those intended for use in the home or factory. Food service products are often refrigerated or frozen, are usually portion controlled, and may be heavily influenced by culinary concepts. This means they are conceived and developed by chefs or people with some culinary training and are meant to be used by kitchen personnel in restaurants, colleges, hospitals and prisons. Consumer food products, in contrast, are often developed by food scientists and food technologists.

Consumer food products tend to be sold in supermarkets, convenience stores and, increasingly, in mass merchandisers. Often these customers have their own distribution systems and centers (DC). Usually, food manufacturers have distribution centers as well, so there can be some redundant handling as a product moves from factory to distribution center to another distribution center and then to the store. Rationalizing the food distribution system is a major cost reduction opportunity, but the ideal solution has not emerged yet.

Some products require direct store delivery (DSD), usually because they are perishable or have such high sales volume that they need frequent deliveries. Bread, milk, soft drinks and salty snacks are examples of foods delivered daily to most stores. DSD is an expensive distribution system because it is labor intensive and because fuel costs have been increasing. DSD driver/salespeople are often paid a commission on sales, which provides a substantial incentive, but adds to costs. Some are company employees while others may be independent contractors who own their equipment. Independent contractors often service vending machines for snacks, soft drinks and confections. DSD once was largely a cash business, with store owners paying on the spot. This is less common now. Managing and controlling a widely dispersed sales and delivery force can be a challenge.

Mass merchandisers have been influencing the food industry because they demand low prices, very good service and, often, special packaging (especially in club stores). They also move very large amounts of product, so accommodating them is a major objective. Food manufacturers often open dedicated sales offices near the headquarters of mass merchandisers so as to service them better.

The case study set up is solved using CPLEX solver in GAMS modeling tool. It is then plotted into Microsoft Excel 2010 for further verification. As predicted, the result shows conflict between the environmental and the economic objectives understudy.

As emission credit is only given to C+TDM, the overall GHG impact is lowered, and the environmental cost for C+TDM is reduced. Thus the total cost for C+TDM is lower than LCEP. This is shown in Fig2.

In terms of environmental impact, stages bp, bpt, bt and ft are assumed to have the same GHG emission factor for both technologies, thus the impact for these four stages look identicial. However, without considering the emission credit, life cycle stage fp for C+TDM immediately rises to more than 160 million kg CO2-eq, which is about 2.5 times the amount for LCEP.

At the same time, the emission credit ec for C+TDM is high as well (almost 100 million kg CO2-eq), which effectively helps to lower the total GHG emission for the conversion technology, as well as increase the profit. This is shown in Fig3.

This section is fundamental to guarantee the final quality of the product, especially as regards parameters such as ash content, ash fusibility, and the occurrence of Cl, N, and other alkali metals, which are elements that directly influence the probability of occurrence of phenomena of slagging, fouling, and corrosion in combustion equipment.

Usually, after the debarking section, the shredding unit follows. These two sections can be connected by different types of equipment, the most common of which are chain draggers (Fig.5.3), which help to eliminate the inerts that are still attached to the trunks, and the metal detection unit (Fig.5.4). Which serves to detect and enable the disposal of ferrous metal parts. It is very common to find remains of saws metal sheets used in the processes of resination.

The purpose of the shredding unit is to reduce the size of the logs to a size that allows them to be admitted to the drying system. This section is usually associated with a sieving system (Fig.5.5) and also an auxiliary grinding system, referred to as green milling, because this milling occurs before the feedstock is dried. As will be seen later, In the case of the production of torrential biomass products, this step is not necessary, one of the advantages presented for this process being compared to conventional.

The feed of raw material to the drying system can be done in several ways, provided that a buffer is created that ensures a sufficient quantity of product to maintain the continuity of the process in case of failure or stop upstream, until the resolution of the situation. One of the ways to make this feed and to guarantee the intermediate storage of raw material is through mobile-floor systems (Fig.5.6). This system allows the storage of product in very significant quantities because the material can be stored and added on the floor. It also allows that in the case of the acquisition of raw material already processed, it is added to the process at this point.

Drying is one of the most determinant processes for the quality of the finished product and even for the fluidity of the production process. There are several types of dryers, but the most used are rotary drum dryers (Fig.5.7). The sizing of the dryer is based on several assumptions for the process to take place as efficiently as possible:

Drying is also one of the processes that consumes the most energy in a biomass pellet production unit. For this reason, it is essential that the process occurs as efficiently as possible, optimizing the energy use, and subsequently the associated energy costs.

The drying units can use different forms of energy, the most common being biomass and natural gas. It is very common for large biomass pellet plants to resort to biomass combustion systems (Fig.5.8), which provide heat to the drying process. This option is essentially due to two factors. First because of the economic option, because it is an energy intensive consumer, the energy costs are very high and biomass, in the form of residual forest biomass or even in the form of wastes from the peeler, always has a low cost and usually in abundance. Second, because of the location chosen for the plants to be closer to the sources of raw material, they are far from the natural gas networks, not allowing their use.

It is also common to have an intermediate storage after milling of dry product. This storage feeds the pelletizing units and must ensure that the system remains under load and with a constant supply. This intermediate storage system is also very useful for any stoppages that may occur, caused by faults or preventive maintenance needs that may occur downstream, particularly in densification systems. The feeding of pelletizers can be done in different ways, being very common The existence of a mixer where the moisture in the sawmill can be corrected and where additives can also be added to improve the qualities and properties of the materials. An example of a mixer is shown in Fig.5.10. Inside is a shaft with a propeller that allows the material to already blend and advance. This ensures homogenization of the sawmill properties, while ensuring a sufficient residence time for the same homogenization.

There are different types of pelletizers, the most common types being called vertical axis or flat matrix, and horizontal or annular array. It will be the configuration of the matrices combined with the type of layers used in the rolls that will contribute to the greater or lesser compression rate of the pellets. The most used pelletizers are those of horizontal axis, having therefore more manufacturers of this type than of pelletizers of flat matrix (Fig.5.11). The horizontal axis pelletizers always have a conditioner at their upper part, which guarantees the constant flow of material falling into the compression chamber (Fig.5.12).

The pellets produced are cut by a set of blades that will allow them to be less than a certain length, usually smaller than 35mm (Fig.5.13). The pellets after cutting fall into a conveyor system, which may be a redler or conveyor belt, which will lead them to the cooler.

The most common coolers are countercurrent, in which the pellets will enter from the top, in the opposite direction to a current of cold air, which contributes to their cooling. After the cooling system, there is very often a sieve, which can be circular or vibrating, which will clean the powder and the fine particles not pelletized, usually of a size of 5mm or less. An example of a countercurrent cooler equipped with a vibrating screen is shown in Fig.5.14.

After sieving, the pellets are ready to be stored and/or packaged, depending on their type and destination. In the case of pellets designated as industrial, with a diameter of 8mm, the most frequent is to be stored in silos or bulk containers, from which they are later shipped (Fig.5.15). In domestic pellets with a diameter of 6mm, the most frequent is to be bagged in 10 and 15kg packages (Fig.5.16), intended for trade and distribution by private customers, who consume them in boilers and domestic greenhouses, such as which are exemplified in Fig.5.17.

corn milling: wet vs. dry milling

Approximately 20% of the annual corn harvest is currently used by industrial corn processors to produce a variety of products such as sweeteners, starches, oils, ethanol and animal feeds. The great majority of the remainder is fed to livestock, poultry & fish. This versatile grain is comprised of four components that make manufacturing of a variety of products possible. Corns components are Starch (61%), Corn oil (4 %), Protein (8%) and Fiber (11%) approximately 16% of the corn kernels weight is moisture.

The Corn wet-milling process is designed to extract the highest use and value from each component of the corn kernel. The process begins with the corn kernels being soaked in large tanks called steep tanks in a dilute aqueous sulfur dioxide solution. The softened kernel is then processed to remove the germ which is further processed to remove the high-value corn oil. The Germ Meal remaining after the oil is extracted and marketed for animal feed use.

Following germ removal, the remaining kernel components are screened to remove the fiber. The fiber is combined with the evaporated, concentrated and dried steep liquor and other co-product streams to produce Corn Gluten Feed. The starch and gluten protein subsequently pass through the screens and the starch-gluten slurry is sent to centrifugal separators where the lighter gluten protein and the heavier starch are separated. The gluten protein is then concentrated and dried to produce Corn Gluten Meal, a 60% protein feed.

Some of the starch is then washed and dried or modified and dried. These starch products are marketed to the food, paper, and textile industries. The remaining starch can be processed into products such as sweeteners or ethanol. An average bushel of corn yields 31.5 lbs. of Starch, 12.5 lbs. of Gluten Feed, 2.5 lbs. of Gluten Meal and 1.6 lbs. of Corn Oil.

While the wet milling process is capital intensive with higher operating costs, the ability to produce a variety of products can be valuable in dealing with volatile markets. The wet milling process results in slightly lower ethanol yields than a traditional dry milling process since some of the fermentable starch exits the process attached to the saleable co-products.

The corn dry milling process is a less versatile, less capital intensive process that focuses primarily on the production of grain ethanol. In this process the corn kernels are hammer milled into a medium-to-fine grind meal for introduction to the ethanol production process. The products of a traditional dry grind ethanol facility are fuel ethanol and Dried Distillers Grains (DDG), a low-value animal feed product.

In recent years, dry fractionation processes have been introduced following the hammer milling operation in an effort to generate income from higher-value co-products. Various processing operations have been introduced to remove non-fermentable components of the corn kernel with varying degrees of success. These dry fractionation efforts always result in co-products with less purity than those produced by the corn wet milling process. Consequently the ethanol yield from a dry grind / dry fractionation process is negatively impacted as the result of fermentable starch exiting the process with the co-products.

AMG, Inc., partnering with Quality Technology International, Inc., have combined their fractionation technology efforts to form QTI-AMG, LLC, to develop the Short Path Frac Germ Wet Milling Process (patent pending). The SPFGWM process provides the capability to cost effectively separate and enhance the quality of dry fractionated germ increasing co-product value and returning previously lost fermentable starch to the ethanol process to enhance ethanol yield.

dry powdered medium milling equivalency study | cytiva

Cytiva currently has three manufacturing sites for cell culture medium production. These sites are located in Logan, Utah (USA), Pasching, Austria, and Tuas, Singapore. As part of a strategy to increase cell culture media production capacity, dry powder manufacturing was upgraded at the Pasching site. The Pasching site was upgraded to a pin mill similar to the Logan and Tuas sites. See Table 1 for pin mill manufacturers. This study was conducted to compare the pin mills and overall dry powdered medium (DPM) manufacturing processes between sites.

Pin mills are impact mills that rely on the force caused by the continuous impact between the medium and grinding components to reduce the particle size of the starting raw chemicals. During the manufacturing process, individual raw chemicals are weighed per the specified formulation, grouped, and pre-blended prior to the milling process. This step controls particle size reduction of the formulation components. When milling is complete, the micronized powder undergoes a final blend to ensure homogeneity.

To demonstrate milling equivalency between the Logan and Pasching processes, an in-depth study compared the critical quality attributes (CQA) of complex, chemically defined DPM formulations manufactured at current good manufacturing practices (cGMP) scale. This study was designed to assess the overall impact each manufacturing process has on DPM functionality. It focused on CQAs that are likely to be influenced by raw chemicals, process, and scale.

It was not feasible to test every DPM formulation produced at the sites. Instead, critical manufacturing traits and worst-case scenarios were considered. Criteria for selection included formulation manufacturability, chemical composition, chemical interactions, medium classification, manufacturing scale, and blending mechanics (Table 2).

Two basal CHO media and two fed-batch supplements were selected as representative formulations. These proprietary animal-derived component-free and chemically defined formulations are from our off-the-shelf media library.

Two approaches were taken. In the first approach, Medium 1 and both supplements were manufactured using the same raw material part numbers, but the chemicals were sourced locally. This approach represents a typical scenario encountered by bioprocess customers when ordering finished product from a specified manufacturing site. It reflects day-to-day operations.

In the second approach, Medium 2 manufactured at both sites shared the exact same raw material vendors and vendor lots. This allowed direct comparison of the pin mills and blenders used at the Logan and Pasching sites, eliminating potential influence by raw material variability.

Critical quality attributes were compared by examining the physical, chemical, and biological characteristics of DPM manufactured at the sites. The physical and chemical characteristics are influenced mostly by the milling and blending processes. The biological characteristics reflect the robustness of the entire manufacturing process.

Following existing manufacturing standard operating procedures (SOP) as a guide, representative samples from each batch were collected at the beginning, middle, and end of blender discharge. The batch sizes evaluated for each formulation are summarized in Table 3.

Table 4 provides an overview of the analytical testing performed on each batch of medium and supplement. All batches used in the study were manufactured according to site-specific procedures and met QC release criteria.

A comparison of physical characteristics was made between multiple batches of DPM manufactured at the Logan and Pasching sites to identify any differences in the appearance, particle size, flowability, or filterability of the micronized powder.

The physical characteristics of powdered media could potentially affect several unit steps throughout a cGMP commercial process. These steps include incoming raw material inspection and workability of the media powder during the hydration and sterile filtration processes. As such, it is important to understand any physical differences between DPM manufactured at the different sites.

An overview of selected analyses is provided here, as well as a summary of the results for all 4 formulations. Data for Medium 1 are shown here; see the tabs at the bottom of the page for data on the other 3 formulations.

Color comparison using spectrophotometry as well as visual inspection showed slight variations in color for some batches of the powder media. Slight variations were noted between Logan and Pasching batches when comparing each sample to a reference standard using a HunterLab spectrophotometer.

Variations in color are likely attributed to specific raw chemicals. Subsequent cell culture performance evaluations suggest that slight variation in color does not negatively affect biological performance of the media and supplements.

Moisture content generally has a direct impact on bulk density. However, it also provides an indication of environmental and process controls during the storage and manufacturing process. Bioburden data, used to determine microbial load of the finished product, can also be used as an indicator of the cleanliness of a manufacturing process (e.g., raw materials, equipment, environmental controls).

Particle size, bulk density, and flowability are important to the workability of the micronized powder. Because the particle size or shape of the pre-blended material cannot typically be modified, the milling process is critical in controlling particle size distribution (PSD). PSD, in turn, directly correlates to bulk density and flowability characteristics.

Data collected for each medium and feed formulation show slight variation between manufacturing sites for PSD and bulk density. However, as the chemical and biological data later confirm, this variability does not negatively affect cell culture performance and can likely be attributed to inherent differences between the specific pin mills used. PSD results for Medium 1 are displayed in Figure 3.

Fig 4. Medium 1. Throughput versus time for samples subjected to 0.2 m filtration. Filtration data represents 0.2 m glass fiber (GF) pre-filtration, and 0.2 m PVDF final filtration. Average of duplicate samples.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches. Analytical data were compared to determine the deviation between the Pasching and Logan manufacturing sites. Representative samples from each batch were hydrated according to current protocols and sampled in duplicate.

All batches of media and supplements manufactured at either site met the specified target (RSD 10%) for the selected amino acids. Analytical data clearly demonstrate chemical equivalence and blend homogeneity between manufacturing sites.

Lot-specific analytical data were also compared to the theoretical levels specified by each formulation to calculate percent recovery. This allows assessment of formulation accuracy and process robustness. To demonstrate a high level of confidence in the overall manufacturing process for each site, a recovery of 90%110% of theoretical values for amino acids was targeted.

Recovery of all amino acids was within 90%110% with little variability between manufacturing sites. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Medium 1 are displayed in Figure 6.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches, as was done for amino acids. Samples were assayed using HPLC. cGMP manufacturing batches were considered homogeneous and chemically equivalent if RSD values were within 15%.

All batches of media and supplements manufactured at either site met the specified target (RSD 15%) for the selected vitamins. Analytical data clearly demonstrates chemical equivalence and blend homogeneity between manufacturing sites.

A percent recovery of 85%115% of theoretical values for vitamins was targeted. The range was higher than for amino acids, because there is much more assay variability with this test. This level of variability could be attributed to the relatively low concentrations often approaching detectability limits. The closer the value to detectability, the more variable the results.

Recovery of all vitamins was within the target range. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Medium 1 are shown in Figure 8.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches, as was done for amino acids and vitamins. Samples were assayed using ICP-MS. cGMP manufacturing batches were considered homogeneous and chemically equivalent if RSD values were within 15%.

All batches of media and supplements manufactured at either site met the specified target (RSD 15%) for the selected vitamins. Analytical data clearly demonstrates chemical equivalence and blend homogeneity between manufacturing sites.

A recovery of 85%115% of theoretical values for metals was targeted. The range was higher than for amino acids, because there is much more assay variability with this test. This level of variability could be attributed to the relatively low concentrations often approaching detectability limits. The closer the value to detectability, the more variable the results.

Recovery of all metals was within the target range. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Medium 1 are shown in Figure 10.

Ultimately, the purpose of cell culture media and feeds is to provide a suitable environment for optimal cell growth and production of a target molecule. When determining product equivalence, cell culture performance should be considered the most critical criterion to assess whether differences in manufacturing sites or processes have a substantial impact.

Medium 1 and both supplements were evaluated in a fed-batch process. To assess the comparability of the medium and feed batches, samples were evaluated in triplicate 125 mL shaker flasks. The study matrix varied only one condition, while the other two conditions used a previously QC released lot. Additionally, two controls were used to confirm validity of the growth assay.

All growth curves are given as a measure of viable cell densities. Growth curves for Medium 1 (Fig 11) and both supplements displayed similar trends over a 11-day period, with DG44 growth peaking at approximately day 6 and comparable cell viabilities.

Slight variation was noted for some test conditions but was within the expected variation of 20%25% for the shaker flask assay used. Total IgG expression for each condition over the course of days 411 in fed batch are displayed in Figure 12.

Protein quality and charge variants were assessed by analyzing the samples for aggregates, monomers, and fragments using UPLC equipped with a UV detector in a size exclusion column. Results for Medium 1 are shown in Figure 13.

In this in-depth equivalency study, an assessment of the physical, chemical, and biological characteristics of representative complex media and feeds was made. Based on the findings, cGMP scale batches of complex media and feeds, representing a wide range of batch sizes, can be produced at the Logan and Pasching manufacturing sites with equivalent results. Although data are not shown here for the Tuas site, results are expected to be similar to those for the Logan site since both sites use the same milling equipment.

Assessment of physical characteristics showed inherent variation for color, particle size distribution, and bulk density. Considering all 4 formulations, mean particle sizes for Logan and Pasching batches were 69.2 m and 50.4 m, respectively. Although there is some inherent variation in the physical characteristics between powdered media manufactured at each site, this variation is likely attributed to differences in site-specific pin mill manufacturers. It is important to note that cell culture performance is not negatively affected.

Chemical analysis of complex CHO media and feed supplements demonstrates equivalence and scalability between both sites. Specifically, amino acids for all batches were within 10% RSD and vitamins and elemental metals were within 15% RSD.

We are a leading manufacturer of dry powdered medium (DPM) formulations used throughout the bioprocessing industry for a wide range of cell culture applications. With global manufacturing capabilities in three major regions of the worldUSA, Austria, and Singaporewe offer the flexibility and assurance of supply to meet customer demands. DPM formulations are manufactured in accordance with cGMP guidelines and follow ISO 9001:2000 certified processes. Each site has been designed with strict environmental controls, dedicated animal-derived component-free manufacturing areas, and robust processes to ensure that product consistency, scalability, and reproducibility are achieved.

Our vision for cell culture media manufacturing is to globally harmonize manufacturing processes at all sites. We have invested $25 million in capacity, quality, and capability improvements, plus an additional $10 million to upgrade the Pasching site, to address the following categories:

A comparison of physical characteristics was made between the batches of Supplement 1 manufactured at the Logan and Pasching sites to identify any differences in the appearance, particle size, flowability, or filterability of the micronized powder.

Variations in color are likely attributed to specific raw chemicals. Subsequent cell culture performance evaluations suggest that slight variation in color does not negatively affect biological performance.

Data collected for each Supplement 1 batch shows slight variation between manufacturing sites for PSD and bulk density. However, as the chemical and biological data later confirm, this variability does not negatively affect cell culture performance and can likely be attributed to inherent differences between the specific pin mills used. PSD results for Supplement 1 are displayed in Figure 16.

Fig 17. Supplement 1. Throughput versus time for samples subjected to 0.2 m filtration. Filtration data represents 0.2 m glass fiber (GF) pre-filtration, and 0.2 m PVDF final filtration. Average of duplicate samples.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches. Analytical data were compared to determine the deviation between the Pasching and Logan manufacturing sites. Representative samples from each batch were hydrated according to current protocols and sampled in duplicate.

Batches of Supplement 1 manufactured at either site met the specified target (RSD 10%) for the selected amino acids. Analytical data clearly demonstrate chemical equivalence and blend homogeneity between manufacturing sites.

Lot-specific analytical data were also compared to the theoretical levels specified by eachformulation to calculate percent recovery. To demonstrate a high level of confidence in the overall manufacturing process for each site, a recovery of 90%110% of theoretical values for amino acids was targeted.

Recovery of all amino acids was within 90%110% with little variability between manufacturing sites. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Supplement 1 are displayed in Figure 19.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches, as was done for amino acids. Samples were assayed using HPLC. cGMP manufacturing batches were considered homogeneous and chemically equivalent if RSD values were within 15%.

The Supplement 1 batches manufactured at either site met the specified target (RSD 15%) for the selected vitamins. Analytical data clearly demonstrates chemical equivalence and blend homogeneity between manufacturing sites.

Recovery of all vitamins was within the target range. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Supplement 1 are shown in Figure 21.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches, as was done for amino acids and vitamins. Samples were assayed using ICP-MS. cGMP manufacturing batches were considered homogeneous and chemically equivalent if RSD values were within 15%.

All Supplement 1 batches manufactured at either site met the specified target (RSD 15%) for the selected vitamins. Analytical data clearly demonstrates chemical equivalence and blend homogeneity between manufacturing sites.

Recovery of all metals was within the target range. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Supplement 1 are shown in Figure 23.

Supplement 1 was evaluated in a fed-batch process. To assess the comparability of the feed batches, samples were evaluated in triplicate 125 mL shaker flasks. The study matrix varied only one condition, while the other two conditions used a previously QC released lot. Additionally, two controls were used to confirm validity of the growth assay.

All growth curves are given as a measure of viable cell densities. Growth curves for Supplement 1 (Fig 24) displayed similar trends over a 11-day period, with DG44 growth peaking at approximately day 6 and comparable cell viabilities.

Slight variation was noted for some test conditions but was within the expected variation of 20%25% for the shaker flask assay used. Total IgG expression for each condition over the course of days 411 in fed batch are displayed in Figure 25.

Protein quality and charge variants were assessed by analyzing the samples for aggregates, monomers, and fragments using UPLC equipped with a UV detector in a size exclusion column. Results for Supplement 1 are shown in Figure 26.

A comparison of physical characteristics was made between the batches of Supplement 2 manufactured at the Logan and Pasching sites to identify any differences in the appearance, particle size, flowability, or filterability of the micronized powder.

Variations in color are likely attributed to specific raw chemicals. Subsequent cell culture performance evaluations suggest that slight variation in color does not negatively affect biological performance.

Data collected for each Supplement 2 batch shows slight variation between manufacturing sites for PSD and bulk density. However, as the chemical and biological data later confirm, this variability does not negatively affect cell culture performance and can likely be attributed to inherent differences between the specific pin mills used. PSD results for Supplement 2 are displayed in Figure 29.

Fig 30. Supplement 2. Throughput versus time for samples subjected to 0.2 m filtration. Filtration data represents 0.2 m glass fiber (GF) pre-filtration, and 0.2 m PVDF final filtration. Average of duplicate samples.

Supplement 2 has three analytes. To protect the proprietary formulation, results for those analytes are provided without revealing their name or identifying attribute. Intra- and inter-batch homogeneity and recovery are presented in Figures 31 and 32, respectively.

Supplement 2 was evaluated in a fed-batch process. To assess the comparability of the feed batches, samples were evaluated in triplicate 125 mL shaker flasks. The study matrix varied only one condition, while the other two conditions used a previously QC released lot. Additionally, two controls were used to confirm validity of the growth assay.

All growth curves are given as a measure of viable cell densities. Growth curves for Supplement 2 (Fig 33) displayed similar trends over a 11-day period, with DG44 growth peaking at approximately day 6 and comparable cell viabilities.

Slight variation was noted for some test conditions but was within the expected variation of 20%25% for the shaker flask assay used. Total IgG expression for each condition over the course of days 411 in fed batch are displayed in Figure 34.

Protein quality and charge variants were assessed by analyzing the samples for aggregates, monomers, and fragments using UPLC equipped with a UV detector in a size exclusion column. Results for Supplement 2 are shown in Figure 35.

The experimental design was conducted according to the details provided in the article. Medium 2 manufactured at both sites shared the exact same raw material vendors and vendor lots. Batch sizes are listed in Table 8.

A comparison of physical characteristics was made between the batches of Medium 2 manufactured at the Logan and Pasching sites to identify any differences in the appearance, particle size, flowability, or filterability of the micronized powder.

Variations in color are likely attributed to specific raw chemicals. Subsequent cell culture performance evaluations suggest that slight variation in color does not negatively affect biological performance.

Data collected for each Medium 2 batch shows slight variation between manufacturing sites for PSD and bulk density. However, as the chemical and biological data later confirm, this variability does not negatively affect cell culture performance and can likely be attributed to inherent differences between the specific pin mills used. PSD results for Medium 2 are displayed in Figure 38.

Fig 39. Medium 2. Throughput versus time for samples subjected to 0.2 m filtration. Filtration data represents 0.2 m glass fiber (GF) pre-filtration, and 0.2 m PVDF final filtration. Average of duplicate samples.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across two batches. Analytical data were compared to determine the deviation between the Pasching and Logan manufacturing sites. Representative samples from each batch were hydrated according to current protocols and sampled in duplicate.

Batches of Medium 2 manufactured at either site met the specified target (RSD 10%) for the selected amino acids. Analytical data clearly demonstrate chemical equivalence and blend homogeneity between manufacturing sites.

Lot-specific analytical data were also compared to the theoretical levels specified by each formulation to calculate percent recovery. To demonstrate a high level of confidence in the overall manufacturing process for each site, a recovery of 90%110% of theoretical values for amino acids was targeted.

Recovery of all amino acids was within 90%110% with little variability between manufacturing sites. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Medium 2 are displayed in Figure 41.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across two batches, as was done for amino acids. Samples were assayed using HPLC. cGMP manufacturing batches were considered homogeneous and chemically equivalent if RSD values were within 15%.

The Medium 2 batches manufactured at either site met the specified target (RSD 15%) for the selected vitamins. Analytical data clearly demonstrates chemical equivalence and blend homogeneity between manufacturing sites.

Recovery of all vitamins was within the target range. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Medium 2 are shown in Figure 43.

Intra- and inter-batch homogeneity were determined by comparing relative standard deviation (RSD) results within and across multiple batches, as was done for amino acids and vitamins. Samples were assayed using ICP-MS. cGMP manufacturing batches were considered homogeneous and chemically equivalent if RSD values were within 15%.

Both Medium 2 batches manufactured at either site met the specified target (RSD 15%) for the selected vitamins. Analytical data clearly demonstrates chemical equivalence and blend homogeneity between manufacturing sites.

Recovery of all metals was within the target range. As with the product homogeneity results, formulation accuracy data demonstrates chemical equivalence between the Logan and Pasching sites. Results for Medium 2 are shown in Figure 45.

Medium 2 was evaluated in a straight batch process. To assess the comparability of the medium batches, samples were evaluated in triplicate 125 mL shaker flasks. The study matrix varied only one condition, while the other two conditions used a previously QC released lot. Additionally, two controls were used to confirm validity of the growth assay.

Batch growth data for Medium 2 was obtained. All growth curves are given as a measure of viable cell densities and displayed similar trends over a 7-day period, with DG44 growth peaking at approximately day 4, as shown in Figure 46. Slight variation was noted for some test conditions but was within the expected variation of 20%-25% for the shaker flask assay used.

Protein quality and charge variants were assessed by analyzing the samples for aggregates, monomers, and fragments using UPLC equipped with a UV detector in a size exclusion column. Aggregate results for Medium 2 are shown in Figure 48.

corn dry milling: processes, products, and applications - sciencedirect

History of original development, main advances, and a brief preview of expected future for corn dry-milling are presented. This industry has changed significantly from a booming state to a stagnant and now evolving into a new more dynamic food application technology. The processing equipment has not changed dramatically with the original processing principles still effectively practiced. Efficiencies have been adapted to new corn hybrids and improved to meet industrial conversion costs. The newly available analytical tools have allowed more targeted corn ingredients that perform appropriately through new processing technologies and food forms. Collaborations across the whole supply chain is becoming more prevalent and needed. Corn ingredients for new food applications are the topic of modern innovation strategies with its limits only established by human creativity, modern health, nutrition and regulatory, and equipment design and control capabilities.

drying and milling - fruitsmart

Thedryingprocess is a balance oftime,temperature, humidity, air flow,andbed depth through a continuous conveyor tunnel dryer.Itis divided into three zones,each with its own controls for regulating temperature and air velocity. The process can produce wholedrypieces and can dry pomaceleftoverfrom juicing.Air dryingisa validatedprocess that gives you afinal productwithwater activity belowthethreshold for microbial growth.After the fruitorvegetable is dried, it is milled to various particle sizes based on productspecification. Utilizing air classification milling, the process can achieve particle sizesas fine as100 mesh.This capability creates powders that work well in a variety of foodsand other applications.