Bulk container

Drug substances are generally solids, but some are liquids or gases. The container closure system for storage or shipment of a bulk solid drug substance is typically a drum with double LDPE liners that are usually heat sealed or closed with a twist tie. A desiccant may be placed between the bags. 

The drum provides protection from light and mechanical strength to protect the liner during shipment and handling. The majority of the protection from air and moisture is provided by the liner. Because LDPE is not a particularly good moisture barrier, a drug substance that is moisture sensitive may need additional protection. An alternative to a LDPE bag is a heat-sealable laminate bag with a comparatively low rate of water vapor transmission. 

The application (or Type II DMF) should include a detailed description of the complete container closure system for the bulk drug substance as well as a description of the specific container, closure, all liners, inner seal, and desiccant (if any), and a description of the composition of each component. A reference to the appropriate indirect food additive regulation is typically considered sufficient to establish the safety of the materials of construction. The tests, methods, and criteria for the acceptance and release of each packaging component should be provided. Stability studies to establish a retest period for bulk drug substance in the proposed container closure system should be conducted with fillers or desiccant packs in place (if used). Smaller versions that simulate the actual container closure system may be used. 

A container closure system for the transportation of bulk drug products to contract packagers should be described in the application. The container closure system should be adequate to protect the dosage form, be constructed with materials that are compatible with product being stored, and be safe for the intended use. The protective properties of the shipping container are verified by the practice of including annual batches of the packaged product in postapproval stability studies. 

Compressed Medical Gases Guideline (February 1989) FDA Guideline for Drug Master Files (September 1989) 

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Containers less than bulk must bear the red diamond-shaped "FLAMMABLE LIQUID" label. Bulk containers must display the red "FLAMMABLE" placard in association with the UN1090 identification. Fire is the main ha2ard in emergencies resulting from spills. Some manufacturers provide transportation emergency response information. A listing of properties and ha2ard response information for acetone is pubHshed by the U.S. 

Large quantities of evaporated milk are used to manufacture ice cream, bakery products, and confectionery products (see Bakery processes and LEAVENING agents). When used for manufacturing other foods, evaporated milk is not sterilized, but placed in bulk containers, refrigerated, and used fresh. This product is caHed condensed milk. Skimmed milk may be used as a feedstock to produce evaporated skimmed milk. The moisture content of other Hquid milk products can be reduced by evaporation to produce condensed whey, condensed buttermilk, and concentrated sour milk. 

Semibulk Containers. Use of semibulk containers falls between bulk handling, eg, accompHshed by tank cars and hopper cars, and individual package handling, which is often performed manually. Semibulk containers are also known as intermediate bulk containers (IBCs), the provisions and requirements for the constmction and testing of which can be found in the U.N. recommendations (4). 

Shipment Methods and Packaging. Pyridine (1) and pyridine compounds can be shipped in bulk containers such as tank cars, rail cars, and super-sacks, or in smaller containers like fiber or steel dmms. The appropriate U.S. Department of Transportation (DOT) requirements for labeling are given in Table 4. Certain temperature-sensitive pyridines, such as 2-vinylpyridine (23) and 4-vinylpyridine are shipped cold (<—10°C) to inhibit polymerisation. Piperidine (18) and certain piperidine salts are regulated within the United States by the Dmg Enforcement Agency (DEA) (77). Pyridines subject to facile oxidation, like those containing aldehyde and carbinol functionaUty, can be shipped under an inert atmosphere. 

Generally, Httle is known in advance concerning the degree of homogeneity of most sampled systems. Uniformity, rarely constant throughout bulk systems, is often nonrandom. During the production of thousands of tons of material, size and shape distribution, surface and bulk composition, density, moisture, etc, can vary. Thus, in any bulk container, the product may be stratified into zones of variable properties. In gas and Hquid systems, particulates segregate and concentrate in specific locations in the container as the result of sedimentation (qv) or flotation (qv) processes. 

Chloroformates are shipped in nonretumable 208-L (55-gal) polyethylene dmms with carbon steel overpacks or high density polyethylene dmms. Eor bulk shipments, insulated stainless-steel tank containers and tmcks provide secure protection. Tank tmck and rail car quantities are shipped using equipment dedicated for these types of products. Materials such as isopropyl chloroformate, benzyl chloroformate, and j -butyl chloroformate that require refrigeration are precooled when shipped in bulk containers. Bulk shipments that are precooled must proceed to the destination without layover. Dmm shipments of IPCE, BCE, and SBCE must be shipped in refrigerated containers. Many of the chloroformates are only shipped in tmck load shipments. The U.S. Department of Transportation (DOT) Hazardous Materials Regulations control the shipments of chloroformates, as described in Table 3. 

When the bulk containing the binder is uniform, it is compressed on pneumatic, hydraulic, or ram-type presses. Compression can be carried out in presses provided with suitably designed cavities or in metallic pans. The pans ate filled with the powder mass, and a plunger with a cross-sectional shape similar to that of the pan is used to compress the tablet. The resulting tablets ate commonly used with powder puffs or cosmetic bmshes. 

Vacuum systems are typically used when flows do not exceed 6800 kg/h (15,000 Ib/h), the equivalent conveyor length is less than 305 m (1000 ft), and several points are to be supplied from one source. They are widely used for finely divided materi s. Of special interest are vacuum systems designed for flows under 7.6 kg/min (1000 Ib/h), used to transfer materials short distances from storage bins or bulk containers to process units. This type of conveyor is widely used in plastics and other processing operations where the variety of conditions requires flexibility in choosing pickup devices, power sources, and receivers. Capital investment can be kept low, often in the range of 2000 to 7000. 

Containers for solids include bags, bulk boxes, cartons, and drums. While the intermediate flexible bulk container (IBC) has become an important package of world commerce, the most used package remains the multiwaU paper bag, supplemented by bags of similar design made of plastic film or plastic woven mesh. 

TABLE 21-25 Flexible-Type Intermediate Bulk Containers Dimension and Capacity Data (Variable Data) ... 

Bulk Containers These containers may be either open or closed. Generally, it is the effect of the weather on the product that governs the choice. High-value materials, such as certain ores, may be pped in open containers, while relatively low-cost items, such as portland cement, require closed containers. Further influencing the choice of bulk containers is whether dehveries are made by truck, railroad, or water. 

The most important bulk containers are railroad hopper cars, highway hopper trucks, portable bulk bins, van-type (ship) containers, barges, and ships. Factors determining the suit ihty of any of these containers (after establishing whether open or closed containers are to be used) depend on product physical properties, the most important of which are ease of flow, corrosiveness, and sensitivity to contamination. 

Brush discharges from flexible, intermediate, bulk containers (FIBGs), plastic bags, stretch wrap, or other plastic film... 

Static charge generation due to too rapid transfer out of drum or flexible intermediate bulk container (super sack). 

Use closed equipment wherever possible (hoppers and intermediate bulk containers (IBCs)). 

Fig. 5-17. Principle of micellar-enhanced ultrafiltration (MEUF). The d-enantiomer of a racemic mixture is preferentially bound to the micelles, which are retained by the membrane. The bulk containing the 1-enantiomer is separated through the membrane [72].

Figure 4.28. STM image of a PtRh(lOO) surface. Although the bulk contains equal amounts of each element, the surface consists of 69% of platinum (dark) and 31 % of rhodium (bright), in agreement with the expected surface segregation of platinum on clean Pt-Rh alloys in ultrahigh vacuum. The black spots are due to carbon impurities. It is seen that platinum and rhodium have a tendency to cluster in small groups of the same elements.

Liquids are most economically stored in bulk containers. When large quantities above 25,000 gal must be stored, the tanks should be constructed to the dimensions given by the American Petroleum Institute Standards (see Table 5-2). These tanks must be field-erected. For smaller quantities more economical shop-constructed tanks should be specified. Field fabrication is always more expensive than shop fabrication. A shop-constructed item, in general, must be less than 11.5 ft (3.5 m) in diameter, so that it can be shipped by truck or train. For any piece of equipment that must be shop-fabricated, or for which the cost of field construction is prohibitive, this limitation should be noted. When barges may be used for transportation, this limitation does not hold. 

To size the amount of space needed for a warehouse, it must be determined how much is to be stored in what size containers. The container sizes that will be used are obtained from the scope. Liquids are generally stored in bulk containers. No more than a week s supply of liquid stored in drums should be planned. Solids, on the other hand, are frequently stored in smaller containers or in a pile on the ground. 

Land Particulate Bulk Contained Contained Absorbed Adsorbed Contained ... 

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