Batch size commercial

The dissolution of soluble sihcates is of considerable commercial importance. Its rate depends on the glass ratio, sohds concentration, temperature, pressure, and glass particle size. Commercially, glasses are dissolved in either batch atmospheric or pressure dissolvers or continuous atmospheric processes. Dissolution of sodium sihcate glass proceeds through a two-step mechanism that involves ion exchange (qv) and network breakdown (18). 

The 1990s reduction process was based on work started in the early 1930s. A magnesium vacuum reduction process was developed for reduction of titanium tetrachloride to metal. Based on this process, the U.S. Bureau of Mines (BOM) initiated a program in 1940 to develop commercial production. Some years later, the BOM pubHcized its work on titanium and made samples available to the industrial community. By 1948, the BOM produced batch sizes of 104 kg. In the same year, Du Pont aimounced commercial availabiHty of titanium, thus beginning the modem titanium metals industry (1). 

Figure 5.19 displays a typical course of discontinuous SSP on the commercial scale (batch size, 221) with respect to the variables of temperature, time, vacuum and intrinsic viscosity. This figure shows the IV plotted as a function... 

Changes in Batch Size Postapproval changes in the size of a batch from the pilot scale used to manufacture product for clinical trials to larger or smaller commercial batch sizes require submission of additional information in the apphcation. Scale-down below 100,000 dosage units is not covered by this guidance. All scale-up changes should be properly validated and, where needed, inspected by appropriate FDA personnel. 

We have now embarked on a program to realize this potential. The U. S. Rubber Co. and Martin-Marietta Corp. have created a new, jointly-owned subsidiary—Isochem, Inc. This new company will build a fission product conversion and encapsulation plant at the Hanford, Wash., reservation to produce fully encapsulated fission products for commercial use (5). The plant is designed with four separate production lines, each for a different fission product. The capacity of each line varies with the process involved and the batch sizes and processing time. The capacity of the single line normally used for cesium-137 has been set at 29 million curies per year to meet the projected market demands of the early 1970,s (1). At these production quantities, cesium-137 should be available at less than ten cents per curie for large irradiators. 

This approach would seem to be an example of concurrent PV [14], which fits well when the development function continues its effort to validate clinical manufacturing processes. It is also an opportunity to validate a process when it is used to produce different batch sizes with a given piece of equipment. It may even be possible to employ differently sized equipment (to make different batch sizes) as part of the validation effort. It remains to be determined whether this kind of approach ought to be extended to the commercial validation effort. Later in this chapter I will discuss the possibility, which should be attractive for the company that is totally involved in TQM. 

Describe the differences in equipment size, type, and operating parameters between the critical development batches and commercial batches. 

Blending of small batches, up to about 4.5 kg (10 lb) is most frequently done in wide-mouth jars, placed on horizontal rollers, tumbling at approximately 15 rpm for about 20 min. Larger, commercial batches, sizes typically 10 to 136 kg (22 to 300 lb) are often prepared in twin-shell blenders (Figure 4.10) by tumbling 15 min at 24 rpm. The blend is screened again, transferred into a storage vessel, and allowed to age for at least 12 hours.8... 

Following successful phase II clinical trials, the manufacture of the dmg substance is scaled up to meet commercialization needs. In addition, the prototype formulation and process is optimized and scaled up to greater than one-tenth of the commercial batch size. 

Regarding batch size and scale-up, a minimum batch size of 10% of the proposed commercial production batch should be used for producing test batches of solid, oral dosage nonantibiotic products. All scale-up procedures should be validated. It is important to keep in mind that the scale-up process should not result in a change in the method of manufacture. 

For scaling up LMOX freeze-drying production, we started with examining the maximum and minimum rate of heat supply to vials from a shelf in experimental and commercial size dryers having a batch size of 2000 and 60,000 vials, respectively. As we had known from our experience that the vial in the center tray received the minimum heating and the vial in the front tray, which was bathed in... 

Figure 21 Scale-up/down study in primary drying process of frozen LMOX solution (22%) regarding thermal deviations. Two types of freeze-dryers were used (—) 2000 vials/batch of experimental size (---) 60,000 vials/batch of commercial size (1) standard program to estimate a thermal deviation (2) optimized program as a result of scale-up/down studies.

Clinical supply manufacturing operations are those areas involved in the manufacture of Phase I-IV clinical trial materials, and may include laboratory (or table-top) scale activities, operations performed in a pilot plant (with batch sizes generally larger than lab scale, but smaller than commercial scale), clinical supplies produced in facilities manufacturing commercially approved products, as well as clinical supplies produced at contract manufacturing sitesJ ... 

The vessel used for the compounding may be different during development simply because of batch size. Compatibility with these different materials is important to consider in preparation for scale-up. Bench-scale studies and small clinical batches may be compounded in glass Erlenmeyer flasks or glass carboys. Commercial-scale manufacturing would typically use larger stainless steel tanks. Compatibility with the different materials that the product comes into contact... 

Internal mixers must be ran in a full or nearly full condition, so a batch recipe is calculated to provide an appropriate volume. If not filled, the ingredients will not be properly sheared and heat transfer will be compromised. Typical commercial mixers have a batch size of at least 100 pounds of compound. A mixer of this size will have a drive motor of no less than 75 horsepower. Proper dispersive mixing is a balance between proper shear, sequence of addition of ingredients, and thermal stability. Mixers have extensive monitoring instrumentation that provides continuous feedback about thermal conditions, rotor torque, and rotor speed. Once a mixing process has been developed, a standard protocol is followed for preparation of the compound. 

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