Downstream processing considerations

Once a suitable amorphous system has been produced, the downstream processing considerations will need to be addressed. Based on the nanoparticles work that has been conducted in this fleld, it is apparent that the amorphous product produced by the SCF will generally be of low density and high porosity and further densiflcation will be required to make flnal dosage form. 

The level of technical service support provided for a given product generally tracks in large part where the suppHer considers thek product to be located within the spectmm of commodity to specialty chemicals. Technical service support levels for pure chemicals usually provided in large quantities for specific synthetic or processing needs, eg, ammonia (qv), sulfuric acid (see SuLFURic ACID AND SULFURTRIOXIDe), formaldehyde (qv), oxygen (qv), and so forth, are considerably less than for more complex materials or blends of materials provided for multistep downstream processes. Examples of the latter are many polymers, colorants, flocculants, impact modifiers, associative thickeners, etc. For the former materials, providing specifications of purity and physical properties often comprises the full extent of technical service requked or expected by customers. These materials are termed undifferentiated chemicals (9),... 

Traditionally, the upstream fermentation and cell culture processes have been viewed as being distinct from the subsequent downstream processing and purification steps, and the two different sets of processes nave been optimized individually. In some instances, careful consideration of the conditions used in the fermentation process, or manipulation of the genetic makeup of the host, can simplify and even... 

The first consideration in any design and optimization problem is to decide the boundaries of the system. A reactor can rarely be optimized without considering the upstream and downstream processes connected to it. Chapter 6 attempts to integrate the reactor design concepts of Chapters 1-5 with process economics. The goal is an optimized process design that includes the costs of product recovery, in-process recycling, and by-product disposition. The reactions are... 

When sufficiently high levels of expression and protein accumulation are achieved, efficient downstream processing protocols must be developed to insure product quality and the economic feasibility of production. As the demand for safe, recombinant pharmaceutical proteins continues to expand, the market potential of plant-produced recombinant proteins is considerable. Molecular farming can produce recombinant proteins at a lower cost than traditional expression systems based on microbial or animal cell culture, and without the risk of contamination with human pathogens. 

So all of these considerations suggest small liquid holdups. However, from a dynamics and control point of view we want enough holdup to be able to ride through disturbances without losing the base level and having to shut down the column, and to be able to change flow rates and compositions slowly to downstream processes. 

Often an improvement in one section of a line or plant will cause the rate-limiting section to shift to either an upstream or downstream process. These types of projects often have considerable value associated with them because of the multiple bottlenecks that exist. 

In addition to characterizing the many properties introduced by the choice of monomers and the polymerization process itself, considerable further characterization is required to quantitatively describe the properties imparted by spinning and subsequent downstream processing. These important properties relate to the crystalline order and microsiruciure of the fibers, and die resultant performance characteristics, such as crimp retention, abrasion resistance, mechanical properties, etc. 

Downstream processing involves employment of a purifying system that can isolate the product in as few steps as possible using the simplest purification technology that will achieve the required purity. While purity is a critical consideration for both small-molecule pharmaceuticals and biopharmaceuticals, the nature of biopharmaceutical administration (typically via injection) and the nature of biotechnology processes require that additional considerations be paid to the purity of biopharmaceuticals. The final product must meet regulatory purity and sterility standards and must be below the maximally acceptable cellular or microbial contamination (Ho and Gibaldi, 2003). 

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