Scale-up Production

Depending upon why a company chose to let a toll, the ability to scale up production may be an important factor. If a toll project was designed to meet a specific, short-term need for a known quantity of material, scale-up capability may not be an issue. However if the goal was to develop a wider market and eventually increase production, a small toller that meets all other criteria for selection could be excluded based upon this factor. Planning for success is essential. 

Synthesis and scale-up production of active pharmaceutical ingredient (API)... 

Despite the frequent use of arc-discharge and laser ablation techniques, both of these two methods suffer from some drawbacks. The first is that both methods involve evaporating the carbon source, which makes it difficult to scale up production to the industrial level using these approaches. Second, vaporization methods grow CNTs in highly tangled forms, mixed with unwanted forms of carbon and/or metal species. The CNTs thus produced are difficult to purify, manipulate, and assemble for building nanotube-device architectures in practical applications. 

Overall, the microreactor provides greater safety for individuals and equipment and reduces the likelihood of loss of process and the consequent disruption and even loss of sales that can follow. In common with other fine chemical manufacturers, most pharmaceutical companies have programs to capture the benefits of flow microreactors as adjuncts to or even replacements for their current batch methods for scaling up production of candidate molecules to satisfy clinical and manufacturing needs. This paper attempts to demonstrate that microreactors can be deployed more widely in pharmaceutical R D than as a tool for enhanced production and that they have the potential to underpin significant paradigm shifts in both early- and late-phase R D. 

Two commercial coal-tar-pitch-based carbon fibres, which were supplied by Osaka Gas Co., Ltd. (Osaka, Japan), have been used as starting materials. In the course of their synthesis, these CFs had been carbonised at different temperatures Tc = 1273 K (Donacarbo S-241) and Tc = 973 K (Donacarbo SL-242). The carbon fibres have been chemically activated with KOH and NaOH (Panreac Chemicals, Barcelona, Spain) at 1023 K under a N2 gas flow. More details concerning the activation conditions can be found elsewhere. Two different kinds of furnaces have been used for the activations. For laboratory synthesis a horizontal tube furnace is used which is capable of activating about 2 g of raw fibres per activation process. For the scale-up production approach an industrial chamber furnace is used. Thereby the amount of initial material could be increased by more than one order of magnitude up to 30 g per activation process. 

A series of carboxyl containing bioerodible polymeric materials, characterized by modulated functionality and hydrophobic/hydrophilic balance, was prepared both on a lab-scale and in the pilot plant. Procedures were setup as amenable for scaled-up productions. Those materials displayed a high versatility to combine with proteins in different proportion and to provide hybrid bioerodible matrices without any adverse effect on protein structure and activity. 

The prepared nanoparticles can be stored in lyophilized form and resuspended in physiological solutions prior to administration. The procedure developed on the laboratory scale has been found amenable to scale-up productions. 

Now the appropriate shaft speed for scaled-up production equipment can be calculated. The tank used for production batches has a capacity of 3780 L. It is equipped with a turbine-type agitator that has a shaft speed range of 20 58 rpm. The diameter of this tank is 167 cm. The diameter of the largest axial impeller is 87 cm. Given the diameter of the production tank, the cross-sectional area can be determined as... 

Preliminary testing has shown these blocks to have strength and durability properties equal to or better than portland cement block standards. The viability of the process has been demonstrated on a small scale and mix designs and process conditions have been optimized. Ongoing work will involve scaled-up production along with extensive product testing. 

Obviously, each material in a formulation can be characterized in this way by use of instrumented press studies and Ileckel plot analysis in research and development. This approach can be of use to formulators in selecting specific excipients for specific drug entities. However, the characterization and performance of the final formulation are the critical measurements in the scale-up/production compaction operation. 

Scale-up product Initial trial for scale-up utilized a batch size of 570 kg, a Hoflinger Karg GFK-1500 capsule-filling machine (H K), and a V-blender, with the mixing time set to 15 minutes. Capsules resulting from this batch did not conform to the dissolution specification (only about 40% dissolved in 45 minutes). To rule out overblending with magnesium stearate, a blend time of 5 minutes in the V-blender was uti-... 

In order to assess the state of SPC, a sufficient number of pilot- or commercial-scale batches should be manufactured (at least 10% of anticipated commercial scale) using the same process anticipated for the scaled-up product. When the formulation is finalized, the critical in-process and final product control specifications will be challenged through process validation studies on at least three full- or pilot-scale batches. 

Once chemists have developed a product in a laboratory, it is up to chemical engineers to design a process to make the product in commercial quantities as efficiently as possible. "Scaling up" production is not just a matter of using larger beakers. Chemical engineers break down the chemical process into a series of smaller "unit operations" or processes and techniques. 

Biobatch and scale-up production lots that differ in formulation and manufacturing procedure... 

Operator Radiation Protection Even for the largest commercial manufacturer of radiopharmaceuticals, the batch volumes are small compared to nonradioactive pharmaceuticals. So even a scaled-up production batch can be contained within a limited space. When scaling up a radiopharmaceutical production, one always has to assure that the radiation outside the contained work unit is acceptable for the operator. 

Principal product specifications are microbial limits and testing methods, particle size, viscosity, pH, and dissolution of components. Process validation requires control of critical parameters observed during compounding and scale-up. Product stability examination is based on chemical degradation of the active components and interac-... 

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