We at Thar Process have a specialized team of professionals who design and fabricate turn-key bio-pharmaceuticals plants for a wide variety of applications, including peptides and insulin. These facilities meet the high regulatory standards of Good Manufacturing Practices (GMP). Our capabilities include the design and fabrication of large-scale chromatography equipment. Thar Process specializes in high-pressure applications in the range of 3 to 600 bar. This includes plant-scale High-Pressure Liquid Chromatography (HPLC) systems and Dynamic Axial Compression (DAC) columns for both low pressure and high-pressure chromatography.
Process Scale Chromatography
We design and customize the HPLC systems in accordance with the process requirements of a given application. The standard gradient system consists of two high pressure pumps to move the mobile phase or sample onto the column. Dynamic mixing ensures uniformity of the mobile phase. A set of inline filters prevents clogging of the column frit. The flow through the filter set is controlled by software that monitors differential pressure. A bypass line is included in case both filters choke. Following filtration is a set of valves for up-flow and down-flow, as well as bypass on the column, all controlled and programmable by the software. A specialized small-volume sample injection valve assembly, with minimum dead volume, is especially useful for system calibration. HPLC systems are controlled by the finest chromatographic Programmable Logic Control (PLC) software, which incorporates maximum features regarding purification. The software can be further customized according to customer requirements. The software complies 21 CFR, Part 11, of the U.S. Code of Federal Regulations.
Process and Instrumentation Diagram of a Thar HPLC system
Plant Scale DAC Column
Dynamic axial compression provides a simple means of packing and unpacking preparative columns, for both for low- and high-pressure chromatography applications. The DAC system allows for accurate column packing of various materials. Thar Process’ design ensures uniform bed compression, eliminating any chance of voids or cracks. DAC columns are scalable from preparative scale to production scale with our unique “Base Factor Value” for scale-up. The yield and purity largely depend on peak sharpness, which is further enhanced by uniform flow distribution.
The DAC column incorporates a movable stopper “End Cap,” which is attached to a piston and hydraulic compressor. The piston applies continuous compression at a defined pressure to maintain the constant height of the bed, thus avoiding degradation of the bed. The cross-integrated expanding type of sealing ensures zero leakage throughout the process. Uniform flow distribution ensures that the sample and the mobile phase pass over the complete surface of the bed, thereby providing maximum interaction with the stationary phase. This increases efficiency, load-ability and also the number of cycles.
Thar DAC installations
Plant Scale Gas Chromatography
Large-scale preparative Gas Chromatography (GC) employs the same chromatographic principle as analytical GC with packed columns. A carrier gas flows continuously through a column packed with the stationary phase. A pulse of a mixture is injected into the carrier gas at the column inlet and the different components of the mixture are eluted at the column outlet at different times, depending on their volatility and affinity for the stationary phase. Preparative and analytical GC use the same carrier gases and stationary phases, as well as the same types of detectors. The goal of preparative GC is not to know the composition of the mixture (as in analytical GC) but to collect purified fractions for further use. For productivity reasons, in large-scale preparative GC, the injected pulses are as large as possible. Column capacity is enlarged (by increasing the diameter), and at the column outlet, instead of discharging the various fractions to the atmosphere, these components are directed to traps where they are condensed and separated from the carrier gas. Two different categories of preparative GC exist that differ in both size and goal: (1) laboratory-scale preparative GC; and (2) large-scale preparative GC. Laboratory-scale preparative GC is very similar to analytical GC. Its goal is to purify milligrams or hundreds of milligrams of compounds in order to identify them. The equipment used is similar to that employed in analytical GC, except that column diameters are increased up to 10 mm and the fraction collector is a simpler device in which sample condensation is often not quantitative. Large-scale preparative GC is made for purification of kilograms and tonnage quantities of compounds.