Novasep continuous technologies: Varicol®

A SMB unit includes 4 zones, the counter-current movement of the solid phase with respect to the liquid phase being obtained by a periodic and simultaneous switching of inlet (feed and make-up eluent) and outlet (extract and raffinate) lines. Accordingly, the number of columns in each zone is always constant (and is an integer).   An even more efficient way to exploit the liquid-solid contact is the Varicol® process, patented by Novasep SAS.

Concept A Varicol® unit includes 4 zones, but all inlet and outlet lines are not shifted simultaneously. Accordingly, the column distribution between zones varies during time. The Varicol® process then allows for optimising the column distribution among zones in a more efficient way in comparison with SMB, because the number of column per zone does not need to be an integer. This offers an infinite number of column distributions. A 3-column Varicol® is feasible but a 3-column SMB is impossible. Typically, Varicol® systems need one or two columns less than SMB systems to achieve similar performances, thus reducing separation costs.

The Varicol® is normally a periodic process: it returns to the same status at the end of the period.
The asynchronous shift of the lines can be better seen in a special diagram (a chronogram) which shows a time distribution of columns during one period. As an example, the figure below shows the chronogram of a 3-column Varicol® process. In the particular case described, the period is composed of four time intervals.

It is important to point out that the temporary superimposition of some lines leads to obvious consequences for the technical design of a Varicol® machine. Between each column, the two outlet lines (extract and raffinate) must be connected before the two inlet lines (eluent and feed) following the direction of the recycling flux.

( More information on Varicol®)

The Product Line
 
The Varicol® line offers competitive and reliable purification tools which provide very high and stable levels of performance for a large variety of substances, including chiral and achiral molecules. The line extends from the Varicol® µ (equipped with pre-packed semi-preparative 10 mm i.d. columns) to large production units such as the Varicol® 6-1000 equipped with 6 columns of 1 m diameter.

MODEL	PRODUCTIVITY RANGE (kg/day)	PHOTO
Varicol® µ	grams/day	view
Varicol® 6-50 (Lab)	0.1 - 2	view
Varicol® 6-100	1 - 10	N/A
Varicol® 6-200	4 - 40	view
Varicol® 6-300	8 - 80	view
Varicol® 6-450	20 - 200	view
Varicol® 6-600	40 - 400	view
Varicol® 6-800	70 - 700	view
Varicol® 6-1000	100 - 1000	view

Solvent recovery: a must for large-scale chromatography processes

A continuous process must be treated as a part of a larger loop integrating solvent recovery and solvent make-up (complete process integration). In this respect, all industrial size Varicol® units are delivered with a solvent regeneration unit. The automation software controls the solvent recovery unit as well as the chromatographic unit. The system provides for automatic readjustment of the eluent composition with a reproducibility typically better than 0.1%.

Solvent recovery yields in Novasep Process units as high as 99.97% have been reported (1) for industrial Varicol® units.

(1) Michel Hamende, UCB Pharma, plenary lecture at SPICA 2004, Aachen.

Optimisation of operating conditions & Assistance
 
The proper adjustment of the operating conditions of a Varicol® unit requires knowledge of the physico-chemical data of the chromatographic system (such as the adsorption isotherms, the plate height parameters, the permeability of the columns, etc.). This information is used by the Helpchrom software to calculate the operating parameters. Helpchrom can also be used to compare different processes, simulate the effects of changing parameters, etc. See Modelling software part.

Additionally, Groupe Novasep engineers are available to assist Customers in other fields, such as the screening of different phase systems (thermodynamic conditions), the selection of optimal operating conditions, the scaling a process, the training of personnel, etc. See Process development part.

Automation & Control.

The Control Software has been designed to provide safe and reliable operation of the Varicol® units. The software is developed following GAMP4 and 21 CFR part 11 guidelines. The different actions and levels of interaction with the software are password protected. A standard industrial system utilises a Programmable Logic Controller (PLC) for direct control of the unit (open/close valves start/stop pumps, read sensors, etc.) and a PC for the user interface.

The systems provided by Novasep Process integrate ancillary equipment such as automatic evaporators, solvent recycling, eluent composition automatic adjustment, monitoring of tank levels, etc.

Novasep Process has developed hardware and software tools, consistent with the FDA’s Process Analytical Technologies (P.A.T.) guidelines . For instance, with the IPM option (In-line Process Monitoring), it is possible to automatically check the internal concentration profiles and product purities. This is very important in order to understand the behaviour of the system and adjust operating conditions if required.For a high level of comfort and reliability, Novasep Process has invented the EASY-Varicol® concept. It allows for efficient maintenance and troubleshooting of a unit, either locally or from a remote location.

Proper Design: performance, reliability and robustness.

Varicol® units used for pharmaceutical applications include short columns (typically less than 10 cm) packed with relatively small particles (20 µm) and switched at a rather fast pace (less than 1 min.). This requires adequate equipment design and control, as well as proper modelling software and assistance in order to determine optimum operating conditions and provide safe, stable and trouble-free operation.

As for any chromatographic system, the column design is of paramount importance. All Varicol® units with a column diameter of 2" and above are equipped with Prochrom DAC columns. This is particularly important for large size units where the column diameter can exceed the column length by a factor 10 or more !