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June 19, 2016

Next-Generation Preparative Supercritical Fluid Chromatography Instrumentation

Preparative SFC has been a preferred method for small scale purification in the pharmaceutical industry for about 15 years, since the prep SFC instrument was introduced by the now defunct Berger Instruments.  Since then several vendors have entered and exited the prep SFC marketplace and a number of commercial instruments are currently available.  However, these prep SFC instruments have some performance and dependability limitations, and are generally considered to be inferior to the Berger Multigram II, a ‘gold standard’ for small scale prep SFC purification that is no longer manufactured.  Consequently, pharmaceutical companies interested in the planned replacement of aging instrumentation are uncertain how to proceed.  In this project, desired hardware and software requirements and performance criteria collected from a cross-pharmaceutical group of SFC users will be shared with potential instrument providers, in the hope of identifying partners interested in developing, optimizing, and/or commercializing the “next-generation” of preparative SFC instrumentation collaboratively.

Download the Request for Information and submit your response.





TYPICAL COLUMN SIZE – 2-3 cm x 25 cm :  This size falls within our current capability, so no issues.  The question is whether or not you would want to have the capability for multiple columns to be installed with a selector valve to choose which column to use? 

Column selector valve is not a requirement.  However, having the capability to switch between columns (for example two prep columns on the oven) can save time and allow for quick and on-the-fly column switching without having to depressurize the system.  Would need to evaluate cost vs. benefit.

PRESSURE – Programmable up to at least 200 bar : Our current BPR is programmable up to 400 bar.  We assume that you would program a specific pressure to be run during the whole method.  Did you mean to infer that the pressure be able to change during a run? 

No, no pressure change during a run.  Just a clarification, we meant BPR control up to at least 200 bar (and system pressure up to at least 400 bars).

COLUMN TEMP – Efficient temperature control to at least 60 degrees C.  Our current oven goes to 85 degrees C.  Would you want to have multiple columns in the oven?  If so how many? 

See comments in Question 1.


  1. Low-pressure with visible GLS :  Can you clarify what is meant by low pressure? <3psi

  2. Does visible GLS mean that you would need to see the inner mechanism of the GLS?  Our GLS design is currently using Peek or Teflon vs. glass construction. Anywhere that a volume of solvent is collected post-BPR, we would like to be able to monitor for precipitation (and the possibility for clogging) and also to be able to verify visual cleanliness post-run.

  3. Separate ventilated collection cabinet to allow at least 2L collection vessels :  This cabinet should allow visibility of GLS and vessels, correct? Yes

  4. Also, do you have specifications for “Recover” and “Carry Over”? Recovery = >95% on baseline resolved test mix.  Carry Over  = not detected on baseline resolved test mix

METHOD EDITING – Simple, graphical (visual), “on-the-fly” editing: Can you be more specific on which parameters would need to be changed on-the-fly?  For example would you want to change the gradient conditions or CO2/Modifier ratio?  Could you provide a prioritized list of editable set points?

Desired editable set points:

  1. Fraction collector settings (time, threshold, slope)

  2. Manual override of fraction collection

  3. Cycle time

  4. End of run time

  5. Injection volume

  6. Number of injections

  7. Modifier/CO2 composition

  8. Flow rate

  9. Method pause during run

REPORTING – Customized Reporting : Our software provides custom reporting, but could you supply an example of the type of reporting that you would like? 

Custom reports are acceptable. Include run conditions (i.e. variables for all editable set points: mobile phase%, flowrate, back pressure, temp, wavelength, cycle time, # injections, collector settings).


FLOW RATE – 150-500 mL/min @ 50% modifier : We can offer a configuration that could deliver 300 mL/min CO2 & 150 mL/min Modifier.  Given this flow restriction would you consider this as a Prep Scale system? 

This would be somewhat restrictive and on the lower side for prep scale.  Ideally would prefer flow at least up to 350 mL/min with at least up to 50% modifier.


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