Dr. Molnár was Chairman of the Symposium „The Future of HPLC-Method Development: Quality by Design – Evaluating the Control Space of Robust HPLC-Methods“ 9th of March 2009 at Pittcon in Chicago.

Speakers were Loren Wrisley from Wyett, John Dolan from LCResources, Portland, Karthik Yajaraman from Bristol Myer Squibb, New Brunswick, Mike McBrian, Advanced Chemistry Development, Toronto, Canada, and Imre Molnár from Molnár-Institute, Berlin, Germany.

The change in the value of an experimental parameter (factor) can be altered between certain limits without a change in chromatographic separation. This means, we can have certain limited variations in pH, temperature, ternary eluent composition, without changes in selectivity. The corresponding “parameter windows” result in a multidimensional geometrical space (or volume), in which adjustments are not considered as changes, therefor adjustments can be done without the need for a new validation. This so called “Design Space” is a new buzzword in HPLC. The advantage of the establishment of the Design Space is the knowledge about different multifactorial influences on peak positions.

There are also a number of other expressions, which might be new for many chromatographers, like QbD = Quality by Design, or DoE= Design of Experiments. Also the expression “Knowledge Space” and “Control Space” are new for many HPLC-users. These expressions are however familiar for chemometricians and find increasing attention at the regulatory authorities such as the ICH (International Conference on Harmonisation, Europe), the FDA (Food and Drug Administration, USA), USP (United Staates Pharmacopoeia, USA), EPA (Environmental Protection Agency, USA) and others.

The session was very well attended, reflecting the strong interest in the above mentioned topics.
The main reason for industrial participants was the flexibilisation of the quality control process, reducing trial and error and increase efficient work in HPLC method development. This can be achieved mainly by more systematic work, design of experiments (DoE) and more scientific  evaluation of the physico-chemical behavior of compounds in a chromatogram using visualisation tools, such as DryLab^®, LC-Simulator or ChromSword. Although a good column is still the heart of the HPLC-system, more and more attention is focussed towards the optimum values on pH, temperature, gradient form, ternary eluent composition and additive concentrations. Column selectivity informations are also available from ColumnMatch (Molnár-Institute) or from POPLC (Bischoff).