Bridging the gap between drugs and regulatory bodies

30th May 2014

Posted By Paul Boughton

It's time to change the way pharmaceutical companies and regulatory authorities communicate, says Dr Imre Molnár.

We have more than 100,000 diseases but drugs are available for just 20,000 of them. Therefore 80,000 diseases have no support from big pharma because it is too expensive to develop new drugs. It takes 10 development projects to bring one new drug to the market; nine projects are dying due to high costs. In 2002, this discrepancy prompted regulatory agencies to try to change the situation. Instead of developing drugs by trial and error, it was decreed that solid science should be applied and that planned design of experiments (DoE) should be developed and conducted.

Since the introduction of quality by design (QbD) principles by the US Food and Drug Administration (FDA) more than 10 years ago, brought forward by Dr Moheb Nasr and his colleagues, a number of things have changed.

Instead of submitting a large set of 'raw data', the submission itself has become a more scientific document - explaining how the analytical part of the process was developed, what is critical, what will likely be improved in the process later on and how that will be managed. Risk assessment tools were applied and the basics of a control strategy for the process have been further developed.

All of the above was enhanced and supported by a better understanding of the principles of modern ultra-high performance liquid chromatography (UHPLC), especially by better communicating details of the chromatographic separation process, which is the foundation of good analytical practice and responsible for reliable quality control. This progress became possible using the capabilities of modelling tools such as the DryLab software, among others. DryLab could visualise a change in a separation by showing the corresponding chromatogram in only one second, in this way contributing to further improvements in column technologies, to higher speeds and to novel instrumentation principles, such as the UPLC line from Waters. This helped to speed up the exchange of information by faster analysis times, and later on, with the UHPLC lines from Agilent, Shimadzu and others.

The analysis time of a drug has now evolved from 50 to 160 minutes down to three to five minutes using DryLab1,2. We are able to better communicate about new drugs using computer modelling to explain precisely how the method was developed in line with the current best practice.

The common workhorse in the pharmaceutical industry is usually still reversed-phase high-performance liquid chromatography (HPLC), and it is important that we understand why out-of-specifications (OoS) occur and how we can correct them without costly bureaucracy. In this way, we can convince the regulatory partners about the science in our methods easier and faster. Only by following this path are we able to get new drugs onto the market for smaller populations of patients, who are waiting desperately for help.

For more information at

Dr Imre Molnár is president of the Molnár-Institute in Berlin, Germany.

References: 1 Using an innovative Quality-by-Design approach for development of a stability indicating UHPLC method for Ebastine in the API and pharmaceutical formulations, Alexander Schmidt, Imre Molnár, J. Pharm. Biomed. Anal., 78-79 (2013), 65-74; 2 Exploring better column selectivity choices in ultra-high performance liquid chromatography using Quality by Design principles, Róbert Kormány, Imre Molnár, Hans-Jürgen Rieger, J. Pharm. Biomed. Anal., 80 (2013), 79-88.





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