Dr. Andrew Teasdale is the chair of AstraZeneca’s internal expert group focused on control of genotoxic impurities and Editor of the book Genotoxic Impurities – Strategies for Identification and Control. He talks to Jonathan Rose for the ChemViews magazine about genotoxic impurities in drugs, what constitutes an acceptable drug risk, and the future of drug development.
H
ow does one determine what is or is not an acceptable drug risk?
All drugs pose some element of risk, most commonly thought of in terms of side effects. The determination of whether or not the risk is acceptable is essentially a case of balancing the risks against the proven benefits provided by the drug. The acceptability of the risk/benefit balance also varies, depending on the disease being treated.
Where do genotoxic impurities fit on the spectrum of drug safety?
Genotoxic impurities (GIs) are simply a sub-set of impurities and the general view is that impurities pose no benefit and hence should be reduced to levels that are as low as possible. This, though, needs to be balanced against the effort required to control the impurities in question. As a consequence for genotoxic impurities, as with other impurities, the focus has been on trying to establish practical limits that strike an acceptable balance between the desire to reduce levels as much as possible while ensuring the effort/cost required remains commensurate with the risk.
What are the most important resources you need and use?
The most important resource for me personally is the team of experts I’m able to call on to help address issues that might arise. I am fortunate to be able to draw on the experience and knowledge of a number of industry leading experts in this area. External to AZ there are a number of networks that relate to GIs. Throughout the time GIs have been an issue, these networks have collaborated very closely with one another and this has helped not only to develop AstraZeneca’s position, but that of the industry as a whole.
Another key resource are sources of toxicological data such as Toxnet. It provides an excellent portal for obtaining access to crucial safety data that may exist in relation to a number of genotoxic compounds.
What motivated you to develop your book?
Current guidelines covering genotoxic impurities provide little detailed advice on how to practically apply the requirements outlined within them. My main motivation, therefore, was a desire to develop and share practical advice so that AstraZeneca and other pharmaceutical companies could ensure they complied with the requirements outlined in the guidelines.
What influence do you believe the book will have?
As well as being a good general introduction and reference for the subject, the main influence I hope the book will have is to make it easier for people to ensure they have effective control over GIs. Through doing this it is hoped it will not only reduce the burden placed on organizations, but also ensure that proper control is exercised over genotoxic impurities, hence, ensuring patients continue to benefit from access to safe medicines.
I also hope the challenges the book poses in relation to concepts such as thresholded mechanisms for DNA reactive compounds helps to promote future debate and research in this area.
Does your book fit into a wider scientific context?
Many of the principles outlined in the book that relate to the appropriate assessment of risk can be applied beyond GIs certainly to the control of impurities in general.
Where do you see the field of drug development in ten years time?
I’m perhaps not the best qualified person to give a view on this, but one significant shift I believe we will see is a shift towards personalized medicines. This is most likely to be seen in relation to oncology where the ability to be able to determine the potential effectiveness of a medicine in advance of treatment should allow for treatments to be far better focused than at present.
Who or what got you interested in organic chemistry as a subject?
My interest in chemistry in general really stems from my father who was a chemistry/physics teacher. He had the great gift of boundless enthusiasm when it came to the subject and this lead me to wish to pursue a career in chemistry. The other big influence was my Ph.D. supervisor Professor David Parker at Durham University, UK. Again David’s enthusiasm was infectious especially when combined with his humility; an extremely clever man without any trace of arrogance.
What are your interests outside of science?
Sport in the main, rugby/football and cricket. If I ever become rich enough, an alternative career as a professional sports fan beckons!
So maybe if your book sells very well … Thank you very much for this interview!
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Dr. Andrew Teasdale is the chair of AstraZeneca’s internal expert group focused on control of genotoxic impurities. He has contributed to the development of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) project guidelines covering genotoxic impurities, through industry associations such as Pharmaceutical Research and Manufacturers of America (PhRMA).
Teasdale studied chemistry at Durham University, UK, and received his Ph.D. from there. He has more than 18 years experience in the pharmaceutical industry working within both chemical, analytical and quality assurance roles at a senior level. Achievements in previous roles include being the project manager responsible for the implementation of the first fully web-based global laboratory information management system (LIMS) and the development and implementation of walk-up generic chromatography systems — systems that allow for the rapid analysis of samples without the need for extensive method development — made possible through the development of a suite of complementary methods.
Genotoxic Impurities: Strategies for Identification and Control
Andrew Teasdale (Editor),
Wiley, Hoboken, USA, 2011.
ISBN: 978-0-470-49919-1.
