Transcript Paul Duckett

Paul Duckett
Brixham Environmental Laboratory
Site Manager
A world class environmental testing Laboratory
Brixham Environmental Laboratory (BEL), located in Devon, England has for over 60 years provided a specialised service
to the chemical industry.
The objective of BEL is to deliver fit-for-purpose, cost effective environmental support to industry world-wide, providing
assessments of the environmental fate and effects of new and existing products.
Key activities at Brixham Environmental Laboratory include the testing and risk assessments required to increase
understanding of the environmental impact of AstraZeneca’s Active Pharmaceutical Ingredients (APIs), manufacturing
intermediates, processes and effluents, to ensure they meet the required regulatory approval.
Brixham Environmental Laboratory provides specialised scientific services to a number of different industry sectors,
helping them understand the lifecycle of chemicals in our environment and the impact this has on the ecosystem.
“A wide range of disciplines”
• Ecotoxicology/Ecology
• Animal Physiology
• Biochemistry
• Microbiology
• Genomics
• Mathematical Modelling/Statistics
• Information Scientists
• Chemical Engineering
World Class
Specialists with an
innovative approach to
Environmental Science
79
4
9
52%
48%
80%
40%
Full Time Equivalent staff
Industrial Trainees
Contractors
Women
Men
Approximately are Graduates
Approximately have a Post
Graduate Qualification
Zebrafish - alternative model for predicting human drug safety
Valuable attributes:
Why are we doing this work?
• Physiology/development parallels mammals
in many areas
• Whole organism
• Rapid life cycle and development
• Transparent embryo/organogenesis
• Small size ~ multiwell plate in vivo (low
compound/space requirements), potential for
automation
• Overall ~ high throughput = more
compounds = earlier use in pipeline
•
•
•
•
Some new drugs have side effects.
Many side effects are not detected until late in
a drug’s development ~ this is expensive if the
drug has to be discontinued.
The zebrafish may allow us to detect many of
these side effects earlier.
This saves time, money, animals and allows
earlier prioritization.
Application of Zebrafish in drug development
Developmental toxicity Early stage assessment of the potential
for chemicals to induce teratogenicity within developing
Zebrafish embryo-larvae. Involves multiple endpoint assessment
such as major organ morphology, cranial facial defects,
abnormal body shape etc. providing a LOEC value in relation to
the LC25. This assay is part of an ongoing, cross-pharmaceutical
company ring test (Gustafson et al., 2012, Reproductive
Toxicology 33, 155-164).
Ototoxicity The lateral line (neuromast) hair cells of the Zebrafish
embryo-larvae are used as a surrogate model for mammalian
inner-ear hair cells as they respond to ototoxic (hair cell
damaging) chemicals in a comparative way. This response can
be used as an early screen for assessing this undesirable side
effect (Buck et al., 2012, Hearing Research, 284, 67-81).
Bioanalysis Assessment of compound uptake into Zebrafish
embryo-larvae forms an integral part of many of our assays, and
can be critical for interpretation of animals responses to chemical
challenge.
Questions
Thoughts
Comments
Reflections
Comments
Questions
Thoughts
Thoughts
Comments
Questions
Reflections
Comments
Reflections
Confidentiality Notice
This file is private and may contain confidential and proprietary information. If you have received this file in error, please notify us
and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized
use or disclosure of the contents of this file is not permitted and may be unlawful. AstraZeneca PLC, 2 Kingdom Street, London, W2
6BD, UK, T: +44(0)20 7604 8000, F: +44 (0)20 7604 8151, www.astrazeneca.com