Science Pool

Learn more about biomanufacturing at Just-Evotec Biologics by downloading this presentation first presented at IFPAC in March 2021.

In this presentation, we touch on:

• Historic manufacturing practices
• Macro trends impacting affordability
• Speed and flexible capacity solutions
• New plan design principles

The skin is the largest organ in the human body. It contains enzymes capable of drug metabolism.

In this presentation, we focus on:

• the physiology of the skin and an overview of skin enzymology
• the role of skin metabolism in absorption, efficacy, homeostasis, drug delivery and toxicity
• adverse reactions in the skin including the mechanism behind skin sensitisation
• in vitro methods for investigating skin metabolism

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LC-MS provides the analytical endpoint for most discovery ADME assays. There is a constant drive to reduce LC-MS run times whilst maintaining quality. 

In this presentation, we focus on:

• a comparison of triple quadrupole MS/MS vs TripleTOF MS
• validation data for performance of the TripleTOF MS 
• use of the TripleTOF in high throughput ADME screening including intrinsic clearance assays and soft spot analysis.

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Due to an aging population, polypharmacy is increasing. Drug-drug interactions account for 5% of UK hospital admissions, and are a particular concern for common co-meds such as statins.

In this presentation, we focus on:

• a background to drug-drug interactions (DDI)
• the use of the mechanistic static models in the prediction of transporter-mediated DDI
• a comparison of the different published models and their performance 

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Pilocarpine is a muscarinic cholinergic agonist which is used as an epilepsy model in rats. 

In this presentation, we evaluate:

• the seizurogenic response of pilocarpine in vitro in different neuronal models including rat cortical neurons, rat hippocampal neurons and a human iPSC-derived co-culture model
• the importance of maturation of the cells (DIV)
• the use of MEA for the sensitive detection of firing, bursting and synchrony of the cells

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Human-derived 3D cell-based models are more representative of in vivo cellular physiology and have improved longevity in vitro.  

In this presentation, we focus on:

• causes of drug failure in drug development
• the advances in high content screening
• developments in 3D cell-based models including organ-specific cellular models
• the prediction of tissue specific toxicities such as hepatotoxicity (DILI), cardiotoxicity, nephrotoxicity and neurotoxicity

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Mitobiogenesis (or mitochondrial biogenesis) is defined as the growth and division of pre-existing mitochondria. Drug-induced perturbations in this process can result in mitochondrial dysfunction or toxicity. 

In this presentation, we focus on:

• mechanisms involved in mitochondrial toxicity including drug-induced mitobiogenesis
• the development of a high throughput high content imaging assay for detecting drug-induced effects on mitobiogenesis
• validation of the assay using known drugs which inhibit mitochondrial DNA and protein synthesis (e.g., antibiotics, anti-viral and anticancer drugs) as well as some non-mitochondrial toxicants.

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The brain is a complex organ. Find out more about the use of in vitro 3D co-culture brain microtissues for predicting human CNS liability.

In this presentation, we focus on:

• a background to drug-induced brain neurotoxicity
• the importance of astrocytes and their function
• the use of brain 3D co-cultured microtissues
• neurotransmitter pathway development over time
• high content screening (HCS) of brain microtissues and validation data

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Cardiotoxicity is a key cause of late stage attrition in drug development. iPSC-derived cardiomyocytes remain viable for more than 2 weeks on MEA plates. As MEA measures electrical activity without addition of any reagents, the cells can be exposed and monitored over extended time periods.

In this presentation, we focus on:

• a background to MEA
• design of the assay for detecting cardiotoxicity following chronic exposure to drugs
• case studies for cardiotoxic drugs with different mechanisms (hERG traffickers, multichannel blockers, specific ion channel effects)

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