Translational medicine is a new concept for getting beneficial treatments to patients sooner. Dr Ciriaco Maraschiello, Harlan Contract Research Services’ director of drug discovery and translational medicines, discusses the benefits of early data on toxicity and efficacy.

Translational medicine is a rapidly growing discipline in biomedical research that aims to expedite the discovery of new drugs, diagnostic tools and treatments by using a highly collaborative and multidisciplinary approach to early research.

Responding to this trend, Harlan Contract Research Services (CRS), a division of Harlan Laboratories, has introduced a dedicated drug discovery and translational medicine programme to speed drug development, minimise the risk of failure at a later stage and reduce the costs of bringing a new product to market.

The advantages of early knowledge

Using advanced technologies, Harlan CRS scientists are able to produce physiologic data related to pharmacokinetics, toxicology and efficacy. By integrating these disciplines at an early stage of drug development, translational research can detect unexpected toxicity that could lead to failure during the preclinical or clinical stages, potentially saving significant development costs.

For example, using biomarkers to detect toxicity and efficacy at an early stage, and implementing the same data within the toxicity studies needed for regulatory approval saves time and reduces the potential for needless development costs.

On the revenue side, early indications of efficacy can add value to the compound and seal private funding or out-licensing agreements. Translational medicine techniques can also help pharma and biotech companies quickly screen promising molecules in their library of candidates by combining in vitro with focused in vivo testing.

Tailored packages

To create this programme, Harlan CRS combined expertise in areas such as metabolic profiling, in vitro toxicity prediction, skin penetration, immunology, pharmacology and bioproducts, as well as its in-depth knowledge of regulatory requirements, to offer tailored screening, profiling and modelling packages.

Among the services typically offered under this paradigm are:

  • creation of a suitable formulation for in vivo testing
  • in vivo toxicity and pharmacokinetic profiling – organ toxicity and accumulation, assessment of bioavailability, and metabolite profiling and ID
  • in vitro screening for genotoxicity, cardiotoxicity, hepatotoxicity, nephrotoxicity and immunogenicity
  • proof of concept studies and early efficacy in vivo modelling
  • pharmacokinetics/pharmacodynamics trials
  • allometric scaling and determination of the maximum recommended starting dose
  • drug-drug interactions and CYP mapping
  • biomarkers of toxicity and efficacy.

Special screening packages have also been developed to meet specific requirements such as absorption, distribution, metabolism, excretion and toxicity (ADMET) information, covering early pharmacokinetic profiling and biodistribution, plasma protein binding, in vitro metabolic stability, acute toxicity, fast bioanalytical development and early safety assessment.

Taken together, these studies provide valuable insight into the development of new chemical entities, biopharmaceuticals and combination therapies or reformulations, and shorten the time between proof of concept in cellular and animal model systems, and proof of concept and dose selection in humans.

Underpinning the drug discovery and translational medicine group is Harlan CRS’s efficient, effective and effortless (E3) programme. E3 uses the best of lean Six Sigma methodology to create a harmonised approach to study execution. Mapping techniques identify areas of duplication, inefficiency and waste that can be eradicated with a reduction in transportation, inventory, motion, waiting, over-processing, over-production, defects and reworking.

Speed is of the essence

In Harlan CRS’s view, getting answers to basic scientific questions about drug candidates quickly and efficiently yields multiple benefits. Promising candidates that pass screening, profiling and modelling tests are moved more quickly into preclinical and clinical development, which reduces the time in which new therapies are made available to patients. Early proof of efficacy can also raise interest and investment to speed development.

By the same token, candidates that fail this early screening, profiling and modelling are not moved into further development, saving clinical trial costs that would otherwise have been wasted.

Techniques such as adaptive trials, risk-based monitoring and translational medicine are aimed at mitigating development costs, improving efficiencies and shortening the time to market. Harlan CRS’s development of the data needed to make a speedy go/no-go decision at the earliest stages of development will accomplish those goals and improve the quality of drugs entering the development pipeline.