Target safety assessment

TARGET SAFETY ASSESSMENTS EVALUATION OF UNDESIRED PHARMACOLOGY AND THERAPEUTIC AREA CONSIDERATIONS... 

TARGET SAFETY ASSESSMENTS STRATEGIES TO UNDERSTAND TARGET BIOLOGY AND ASSOCIATED LIABILITIES... 

Target Safety Assessment for Biopharmaceuticals Targeting the Immune System... 

In addition to the role of genetically modified animals in target safety assessment and investigating mechanisms of toxicity, a key use of these animal models is the assessment of drug metabolism and toxicokinetics of experimental therapeutics, with drug exposure playing an important role in overall safety. The properties of absorption, disuibntion, metabolism, and elimination (ADME) for small-molecnle... 

Screening hundreds of compounds against 80-100 targets/year is an expensive research endeavor Ho vever, it is one of the crucial parts of predinical safety assessment and is also required by regulatory authorities [9]. Beside a better understanding of compound bioactivity profiles, which in some cases can be reliably linked to clinically observed side effects, there is also a particular aspect of the generated data which makes it worthwhile to be analyzed in more detail. 

Frequently, a simple approach of pH adjustment or cosolvent is not enough to achieve the target concentration. Cosolvents are often used in combination with pH adjustment to further enhance the solubility. Using this approach, Lee et al. (2003) observed that nearly 85% of PLzer, Ann Arbor discovery compounds (> 300) submitted for discovery and preclinical injectable formulation development in the year 2000 could be formulated by pH adjustment, cosolvent addition, or a combination of the two approaches. It was also observed that 11% of compounds were not formulatable using this approach, and another32% ofthe formulation used more than 55% cosolvent. The high solvent content can limit the pertinent safety assessment of lead compounds. Therefore, the synergistic combinations of pH adjustment and cosolvent are not sufLcient to develop commercially... 

Pharmaceutical companies wishing to register new products must submit a dossier of data, relating to trials and investigations on the product, to MAFF. When MAFF (VMD) is satisfied that the data are complete and the research has been properly conducted to internationally accepted standards of competence (Good Laboratory Practice - GLP), the dossiers are passed to the VPC. The VPC then assesses the quality, efficacy and safety of the product. The safety assessment on the product includes the target species, human (operator, consumer) and environmental impact. If there are any substantial doubts, the licence may be refused and/or the company advised to carry out further investigations. 

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