25 years of attempts of bringing better drugs to patients

In the eighties drug development was rationalized to produce molecules (new chemical entities, NCE’s) designed to have a fit with (new) receptors or receptor-subtypes. Binding of these designed chemical compounds to the receptor resulted in agonism or antagonism at the receptor-site and therefore enhancement or inhibition of a pharmacodynamic effect (symptom or disease) caused by endogenously released compounds e.g. hormones or neurotransmitters. In the nineties a paradigm shift from computer-designed drugs towards the trial and error approach of large numbers of new compounds that could be produced with combinatorial chemistry are observed. Minute amounts of chemicals are tested against various target systems and nowadays a high percentage of the compounds in early discovery is generated using this approach. But, in addition, these chemical compounds now have to compete with drug candidates with a biological origin, like peptides, vaccines and monoclonal antibodies. Looking at these developments an increasingly higher number of new drug applications was to be expected, but unfortunately reality shows the opposite (figure). The number of new drugs (NCE’s) becoming available to the patient population decreases each year and the budget needed to bring the drug to market increases every year.

Changes at NOTOX
Increasing numbers of innovative drug development companies found us, because of the unique tail-cuff system we had invented to improve the short- and longer term (until 90-days) continuous infusion studies in rodents. The client base was extended during the many business trips ranging from Spain to Finland and from the USA to Japan. The efforts to become a global player were intensified by the introduction of NOTOX offices with representatives / senior scientific advisors in three major industrial areas, Basel (1994), New Jersey (1997) and Tokyo (1998). The service portfolio was extended from genetic and in vivo toxicology and ADME, with full (bio-)analytical support in the nineties, towards  activities that made us the CRO that currently offers full preclinical safety programs: safety pharmacology, immunotoxicology, in vitro toxicology and ADME in the new millennium.