PreClinical / NonClinical

Design & management of preclinical programs.
Preclinical Toxicology and Pharmacology consulting expertise and management.
Pre-IND nonclinical activities.

 

Preclinical programs are geared towards generating and collecting critical safety / toxicology / phamacology data required to allow first in man studies.  These preclinical activities are usually aimed at generating the data required for IND submissions, as well as pre-IND packages as the situation may require.  The focus is to determine and characterize a drug's pharmacodynamics (PD), pharmacokinetic (PK), ADME (absorption, distribution, metabolism, and excretion), and toxicity profile.

 

Intelligent and strategic planning is required to make the best use of, and to generate the most useful data, to provide predictive indicators for the success of human clinical trials on efficacy and safety.  Today, modern science allows for the best opportunities to streamline and improve upon drug development programs.  Nonclinical studies can and should be, a tremendously cost-efficient route to reducing overall drug development programs.

 

The chances for a New Chemical Entity (NCE) becoming an FDA approved drug product are relatively low.  A well designed and focused implementation of a preclinical program helps to reduce these risks, and improve upon that one scenario for a successful drug candidate.

 

Stages of preclinical testing:

 

Stage 1;   fast, cost-effective, non-GLP, in-vitro studies

  1. Physiochemical properties, the solubility of test drug in various buffers, cell culture media, biological fluids.  Solubility determined by HPLC or LC/MS analysis.  Chemical stability simulated in gastric or intestinal fluids.  Buffer and pH stability of test drug tested and measured.

  2. In-Vitro ADME Tox Screening.  permeability, cell-based toxicity, cyp inhibition screen, microsomal stability.

  3. Detailed In-Vitro, toxicity, ic50 cyp inhibition, hERG

  4. Advanced Lead Characterization; cyp identification, metabolite profiling:  (Guidance for industry, Safety testing of drug metabolites, FDA, November 2016 )