Our CEO, Dr. Stefano Palea, recently wrote an expert insight note for GoINPharma (to read all of it, click on the link) about the value of human tissue studies in translational research.

In this article, he shares his vision and explains what is – sometimes – going wrong in the preclinical studies process, and how to improve it with human tissue. For instance, he explains the perks of using human tissue to study drug candidate’s efficacy and safety.

Debates have emerged since 2000s about the gap between R&D expenditures and the number of new medicines approval. Top pharmaceutical companies do not launch enough drugs to meet their growth objectives (source: 1) and for 5,000 to 10,000 compounds in the pipeline, only 1 ends up on the market (source: 2). As the cost for drug discovery and preclinical development represents around 33% of the total expenditures (source: 3) to put a new chemical entity on the market, reliable and predictive preclinical studies of fundamental importance.

Most of the failures in Phase II are due to a lack of efficacy. This fact raises the question of the translational values of preclinical tests used to select and asses the efficacy of drug candidates. A number of unanticipated differences between animal models and human could be responsible for the lack of efficacy in clinical studies.

Advantages of studying drug efficacy on human tissue:

Fresh, frozen, or formalin-fixed paraffin embedded human tissues can be used for multiple reasons:

  • To confirm efficacy data obtained with recombinant cells or animal
  • To identify potential side effects in vital organs that could be due to off targets activities specific to human
  • To validate new targets using biomarkers
  • To replace or reduce animal experimentation

Moreover, these studies could bridge the gap between in vitro cell-based studies, in vivo animal studies and clinical trials.

The use of human tissue can also be very useful to study safety as the preclinical toxicology species are not always representative of human condition. Non-clinical safety pharmacology studies performed on human tissues can be used for marketing authorization and clinical trial application, with considerable cost cuts. It also allows to replace the use of animal experimentation and above all, to provide more predictive and relevant tools to determine safety of drugs entering clinical trials.

Unfortunately, the use of human tissue in preclinical studies remains quite rare. Yet, a lot of tissue is available, but difficult to obtain because of logistic and technical difficulties, as well as the lack of incentive from surgeons or healthcare staffs, and the need for flexible working timetable for the manipulating staff.

Because of this complexity, only highly specialized, reactive and flexible CROs having years of experience in human tissue research can lead these preclinical studies.

NB : GoINPharma provides detailed and up-to-date information for professionals who wish to broaden their horizon quickly and freely. The journal is produced by a team of international professionals and is free of charge.