Stringent safety pharmacology studies help to prevent fatality and serious injuries of volunteers and patients who are part of the clinical trials. Sensitive and predictive safety pharmacology  tests contribute to reducing attrition during clinical development and marketing safer medicines. It also assists in  compound selection, assess the potential risk of failure, predicts potential injuries due to Adverse Drug Reactions (ADRs) and define a therapeutic window for acute dosing in humans, stated Dr BR Jagashetty, Karnataka drugs controller.

With recent drug withdrawals from the market and the implementation of the International Conference on Harmonization (ICH) guidelines, safety pharmacology have now become a more important phase in drug development. The tests need to be carefully selected and adequately validated in-house, stated Dr Jagashetty in his inaugural address at a workshop on safety pharmacology, organized by Advinus Therapeutics.

The  quality and reliability of non-clinical safety studies is achieved through the conduct of the studies in compliance with Good Laboratory Practices (GLP). Due to the unique design of some safety pharmacology studies, it may not be feasible to conduct these in compliance with GLP. There should also be considerable emphasis on  data quality and integrity in safety pharmacology studies  even in the absence of GLP through adequate documentation of the study and archiving of data, he said.

Safety pharmacology investigations can be part of toxicology studies but it should be conducted in compliance with GLP. Primary and secondary  pharmacodynamic studies do not need to be conducted in compliance with GLP. But the results from secondary pharmacodynamic studies conducted during the compound selection process may contribute to the safety pharmacology evaluation for potential adverse effects in humans, stated the Karnataka DC.

Signals identified from safety pharmacology studies are candidates for biomarkers, which when established or  validated, can enhance cross-species-based risk assessments and risk management in clinical trials. Its review will help to trace the signals generated from safety pharmacology studies. Biomarkers generated from safety pharmacology studies helps to  predict risk in humans based upon physiological measurements conducted in animal studies.

Although deaths and life-threatening Adverse Drug Reactions (ADRs) in phase I clinical trials are extremely rare, less severe ADRs occur with an incidence of over 13 per cent. Of the candidate drugs that fail prior to marketing, it is generally acknowledged that about 1 in 5 do so because of ADRs in the clinic. Once New Chemical Entities (NCEs) are on the market, ADRs are estimated to be the fourth leading cause of death in the USA. “These global  statistics indicate that there is room for improvement in preclinical safety assessment. Rather than `bundling' the safety pharmacology studies together just prior to phase I trials, a step-wise, streamlined approach can be adopted throughout the drug discovery process. In this way, the safety pharmacology information can contribute to making informed judgements throughout the preclinical drug discovery process,” stated Dr Jagashetty.