An Ultimate Guide to Designing Preclinical Studies

Pre-clinical studies encompass all the activities that are linked to different aspects of drug discovery and development. Such studies are majorly designed for the identification of a leading candidate amongst several drug candidates that are in line to be tested. Amongst its multi-dimensional use, a pre-clinical research service provides valuable information on selection of the best formulation, determination of the route of administration, and frequency and duration of the drug exposure. All this information ultimately supports the development of the intended clinical trial. 

Usually, a preclinical study involves testing of the drug products on rodent and non-rodent animal models to determine the pharmacokinetic profiling, general safety, and identification of the toxicity pattern of the drug candidate under analysis. 

The results derived both from toxicology and pharmacology testing contribute to the selection of the potent lead candidate. Once a lead candidate has been identified there are six significant efforts contributing towards the development of pre-clinical studies in CRO – 

  •       Manufacturing of the drug substance or the active pharmaceutical ingredient
  •       Designing of a pre-formulation and a formulation
  •       Development and validation of analytical and bioanalytical methods
  •       Determination of pharmacokinetics and metabolism
  •       Toxicology, genetic toxicology, and safety pharmacology
  •       Good manufacturing practises
  •       Manufacturing and documentation of the pharmaceutical product to be used throughout the process of clinical trials

Objectives of the Pre-Clinical Study

The main goals of performing the pre-clinical studies are as follows –

  •       These are important for the identification of biologically active dose levels
  •       It aids in the selection of a starting dose, schedule for dose-escalation, and dosing regimen
  •       The pre-clinical studies play a critical role in designing the early phases of clinical trials
  •       It helps in the identification of physiological parameters that can help throughout the process of clinical monitoring
  •       They help in the establishment of dose-response estimation for assessing both the pharmacological and toxicological effects of the potent drug candidate
  •       They contribute towards determining the rate and extent of distribution of the drug candidate under analysis
  •       They play a critical role in the identification of kinetics, metabolic, and elimination pathways of a pharmaceutical drug candidate under clinical trial
  •       They help in assessing the reproductive toxicity, carcinogenicity, and teratogenic potential of a pharmaceutical candidate under analysis

Essential considerations for the pre-clinical CRO to accomplish their pre-clinical studies

Following factors are integral to achieving the pre-clinical trials –

  •       Selection of the relevant animal model to be used as study subjects
  •       Age of the study subjects
  •       Physiological state
  •       ROA
  •       Delivery system
  •       Product classification and regulation
  •       Stability of the pharmaceutical product
  •       GLP and Non-GLP
  •       CRO selection

Maximum Tolerated Dose

The drug discovery process involves evaluating a drug candidate for determining both its ADME properties and toxicity. One of the essential aspects of the pre-clinical drug development process is defining the dose and schedule to proceed ahead with phase 1 clinical trials. There are five different ways through which the dosing schedule can be described –

  •       MTD or Maximum Tolerated Dose
  •       MFD or Maximum Feasible Dose
  •       Limit Dose (1000 mg/kg)
  •       Dose providing exposure to 50-fold margin
  •       Exposure saturation