Solutions with the Speed and Sensitivity for Clinical Trials

Clinical trials are the area of pharmaceutical drug development where drug candidates are tested in human subjects. If microdosing studies are included, there are five phases (0-4) of clinical trials designed to exhaustively evaluate the potential drug in order to ensure safety and improved efficacy over existing treatments. Sample matrices are biological fluids which present challenges to an analytical system’s robustness. Thousands of samples are generated which push system speed and reliability to the limit.

Dionex RSLC, x2 Dual and IC system solutions offer robustness, reliability, speed, and sensitivity that enable drug development chemists to achieve unparalleled productivity in all phases of pharmaceutical clinical trials.

Microdosing Studies

In phase “0” clinical trials, also known as human microdosing studies, new drug candidates are tested in healthy humans at sub-therapeutic dosage levels. The goal is to verify that the investigational pharmacokinetic/pharmacodynamic data developed during pre-clinical in-vitro and in-animal studies holds true for humans. The results allow pharmaceutical companies to rank potential drugs based on their PK/PD performance. Based on these rankings a company can decide which candidate to move forward first. The data also enable companies to make go/no-go decisions. Because the dosage levels are quite low, sensitivity is very important.

Dionex system solutions offer highly sensitive variable wavelength and diode array detectors. These detectors are specifically designed for fast UHPLC separations with scan rates of up to 100Hz producing sufficient data points for accurate and precise quantitation.

Determining Safety in Health Humans

Phase 1 of clinical trials is where drug candidates are first tested in humans at therapeutic levels. Although pre-clinical trials data indicates the drug is safe, phase 1 clinical trials validate that conclusion with healthy human subjects. Phase 1 also determines how the human body tolerates the drug. Finally, it is the first chance to collect and study human-relevant pharmacokinetic/pharmacodynamic data. The result is that a therapeutic dosage level can be determined for phase 2 and 3 trials.

Determining Efficacy in Ill Patients

In Phase 2, patients exhibiting the targeted illness are tested with the drug to determine its efficacy (how effective the drug is) and optimum dosage levels, frequency, and duration. To ensure high confidence levels, hundreds of subjects are tested and large numbers of samples needing analysis are generated. If the drug works as anticipated and does not exhibit unusually harmful side effects, it progresses on to Phase 3 testing. It is not unusual to find Phase 2 testing contracted out to organizations specializing in this particular area of drug development.

Analytical systems, such as the Dionex UltiMate^® 3000 and ICS 5000 deliver the high throughput and reliable performance that Phase 2 testing demands. Combined with the world-class Chromeleon^® data system software, these hardware/software platforms present solutions that are easy to implement, easy to learn, and easy to use.

Determining Comparative Efficacy

Now that the drug has been determined to be safe and effective and its dosage requirements determined, it is time to compare the drug’s performance against existing available therapies. Through the testing of thousands of patients exhibiting the targeted illness, a comprehensive assessment is performed. It may also be discovered that the drug has positive therapeutic properties against other illnesses and can result in “label expansion”. Analyses are fairly routine but in extremely high numbers requiring the high speed and reliability of systems such as the Dionex RSLC, UltiMate, and ICS systems.

Post-Approval Long-Term Studies

Phase 4 of clinical trials provides post-approval data as a follow-up to marketing the released drug. This phase provides the drug company with safety data that could not be collected during earlier phases such as long term effects and specific patient profiles (i.e., pregnant subjects). Even though the drug has already been approved by the appropriate regulatory agency, data suggesting previously undiscovered harmful effects can lead to the drug being withdrawn from the market. Consistent testing and data security are important aspects of analyses supporting Phase 4 testing.

The Chromeleon^® data system’s designed-in data security holds up to the most rigorous requirements and regulatory audits.