What Is Preclinical Research? Understanding the First Step in Drug Development

There are multiple phases that a new medication, biologic, or medical device intended for human use needs to go through. These investigational products (IPs) have to first undergo extensive research in both preclinical and clinical settings. While healthcare providers typically become involved during Phases 1-4 of clinical trials, it is important to understand the preclinical stage. This helps provide a complete understanding of the investigational product’s progress through the development pipeline.

Preclinical research provides the initial and foundational scientific assessment for every clinical trial that follows. It is designed to answer a fundamental question:

Is this investigational product safe enough to be tested in humans?

What Is Preclinical Research?

Preclinical research is made up of research studies that are done n an IP before studies can be tested in humans. These studies are usually performed in controlled laboratory environments. Depending on the IP, these studies can be done in cell cultures and/or animal models. Similarly there can be extensive computer modeling performed at this stage. 

These investigational methods are chosen so that researchers can evaluate the biological activity of the IP. This also provides them with preliminary information on the safety profile of the IP. The goal of this phae is to identify any potential risks that the IP may have before using it in human participants. 

Objectives of Preclinical Research

There are many reasons why sponsors conduct preclinical studies. Amongst other items, they are trying to understand their IP’s: 

Biological Activity: Researchers test their IP’s ability to produce the desired biological effect. For example, this could involve evaluating a proposed diabetes medication to lower blood glucose in animals. It may be determining whether a cancer therapy inhibits cell growth. It could also be evaluating a dental regenerative product for promoting tissue healing. 

Toxicity Assessment: Preclinical research also is focused on identifying any potential toxicities that their IP may exhibit. This can include different effects such a as organ toxicity, neurological effects, and other potential short term and long term exposure controls. These findings are used to help establish future study safety parameters. 

Dose Determination: With the data collected during pre-clinical studies researchers are able to determine a starting dose and maximum dose for human testing which is critical for phase 1. This also allows them to establish safe dose escalation strategies for human testing. 

During the pre-clinical phase, if the proposed IP does not demonstrate meaningful activity, development may stop before human testing begins. In fact, many IPs never make it past the preclinical phase. This may seen like a setback, but it helps protect future study participants from any safety concerns and decreasing the overall investment for the IP study for the sponsor. This is a crucial safeguard to help ensure that only promising IPs advance to human studies. 

Regulatory Requirements Before Human Testing

If an IP seems promising, it can potentially advance to human studies. Before it can move forward the sponsors must submit extensive preclinical data to regulatory agencies. 

In the United States, sponsors would need to submit an Investigational New Drug (IND) application to the FDA. In this application the sponsor makes a case for the new product to be testing in human trials. This is done by providing the following information as well as any other specific required data:

• Preclinical safety data 

• Manufacturing information 

• Proposed clinical protocols 

• Investigator information 

Regulators review this information before allowing clinical trials to proceed.

From Preclinical Research to Clinical Trials

Once sufficient safety data has been collected, submitted, and the IND application is approved, sponsors can begin Phase 1 clinical trials. This transition from pre-clinical to clinical trials denotes the first time the IP will be used in human research subjects. This is a major milestone in the IP development. 

Although providers do not typically participate in preclinical research, it is useful to have an understanding and deeper appreciation of this phase of clinical research. At Tristar Clinical Research Consulting (TriStar CRC), we help providers understand every stage of the development process and prepare for successful participation in clinical research programs.