Preclinical development processes for biopharmaceutical products refer to drug discovery, drug research and experimental testing on life forms other than humans that occur prior to clinical trials on human subjects. The major objective of preclinical processes is to discover new drug molecules/combinations. Usually, such processes take place inside research laboratories.
New drugs undergo three major processes before entering the initial phase of clinical trials. These are:
- Drug discovery
- Pre-clinical testing
In laboratories, researchers initiate the process of developing new drugs by first determining the disease they wish to target. They study the existing modes of treatment and available drugs and hypothesize new compounds and treatment methods to treat the cellular/molecular structure responsible for the disease. Drug discovery is enabled via three methods.
- Classical pharmacology involves testing large numbers of crude extracts for biological activity. If any activity was discovered due to a substance, it was shortlisted.
- Specific targeting involved producing small molecules to target specific pathological pathways or structures. This was an improvement over classical pharmacology
- Reverse pharmacology is a relatively recent method wherein modern biotechnological tools like cloning are used to screen for producing a list of potential candidates from already existing medicinal drugs. These drugs may sometimes originate from traditional medicinal systems like reserpine.
Despite biotechnological libraries storing chemical equivalents of natural compounds, most drugs are still sourced from natural sources like plants, microorganisms, etc. In addition, research attempts to source compounds from natural sources in different environments like forests, oceans, geyser pools, undersea vents, etc. Thousands of compounds are discovered and listed at this stage.
The list of compounds that were identified as being potential drug candidates is now screened for narrowing down the list to the best possible drug candidates. With the advent of modern biotechnological tools, it has become easier to screen for new drugs. High-throughput screening is an often used tool in laboratories around the globe for short listing the best possible candidates for pre-clinical testing. Through this method, thousands of compounds discovered earlier can be compared at an accelerated rate while simultaneously incorporating various criteria. For example, if a target is a protein, the screening can be computerized to shortlist those compounds that are inhibitors of the particular protein.
Expectations by identifying a perfect drug candidate after screening can lead to disappointment for many of the compounds may exhibit some level of activity against the target. Researchers attempt to introduce more criteria for narrowing down candidates like reducing the effect of the drug candidate on unrelated target. The final list, which is significantly lower in number of drug candidates, is sent for pre-clinical testing.
The main aim at this stage is to identify a fewer number of drug candidates by experimenting them on animals. Those that achieve specific activity on the intended target are assessed for required dosage levels to be used in the first human trials. Along with dosage calculations, side-effects, adverse reactions, and lethality of a drug candidate are assessed during the animal tests. These tests enable the company sponsoring the drug development to seek regulatory approval for progressing to testing the drug candidates on a human in clinical trials.
Click here to learn more about Drug Safety and Pharmacovigilance.