Would you believe that every year only a small fraction of the total number of drugs that undergo clinical studies get approved? In fact, according to a recent report published on Medicine.net on drug development in the USA, it was revealed that for every 5,000 preclinical drugs reviewed, only five get tested on humans. And of these five, only one is likely going to be approved by the Food and Drug Administration (FDA).
What this means is that those drugs we find on pharmacy shelves are just a small fraction of the actual number of drugs that could have been in existence. But since lots of drugs fail the series of tests and trials they're put through, we only get to see a few on our medicine cabinet. Consequently, those few that manage to see the light of the day come for huge prices.
So for those of us who're still wondering why some drugs are so pricey, I guess that explains why. But what exactly qualifies a drug for approval? You may wonder!
Well, the answer to that is what we aim to divulge within the context of this post.
The stages of approval
Before a drug can be accepted and approved for human consumption, it needs to first pass through nine developmental, testing, and trial phases.
Phase 1: Drug discovery
In this stage, the drug development company identifies a molecule (could be a protein or a gene) to target with a drug. Usually, this molecule has to have some relationships with the disease or condition that the said-drug is going to combat.
In reality, the drug development company could have many molecules to work with at this stage. But at the end of this phase, they would have identified those molecules that actually have a good promise for the stages ahead.
Phase 2: Preclinical testing
This phase is divided into two stages, which are the in vitro and the in vivo testing stages. The in vitro testing stage, which is otherwise known as the "test-tube experiments," is conducted in a laboratory to examine the interactions of the selected drug molecules in test tubes. The in vivo testing, however, involves testing the drug molecules on animal models and other living microbial cultures.
At the end of this phase, the hundreds or thousands of molecules that were once identified as promising would be reduced to between one and five. The preclinical testing phase is one of the most tedious processes in the development of a drug, as it could last for a number of years.
Phase 3: Investigational new drug application filing
In this stage, the development company would send an Investigational New Drug Application to the FDA, informing them about your intentions. The FDA will now scrutinize the results you got from the preclinical testing phase, analyze for side effects, safety concerns, and other necessary features. Once approved, the drug developer is free to move on to the human trial phase.
Phase 4: Step 1 clinical studies
The first step of the human clinical testing begins by testing the drug on a few dozen healthy persons. Usually, the goal here is to observe how the drug is absorbed and removed from their body, as well as possible side effects, and whether it produces the desired result or not.
Phase 5: Step 2 clinical studies
This is the mid-stage trial phase, and the difference between this phase and the early-stage trial phase above is that the patient pool widens from a few persons to a 100 or more. And that's not even all; the people being treated in this phase are no longer healthy volunteers but actual patients that are suffering from the disease or condition the drug is supposed to combat.
Phase 6: Step 3 clinical studies
This phase is designed by the drug developer but approved the FDA with guidelines for a clearly defined primary endpoint to determine the success or failure of a tested drug. This phase involves even more patient, perhaps a few hundreds or thousands. And it is, by far, the costliest of all the phases of a drug development process.
Usually, due to the expensiveness of this phase and the previous phases leading up to this point, most drug developers outsource their clinical trials to a contract research organization (CRO) like Promedica International. The CRO will help them handle all aspects of their clinical trial, from site selection and patient enrollment, through to final regulatory approval from the FDA.
Phase 7: New Drug Application (NDA) filing
This is the stage where the drug developer sends their NDA to the FDA, telling them to "kindly look at their drug." However, it should be noted that the NDA can be tens of thousands or even hundreds of thousands of pages long, depending on the extent of research involved in arriving at the final result. It should contain all the research that has been done, as well as all the safety data examined during each of the six prior phases.
After the NDA is accepted, a Prescription Drug User Fee Act (PDUFA) is set 10 months down the road, for the FDA to make its decision.
Phase 8: PDUFA date and decision
Upon the PDUFA date, the FDA will respond in any of these ways:
- Approve the drug
- Outright deny the drug
- Request additional information by sending a complete response letter (CRL).
