The drug development and approval process in the United States is confusing, mysterious, and often misunderstood. As pharmacists, we are always on the lookout for cutting edge new prescription medications, and it’s part of our training to intimately understand how a drug gets onto our pharmacy shelves. However, we believe everyone should have access to this knowledge—not just healthcare experts.
In this article we’ve laid out exactly how a drug goes from pipe(tte) dream to pill bottles, and how that process might be sped up given the current coronavirus crisis.
In this first section, we’re going to take a look at exactly how new treatments and drugs are traditionally created.
STEP 1: Inventing the idea
Like with any new concept, someone needs to think of the new idea. This often occurs in university and hospital laboratories, where graduate and doctoral students, professors, and researchers receive grants to research potential new treatment avenues. Often, these grants come from pharmaceutical companies themselves.
STEP 2: Preclinical testing (~3.5 years)
Before a drug can be tested on humans, a pharmaceutical company must test the drug in laboratory settings (such as through computer models) and cell and animal studies. In these preliminary trials, the drug must show promise as a treatment for the target disease. This is an important safety step.
STEP 3: Investigational New Drug Application (~30 days)
This is when the U.S. Food and Drug Administration (FDA) gets involved. The drug manufacturer that performed the preclinical testing must now file an Investigational New Drug Application (IND) with the FDA. This application includes information such as the results of STEP 2, the plan for testing the drug on humans, the chemical description of the drug and its mechanism for working in the body, side effects or negative consequences found in animal testing, and the manufacturing process of the drug. As long as the FDA does not reject the IND within 30 days and it is approved by the Institutional Review Board (which ensures ethical testing), then the pharma company can now move forward with testing the drug in humans.
STEP 4: Clinical trials (~6 years)
Over the course of three phases of studies, the drug manufacturer will investigate how the drug works in humans:
- Phase I (~1 year): The drug manufacturer will rely on around 20 – 80 healthy people to volunteer for the study. The point of this step is to figure out the range of safe doses for the drug, how the drug is absorbed and processed by the body, and how long its effects last.
- Phase II Clinical Trials (~2 years): Now, around 100 – 300 volunteers with the target disease participate in a study to see how effective the drug is at treating the intended disease. This is also when minimum and maximum doses are established.
- Phase III Clinical Trials (~3 years): This is one of the most important studies done on the drug because it is these results that are submitted to the FDA to get the drug approved. Around 1,000 to 3,000 people participate in these large, randomized studies in order to definitely determine side effects and effectiveness.
STEP 5: New Drug Application (~2.5 years)
The drug manufacturer now files this application, which includes all of the data, results, and analysis from the clinical studies done in STEP 2 – 4. The average length of one of these applications is 100,000 pages. The FDA then reviews all of this information to ensure the safety and effectiveness of the proposed drug. It is advised by the FDA Advisory Board, a team of physicians, pharmacists, chemists, pharmacologists, statisticians, and patient representatives who make a recommendation regarding whether or not to approve the drug.
STEP 6: Release the drug to the public
Once a drug is approved by the FDA, it may be eligible for market exclusivity. This grants the sponsor exclusive rights to market the drug, typically for 5 years (but it’s often extended). In other words, their version of the drug will be the only version on store shelves for that period, and they alone may profit off of its sales. That means in normal circumstances, drugs are often much more expensive at least for the first 5 years on the market.
The period of market exclusivity granted to the manufacturer is an incentive for companies to complete this timely and expensive process. It also may overlap with the manufacturer’s patent protection. So depending on when the manufacturer files the patent for the drug, their exclusive marketing rights might be even longer than the 5-year exclusivity period granted by the FDA. However, once their patent expires, other drug manufacturers can develop generic versions of the same medication, which usually drives the price down.
STEP 7: Phase IV Studies
These studies occur after a drug has been approved by the FDA. They collect information from patients already taking the approved drug outside of a clinical trial setting. This allows researchers to answer questions like:
- How does the drug work in groups of people who may not have been represented in the clinical trials?
- Does the drug remain effective if you take it for a long time?
- Are there side effects of the treatment that you only see a long time after starting the medication?
- If a patient is not closely monitored for side effects, what outcomes might they have?
These studies aim to make up for the limitations of previous clinical trials, which often have a limited duration of treatment and follow-up with the patient and limited sample size, potentially excluding the elderly, children, and patients with conditions in addition to the one being treated.
Expedited process possibilities during COVID-19
It is rare for drugs to be fast-tracked, but sometimes, special circumstances arise that necessitate an expedited version of the drug approval process. The current global coronavirus health crisis is a prime example. In this case, some modifications such as the following might be made.
Inventing the idea
Not every idea needs to be completely new. A drug approved for one disease might be a viable treatment for a completely different condition. For instance, bupropion (Wellbutrin) was first approved to treat depression and later approved for use in quitting smoking (Zyban).
This also applies to COVID-19. Since researchers are pressed for time to find a viable treatment, it can be faster to first look at existing drugs to see if any of them could help with the novel coronavirus. You might have seen news coverage about remdesivir, hydroxychloroquine, and other drugs being investigated as a potential treatment for the coronavirus in addition to its existing uses.
The FDA approval process
There are a couple of different ways in which this approval can be sped up so that a drug might become accessible to the public faster.
- Accelerated approval of the new drug application: Introduced in 1992, this allows drugs for serious and life-threatening conditions to go to market faster. Studies are done in tandem to prove that the drug is truly working. If those studies do not show results, then the FDA accelerated approval is withdrawn.
- Fast track: This is for drugs that show promise for serious medical conditions that do not currently have any treatments. They must first show some positive results from studies done on either humans or animals.
- Priority review: In this case, the FDA prioritizes reviewing this new drug application within 6 months rather than the typical 10 months.
- Compassionate use: The FDA authorizes an existing drug to be used to treat a condition different from the one it is officially approved for. We saw this in the case of hydroxychloroquine and remdesivir for treating severe cases of COVID-19. This option is typically reserved for life-threatening cases of a disease where there are no other options for adequate treatment. This usually only applies to inpatient treatments.