By: Nainika Majumdar; An Interview With Dr. Kaushik Mitra
Technology and an ever-changing consumer market promise to further revolutionize our pharmaceutical industry. With recent and exciting advancements such as the creation and development of the COVID-19 vaccination and effective cures for cancer, it is increasingly important for us to understand the drug development process and to distinguish
misinformation from facts.
To help us understand the process, we sat down with Dr. Kaushik Mitra. Kaushik Mitra is a scientist at Johnson and Johnson and is involved in the discovery and development of medicinal drugs for a wide variety of diseases such as Alzheimer’s, cancer, kidney diseases etc.
Our Interviewee:
“When I was around the age of 15, my grandfather passed away from cancer. I think that’s what first piqued my interest in the whole pharmaceutical field. After that all the pieces
kind of fell in place” he recalls.
As a young undergraduate, he studied with honors or majored in chemistry. After moving to the U.S. he earned his Ph.D. in organic chemistry at the University of Missouri, Columbia, and subsequently conducted post-doctoral research in biological engineering at the Massachusetts Institute of Technology (MIT).
Dr. Mitra states, “The drug development process is long. It takes on average 10-12 years and at a cost of around 2 billion USD to create, test, and export market one, particular drug.”
The first step in the drug development process is to choose the disease one is
targeting to cure.
The First Three to Four Years:
To begin creating a drug, one must first understand the molecular biology of the disease and
identify the mechanism or process by which the disease spreads. They then have to identify the target or the particular biological pathway/molecule in the body which aids the mechanism. The drug will then be designed to combat that specific target. To find the target, scientists have to find the “players,” or the molecules that will interfere with the biological pathway that is involved in the disease mechanism.
After understanding the mechanism and establishing the molecule, one has to prove
that it is not only effective in curing the disease, but is also safe.
“Once you find a drug that works to cure the disease, you realize I don’t wanna cure someone with Alzheimer’s and give them cancer. I know that this [the drug] works, but now I have to derisk it; make it safe,” he explains.
Preclinical trials start with the invitro process, during which drugs are tested on animal, and human body samples such as blood or tissue. The invitro process does not involve nor affect any living organisms. After studying the molecule in vitro and then in vivo in animals, the next 3-5 years are spent on clinical trials that probe the efficacy and safety of the molecule in humans.
Clinical Trials:
Animal and human trials follow.
In the first phase of human trials, a small sample of around 10-30 healthy individuals are dosed with low amounts of the drug. After two-three weeks, the dosage amount is increased in small increments. The purpose of this phase is to test if the drug is safe for humans and to collect data about the drug’s pharmacokinetic behavior. It is important to note that the first phase does not test the drug’s success.
In the second phase, the drug is tested on patients. The purpose of this second phase is to test whether or not the drug is effective. In this phase, the testing population increases in size. On average, at this stage of clinical trials around several hundred people are tested. Like in the first phase, they receive a gradually increasing dosage of the drug over a period of time.
The last phase of the clinical trials is to test the drug on thousands of patients from all over the
world. Testing the drug internationally ensures that the drug is effective and safe for people from all sexes, races, ethnicities, and genetic backgrounds.
After concluding the clinical trials, scientists normally reach the 9th or 10th year of the drug
development process.
At this point in the process, it is important for scientists to understand and assess the long-term effects of the tested drug, as clinical trials only run a course for a couple of months to a couple of years. How are scientists sure of how the drug is to react 10 years from the clinical trials?
Well, scientists arrive at that answer by putting together data, at a molecular level, from the
multiple studies already conducted.
After animal trials are concluded, animal body samples are studied in detail down to the cellular level. If there are observations or changes after a year or 18 months of dosing, even though they are not expressed as adverse effects, the drug can potentially be taken off the market. In addition, even after the drug hits the market, all data received from the drug and its
effects on patients are evaluated. Though rare, there are cases where side effects aren’t
caught in animal and human clinical trials. In consultation with regulatory agencies across the
world, such cases are studies and details, and decisions are made whether the benefits from the drug outweigh the potential risk. Often, these cases receive a “Black Box Label”, issued by the regulatory agencies such as the Food and Drug Administration or FDA, that specifically informs patients of adverse side effects
“I recall an experience when I had been working on a drug to treat obesity. We had reached the final stage of our clinical trial when we got reports of severe anxiety and depression in subjects” Dr. Mitra explains a case earlier in his career. for.”So, while the drug was effective, it
could not be marketed due to such adverse effects.
So as you can see, it is quite clear that clinical trials are taken very seriously.
“The Amazing Covid Vaccine”:
As previously mentioned, it takes a minimum of 10 years to fully create, develop and
market a drug. So how were scientists and drug developers able to achieve a decade’s worth of work in a couple of years for the COVID vaccine?
Having recently attended a conference discussing the same idea, Dr. Mitra explained the
importance of innovation.
“At the time of COVID-19, there were external influences that forced us to work smarter. There
was a need. Now the question arises: could we as a scientific community be more innovative
just by creating those artificial pressures ourselves? Why do we need COVID to respond
intelligently?”
As a result of the EUA or Emergency Use Authorization announced by the FDA, the COVID,
vaccine distribution was expedited. However, the vaccine did still meet all necessary testing
requirements. This means that contrary to popular belief, COVID vaccination testing did in fact
complete all its clinical trials. Note that research on the SARS virus, of which COVID is a particular kind, was already decades old as similar viral outbreaks had happened earlier, so
scientists could leverage that knowledge.
While there were some adverse effects caught later such as mild neurological symptoms, or
inflammation of the heart muscle, there is a clear positive benefit vs. risk assessment with this vaccination -its a question of whether people are willing to experience some short-term side effects, or contract COVID which may be fatal.
“It is also important to remember that COVID infection results show up within hours, days, or
weeks so it is easy to monitor how the drug is responding. Hence the clinical trials are moving at a much faster pace compared to say Alzheimer’s disease where there is a much
longer natural period needed for those results to appear in people, thus shortening the time
frame.”
What many often forget as well is that the COVID-19 virus is a viral infection that is much
different from Alzheimer’s or cancer. While we understand the mechanisms of viral diseases, we are still struggling with understanding the mechanisms of other more complex diseases.
“For example, the mRNA technology Moderna used for their vaccination has been around since the 1970s. While it took some time to figure out how to apply the technology to the specific COVID vaccination, scientists have experience and significant knowledge of the technology and its versatile uses.”
The Future For Our World:
As the new generation of drug developers, and scientists make their way out into the world, it is only natural for new, major changes to occur in the pharmaceutical field. A. I (artifical
intelligence) technology, for example, is starting to make a change in the drug development
field. AI is a branch of computer science that can simulate human intelligence. Let us think about Netflix. As you use Netflix, it gradually begins to suggest movies or TV shows that the website thinks you may like based on shows you have watched, and others with similar taste.. This is a simple example of artificial intelligence. Biology is not that simple. Just because one patient experiences one specific side effect doesn’t necessarily mean that another will experience it the same way or at all. Biological pathways are so varied and diverse that it becomes difficult to design or curate “patterns” in data which is essentially what artificial intelligence is all about. Thus, application of AI in drug discovery is quite complex and scientists are still exploring on how to best leverage this powerful tool. However, according to Dr. Mitra, there are gradually more and more versatile uses of AI technology being applied to specific sections of the drug discovery process, such as designing clinical trials with lesser number of subjects or for a shorter time period with no compromise in data quality.
Aside from his work as a scientist at Johnson and Johnson, Dr. Mitra will be partnering
with the University of Missouri this fall to create a multi-semester course that takes
students in-depth into the drug development process.
“I hope to see an unbridled passion and curiosity for innovation in the new generation of scientists,” he says.