PharmaFiles #4

How Government Regulators Turn Into an Extension of Big Pharma.

Understanding the role of Government Regulators and the drug approval process is essential to get a clearer picture of why an experimental mRNA vaccine that was not thoroughly tested for long-term side effects got released to the entire population.

There are two main hurdles when Big Pharma wants to sell a brand new drug in any country. First, they need to get approval for the drug. Secondly, some countries must negotiate and agree on the drug's price with the Central Government purchasers.

Approval of drugs is done by presenting data to the regulators. The departments in Pharma responsible are the Regulatory departments. These are heavily funded departments. Regulatory Departments are responsible for understanding the official approval process, as every country has different nuances. They need to know the government stakeholders, their approval processes, timelines, meeting schedules, etc.

Usually, these Government regulators meet at a specific frequency and have a stack of "New Drugs" to approve. In addition, there are committees of experts from various specialties depending on the type of drugs to approve.

For example, for approval of Vaccines, they will engage virologists, vaccinologists, immunologists, epidemiologists and other experts in their respective fields. And for a cardiovascular drug, they will engage a team of cardiologists.

The Pharma companies submit a large stack of documents called "Clinical Trial Dossiers". These contain all the clinical data from the clinical trials of Phase 1, Phase 2 and Phase 3 of the New Drug.

There are various stages in Clinical Trials. I will simplify each of the stages here.

Preclinical - The Preclinical Stage involves in vitro and in vivo experiments. In layman's terms, In-Vitro means testing them in Petri dishes and test tubes. In vivo means experimenting with them in animals.

Phase 1 trials are the first tests of a drug with a small number of human subjects. They are designed to assess the safety and tolerability of a drug. Usually, this process takes a few months. When a drug passes Phase 1 trials, it goes to Phase 2. Usually, less than 30% of drugs pass through Phase 1 because of severe side effects and sometimes death.

Phase 2 trials are performed on larger groups of patients and are designed to assess the drug's efficacy and continue the safety assessment. Usually, this process takes a few months to a few years.

Phase 3 trials are randomized controlled multicentre trials. This is the most critical part and provides the most long-term safety data. They are tested in multicentre to get a varied population demographic - for example, trying them on different countries because different races react to different dosages (i.e. Asians generally having smaller body mass sizes might respond to a different dose to a Westerner). Usually, Phase 3 trials last 12 months or longer with thousands of Patients. 

Once Phase 3 is complete, and if they get a favourable result, this is where Pharma presents all the data in the "Clinical Trial Dossier" to Government Regulators.

The Clinical Trial Dossier will include all kinds of data, from the drug's efficacy to side effects, including Pharmacokinetic and Pharmacodynamic studies.

Pharmacodynamics means "what are the effects of drugs on the body" (i.e. does it kill the virus, harms our cells etc.).

Pharmacokinetics means "what does the body do to the drugs" (i.e. how long does the drug remain in our body, how does our body expel the drug etc.)

Usually, the approval process by Government Regulators takes anywhere between 6 - 18 months, depending on the type of drug and whether there is an urgent need. An urgent need means for a particular disease, there may not be existing treatments, so in such cases, they accelerate the approval process.

So, in general, a drug goes through 5 to 7 years of Phase 1 to Phase 3 studies and another 6-18 months of discussions with Government Regulators before they are approved to be sold in a market.

Then, they move on to Phase 4, called Post Marketing Surveillance trials, because these drugs are now distributed to the population.

Many decades ago, clinical trials used to be rigorous. Government Regulators demanded a high number of human test subjects in Phase 3 studies, usually in the thousands, because the more human subjects, the more accurate the study is.

But in the last 20 years, it has become more relaxed. For example, in 2013, Gilead's Hepatitis C drug Sovaldi only went through a Phase 3 Clinical Trial with 450 participants. Many of us in the Pharma industry were surprised that the FDA approved a drug with a small number of human subjects.

So over the years, Big Pharma started finding ways to shorten the Regulatory processes to avoid costly clinical trials.

Regulators became more and more relaxed because, over time, the government started hiring Pharma folks because they knew the approval processes intimately. They are also well acquainted with each other because they have attended many meetings and discussions. As a result, relationships developed over time.

In the end, instead of having extensive meetings to discuss Clinical Trial Data such as Pharmacokinetics and Pharmacodynamics, it became efficient to say, "trust me, bro", to some ex-colleagues you worked with before. Eventually, Big Pharma penetrated the highest level of government regulators and started playing musical chairs with the industry. That's why you get something like this.

When Donald Trump launched "Operation Warpspeed", it cut the regulatory processes even further. Instead of having Phase 1 to 3 done over 5-7 years, many shortcuts were approved, and the process took only two months!

Because it took only two months, many studies were skipped, such as the Pharmacokinetics and Pharmacodynamics of the mRNA Vaccine. On top of that, the vaccine was rushed through FDA's approval haphazardly, and they did not engage the proper experts in approving the mRNA. The reason is that the mRNA is gene therapy, but it went through the FDA's vaccination committee. As a result, they had the wrong experts going through substandard clinical trial results and then fast-tracked through a process called Emergency Use Authorization (EUA).

Usually EUAs are reserved for terminally ill patients who are already dying. In those cases, most of them are willing to try any experimental drugs regardless of side effects. However, because of Pharma fear-mongering, the mRNA vaccines were rushed through EUAs and deployed into the entire population. With more than 65% of the world's population vaccinated, it has created a time bomb because we do not know the long-term side effects.