According to the official government count, for the first time record, Indonesia hits the top 100,000 confirmed COVID-19 cases at the end of July 2020 and it still rising with 6,277 deaths as per 18th August 2020.
The chief of COVID-19 vaccine clinical trial coordinator, Professor Kusnandi Rusmil from Padjajaran University said President Jokowi requested the research team to expedite the potential vaccine candidate’s trial to just three months during a private meeting held at the State Palace in Jakarta on 21st July 2020. He added it could be impossible since we have WHO-regulated procedures to be followed for ensuring safety and efficacy.
Learn from the past
According to WHO, vaccination is among the most important developments in human health, saving 2-3 million lives a year. Currently, we are facing these overwhelming conditions, the outbreaks of coronavirus. Knowing it may be a long time for getting back our normal days – life without social distancing, wearing masks, school disclosure, and other control measures – until we found an ultimate weapon against this viral onslaught: a vaccine. Apparently, everyone on this earth has the same question, how fast will a vaccine be ready?
Almost all experts say that the 18-months target is too optimistic, the best-scenario could happen probably in the spring or even fall 2021 since the history of vaccine development is not encouraging. It took 26 years to develop a vaccine for the human papillomavirus, for instance, and 25 years to secure one for rotavirus. That’s for the ideal situation, but we all know these are not normal times, unprecedented.
Fortunately, With COVID-19, scientists already have a big head start, they are relying on groundwork from SARS and MERS outbreaks in 2003 and 2012, respectively. This isn’t the first coronavirus they’ve tried to make a vaccine for and spurred a lot of academic research on it. SARS and SARS-CoV-2, the virus that causes COVID-19, are roughly 80% identical. So researchers already knew a good target for a vaccine: the spike protein that sits on the surface of the virus, and especially the part that binds to human cells, enabling the virus to gain entry. The scientists are already on their fast-track and they can move to focus on other crucial parts ahead: the trials.
Step-by-step how a vaccine is made
There are 139 candidate vaccines in the preclinical evaluation and only 26 that are succeeding continue to clinical evaluation according to a compilation made by the WHO on 31st July 2020.
As a rule, researchers don’t begin testing people with experimental vaccines until after rigorous safety checks. It starts with a preclinical toxicology study in a laboratory scale that assesses whether a drug is safe to use and is tested on animals. That usually takes 3 to 6 months depending on the study’s design. Here are some few different strategies that they normally use to develop a vaccine:
- Inactivated the virus
- Live attenuated virus or heavily weaken the virus’ strain
- Pull out the virus genetic sequence (DNA or RNA)
If the evaluation is successful, the candidates go through to the three phases of testing in people, also known as clinical trials. Each phase has its special treatments, duration, and regulations.
Phase 1: The first trial starts on a small batch of people, a few dozen adult healthy volunteers to assess the safety and determine the type of immune response that candidate vaccine provokes, also gives a rough idea of how much vaccine is needed.
Phase 2: After that, researchers work out dosing and safety in more detail (immunogenicity, dose-response, immunisation schedule, and method of delivery) in a larger group. Especially, few hundreds of people who are at risk for infection, healthcare workers for example. Normally, both phases take 1-3 years to be done so that researchers can review the findings and get approval for the next phase, but these preliminaries can be dealt with just within a few months in case of an emergency.
Phase 3: The most time-consuming step in testing, because the researchers have to wait for enough volunteers to be exposed to a virus naturally. It must be given to a much larger group and compared with an unvaccinated control group, to see whether it really prevents the disease.
It needs thousands of populations to assess the safety and rare adverse events, simultaneously vaccine manufacturing consistency is confirmed.
The final part before the vaccine can be launched to the market is government approval. Sounds like a bureaucratic formality, but we need to keep in mind that their rubber stamp could cost lives. Typically take a full year for scientists and advisory committees to review the studies to make sure that the vaccine is really safe and effective as it is.
Moving at the pandemic speed and the roadblock
So, when the regulators expedite issued an emergency-use provision, the manufacturers start to speed the deployment, and what’s next? It doesn’t mean we’re going to get it; millions of people could be in line before us. Otherwise, before it gets massed produced, the doctors, nurses, and other essential workers could get vaccinated right away.
Developing biologics can cost hundreds of millions or even billions of dollars. We deal with a long, complex, and expensive process. Normally, less than 10% of drug trials are ultimately approved. The rest is failing whether due to less efficacy, the wrong kind of immune response, have too many side effects that weren’t previously noted, and sometimes can even make a disease worse. It can only find by researchers only after thousands or millions are vaccinated with that fast-tracked vaccine product. This stage is called post-approval monitoring.
Additionally, economic and financial hurdles are getting real. The manufacturing task is overwhelming, costing at least three times more than conventional pharmaceutical factories. That’s one of the reasons why most of the phase 3-vaccine candidates all over the world chose to develop DNA or RNA vaccines. Because RNA vaccines don’t need to be cultured in large quantities and then purified, they are much cheaper, easier, and faster to produce. On the other hand, it’s riskier than other established strategies since no one has ever made for humans before. One big open question is how safe and effective it really is.
Is it possible that Indonesia makes its own vaccine?
Start on 11th August, there are 1,620 volunteers aged 18-59 years involved in phase 3 clinical trials lead by the Faculty of Medicine, Padjajaran University, the collaborating project of state-owned pharmaceutical holding company Bio Farma with Chinese company Sinovac Biotech to secure access to vaccine candidates that using an inactivated virus method. The following projects soon to be confirmed also with the Bill Gates-backed Coalition for Epidemic Preparedness Innovations (CEPI). Furthermore, in the next months, the homegrown established health company Kalbe Farma will be partnering with Genexine for the phase 2 clinical trials of Genexine’s DNA vaccine.
The Indonesian government aware that they need to cover its large population of some 270 million people and it’s not enough to just rely on the outsources partner. Slow but sure, for a long-term strategic plan, a national consortium under the Research and Technology Ministry is working on developing its own vaccine, led by the Eijkman Institute for Molecular Biology. Currently, the vaccine candidates are on laboratory testing, using the recombinant protein methods to deploy the virus in the pre-clinical phase, they named it ‘Merah-Putih’ vaccine.
Despite these various efforts, targets, and different approaches to developing the vaccines, we have one big goal together that is to successfully eradicate COVID-19 in our life. Whichever company or university, whether it’s come from US, Europe, Russia, or Asia; that wins the race for the COVID-19 vaccine, it would be better to swiftly transfer its biotechnology as a pioneer across borders. We hope it can reach global access that might lead to the creation of more than one vaccine, effectively with different markets and different prices.
What we can do as an Indonesian citizen at this moment? The simplest thing is giving our best mental support to the government. They are really working so hard for the sake of national resilience from all aspects, health, and economics. Please put aside the underestimate biases and stigma that our volunteers as “guinea pig” of the experiment, specifically if the Sinovac vaccine trial that currently on-going turns out to bring the disappointing result since it is very normal to happen in the developing of biologic products that have 42% of failure rate in phase 3 of clinical trials. If it is yielding a positive result exactly on-time with the expected target from the government which is in January 2021, that possibly will be the fastest vaccine discovery ever in human history.
All those things above may seem like a long time to wait, but it’s worth every single action that comes from our scientists and health care workers. The most valuable thing that everyone can do right now is to help them to follow public health recommendations. Therapeutic drugs might likewise help to fight against COVID-19, at least they could lower the number of hospital admissions and help people recover faster, but still, take as many precautions as we can to prevent ourselves from getting this infection: wear a mask, regularly wash your hands, and keep social distancing.
written by: apt. Dian Rahma Bakti, S.Farm
a pharmacist who formerly worked for a giant multinational pharmaceutical company as a safety data management specialist, alumni of Fakultas Farmasi Universitas Indonesia.
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