Dr Rina Irene Fermont
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Neichü Mayer
Israel
Dr Rina Irene Fermont, MD, MSc, an internationally known figure in the field of Pharmacovigilance, is a Physician and Immuno hematologist with an additional masters’ degree in Bioengineering from Ecole Centrale Paris. Her leadership and initiatives in creating Pharmacovigilance departments in France led to the definition of ‘misuse and medication errors’ in French Good Pharmacovigilance Practices, years before the European guidelines came into being. She is an ‘EU qualified person for Pharmacovigilance’ (EUQPPV), who is legally responsible for the continuous evaluation of the benefit and risks of medical products within the EU, and responsible to ensure that the marketing authorization holder’s Pharmacovigilance systems are in compliance with EU requirements. She has over 25 years of experience in drug and vaccine safety monitoring, risk management and risk communication. For years her IFC consultancy firm had offices in Paris, London and Jerusalem, which provided strategic consulting in Pharmacovigilance and risk management.
Prior to becoming a drug safety expert, Dr Fermont was responsible for the creation of a bone marrow graft unit in France, including both the treatment of patients and the recruitment of donors.
In 2013, Dr Fermont and her husband moved to Jerusalem, Israel, to be near their children and grandchildren. Her outstanding contribution to Israel in the field of drug and vaccine safety has been hugely applauded, and she has made the French immigrants in Israel very proud. She believes her Jewish faith has a major role in shaping her outreach in the world.
Today, Dr Fermont is an active member of the International Society of Pharmacovigilance (ISOP) and is chair of the Israel chapter of ISOP, which functions now under the new association she created, ERANIM ISRAEL Society for Medication and Vaccine Safety, and they have been closely, monitoring the rollout of Covid-19 treatment guidelines and vaccines.
I sat with her to hear her take on Covid-19 vaccines and its impact on the world opening up again.
Q: In March 2020 when our country went into a complete lockdown and many of us found our lives come to a standstill, you became extremely busy researching, communicating with experts around the world, trying to understand what was going on and finding ways to help bring sense to the situation. What was that like?
A: It was incredible. For the first time in my life, I saw in real time the resilience, the human capacity to cope with uncertainty, but most importantly the willingness to work together and learn from each other like never before. As soon as we had the genome coding of the new coronavirus from China, (which later became known as Covid-19) in January 2020, the scientific community realized that everyone will need to work together unreservedly towards the development of an effective vaccine suitable to everyone in the world. For someone like me who has seen for more than 25 years the struggle for investments in effective vaccines, or critical life-saving drugs, it was exciting to watch governments and philanthropists pledging grants and support towards Covid-19 vaccine development. It was also a very difficult time as we were all watching the toll on our health system and so many people dying all over the world, unable to breathe. It was scary because we didn’t know how long this was going to last and if our economy and social systems will survive the threat. People were very confused. Even people who understood diseases and knew how to treat them, were at a loss. One moment you think it was a temporary condition, which will go away with time or with the change of weather, and the next moment you realize that it is going to get even worse and that there is no certainty whatsoever, regarding the disease itself or the treatment. We were facing a global threat, a pandemic.
All my life I have been engaged in monitoring and communicating risks related to drugs and vaccines. My audience has always been health professionals or experts. When Covid-19 struck, I realized I have a responsibility to communicate not just to health professionals but also to common people from all walks of life. As news of the spread of the virus broke out, we were bombarded with questions and enquiries from all over the world. We had to talk directly to the people. We had to communicate what was happening whether it was about treatment or the processes with vaccine development. A team of 20 volunteers, high-level physicians, pharmacists and scientists was set up in a blink, as the Vaccine Task Force to deal with this challenge.
Since the outbreak of the virus, we have facilitated over 40 webinars and answered hundreds of questions in writing or otherwise, and till today continue to share what we are learning in real time, in French, in English and sometimes even in Hebrew. Covid-19 has changed the way we deliver health services completely. For over 10 years we have been talking about the importance of Telemedicine, and the use of Robotics and Artificial Intelligence in health care delivery. Now we are using these technologies, and using them effectively. Those of us committed to health protection and safety formed a global network and activated each other to think and act outside the box. I have never seen anything of this nature. The manner and speed at which the vaccine was developed must be understood from this perspective too.
Q: Our country, Israel, is now known to be the most Covid-19 vaccinated country in the world, we lead the world in providing real time data on vaccine efficacy and we are the first country to introduce booster shots. You have been following closely all the data coming out from Israel. Can you say that the Covid-19 vaccine is effective? What is your take on the Israel experience?
A: From what we now know about the vaccine, we can say it works and it works effectively. From the very onset, we acknowledged that these vaccines would provide protection from severe disease, hospitalization and deaths, and that is exactly what it is doing. Here in Israel we are using mostly the mRNA vaccines from Pfizer-Biontech and Moderna. Most of us were fully vaccinated by January 2021. However, during last few months we have seen strong data indicating the waning of antibody levels after a period of six to eight months. And that is why we decided to go for a booster shot. It was a very courageous decision. I must say it was a bet, even if taken on a very plausible immunologic mechanism, that Israel chose to be 1st to take this decision. It turned out to be a good strategy, followed by the FDA, by the EMA and many other countries
The latest data from our largest health management organization, kupa tholim Clalit, with support from Harvard, is showing that the booster shot is hugely effective, especially in coping with the easily transmissible delta variant, and hopefully, it will work for other variants, too. I want to explain to you how the booster shot works. The 1st and 2nd jab of the vaccine enables our bodies to develop antibodies that give strong immunity against the virus. These antibodies help to lower the risk of infection or even if infected, it lowers the risks of getting very sick. But after a few months, the level of antibodies begins to drop, although the efficacy of the vaccine still remains fairly high. So a booster shot is given to boost the existing antibodies so that they can reproduce and remain strong. There is strong evidence showing that with this additional shot, the body starts making higher quantity antibodies that are stronger at recognizing and blocking new variants of the virus. I think we can say that because of the efficacy of the booster shot, although we had a very high infection rate with the delta variant during the months of July to September this year, we were able to stop the 4th wave extension.
To your question about the Israel experience, let me add this - Israel became a pilot country for collecting real time data on Covid-19 vaccine efficacy and safety because of the very high standard of our health system. The health data management system we have here, even most developed countries in the world do not have. We were able to analyze every aspect of the vaccine safety and efficacy in real time. We were the first country in the world to report what has now become a rare side effect of the Pfizer-Biontech vaccine amongst young male adults, myocarditis a heart inflammation condition. We identified this issue very quickly, and immediately informed and educated our health care providers about it, which led to quick diagnosis and treatment. So although we see this side effect, it does not alarm us because we know how to deal with it. Data also shows that this side effect is not severe and is rare when compared to the severe myocarditis observed in Covid-19 patients. Likewise, we are aware of other side effects from the vaccine itself or from the booster shot such as local reactions, flu-like reactions, allergic reactions, rare facial muscle weakness or in some women changes in menstrual condition. Our approach is to always weigh the risks by comparing the risk of taking the vaccine or the risk of not taking the vaccine. And the real life data have shown repeatedly that the benefit of the vaccine outweighs by far the risk of adverse reactions. Whatever we learn from our experience here we are sharing with the world and we are leading the world in analyzing real time data on all aspects of Covid-19, whether about treatment, vaccine or preparedness for other such pandemics.
Q: What is the difference between immunity from having Covid-19 and immunity from getting the vaccine?
A: It is interesting that you are asking this question because only this morning I read a paper claiming that if you have had Covid-19 and later took the vaccine, you become super immune. More studies need to be done to prove this but already we are seeing that immunity from having had the virus and from the vaccine added together is very high. However, natural immunity from having had COVID-19 varies from person to person and although it looks quite strong, it seems less predictable than immunity after vaccination. Previously infected people could very well become ill a second time, especially with new variants, as observed with the Delta variant, everywhere.
As mentioned earlier, we have very strong evidence of the effectiveness of the vaccine. Therefore it is very important to receive the vaccine even if you have been infected with the COVID-19. What we also know is that COVID-19 is a very serious life-threatening disease that can have long-term consequences. A cardiologist colleague of mine kept reminding me that this disease is extremely awful, and its consequences are much worse than we predicted. So, it is much safer to get vaccinated than to risk getting the virus. COVID-19 vaccines have been authorized by the highest health agencies in the world and have been safely given to billions of people. We encourage everyone to get vaccinated not just to protect themselves but others around them too. My daughter said that she is very proud of the fact that all her family members eligible to get the vaccination have done so because ‘it is our civic duty’. I thought that was so true and it touched me to hear that. We all have a responsibility to keep each other safe.
Q: Can you please explain how the various vaccines work and if all the existing ‘approved’ vaccines are considered effective?
A: Let me begin by explaining that when a vaccine is approved for use amongst the general populations, it means that the vaccine has been evaluated by experts from different disciplines - toxicologists, epidemiologists, clinicians from several specialties such as infectious disease specialists, immunologists, geneticists, pediatricians, pharmacologists, etc., and it also includes statisticians and methodologists, Pharmacovigilance specialists and risk managers; and quality control experts. And then, authorization for manufacturing of these approved vaccines is subject to the manufacturer’s risk management plan, mandatory vaccine monitoring, the continuation of clinical trials, logistics monitoring and regular inspection of factories and companies. This shows that getting a vaccine approved is a rigorous process and usually takes 10-15 years. The covid-19 vaccine has been one of the fastest approved vaccines in human history, and there is an explanation for this but sadly, many people are unwilling to go the extra mile to learn about it.
The following chart explains the difference between the traditional approach and the new technology approach, used specifically in the Covid-19 vaccine development:
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The unprecedented development of the Covid19-vaccine, especially the mRNA vaccines was due to several factors. These include the use of a new technology, mRNA, which allows the coding of the antigen of the spike without any contact with the virus, and which is very quick to manufacture; going through different phases in parallel; a study of the dossier by the agencies in real time during the development and not at the end as usual, with prioritization of all human resources toward this dossier; the massive funding and taking of huge financial risks in building the manufacturing plant during the development without knowing if the vaccine will be authorized.
The technologies using DNA and mRNA have been going on for 15 years. The companies Bion Tech-Pfizer and Moderna, which use the mRNA technology, have been able to rely on their existing experience in pre-clinical (animal) studies and also in small clinical studies (in humans) during Ebola, Zika, MERS, SARS1 pandemics. The pre-clinical and clinical data collected during that time was very helpful to start more quickly the clinical trials for COVID-19 vaccines. The new technological platform was also used with other vaccines such as Ebola, Zika and also in cancer indications and veterinary medicine.
Covid-19 vaccines have been developed using the following new technologies:
• mRNA and DNA technology, a cutting-edge approach that uses genetically engineered RNA or DNA to generate a protein that itself safely prompts an immune response. E.g. Pfizer- Biontech and Modernam RNA vaccines
• Inactivated or weakened virus vaccines, which use a form of the virus that has been inactivated or weakened so it doesn’t cause disease, but still generates an immune response. E.g. Covaxin
• Protein-based vaccines, which use harmless fragments of proteins or protein shells that mimic the COVID-19 virus to safely generate an immune response, E.g. Nova vax
• Viral vector vaccines, which use a safe virus that cannot cause disease but serves as a platform to produce coronavirus proteins to generate an immune response. E.g. Janssen/Johnson & Johnson and Astra Zeneca and Oxford University
In summary, the new technology is used in both conventional vaccines which contain the antigen and the genetic vaccines which used messenger RNA and DNA to give the code that will encode the antigen.
Three drug and vaccine approval agencies are considered the gold standard in the world. They are the agencies of Europe, the USA and Japan. Any drug reviewed by these agencies I personally consider highly safe. There are other agencies that also have strict and rigorous approval procedures and they too are reliable. However, in some countries, the data they provide do not match the international standards of regulatory requirements and sometimes their data are not fully reliable. So I tend to have some reservations.
Democratic countries have counter-power. They have watchdogs. They have active investigative journalism and civil society organizations that demand accountability from their governments. So it’s easier to trust data coming from democratic countries, also because you can ask them difficult questions. Having said that, I must also mention that many countries in Latin America are using Chinese and Russian vaccines, I can say that in Latin America there are some very professional and efficient agencies and they are saying that these vaccines are working, so this news makes me hopeful.
Q: I know you love India, like many Israelis. Tell me more about the Indian vaccines. What are you learning?
A: I have been to India privately and professionally. I have amazing Indian colleagues that I keep regular contact with and I am following their research closely. Over the years, India has been the largest manufacturer of vaccines in the world and also for other life-saving drugs. We have great faith in India’s manufacturing capacity. India plays an important role in the manufacturing of Covid-19 vaccines, which are distributed in many countries. Sadly, when the delta variant broke out in India, the massive spike in cases trampled their health systems badly, and they found themselves lacking sufficient vaccines for their own citizens. That was very unfortunate and painful to watch.
Now that their vaccination campaign is back in full swing and showing encouraging positive results, I think we can expect some valuable data for all of us to analyze. I am very impressed to see that within a few months India has been able to vaccinate more than a billion people.
The two WHO-approved Indian Covid-19 vaccines are Covishield and Covaxin. The Serum Institute of India is one of the largest manufacturers producing Covishield for Astra Zeneca, not only for India but also for the world.
Covaxin is the first Indian Covid-19 Vaccine produced by Bharat Biotech, as a whole inactivated virus. On 3rd November 2021, the World Health Organization (WHO) issued an emergency use listing (EUL) for COVAXIN® adding to a growing portfolio of vaccines validated by WHO for the prevention of COVID-19 caused by SARS-CoV-2.
Learning lessons from India is very helpful to the world. India has a massive size and scope like no other. I hope the lessons they learned from this crisis will help to improve their health systems.
Q: Almost all countries are facing vaccine hesitancy despite high evidence of safety and efficacy of the vaccine. Why is this? What are we missing in our communication strategy?
A: We are living in unprecedented times. The speed at which the vaccine has been developed impressed many of us but has also caused many to doubt and fear. As I mentioned earlier, the use of extremely mind-boggling new technology, the unimaginable collaboration across the globe and the massive investment in the development of the vaccine led to where we are now and yet there are more fake news and conspiracy theories thriving than science-based evidence. In human history, there has always been a cynical group of people who opposes vaccines of any form. And they have their own agenda for that. Unfortunately, the same technology that has helped us to connect with another instantly and share information and get help, is now being massively used to spread misinformation. I think the only way to break through this is to continue communication directly with the people with evidence-based information. Each of us is responsible to answer to fake news and to stop spreading it.
Q: May I ask if the existing vaccines can keep up with any possible variants?
A: I don’t know. Nobody can answer that question. But I can say this, we have learned a great deal from the delta variant. In May 2021, here in Israel, we decided that we are going to open and rebuild our economy and all other institutions, which suffered hugely from the lockdown and all the restrictions. We were very optimistic. We have had a successful rollout of the vaccine, we have found some very effective treatment regiments, and our daily infection rate has reached the lowest in months. And we were all getting exhausted from the isolations and restrictions. We let go too much too fast. So boom, suddenly the delta variant was detected and the transmission rates shot up in no time. We were back to a crisis, a very bad one. Fortunately, we managed to curb it with the booster shot and placing restrictions on indoor gatherings and installing the green pass again. We learned from this experience that we cannot afford to drop our guard.
We need to be vigilant and to continue strict monitoring of our airports and borders, besides keeping the basics of mask-wearing and social distancing. With most people having been vaccinated and thereby becoming a herd community, we may be seeing a small light at the end of the tunnel. Experiences from the 1918 Spanish flu and also the 1968 Hong Kong flu, shows that when the virus is unable to mutate it begins to die off naturally. So that too is a possibility with Covid -19. But we don’t know yet.
Q: Despite most of us being fully vaccinated, mask-wearing or social distancing is still highly recommended and it seems that it will continue long term. Why?
A: Yes, the virus is still out there and active. And there is sufficient evidence to indicate that we are nowhere near the end. We also know that the virus is mutating into various variants, some of which are proving to be highly contagious. So we need to keep the mask and maintain social distancing to prevent the spread. Sadly, many adults refused to be vaccinated and that has put them and others around them at higher risk.
Q: Your grandson, Ethan and my son have been best friends from kindergarten. They are both turning eight years of age, and just this week our government has decided to offer the Covid-19 vaccines to them and all children ages 5 to 12 years. I understand you have other grandchildren around those ages. Should we comply with the directive from our government and vaccinate our children or should we wait to see more data related to vaccine safety for children?
A: Look, I am also French. I cannot stop myself from hugging and kissing my grandchildren. But every time I cuddle them, I am conscious of the risk of such close physical proximity during corona times and it is not a good feeling. Just as much as I feel safe having been vaccinated, I want my grandchildren to feel the same. Having said that, vaccines are always first approved for adults and only after sufficient evidence of safety are recommended for children. I am more concerned about the many adults who still have not received the vaccine than about vaccinating children. The recommendation for children is a much lower dose, and we are closely monitoring the impact or risks if any. Now in the US, FDA has also approved vaccinating children. Within one to two months, the USA will provide data on the vaccination of children. Parents who hesitate to vaccinate their children will soon have more information to make their decision. Personally, I would like to see more pressure on unvaccinated adults. Many vaccines in the world are mandatory, which have been accepted and complied by all. I don’t understand how we can speak of individual freedom in a time of pandemics when your decision endangers others and the high number of non-vaccinated severe patients is massively contributing to overwhelm the healthcare system. This issue is highly concerning for me.
Q: Lastly, we are opening our borders after nearly two years of imposing complete travel restrictions. Are you concerned?
A: The airport will be one major gateway for new variants to enter. We must keep our guard fully on and do everything possible to monitor the situation, anywhere in the world. Should there be an indication of any major breakout anywhere, we need to act swiftly and responsibly. If our government is putting all the safety systems in place, I think it is only befitting for us to open our borders again. But we need to do it slowly and vigilantly.
Q: Thank you very much, Dr Fermont for your most valuable insights. I look forward to continuing this discussion in the coming months.
A: You are welcome. Shalom.
