Crafting Vaccines for a Better Tomorrow: Dr. Ramesh Matur's Story

Dr. Ramesh Matur is a distinguished Global Research & Development Executive with over a decade of experience in vaccine development and biopharmaceutical innovation. As the Senior Vice President and Head of R&D at Biological E. Ltd., he has led pioneering initiatives in the development of bacterial and viral vaccines across various platforms, from conception to securing global marketing authorizations. Known for his interdisciplinary expertise in integrating biology, chemistry, and engineering, Dr. Matur has a profound focus on regulatory compliance and strategic project management. His career includes leadership roles in clinical and product development, with a strong foundation in drug discovery, honed at esteemed institutions like Wyeth Research in the United States. With a portfolio that includes 29 published papers and nine patents, Dr. Matur is a recognized thought leader in vaccines and biotechnology, dedicated to advancing high-impact, globally significant healthcare solutions.

Pharma Now: Hello, Dr. Ramesh Matur, welcome to Pharma Now. It’s a pleasure to meet you. From what I know about you, you used to live in a small village, Warangal, and now, you live in the US and you lead the R&D Division of Biological E. Limited. It sounds like you had a fascinating journey. So, Dr. Ramesh, I would like to know more about your journey and how you ended up becoming the Division Head at Biological E.?

Dr. Ramesh: That's an interesting question, but let me make a small correction: Warangal is a town big enough to have its own regional centre, university, medical hospitals, and so on. So, I grew up in Warangal, and since my childhood, I wanted to become a scientist. But, I didn't know what a scientist did. I was always impressed by a saying in Telugu, which roughly translates to, “Scientists discovered this”. So, I always wanted to know how they discovered things. This was the inspiration I carried with me for a very long time. 

Many families in India want their kids to become engineers or doctors. So, even though I wrote the MBBS entrance, an unspoken thought remained in my mind: “If I get a seat, would I become a scientist–something I always wanted to be?”

Unfortunately, I didn't know how to become a scientist, because when I was growing up, information was very limited. In my childhood, my grandfather would walk three kilometres every day to go to the central library, which was in Warangal. He would spend 2-3 hours reading books and newspapers and then come home to have lunch. Then, at three o'clock, he would go to a park. So, following in his steps, I started visiting the central library and government library. The central library had books to read, to self-educate. This gave me an opportunity to understand and know more about science outside the school. 

Pharma Now: So, this is how you learned more about science. Is this what pushed you to apply for masters in Osmania University? How did you decide to pursue further education?

Dr. Ramesh: I finished my Bachelor’s in Warangal at Kakatiya University and went to Osmania University. There, I was fascinated by microbiology. There, too, I wanted to learn chemistry and complete a Master's in chemistry. But, I also had good marks in biology. Unexpectedly, I didn't get chemistry only, but I got biology also. So, microbiology is a  field which requires high scores in chemistry and biology, and I always wanted to study microbiology. I didn't know how to pursue it, but it happened by God’s grace. I got a seat in Osmania University’s Masters in Microbiology program and completed my master's. Then, one of the faculties suggested that I should pursue a PhD at the Central Food Technological Research Institute (CFTRI) in Mysore. At the CFTRI, I got a CSSR scholarship and completed my PhD. 

In those days, the Indian industry was too small to absorb PhD graduates. So basically, India was turning away educated people. There was no company or academy giving jobs to PhD graduates. So, if you were doing well in your field, the only way to make a living was to leave India, complete a postdoc abroad, and come back. So, many Indians who completed their PhDs from the CFTRI went abroad, either in Europe or the US.

That's how I ended up in Michigan. There, I completed my first postdoc. Later, at Ohio State University, I completed my second postdoc and started my career in the pharma industry. So, whatever I learned in India helped me during my industry career in the US. People say, “You always come back home.” So, after a long career, I came back to India. Whatever I learned, I got a chance to apply it–maybe, several years later if not immediately. 

Pharma Now: That’s very fascinating. Can you tell me more about your career in the US? How did you start it, and which companies did you work in?

Dr. Ramesh: So, I first started my first industry career, I worked at Wyeth Pharmaceuticals, which was acquired by Pfizer in 2009. I worked at Wyeth till 2008 at Pearl River, New York. Then, in 2008, I got an opportunity to work for DuPont, India, because DuPont was setting up an R&D centre in Hyderabad. At that time, my son was in middle school and my daughter was in second grade. So, this gave me an opportunity to come back to Hyderabad with my family. It was never planned. Suddenly, an opportunity knocked so I left pharma.

Suddenly, I was changing my industry, country and company. At that time, a lot of re-learning happened in India. But, there was always an opportunity to stay in the science and technology field. After leading the industrial biotechnology sector, DuPont decided to change their business direction. So, I joined Indian Immunologicals, where I led veterinary and human vaccine development along with R&D. Then, approximately 2 years later, there was once again a huge management change. Just before I left DuPont, Biological E. approached me to start leading their vaccine program. So, two and a half years later, I came back to Biological E. to start the development of pneumococcal conjugate vaccines, human papillomavirus (HPV) vaccines and other vaccines. Basically, they hired me to establish strong R&D divisions. So, in Biological E., I started the R&D department with 7-8 people, and they also showed a commitment to establishing the department. 

Pharma Now: So, you started the department with only 8 people. How did you plan your work, or which vaccine did you start working on first? What challenges did you face?

Dr. Ramesh: In 2013, I moved to Biological E. They were building and renovating R&D labs, so we had to give up the lab space because we couldn't do much. But, at the beginning of 2014, we got the lab set up, new equipment, and new labs. So, we started working on pneumococcal conjugate vaccines.

My journey at Biological E. started in February 2014. So, we started on this project. It's a very complex vaccine, and every company outside the US or within the US had wanted to develop it or at least wanted it in their portfolio. But none of them were able to take their developed vaccine to clinical trials. The development of this vaccine was very complex and unknown, so there were a lot of challenges. Scientifically, I was very confident, but it didn’t mean much because company investors and owners invested in us. We started small and then incrementally added and attracted talent to develop the different aspects of the vaccine development program. 

Polysaccharides, microbial strains, polysaccharide fermentation, and many other technologies–multiple technologies are required to build vaccines. So, we developed all these technologies in-house. No external consultants or technologies were borrowed or licensed, other than a licensed bacterial strain because there was no other way to get it. But, we developed everything from scratch, and multiple technologies were developed. We also filed a lot of patents. 

For some of the technologies, no one else had them other than MNCs because they had already gotten their products approved. So far, there are three MNCs–one in Europe and the other two in the United States–who have gotten approval for their products. But among these three, only two products are strong. The third company is not doing well because of some product weaknesses. But, we had developed a 14-valent pneumococcal conjugate vaccine (PCV14). Even the WHO wanted to have at least one developing Asian country to be the supplier of PCV14.

Pharma Now: Sorry to interrupt you, but for our audience, can you share what the importance of this vaccine is? How does this affect us ordinary people?

Dr. Ramesh: In India, this bacterial infection causes almost 75 deaths of infants or children below 5 years every year. It can cause pneumonia, middle-ear infections, meningitis, and many other invasive pneumococcal diseases, what we call lung infections. So, if it is not treated on time, it is fatal. It causes thousands of deaths every day; it’s assumed that in every seven minutes, a child below 5 dies because of this disease. So, it was immensely satisfying to develop the PCV14 vaccine. But on this journey, I had my team, and I highly acknowledge the contributions of different functional leads. They have also contributed enormously to the success of this project. 

Pharma Now: I imagine the development of this vaccine had a gruelling process and required a lot of time. Can you tell us how long it took to develop and licence the product?

Dr. Ramesh: So, within 8 years, we got this product approved and licensed in India. However, we quickly made a lot of progress up to Phase II clinical trials in India. Then, getting ready for Phase III clinical trials was a totally different ball game because we had to scale everything to regulatory compliance. So, we met all regulatory guidelines. But, while designing the clinical trials, we were asked, “Why are you so confident that you will succeed in this?” For vaccine approval, you have to use an already approved vaccine as a comparison and demonstrate that your product is not inferior to the already approved product on the market. The product you use for comparison should belong to one of the MNCs established in the US. So, we had to use that product as a comparison and demonstrate the non-inferiority of our product. 

We were already confident that we would demonstrate non-inferiority. Our product was as good as the approved MNCs product–that was our intention. Later, when we were questioned, there were a lot of sceptics. We addressed everybody's concerns using our logic for the success of this project. We developed so many analytical methods. My team, one of my functional leads, developed all new methods. We created a team that would understand the science behind the vaccine development and developed everything on our own with very little or no help from other companies.

So, there are 14 different antigens, but you cannot have 14 different processes. One process should combine all. This was the strategy we developed. So, we were able to quickly develop the vaccine. In 2016, we conducted Phase I clinical trials. In 2017, we conducted Phase II clinical trials. By 2018, we had completed Phase II clinical trials and were ready to send our clinical trials summary report. 

However, for performing Phase III clinical trials, we needed to manufacture the product at a commercial scale, which means using thousand-litre fermenters. While we were developing our product, the company owners had to invest in building a facility that had this huge commercial capacity. In the process, we approached the Indian Department of Biotechnology (DBT) and Biotechnology Industry Research Association Council (BIRAC), who gave us a loan to build a facility. Now, that loan has already been repaid. 

Using that facility, we created our commercial supply. The facility can produce at least 100 million doses per year because we want to supply this vaccine not only in India but all other developing countries.

So with that, we conducted Phase III clinical trials, which was during COVID. So, our clinical trial team had to go to sites and make sure all things went fine. They took a lot of risks during COVID. What I'm trying to say is: everyone in the R&D department contributed in one way or another. So, in June 2022, we submitted our phase III clinical trial application to the Indian Government. In September 2022, we got the subject expert committee review, approval, and recommendation to supply this product, and the Drug Controller General of India (DCGI) inspected our commercial facility. By December 2022, our commercial facility got the approval to manufacture the product. So, the entire journey of this product took 8 years, from the beginning of 2014 to the end of 2022.

Pharma Now: I’m not an expert, but I think 8 years is an extremely short period of time! I think you had developed a very precise plan and created an excellent product?

Dr. Ramesh: Yes, 8 years for a complex product like this is a significant achievement. Still, we thought we were late–according to our aggressive plan–because of COVID and other regulatory approvals. But, 8 years is a significant achievement. However, throughout the process, we created a team that had the talent and capability to complete vaccine development: from idea development to Phase III clinical trials and regulatory approval. We had set up a team with a very broad capability, and the whole process was very gratifying personally. 

Pharma Now: I can only imagine how proud and happy you must have been to get your product approved–like seeing your child win a gold medal, I think. How or what do you credit this success to?

Dr. Ramesh: I lived in the US for 20 years. My children were born there, and they were there until middle school. So, the main difference is, until I finished my PhD, I paid very minimal fees for my education. Until college, I paid very nominal fees. So, the government helped me get my education. During my PhD, I received a CSSR fellowship. So, the government gives scholarships for you to get a degree. This project was one way to pay back to my country and to the world. So, my education in India and what I learned in my career in the US all came together, and there I could pay back to society. That's another personal gratification. 

Pharma Now: So, you lived in the US for 20 years. But after that long, coming back to India is a very tough decision for people, to leave their comfort zone and return to India is difficult. Plus, back then, pharma was not booming as it is now. If I’m right, in 2007- 2008, the Indian pharma sector was not as large or happening as it is now. So, coming back was a very huge risk for you. Plus, your children were in school, they had a different life altogether and coming back to Hyderabad was completely different. How did you make such a difficult decision?

Dr. Ramesh: It was an emotional decision for me and my wife to return because it was an attachment. We also wanted our children to have “a living experience” in India rather than just “a visitor experience”. I wanted them to see the life and struggles here. Of course, there are struggles in the US as well. However, the difficulties or the day-to-day limitations are different in each country. What you have here, you will not have there and vice versa. You need to adjust to local conditions. That's the important thing. But overall, it was a very gratifying experience. 

Pharma Now: You’ve worked on many other vaccines in your career. Can you tell us a little more about the vaccines the team at Biological E. is working on?

Dr. Ramesh: Throughout my journey at Biological E., we have worked on other vaccines, such as the HPV vaccine. HPV is the virus that enters people’s bodies, and within some time, a person's immune system is compromised. It mostly happens in kidney transplant patients. Once the patient gets a solid organ transplant, physicians have to treat them with immune-suppressing steroids so that the organ is not rejected because it is a foreign organ. However, the immune system is also weakened during the whole process. So, because HPV is present in the environment, the innate latent viruses resurfaces, affecting the organ and the health of the patient. 

So, we in-licensed the developed technology and concept, but it was not licensed. No industry showed interest in NIH in the US. So, I came across that product sitting on the shelf. Then, I decided to bring it here, and we fully developed it. We licensed it exclusively and developed it. It's also one of the most complex virus-like particle (VLP)-based vaccines we have developed. We have completed preclinical biology and development. Now, we are manufacturing the materials required for clinical trials for that vaccine. If it is successful, it will be a novel vaccine because no other MNC has a similar vaccine in their pipeline. 

We also have pneumococcal conjugate next-generation vaccines and several other viral vaccines. We have established all the different available platforms for vaccines, including mRNA, which we established very recently. So, we have preclinical studies happening right now, and proofs of concept are being developed. So, that's where we are today. 

Pharma Now: So, I want your perspective on a question as the Head of the R&D Division: The global expenditure on R&D, particularly in the pharma industry, is very high, maybe 3-5%. But, the expenditure on R&D in India is 1-1.2%. What is the outlook on R&D growth in India? 

Dr. Ramesh: I'm glad that you asked me that question. So, my answer is going to be a little bit broader. In Indians, there is always a burning desire to be good or the best in science and technology. You can take any field–engineering or management. Everywhere you see it, there is always a desire to be very strong. We were strong in chemistry, mathematics, and physics. In biology, we were weak. But still, biology was there. 

However, India has talent and a large intellectual pool, which needs direction. Since 2008, the landscape has changed: there’s a commitment to invest in R&D and in-house product development. The mindset is changing, and we need to invest in R&D to develop new products and markets and to improve products. I've seen DuPont in India and many other local pharma companies. 

To answer your question more specifically, the percentage difference in R&D spending may be because we should not look at it as percentage or quantity. The Indian Government and the DBT are providing grants to encourage R&D, investment in R&D, to develop and support technology and clinical trials, through different mechanisms. 

So, if you look at all these things, there is an encouraging atmosphere overall, yes! We are investing much, much less in terms of numbers or currency compared to the US and Europe. But, we are much better off now than we were 10 years ago in terms of interest and investment in R&D. Now, private investments are coming, but biotechnology has always been a challenging field, not only in India but also in the US and Europe. Also, the success of the product is very different. In the case of vaccines, the success rate is high, but around 3-4% of vaccines get approved, and the success rate is 30-40%. 

Pharma Now: Speaking of investments, currently, contract research organisations–as well call them CROs–are growing a lot. So, does this mean companies are outsourcing research facilities? What is the outlook on this front? 

Dr. Ramesh: CROs or contract development and manufacturing organisations (DCMOs), as we say in India, have a pretty good outlook. A recent report published on the new developments in biology, technology development, development, computational power, data analysis, and artificial intelligence in the US. In the future, there will be an abundance of information, I would say, in biology. So, you need a lot more information processing and testing. So, when you have to test your candidates in the US, they are beyond the local capacity. Also, India stepped up in terms of the service quality provided, and it is at least 30-50% less than the US, which has the same activity in the US and Europe. So that's one of the reasons there is a pretty strong growth in CROs and CDMOs in India than the US. 

Pharma Now: That’s interesting. Let’s come back to R&D. So, as the Head of the R&D Division, how are you looking at digital transformation and integrating DIP technologies in R&D?

Dr. Ramesh: There are two parts to your question: digitalization is always a good thing. However, change management is required. We are looking to digitise everything: electronic lab notebooks and electronic capture of all data. In fact, when I was at DuPont, they had already initiated the change in 2009-2010; the entire pharma industry took time to grasp it. 

Digitisation happens phase-wise, you cannot do it overnight. It's change management, culture management, facility investment, and data storage capture, with no data breach. Many other things have to be put in place before digitisation. During COVID-19, there were a lot of hackers targeting the pharma industry and unpleasant things happened. However, digitalization is always a good thing as long as it is protected. 

It gives the advantage of readily reviewing and analysing the information. But it's a challenge. It's not easy to implement because, traditionally, people are used to data entries on paper, which have to be digitised. People have to be trained, especially in science and technology. A lot of activity data is distributed on hard paper, and different instruments that have to be linked, captured, and put in one place. So that's the challenge. All this activity has to happen every day, and then, data has to be backed up and protected. So, these are all different issues, but they can be addressed. In some pharma companies, only commercial manufacturing is truthfully displayed. That's easier to do than R&D. R&D also has to be done, but it's a slow process, but there is a good value for that. 

Pharma Now: Amazing. I’ve recently heard a lot about DeepTech. What do you think about DeepTech?

Dr. Ramesh: DeepTech is another thing that I'm looking into. I’m trying to link DeepTech to artificial intelligence (AI). So, there are two parts to it. The first is data analysis using AI and the systems using the brain with algorithms. The second is the quality of information you upload for analysis and comparison with other information.

So, it is a stepwise process. AI is probably too advanced, and for India, it has to be matured. However, again, each field and sector is different, especially AI for biology and vaccine development. For example, if you want to use AI for developing different marketing strategies or for customers, it is different and doable. But, in hard science and technology, for example, industries like vaccines and biotherapies, it’s a slightly different ballgame. But, AI is much more powerful and useful and always has a positive effect on vaccine development. 

Pharma Now: I think AI is bringing many things to the table, and I think a lot of innovation is also happening around the industry. But, let me redirect our conversion a little bit: many pharma professionals want to get into R&D but don’t know the right path to take. So, what would be your message to them? How should they look at it as a career? 

Dr. Ramesh: So, to answer your question more precisely, people who get into R&D after their masters or PhD, should always try to do their best. Don't ever compromise on the small things. Your ethics always keep your integrity. In order to do that, you should associate yourself with accomplished people in the field. Whatever field it is, whether it be engineering, science, biology, medical field, or healthcare. Whatever it is, always try to do your best and be the best person in whatever you do. You should like whatever you do. Money will always come, perhaps a little bit later, but do not be focused on money. These days, money is more important because the cost of living is increasing. So, hopefully, the industry will compensate people accordingly. In that case, the cost of living should disappear, but you should be the best in your actions. Then, you will be successful.

Pharma Now: Fantastic, that's a really great message. Thank you very much, Dr. Ramesh. Thank you for joining us at Pharma Now and sharing your thoughts, experience and insights.

Dr. Ramesh: Thanks for giving me that opportunity. I'm glad I met you. 

Pharma Now: The pleasure is all mine. Thank you very much.