Inside Bioprocessing: Dr. Patra on Biosimilars & Leadership

Pharma Now: Hello Dr. Patra, welcome to Pharma Now. First of all, thank you for joining us and giving us your time. I was going through your journey, it’s truly mammoth. You now have more than a couple of decades of experience, and you’ve been one of the earliest leaders to help set up bioprocesses in India. Let’s start from the very beginning. Where do you come from originally? Odisha?

Dr. Ashok: Yes, I was born and brought up in Odisha. My entire education up to my Master’s was in Odisha. In fact, before this interview, when you asked me what the initiation point was for getting into biologics, I tried to recollect what really triggered it.

It goes back to my graduation days in one of the leading colleges. My teacher, Dr. Shiva Prasad Mohanty, was an excellent zoology teacher. He used to tell us about how biological resources could be utilized for business. Way back in 1986, he was already talking about things like large-scale vermicomposting. That was probably my first exposure to the idea of bioprocessing, using worms to develop compost. It fascinated me, the way you could use small organisms to produce something meaningful.

Later, I pursued my MSc in Life Sciences, specializing in genetics and molecular biology. That’s when I began to understand how bacteria play such a vital role in our internal systems, particularly in anatomy. After my Master’s, I worked for a couple of years as a lecturer, and then I went on to do my PhD at North-Eastern Hill University in Shillong.

After that, I joined the National Institute of Immunology (NII) for my first postdoc. That’s where my actual journey in bioprocessing began. Under Dr. Panda, in what we called the Product Development Lab, I learned hands-on process optimization. The institute itself was established with the vision of developing a vaccine, specifically, an anti-fertility vaccine against hCG (human chorionic gonadotropin). Dr. Talwar was one of the visionaries behind that initiative.

Although developing that vaccine had many challenges, we also worked on several other projects, like producing human growth hormone, ovine growth hormone, and bovine growth hormone. Around 1998, we were using what I’d call primitive bioreactors. We started with small 2-liter scale fermentations, but even scaling that was a big challenge.

That was the time I truly learned process control, oxygen, pH, pressure, feeding strategies, everything. Back then, most microbial labs could only achieve 10–20 ODs in culture. In our lab, we managed to push it to 50 OD. Now, of course, 50 OD isn’t considered very high, but in the late 1990s it was a big achievement.

But with high expression came another challenge. Proteins were being produced in inclusion bodies, insoluble aggregates. So the question was: how do we purify and refold them into active proteins? That’s when the downstream challenges started.

We developed processes for solubilization and refolding, and I was fortunate to be part of that effort. We achieved nearly 25–40% of protein as inclusion bodies, which was considered very high then. But the real breakthrough was that we were able to optimize the process to purify the protein into an active, soluble form with around 30% recovery.

We published our work on the folding and characterization of human growth hormone, and that paper has since been cited more than 300 times. That was one of my biggest achievements. After that, we applied similar processes to other proteins like ovine and bovine growth hormones, with some modifications.

Today, of course, with advanced systems, microbial cultures can easily reach 100–150 ODs, but back then, what we achieved in 1998 was considered cutting-edge. I still remember looking into the fermenter vessel and seeing that dense culture, it felt like a milestone moment.

Pharma Now: Okay, that was your academic life. How did the switch to industry happen?

Dr. Ashok: In the 1990s, the trend for most of us was clear, after doing a postdoc at NII, the next step was to go abroad, usually to the US. NII was like a launchpad; after two years of postdoc, everyone aimed for opportunities overseas. I followed the same path.

Because of my experience producing large amounts of protein in inclusion bodies and purifying them successfully, one professor in the US selected me, and I went there. But little did I know that the path would not be as smooth as I expected. Just because you succeed once, doesn’t mean everything else will come easy.

I started working at Boston Polytechnic Institute in Massachusetts. This time, the challenge was completely different. The protein I had to work on came from Archaea, microorganisms that grow in extreme environments like hot springs at 75–80°C. The protein was a copper transporter. Now, the challenge was that while these organisms thrive at very high temperatures, we were trying to express the protein at 37°C. It simply didn’t work. The protein wouldn’t express. We tried multiple strategies, but nothing helped. Eventually, the professor gave up, saying, “Forget it, this is not going to work.”

I didn’t want to stop there, so I switched to Boston College. Initially, things looked good. The protein was expressing well, it was soluble, and we were able to purify it successfully. But then came the next challenge, getting an active protein. You can produce protein at high levels and even purify it, but if it’s not functional, it has no value, whether in research or therapeutics.

This time, I was working on aspartate transcarbamoylase, a protein relevant as a cancer target. The challenge was to restore activity after purification. The enzyme has regulatory and catalytic domains that need to come together properly to form an active protein. We did manage to assemble it, but the activity level was far below expectations. We struggled for a couple of years, and although we achieved partial activity, it was not ideal.

Step by step, through these experiences, I was learning the real challenges of bioprocessing: first, how to ferment and produce protein; second, how to purify it; and third, how to ensure the protein is active and functional. Each stage came with new lessons.

After my visa expired at the end of three years, I had an offer from Roswell Park Cancer Institute in Buffalo, Chicago. But by then, I had already spent three years away from India. I felt it was time to return. That’s when I joined Ranbaxy.

Pharma Now:  Being in those three years, you were struggling to achieve success every day. What did those days look like?

Dr. Ashok: Those were my younger years. During my PhD in Shillong we often worked overnight without sleep. In 1992–93 there was no automation, so everything had to be done manually. If I set up an experiment I had to complete it, so I stayed overnight, often 18–20 hours a day, throughout my postdoc both at NII and later in the US.

The struggle was not financial but about obtaining the desired results. For example, I had a fixed target to produce a highly active protein; I might achieve around 50% activity, not 75% or 90%, which made recycling difficult. We tried different conditions and methodologies every day. The thought of giving up never came from my side; sometimes my boss suggested stopping. For example, with the copper transporter project the source organism grows at 75°C while we were expressing it at 37°C, an intrinsic challenge that required modification.

In my second postdoc in the US, I could complete the work but with reduced activity; we could not reach the goal of targeting that enzyme as an anticancer agent. That was a failure, but failure is part of research, you do not get breakthrough results every day. I learned to build upon failures and moved gradually toward complete process development.

Initially it seemed straightforward, but each day brought new problems: buffer changes caused issues, composition variations created problems, and so on. Back then we used a one-factor-at-a-time approach. Today, with machine learning and available data, we can design experiments and let algorithms suggest optimal conditions, providing several viable solutions instead of testing millions of parameter combinations.

Pharma Now: Right. you came back to Ranbaxy?

Dr. Ashok: Yes, I joined Ranbaxy at that time. They were mainly focused on small molecules, Ranbaxy was always a small molecule manufacturing company. R&D was strong, and leadership was excellent. But since I am not a chemist, my role was more as supporting staff for molecule development. I worked on developing cell lines that could be used for assaying those molecules.

That was when I realized how different industry research is from academic research. In academia, you usually work on a single project and drive it forward, often publishing after showing efficacy in limited conditions. In industry, however, every result must be validated thoroughly, across multiple conditions, multiple techniques, and even in multiple labs, before it is accepted. That was my first real learning.

At Ranbaxy, I focused on cell line development, which was my strength. We successfully developed around 10 different cell lines to assay small molecules, including anti-BPH and antimuscarinic molecules. After two years, I moved to Jubilant Biosys for another two years. These experiences exposed me to different molecules, business perspectives, and broadened my outlook.

The real turning point came when I joined Panacea Biotech. That’s when I felt I was finally back into true process development work. In 2008, I started working on erythropoietin (EPO) and darbepoetin. At that time, processes were not as advanced, many didn’t even know how to run fed-batch processing. They were only doing batch cultures, which could last 7–10 days at best. By switching to fed-batch, we could double the run length, increase cell density, and significantly boost yields.

Then in 2009, the H1N1 pandemic hit. Panacea, being a vaccine company, immediately redirected efforts to H1N1 vaccine development. I worked closely with Dr. Neeraj Agrawal, a virologist (now at ICMR). We developed the process using embryonated eggs—starting with 10–12 eggs in R&D, scaling up to 5,000 eggs, and finally transferring the process to a facility in Punjab where we scaled to 65,000 eggs.

The biggest challenge was automation. Manual inoculation and harvesting worked fine at small scale, but at large scale the automated system extracted less allantoic fluid (6 mL instead of 8–10 mL manually), causing up to 40% yield loss. We had to troubleshoot and optimize to recover as much as possible without compromising quality. Despite the challenges, we developed a robust process, filed a patent, and were ready for commercialization within 6–7 months. Unfortunately, due to business and commercial reasons, the vaccine was not launched.

After that, I continued working on biosimilars at Panacea until I met Dr. Singh, who shared his vision to set up a small facility for biologics and biosimilars. That’s when I joined him at Imgenex. We built a small R&D lab, developed processes at 2–5 L scale, and worked toward preclinical studies.

However, when COVID-19 struck, everything came to a halt. A molecule we had prepared for preclinical testing had to be discarded, which was a big setback. From that experience, we changed our strategy: rather than taking molecules all the way to preclinical trials ourselves, we now focus on early-stage development—demonstrating potential, efficacy, full physicochemical characterization, and initial process development, then partnering with others for the next stages.

Currently, at Imgenex, we’re working on two novel antibody-based molecules. One is an anti-hyperlipidemia candidate, designed through in-silico optimization as a fragment of an existing cholesterol-lowering antibody. The other is an in-house novel antibody identified from our own reagent antibody library. Both are progressing at R&D scale, and we also have plans to expand into additional novel molecules in the future.

Pharma Now: In between, you talked about biosimilars. So I think biosimilars are creating a lot of buzz in India nowadays. Let’s talk about what’s the actual reality and what’s just hype. How is India really doing in biosimilars?

Dr. Ashok: You know, India is actually not doing very well in terms of biosimilars. But if you look at the market, India has the highest number of biosimilars already approved, I think around 98. That clearly indicates India has a big market, and a lot of companies are working in this space. You name any big pharma company, Dr. Reddy’s, Cipla, Zydus, they are doing pretty well.

The reason is simple: biosimilars don’t need a lot of fresh research. The molecule already exists, the pathway is already established, so you don’t have to spend heavily on discovering new molecules or pathways. The information is already available. It’s basically the same kind of approach we see in small molecules. For small molecules, once you know the pharmacophore, you do reverse engineering, make modifications, and then produce a molecule.

Similarly, for biosimilars, the sequence is already known, the target is already established, you just have to demonstrate similarity. But the big challenge is overcoming the scientific and technical hurdles to prove that similarity. That’s where companies like Dr. Reddy’s, IPCA, Cipla, and others are investing heavily, in infrastructure upgrades, high-end machinery, and advanced analytics.

They’re bringing in technologies like high-throughput screening, advanced analytical instruments such as HPLC, Raman spectroscopy, mass spectrometry, infrared and near-infrared systems, SPR for binding studies, and more. Huge investments are going into these machines and capabilities, and that’s what’s enabling Indian companies to compete strongly in the biosimilars space.

Pharma Now: So, is the initial investment or capital cost a big challenge in biosimilars?

Dr. Ashok: Yes, for a small company, it’s definitely a challenge. In fact, the Government of India is trying to facilitate this. What the government is doing is establishing facilities that provide high-end infrastructure. For example, in Bangalore they have a pretty good setup, and NCCS Pune also has very strong facilities.

These centers have the machines and trained professionals in place. So, if someone has limited funds but wants to develop a biosimilar, at least the initial R&D and proper characterization, they can approach these facilities. They can utilize the infrastructure without having to make huge investments up front.

It’s almost like incubator support: you just go, take the service, get your results, and move forward. And the advantage is that these facilities provide GLP-level services. Most of them are accredited labs, so the data generated there is acceptable from a regulatory and quality assurance standpoint. Using that data, you can approach agencies for parallel approvals.

So yes, while the capital investment is high, the government’s efforts in setting up shared infrastructure and facilities are helping small companies reduce that burden significantly.

Pharma Now: What kind of opportunities are the Indian market, or perhaps other developing countries, offering for biosimilars manufactured in India?

Dr. Ashok: At the moment, biosimilars are still somewhat expensive. For example, take Trastuzumab. Initially, it cost around ₹1.5 to 2 lakhs. Today, it is available at ₹7,000–8,000 per dose. But even ₹7,000 per dose is still unaffordable for many patients, for instance, someone with blood cancer. So yes, it is cheaper now, but still costly.

That said, prices are gradually coming down and biosimilars are becoming more affordable. I wouldn’t say they’re as cheap as conventional tablets or capsules, but they are becoming accessible. For instance, in breast cancer treatment, the regimen may involve two to four injections per month, continuing for two to three years. For patients with insurance coverage, these therapies are already quite manageable.

So, there is a big and growing scope for biosimilars in India. The affordability curve is improving, and the market is slowly building up momentum.

Pharma Now: You also mentioned the new technologies coming into this industry, AI infusion, rapid upgrades in characterization tools, and advancements in chromatography. What’s your take on this digital transformation in bioprocessing?

Dr. Ashok: The main benefit is the elimination of human error, which is a big advantage. You cannot expect a person to monitor a machine continuously, day and night. With digital technologies, particularly AI, many of the errors caused by human interference are minimized, if not eliminated completely. Of course, machines can malfunction, but overall, accuracy improves significantly.

Another major advantage is ease of operation. You don’t need to overthink or manually control everything, the process is already programmed. You just set it up, feed in your inputs, and the machine takes care of the rest.

Pharma Now: Are you implementing any such technologies in your lab?

Dr. Ashok: Yes, we are at a very early stage of adoption, but we do plan to integrate advanced technologies. Specifically, we’re looking at high-throughput screening systems.

In manual conditions, we could screen maybe 10, 20, or 50 variations at most. But with new high-throughput technologies, we can simultaneously run hundreds of variations and generate far richer data. These machines also come with inbuilt probes, which provide much more precise process control.

When you work manually, these probes aren’t available, so process-related defects can creep in. But with the new machines, that problem is largely eliminated. This will give us a big advantage going forward.

Pharma Now: With the extension of AI simulators, machines today can produce amazing results and save a lot of time. They can generate clear simulations, model various scenarios, and provide probable combinations, which researchers can then test further. That really changes the way science works, doesn’t it?

Dr. Ashok: Absolutely. It’s transforming the way we approach research and development.

Pharma Now: Now, shifting gears a bit, I’d like to talk about leadership. In biosimilars, building teams is crucial. It’s all about teamwork, persistence, and patience. How do you keep your team motivated to stay focused on one target for years?

Dr. Ashok: It starts with finding the right people—those with a true scientific mindset and a clear focus on developing something meaningful. Such people are not easy to find. Many professionals today move from one opportunity to another for better pay, which is natural. But true scientists, the ones with passion, stick to a project because they genuinely want to see it succeed.

When I interview or onboard someone, I make sure to understand what they really want. From the beginning, I explain the nature of our work, it’s not as simple as “putting protein here and collecting it from there.” There are complexities and variables. When people understand these nuances, they begin to appreciate the process, and that creates interest.

I often compare it to coffee. If you just taste it once without context, you may not care. But if I explain what’s inside, the ingredients, the chemistry, the health impact—you become curious and start exploring different varieties. Similarly, when I explain to young scientists the details of upstream and downstream processes, and what happens if each step is not optimized, they start seeing the beauty in it.

For example, recently, one of our team members was working on downstream processing. At first, he thought it was just about running a solution through a column and collecting protein. I gave him a sample, asked him to try, and the results were below expectations. That’s when I explained the variables, selecting the right resin, packing the column correctly, choosing the right buffer, adjusting flow rate, monitoring pressure. Only when he understood the design-of-experiment approach did he realize the depth of the process.

This one-on-one mentoring makes a big difference. When students or young researchers see the intricacies of science and understand the “why” behind each step, they develop real interest. Without that understanding, if you just tell them “do the processing,” they lose motivation. But when they see the bigger picture, they stay engaged and committed.

Pharma Now: Over the years you must have mentored and trained hundreds of researchers. Is there a particular story where a mentee really surprised you or made you proud?

Dr. Ashok: Yes, quite a few. I’ve been mentoring people since my postdoc days, when students would come for training. One case that stands out is a student who was deeply interested in downstream processing and chromatography. At the time, we were working with a cation exchange column, if I recall correctly, the resin was from Amersham. Proper packing of the column was critical to achieve good separation.

I asked him to purify two very closely related proteins using this column. I encouraged him to go step by step, identify the problems, and understand why separation wasn’t happening. He took it very seriously, studied the complete physiology of the resin beads, analyzed buffer compositions, went through the guidelines in detail, and eventually designed a new buffer system with different ingredients. Using that, he successfully separated the two proteins. That showed me he had a true researcher’s mind. Today, he’s continuing his career in the US, and I feel proud of his journey.

Pharma Now: That’s inspiring. Finally, what would be your one message to the young generation aspiring to enter biopharma and biologics?

Dr. Ashok: My advice would be: keep developing your skills. With AI and machine learning becoming integral, students need to stay updated and adapt quickly. Along with hands-on training, they must also learn these digital tools. But above all—consistency and perseverance are the key.

Failure is inevitable in science. I’ve had many failures in my own career, and biopharmaceutical processes are full of surprises, you never know when a challenge will appear. But don’t get disheartened. Each failure is a step towards success. As people say, “failure is the pillar of success.”

Pharma Now: That’s a powerful line, failure is the pillar of success. I’d even add: in science, there is no failure, only learning. Every challenge teaches us something new, and those learnings push us toward fresh innovations and milestones. Thank you, Dr. Patra, for sharing your experiences and insights. I’m sure our readers will find this conversation inspiring and motivating.

Dr. Ashok: Thank you very much. It was my pleasure.