Regulatory Affairs Decoded: Insights from Biocon’s Varma Bhupathiraju

Pharma Now: Mr. Varma, a very warm welcome to Pharma Now! Let’s begin by understanding your role a bit. The title AVP, Regulatory Affairs certainly sounds impressive and expansive, but for those outside the industry or new to it, could you help us decode this role?

Mr Varma: Yeah. As you introduced, I am currently working as Assistant Vice President, Regulatory Affairs, at Biocon Biologics. I moved to Biocon Biologics this March. Prior to this, I was with companies like Biological E Limited in Hyderabad. Before that, I was with Serum Institute of India, Pune, where I worked for almost five and a half years. Before that, I was working with companies like Aurobindo Pharma and Gland Pharma. I have almost 22 years of experience now.

I started my career with a bulk drug manufacturing company, where I worked for one year. Then I moved to Gland Pharma Limited, a pharmaceutical manufacturing company renowned in the parenteral field. It was the first USFDA-approved PFS facility in India, a very renowned company. I worked there in Quality Assurance for about three and a half years. Then I moved to Aurobindo Pharma, again a renowned company in solid oral dosage forms. I was there for three years, in plant regulatory compliance, which is called plant regulatory, where we used to maintain all the regulations and support the actual Regulatory Affairs department.

After my stint at Aurobindo, I moved to Serum Institute of India, a Pune-based vaccine manufacturing company well-known worldwide. That’s where I transitioned into Regulatory Affairs. The main reason for my shift from Quality Assurance to Regulatory Affairs was that Regulatory Affairs is a key function in any product approval process. They are basically the face of the company to the regulators. That’s how I started my career in Regulatory Affairs at Serum Institute. There, I was responsible for registering our vaccines in more than 140 countries around the globe, covering almost all regions except the US and Europe. In India, no company was catering to the US market at that time due to reasons like trial requirements and FDA expectations. There are several reasons why no Indian vaccine manufacturer was targeting the US market then. However, post-COVID, people have started exploring US opportunities as well.

I worked at Serum for around five and a half years. After that, I moved to Biological E, where I was deeply involved in the development stage of vaccines. At Serum, I was Deputy Manager. At Biological E, I joined as AGM and moved up to Senior Manager. I grew periodically through almost five roles. I was fortunate to be involved in every development activity, starting from POC—Proof of Concept—to preclinical stages and all relevant regulatory approvals. I was part of almost all key vaccine development projects, preclinical development, clinical development through different trial phases, and licensing pathways.

In the pharmaceutical field, approval is just one part. You also need to maintain the lifecycle of the product. There are many changes in processes and specifications that need to be managed. I was involved in all those activities and headed Regulatory Affairs there.

Recently, I moved to Biocon Biologics. Since my previous experience was in tablets, capsules, and vaccines, I felt biosimilars were the next logical step in my career. That’s why I chose Biocon Biologics. Biocon Biologics is one of the largest biosimilar companies recognized globally. It also acquired a major biosimilar portfolio recently, and we have been expanding. We've been supplying biosimilar products and, later, insulins too. As you know, insulin is a big part of the diabetes treatment portfolio. We have been supplying biosimilars and insulins globally, including to the US and Europe.

It gives a great sense of satisfaction because, in monoclonal antibodies and biosimilars, we’ve developed anti-cancer drugs for conditions like breast cancer, osteoporosis, and neck cancer. I'm fortunate to be part of Biocon Biologics and plan to continue here for some time. This hasn’t been an easy journey. Initially, I was planning to go into the software field. In fact, I completed my Java courses way back in 2000. At that time, Java was in high demand, especially in the US. But due to the recession and global slowdown in software, I shifted to pharma, as I come from a pharma background.

After that, I started developing an interest in the pharmaceutical field. There’s a cause behind it, you’re essentially helping to save millions of lives around the world. That’s why I chose to continue in pharma, and I’ve been in this field for the past 20 years.

Pharma Now:  Fantastic. This must have been a great journey. So, a quick question: you’ve moved across various brands and handled many different types of products, vaccines, drugs, and biosimilars. As the head of a regulatory affairs division, what differences have you observed between these products across the companies you’ve worked with?

Mr Varma: I would say the major differences in regulatory affairs are less about the companies and more about the types of products, solid orals, vaccines, and biosimilars, each with their unique challenges and regulatory pathways.

For example, in pharmaceuticals like tablets and capsules, solid oral dosage forms the regulations are somewhat more relaxed. These products usually don’t require full-scale clinical trials. What generic manufacturers typically do is reference an innovator product, replicate the formulation, and demonstrate bioequivalence. This is done in a relatively small number of subjects and focuses primarily on parameters like dissolution, content uniformity, and other quality attributes. Since these are generics, there's no need for extensive clinical testing. The time frame for regulatory approval, in the U.S., is much shorter, especially under ANDA (Abbreviated New Drug Application) we call generics as ANDA. That’s one reason why many Indian manufacturers focus on solid and liquid oral.

On the other hand, with vaccines, the regulatory landscape is entirely different. Every vaccine is treated as a new drug, even if similar vaccines are already on the market. This means the manufacturer must go through the entire development lifecycle: Starting with proof of concept, then pre-clinical studies including single-dose and repeat-dose toxicity, Followed by clinical trials in phases I, II, and III. Preclinical studies begin with small animals like rats, mice, and rabbits. Only once safety is proven at this stage can human trials begin. Phase I focuses on safety, usually in 10–20 healthy volunteers. Phase II is typically a dose-finding study, but in some cases, like for an already approved vaccine, this may be skipped or merged with Phase III, often called a Phase II/III hybrid study.

Unlike pharmaceuticals that are used reactively, vaccines are prophylactic, aiming to prevent disease. Designing vaccine trials is particularly challenging because they target specific populations and immune responses, and the types of vaccines viral, bacterial, and subunit, add further complexity.

In India, the regulatory process is multi-tiered. You first need a development license, followed by generating data for submission. After this, the CDSCO (Central Drugs Standard Control Organization) requires product testing at the Central Drugs Laboratory. Only after passing this evaluation can the product be approved for clinical use. Pre-COVID, this process could take 8–12 years, but during the pandemic, accelerated pathways and interim data approvals helped speed things up. The industry hopes that these fast-track models will continue post-pandemic.

Now, coming to biosimilars, which I’m currently working on at Biocon Biologics, these are somewhat similar to generics in principle but far more complex in execution. Like ANDA products, biosimilars are assessed against an innovator product, but here, the requirement for Phase I and Phase III trials remains. The major challenge lies in matching the reference biologic not just clinically, but also at the CMC (Chemistry, Manufacturing, and Controls) level.

Developing biosimilars involves significant characterization, comparability studies, and high costs, often in the range of millions of dollars. This level of investment and technical depth means only a few manufacturers can participate. That’s one reason I chose to move into this space, because I saw it as the next big challenge and opportunity in my career.

My message to young professionals in the pharma industry is simple: Choose your path with purpose. This industry gives you a chance to save millions of lives, take that responsibility seriously. Uphold ethics, quality, and patient safety in everything you do. When you follow Quality by Design (QbD) principles and build quality into your process from the start, everything else, efficacy, safety, and compliance, will fall into place.

Pharma Now:  That’s wonderful! Just a quick follow-up: You explained the entire development process in detail, whether for vaccines or biosimilars, but what exactly is the role of Regulatory Affairs in all this? What does a regulatory professional like yourself actually do?

Mr Varma: Yeah, as I was mentioning, Regulatory Affairs is a function that acts as the face of the company to the regulators. For any product you want to develop or get approvals for any approval you need a Regulatory Affairs professional. They come into the picture because they are the face of the company among the regulators.

Similarly, on the audit side, it depends on the company. In some companies, QA people handle the audit, and in some companies, Regulatory may lead the audit, with all cross-functional team support. It depends from company to company, but we are definitely involved because the inspections are arranged by us. Whoever is facing the audit whether it’s QA, Regulatory, or the corresponding cross-functional team, will face it together.

Once the audit is successful, a report is issued. The company has to respond to the observations, if there are any. The regulators need to be satisfied with the response. Only then will the audit be closed. So, this is a lengthy process, basically.

Pharma Now: Nowadays, especially after COVID, regulators have become very vigilant across various aspects. How is the current regulatory landscape evolving? Are they adopting new techniques? Are they aligning more with global policies? How are the regulators behaving today?

Mr Varma:  I'll tell you, if you look at traditional vaccines in the earlier scenario, most of the quality assessment relied heavily on animal assays. A lot of animals were required. For example, childhood immunization vaccines like pentavalent vaccines like diphtheria, tetanus combination vaccines, used to require significant animal testing. However, over the past couple of decades, newer vaccines like polysaccharide vaccines, conjugate vaccines, and others have emerged, and the assessment methods for these are no longer based on animal testing. These newer methods are more sophisticated, reliable, and accurate. That said, the old methods are still valid for older vaccines.

In the current scenario, many advanced techniques have been introduced, and the landscape has changed considerably. Regulators today are not the same as before; they actively engage with the industry to understand challenges. In some cases, they even guide companies. We also follow international practices, looking at how MNCs operate and align with global regulatory pathways. Even Indian regulators are now adopting similar approaches. For example, if you look at CDSCO back in 2005 or 2010, the regulations were not very stringent. But they've evolved significantly.

Especially during COVID, they evaluated several vaccine candidates, which gave them a lot of exposure and knowledge. They also receive frequent training from premium global regulatory bodies. So they've matured a lot, which is helping the industry. Still, I believe there is room for further simplification in the Indian regulatory process.

Pharma Now: So, we are traveling or rather, driving, towards more simplification, correct? That’s really wonderful. Mr. Varma, you already spoke about how the landscape is evolving, so do you feel that India has the potential to further become a global exporter of vaccines, biosimilars, and various other types of drugs?

Mr Varma: 100%. If you look at COVID, I would say, other than the US and Europe, the rest of the world was saved by India. In the initial days, the US and European manufacturers who developed the early versions of the COVID-19 vaccines were supplying only to their own countries. Whereas in India, if you see all the other manufacturers from India, like vaccine manufacturers, they serve the world. So, India has huge potential, and more than that, huge capacities and expertise. There are three big manufacturers in India, whether you take Serum Institute of India, Biological-E, or Bharat Biotech, these manufacturers are actively enhancing their manufacturing capabilities and expanding their product portfolios.

From a manufacturing and regulatory standpoint, Indian manufacturers are in no way behind any multinational companies. The only difference might be in the way outsiders perceive them, but that’s changing now. Yes, it’s time to change the outlook.

Pharma Now: That's wonderful, Mr. Varma. I think it was really a pleasure talking to you and gaining insights about regulatory affairs, how things are progressing and how RA is truly creating an impact on the entire process, making this country even more proud. Thanks a lot for your time and for this valuable conversation.



Mr. Varma: And thank you for your invitation as well. Thanks.