Dr Hemanth Nandigala: ‘You cannot quicken the process of manufacturing vaccines too much’

Interview with Dr Hemanth Nandigala, managing director, Virchow Biotech Private Limited.

technology is owned by the Russian Direct Investment Fund (RDIF), is the only COVID-19 vaccine approved in India that is being manufactured locally from a diversified manufacturing base. Although production at scale is yet to commence, it is likely to produce significantly large volumes by the end of the year. Speaking to Frontline , Dr Hemanth Nandigala, managing director of the Hyderabad-based Virchow Biotech Private Limited, one of the Indian Sputnik V contractors, explains the constraints in scaling up capacity quickly. Excerpts from the interview:

Virchow is one of the companies manufacturing the Sputnik V vaccine in India. What has been your experience and what are the challenges in establishing and expanding capacity?

We are one of the many companies that have taken up the licence to contract manufacture the Sputnik V vaccine. In all, there may be 8-10 companies producing the vaccine in India. It is a fairly open technology in the sense that anybody with manufacturing capability can approach the RDIF, present their manufacturing credentials and they are fairly open to allowing you to make it in India. They have helped in terms of putting together a technology transfer team. And this is not for the payment of a fee or anything of that nature. The intention is to make sure that if they contract manufacture it here, they can distribute more of their vaccines across the world, including in India. I presume initially they will want to do the manufacturing here primarily for India.

What line of existing activity positions companies to take up this line of activity?

Broadly speaking, any company exposed to biotechnology manufacturing can adapt, with some modifications, to produce vaccines.

What prompted you to take up Sputnik V? Was it determined by technical factors, or was it the ease of doing business?

The ease. The access to technology was much easier with Sputnik. If we have to recreate our own Sputnik V, we would have lost another six months. For a non-vaccine player there is a learning curve in terms of the regulatory pathways. The [regulatory] officials have to get familiar with your processes, they have to approve them, so you lose a lot of time in doing that. Contrast this to a vaccine player who is already doing this. They have a head start. The only way to catch up is by cutting short the technology optimisation timeline. And, RDIF enabled us to do it. We approached them first in November 2020. If somebody had given us Covaxin technology we could have done that as well. But nobody was actively offering us that. I am not sure whether it is as easily accessible as Sputnik.

What about Indian clearances?

Those we will get on our own. Since we have been in biologics that is not difficult.

When did you start work on this project?

About six months ago. We have completed the initial small scale and are now scaling it up. At full scale our intended capacity is to produce around 15 million doses a month. But it takes time to ramp up.

Can you explain the constraints in ramping up?

Let me take a crude example to simplify it. Say, you want to make coffee in a cup. You know how much coffee to add, how much sugar, how much milk. Let us now say we need to make it at a 10,000 litre scale. You may extrapolate the requirements of the ingredients at which you are making coffee in a cup to make it at much larger scales. You will tend to calculate the requirements of ingredients, But the challenge of adding them, the challenge of mixing them, the challenge of collecting it all multiply. Suddenly, you are doing it at a very very large scale. That is the challenge we face. It cannot happen overnight.

And, because this is biologics, you cannot quicken the process too much. Everybody makes curd at home. You will generally use the same vessel or the same method to make it. Try making it in a larger vessel or in a different way. Something will go wrong. You may have added the same proportion of the curdling agent, but biologics don’t work like that.

Why is that?

Imagine these agents as organisms that are working when you make curd. You expect that proportions would work as they scale up. Basically, that is a non-living pattern of thinking. Living beings work differently. Suppose you double the number of people in an organisation. Can you expect that output will double too? That is because the people have to generate output working together. Maybe they compete for the same resources. Maybe the space is not perfect. Maybe the temperature is not ideal. There are too many variables when you are dealing with biologicals.

At the level of manufacturing, what is the difference between the first dose, the second dose and the Lite dose of the Sputnik V?

The Lite version is basically the first dose. With any vaccine, you get some immunity with the first shot. The second dose is a booster. The clever trick in the Sputnik V vaccine is that the booster is another vaccine. Two different viral vectors are being used in the two doses, both of which carry the same gene. The second dose of the Sputnik V vaccine is supposed to generate a higher level of efficacy than other similar two-dose vaccines because the antibody response is greater. Of course, producing two different doses of the vaccine is a logistical nightmare because it is almost like producing in two different locations because you don’t want cross-contamination.

But once you get the formula right, at scale, is it as simple as replicating this over and over again?

You increase your chance of success, but every once in a while it will not go just about right, just as it happens with making curd.

What about accessing raw materials and equipment?

That is obviously an acute constraint right now. The world has never needed the kind of quantities of raw materials that we are now asking for. So, the supply chains that are needed for these never had to access the kind of quantities that we need today. This is not just for raw materials for vaccines but across multiple products. Take the case of the drugs for treating black fungus. It is not as if the drug is not being made. It is just that it was never needed in the quantities they are needed today. How do you prepare for this?

It is not very difficult in normal times to get equipment like bioreactors from a vendor. But in the pandemic vendors are stressed and unable to get the materials they need because of the spurt in demand all around. This has a cascading effect and by the time supplies catch up, you have lost crucial months. Supplies of bioreactors, bags, tubing and other plastic material, filters and other components are also impacted.

How much of this is import-dependent?

For raw materials, consumables and equipment, about 90 per cent, mostly from the Western world. These are very high-end items, required in small quantities, which were never required in the kind of quantities we need today. The more expensive a product is, the more the supply chain tends to shift Westward; the more volume intensive go East.

What kind of technology facilitation has been provided by the Russian side?

They have provided the cell lines, the cultures, the formula for growing it, the temperatures they should be subjected to, the kind of media to use, the nature of the feed. Basically, they have provided us the recipe to make the vaccine.

Even if we are only doing what the other Sputnik contractors are doing, according to the recipe, we still have to do the actual scaling up on our own.

How long does it take to make a batch of vaccines?

From start to finish it would take about 60 days—from the time you put in the ingredients to the vial to rollout. But manufacturing batches does not happen sequentially. It is like an assembly line. As soon as you finish the first step with the first batch, you start that step for the second batch. So, the first batch might take 60 days, but the second batch may roll out a week later. We are doing bulk as well as fill-and-finish production.

What is the target date for finishing your first batch?

By June or July we should be able to scale up our process. The successful rollout will depend on us getting the regulatory clearances and the government accepting those (the clearances). But many companies are producing at-risk because they do not want to wait for approvals before scaling up. There are clinical trials to be done and the regulatory process does take some time. July may not be feasible for full scaling up.