“Like any other company in the pharmaceutical space, we too did not anticipate that we will have continuous manufacturing to produce 100 crore doses of vaccine such as Covishield,” says Ashish Sahai, Additional Director - Viral Vaccines, Serum Institute of India.

Sahai was speaking at the panel discussion, 'Strategies in pharmaceutical manufacturing and development' at the recent CPhI P-MEC India Conference organized by the Informa Markets.

“When the pandemic happened, none of the companies were geared up to offer any immediate solutions. Fortunately, we were expanding for a few other vaccines and we had enough capacities to cater to sudden demand. Since we have 50 different kinds of products, obviously the filling lines were never dedicated but only used for batch manufacturing. While continuous manufacturing wasn’t a regular practice, it is not that we never explored the new innovative vaccine manufacturing platforms. We did it in the case of biologics and we had single injection platforms. We imagined the need for continuous manufacturing, from start of filling to end but it has been difficult until now. Only with Covishield, we have started having it from bulk stage to filing and succeeded in producing billion doses. It is difficult to have such production unless there is a pandemic like market demand where one requires to produce 10 crore doses. For a few lakh doses, we can't have continuous manufacturing. We have worked with a few American companies who provided the pre-filled syringes. There are innovative platforms that we are working on with the University of Columbia and Particles of Humanities, funded by Gates Foundation. Non-viral vector-based approach in biologics which is a nanotechnology platform. These are becoming popular with many players now. We also have single use bioreactors that don't require the repeated regulatory inspections. We also have single use testing instead of animal testing that takes 20 days and is difficult to validate. Such technologies are emerging and we are all set to adopt them,” adds Sahai.

Mahesh Murthy, Senior Director of Operations - Medical Device, Biocon Biologics feels that the pandemic has opened up a lot of thinking across industry and as time moves, there will be changes in the manufacturing process.

“The continuous manufacturing has picked up pace since 2008-09 onwards, with a lot more FDA instructions on how to do it. However, we haven't achieved a breakthrough of sorts yet. Even now, it is highly driven by upstream and the bulk whereas downstream is batch manufacturing. Given the stringent requirements from regulatory agencies and expectations in terms of the product quality etc., the mindset is still of the batch manufacturing. We will not be able to change that because it requires infrastructural and regulatory changes besides maintaining quality throughout this. With Covid-19, the manufacturing and product delivery timelines have been crushed significantly. If you see the whole thing in terms of vaccines, in the last 12-15 months, a lot of things have turned around, otherwise what it takes years to develop. And it is not just to develop but develop with effectiveness, with least amount of side effects and fighting back the virus. When it comes to biology, it is complex and not that straightforward. The volumes may not be necessarily like vaccines, i.e. millions of units in one shot. The trend is going on but it is more of an evolution than a breakthrough. A switch over will take some more time,” added Murthy.  

As per Amit Kale, Associate VP - Sourcing and Supply Chain, Reliance Retail, the continuous manufacturing is driven by market demand as shown in case of Covid-19 vaccines where millions of doses were produced in quick succession. 

“While in case of batch manufacturing, there is small volume and better control in terms of if something goes wrong, that's not possible in continuous manufacturing. There is huge labour involved for humongous activity of batch manufacturing whereas in future it might get difficult to get enough skilled workers. In the batch process, labour has to get involved at every stage. For example, adding a batch or adding a raw material or taking it out. Therefore, continuous manufacturing is the way forward due to lesser manpower and advanced technology. It is plug and play with no interference. At the same time, continuous manufacturing is not just about bulk production but a complete end to end process where the product is on the belt and will go up to the truck directly, without interference of humans. Due to shortage of human resources, most European and American companies have a process where batches are produced in small quantities and the batches are transported in laser guided vehicles inside the warehouses. Then it is stored into the ASRS system, automatically loaded into trucks,” added Kale. 

“For blockbuster molecules to be used at large scale, we need continuous manufacturing. The challenges include the absence of regulatory guidelines and need for the same line for producing multiple products. Molecules for chronic use can be manufactured by using such technologies,” concludes Rahul Gupta, Vice President, Regulatory Affairs, USV.