KOL perspectives: Dr Sudeep Srivastava on vaccine manufacturing trends in India

Syamala Ariyanchira interviews Dr Sudeep Srivastava about the vaccine manufacturing trends in India for our latest KOL perspectives article.

India has emerged as the global hub for the production of low cost vaccines. The country accounts for almost 45% of the global vaccine supply. While vaccine companies in developed countries are moving away from manufacturing due to cost pressures, Indian companies are tapping the opportunity and are filling the gap between the growing demand and supply of vaccines. In addition to low cost vaccines, a rising number of Indian companies are involved in the manufacturing of innovative high quality vaccines as well. Cost-effective processes developed by these companies contribute significantly to improve the affordability of recombinant vaccines in developing countries.

On behalf of pharmaphorum, Syamala Ariyanchira explores the emerging trends related to recombinant vaccine development and manufacturing in India with Dr Sudeep Kumar Srivastava, Vice President-Biotech at Cadila Pharmaceuticals, India.

Interview Summary

SA: Could you please describe your background and current role?

SS: I have been working in the biotech field for over twenty years. My basic research experience covers fields such as enzymology, protein biochemistry, and molecular biology. I completed my PhD in Microbiology in India, and later moved to the Institute of Agrochemistry and Food Technology (IATA), Valencia in Spain for post-doctoral research. I came back to India in 1996 and have been working in the field of recombinant proteins and vaccines since then. I have handled E. Coli, mammalian, and insect cell cultures for the production of recombinant products. I have also been involved in the design and establishment of new manufacturing facilities for recombinant molecules that are in compliance with the regulatory guidelines.

At present I am working as Vice President-Biotech at Cadila Pharmaceuticals and looking after complete operation. Cadila has presence in many countries, and is focussing on several therapeutic classes. We are into formulation and have also started Bulk API manufacturing in small scale. We are active in biotech field for many years now, with a focus on recombinant therapeutic proteins, vaccines, and diagnostic kits.

SA: What are the common protein expression platforms used for the production of vaccines in general?

SS: Several platforms are in use for vaccine manufacturing. Some of the common ones include Vero cell, Insect cell line/baculovirus, E. Coli, yeast, duck embryo, and egg based platforms.

“…for vaccines, the best expression systems are either mammalian cell lines or insect cell lines.”

SA: Can you please give a general idea about some of the unique challenges and needs associated with various expression systems?

SS: Each expression system has its own advantages and disadvantages. The selection of expression system is based on the type of protein that needs to be manufactured and the complexity of the structure of the protein.

Generally for vaccines, the best expression systems are either mammalian cell lines or insect cell lines. Yeast and E. coli are also used in some cases, but these are mainly for simple molecules.

With respect to E. coli systems, even though protein expression is higher compared to other systems, purification process is longer. The threat of Endotoxin in the final product as well as in the facility is another concern associated with E. coli systems.

Mammalian as well as insect cell lines do not have any such issues. Moreover, product purification is easier when these systems are used.

SA: What are the most common platforms used by vaccine companies in India – for recombinant as well as non-recombinant vaccines?

SS: Non-recombinant vaccines are mostly produced through vero cell line (cell culture). Some companies are using duck embryo cell for the rabies vaccine.

Recombinant vaccines are produced either through E. coli or Yeast expression system.

SA: What are the main factors taken into consideration by Indian companies while choosing an expression platform for the production of a particular vaccine?

SS: Main factors considered while choosing an expression system include cost, scalability, and infrastructure. Expertise available within the organisation and availability of skilled personnel familiar with a particular expression system in the country are also important factors to be considered.

“Main factors considered while choosing an expression system include cost, scalability, and infrastructure”

SA: What are the emerging trends in terms of protein expression systems for vaccine manufacturing in India?

SS: The vaccine industry is moving to recombinant vaccines. Baculovirus / insect cell line systems are becoming the most preferred systems for the production of recombinant vaccines. This is an important trend in vaccine production. The system is unique and safe because baculovirus is non-pathogenic for humans. Moreover, baculovirus is very specific for insect cell line infection.

SA: Based on your experience, can you please list a few points regarding the “best practices” for vaccine manufacturing?

SS: The best and safest practice is to use cell culture systems for vaccine manufacturing – for non-recombinant as well as for recombinant vaccines. This will give flexibility in terms of scaling up the process. Cell culture systems lead to better yield as well. These are much safer in comparison to egg-based vaccine manufacturing processes. Cell culture processes are much easier to handle. Since the time to process each batch is much shorter, vaccines can reach the market in significantly shorter time period.

An important and emerging ‘best practice’ is related to vaccine manufacturing facilities. Currently, mostly companies in India are using fixed and dedicated facilities for the production of each vaccine. This is changing with the availability of disposable systems. The disposable systems eliminate cleaning time from the process cycles, which can speed up vaccine production significantly. Another advantage of disposable systems is flexibility to use the same facility for the production of multiple vaccines based on the same expression system.

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About the interviewee:

Dr Sudeep Kumar Srivastava is a Biotechnologist by education. He did his Post-doctoral work in the field of molecular biology from IATA, Valencia, Spain between 1994 and 1996. His basic research experience lies in the areas of enzymology, protein biochemistry and molecular biology fields. He has more than 20 years of research and manufacturing experience in this field. His Industrial core competence lies in the area of process development and scale up – mainly for recombinant protein molecules and other large scale fermentation based products. He has expertise in working with E. coli, mammalian as well as insect cell cultures for manufacturing recombinant products.

He is currently working as Vice President-Biotech at Cadila Pharmaceuticals in India, where he looks after all biotech operations. Dr Srivastava has been actively involved in facility designing, commissioning, and getting approval from US FDA for large scale fermentation plant facilities. He was involved in insulin / vaccine project planning for Novartis in relation with Chiron acquisition. Other important highlights of his career include technology transfer and project management of VLP based platforms from Novavax in USA and ARTES in Germany.

About the interviewer:

Syamala Ariyanchira, PhD., is principal consultant and director at AcuBiz Consulting (www.acubiz.com.my), based in Malaysia. She can be contacted at syamala@acubiz.com.co

What are the emerging trends in vaccine manufacturing in India?