1. INDUSTRIAL PERSPECTIVES FOR VL VACCINE DEVELOPMENT: DEVELOPING COUNTRY
Dr Gaurav Gupta,
Head Viral and Genetic engineered vaccines, Zydus Cadila

2. CONTENTS Zydus Cadila- Overview Vaccine Commercialization Capabilities
Vaccines in Pipeline
Need of V L Vaccines in India
Zydus perspective on Leishmania vaccine development
Current Status
Future plans

3. Zydus Cadila- Overview

4. ZYDUS NEXT MILESTONE IS TO BECOME RESEARCH BASED PHARMACEUTICAL COMPANY BY 2020.

5. VACCINE COMMERCIALIZATION CAPABILITIES

6. Zydus Rabies Vaccine : WHO approval

7. Zydus first to develop and launch H1N1 Vaccine in India

8. Acquisition of Etna Biotech

9. Vaccine Technology Centre
Spread over a area of 812 m2
Vaccine technology centre is state of art vaccine research & development centre under GMP for process & analytical development of different vaccines- viral, bacterial and genetic engineered for phase 1 clinical trials.
Ground floor is equipped with QC for clinical trials as well as commercial batches.
First floor is equipped with upstream, downstream , formulation, filling & lyoohilization sections of various types of vaccines under BSL 2 & BSL 3.
Second floor has regulatory, QA and utilities for GMP activities.

10. Live viral Vaccine Manufacturing plant
Spread over a area of 2005 m2 a dedicated facility for production of Mumps, Measles, Rubella and Varicella vaccines.
Independent suites for active viruses and mammalian cell lines (2 in No’s); completely segregated upstream and downstream , formulation , filling and lyophilization operations.
Contains a large capacity roller bottle apparatuses and incubation area, Large cell and virus preservation freezers, Fully automated lyophilizers and filling machine for sterile filling.
Capable of making 100 million bulk doses per annum per product and expandable

11. Cryostorage System
Corridor
Filling line
Lyophilizer

12. Recombinant Vaccines Manufacturing plant
Spread over a area of 1000 m2 a dedicated facility for Recombinant vaccines like Hepatitis B and HPV.
Completely segregated upstream and downstream operations, Sterile filtration area.
Contains 200 L capacity fermentor, 200L capacity TFF, Microfluidiser, West falia continuous centrifuge, Depth filtration system, Zonal centrifuge
Capable of making 5 million doses per annum

13. UPSTREAM AREA
200 L Production Fermentor
20L Seed Fermentor

14. DOWNSTREAM AREA
Cell Separator
Ultrafiltration
Cell Disruptor/Homogenizer

15. Influenza vaccine Manufacturing plant
Dedicated facility for Influenza vaccine (Split).
Independent suites for active viruses and egg incubation; completely segregated upstream, downstream , inactivation & filling operations
Fully automated egg inoculation and harvesting
Capacity of 10 million doses per annum of tetravalent Flu and expandable

16. Bacterial Vaccine Facility
Manufacturing capabilities (Drug substance)
Tetanus Toxoid Purified Bulk
Diphtheria Toxoid Purified Bulk
Whole cell Pertussis polled Bulk
Haemophilus type- b PRP-TT Conjugate Bulk
Typhoid Vi-polysaccharide Purified bulk
Typhoid Vi-TT Conjugate bulk
Manufacturing capabilities (Drug Products)
Tetanus Vaccine
Diphtheria & Tetanus Toxoid Vaccine
Diphtheria ,Tetanus Toxoid & W. Pertussis Vaccine
Diphtheria ,Tetanus Toxoid, W. Pertussis & Hib PRP-TT Conjugate Vaccine
Diphtheria ,Tetanus Toxoid, W. Pertussis ,Hep B (rDNA) & Hib PRP-TT Conjugate Vaccine
Typhoid Vi-polysaccharide Vaccine
Typhoid Vi-TT Conjugate Vaccine

17. Marketing Authorization
Vaccines Pipeline
Projects
Research
Development
Preclinical
Studies
Phase I
Phase II
Phase III
Marketing Authorization
H1N1
Rabies
Typhoid
DTwP-HiB
Q1, 2016
MMR
Varicella
Q2, 2016
MMR + V
Q4, 2016
Hepatitis B
Q2, 2017
Pentavalent
Q4, 2017
Typhoid Conjugated
HPV
Q3, 2018
Malaria
Leishmania
Hepatitis A
Q 4, 2018

18. Marketing Authorization Japanese Encephalitis Congo Hemorrhagic Fever
Vaccines Pipeline
Projects
Research
Development
Preclinical
Studies
Phase I
Phase II
Phase III
Marketing Authorization
Hepatitis E
Immunogenicity established
Japanese Encephalitis
Clones established
Universal Flu
Collaborated with NIBSC under EU grant
Congo Hemorrhagic Fever
Clones are established
Ebola

19. Need of VL Vaccine in India
Leishmaniasis is responsible for the second-highest number of deaths due to parasitic infection globally.
More than 90% of global burden of million VL cases occur in just six countries: India, Bangladesh, Sudan, South Africa, Brazil and Ethiopia.
India is one of the most important foci in the world for VL. The state of Bihar and neighboring areas of eastern Uttar Pradesh and West Bengal remain particularly badly affected by VL.
The annual incidence of VL in India is approximately 100 000 cases, and the state of Bihar accounts for more than 90% of these.
High percentage of asymptomatic individuals serve as reservoirs
Failure of control programs, high cost of treatment and drug resistance
Spread of VL in non-endemic regions
Cost effective vaccine would have the potential to decrease both the direct and indirect health cost burden in the affected developing countries.

20. ZYDUS PERSPECTIVE ON LEISHMANIA VACCINE DEVELOPMENT
Collaborate with advanced Know-how carrier Institutes in Leishmania vaccine field to test advanced vaccine candidates
To co-develop and Execute preclinical and clinical studies for selection of final vaccine candidates under GMP
To Commercialize a safe, effective & affordable vaccine for India and Global need

21. CURRENT STATUS

22. GLOBAL PROJECT TO DEVELOP VACCINE AGAINST LEISHMANIASIS
European Research Center of Zydus Cadila has won highly competitive Frame work program 7 projects to develop a new vaccine against Leishmaniasis
Collaboration centers include Universidad Autónoma de Madrid, Spain; Instituto de Salud Carlos III, Spain; Instituto de Biologia Molecular e Cellular, Portugal; Istituto Superiore di Sanità, Italy; Swiss Tropical Public Health Institute, Switzerland; Meditox, Czech Republic; AMVAC Ag, Switzerland; NIH in Bethesda & IDRI in Seattle, USA
Overall Budget sponsored by European Union 5.4 million Euros
This Project foresee the phase I/II clinical trial in humans

23. PROJECT APPROVED BY DBT, INDIA
ANIMAL STUDIES
To evaluate proposed vaccine formulations in rodent models and Langur monkey challenge experiments
HUMAN STUDIES
To evaluate in vitro cellular immune response in Leishmaniasis with and without our proposed vaccine formulations from active VL patients, cured individuals and healthy endemic control subjects from their PBMCs (BUS, Patna and AIMS, NEW DELHI)
Final potential candidate Vaccine formulations will be further evaluated in clinical trials for safety and efficacy by Zydus.

24. Collaboration with IDRI, US

26. FUTURE PLANS ON VL VACCINES
To generate clinical data based on EU project and to plan Indian Clinical trials accordingly for safety & efficacy
To commercialize a affordable, safe and effective vaccine for India and Global use as soon as possible

27. SUMMARY
Zydus has know how of vaccine technologies- Classical, Genetic engineered for process development, preclinical studies and clinical studies in house.
We are fully installed with preclinical and GMP manufacturing facilities qualified and ready for any kind of vaccines.
We have proven capabilities in vaccine commercialization.
Therefore we will launch Leishmania vaccine in shortest time depending upon regulatory approvals.

28. THANKS
THANK YOU