Managing cost considerations and access to technology for cost effective vaccine manufacture in developing countries.

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1 Managing cost considerations and access to technology for cost effective vaccine manufacture in developing countries. Amol R. Dindokar Serum Institute of India ltd.

2 Overview Disease Control Priorities in Developing Countries contributes substantially to global initiatives to improve the health of all peoples. Over the past 20 years, immunization has prevented approximately 20 million deaths from vaccine-preventable infections. Without vaccines, disease would become more rampant, the public health system would be overburdened with treatment costs

3 Apart from the high disease prevalence, growing population and emergence of new pandemics are important growth drivers of the global vaccine market. During the past 30 years, advances in biotechnology, genetic engineering, and information technology have resulted in acceleration in the pace of vaccine development. Investment in research and development largely by the pharmaceutical industry has resulted in a broad range of vaccines targeting more than 25 infectious diseases.

4 A majority of the world s children receive basic childhood vaccines. Millions more remain unimmunised and several important newer vaccines have yet to reach children in most developing countries. The vaccine industry has recently introduced a number of new vaccines, such as those against cervical cancer, meningococcal infection, potentially pandemic influenza, pneumococcal diseases, rotavirus diarrhea, and varicella zoster. The major barriers to access are High Vaccine Prices

5 Vaccine Manufacturing Vaccines are complex and diverse biomolecules ranging from recombinant subunit antigens to live organisms. Therefore, their manufacturing has traditionally been relatively inefficient and technically challenging. Producing a safe and effective vaccine requires about 5 7 years of research and is estimated to cost between $100 million and $1 billion, depending on the type of vaccine being developed.

6 The global vaccine market has experienced robust growth over the past few years, with economically emerging countries, such as India and China contributing effectively towards the industry's development. The global vaccine market is expected to increase by more than 100%, from $24 billion in 2009 to $56 billion in Multinational vaccine companies historically have conducted much of the innovation, research, and development in the field of vaccine production.

7 Cost of Vaccines Many factors seem to discourage vaccine research and development, including liability concerns and price limits due to bulk purchasing Manufacturing costs Include variable costs - cost of goods Semi-fixed - costs associated with each production batch. Fixed Cost - costs of plant and equipment. Semi fixed and Fixed cost contributes to the 85% of the total costs.

8 Factors - Determine Manufacturing Cost Production Technology. Manufacturing Scale & Presentation. Average costs fall with increasing volume over a large range.

9 Production Technology & Manufacturing Scale. Utilizing Bioreactors to increase production in Vaccine manufacturing. Bioreactors also offer the advantage of optimal culture conditions Large-scale production reduces the total number of batches Improving the Media to Increase Vaccine Yield. Strategies for improving Yield in Vaccine Manufacturing Improve the overall quality and safety profile for vaccine production. Purity considerations, because some vaccine impurities have an immunomodulatory effect and can act like an adjuvant to the vaccine. Therefore, manufacturers have to scale up their production without losing the potency of the mixture of the vaccine and the impurity.

10 Presentation The form in which vaccines are packaged and the number of doses per unit can also contribute significantly to cost. Pre-filled syringes are more expensive than single dose vials. The relative contribution of presentation to total cost is greater for cheaper vaccines.

11 Managing Cost consideration-challenges There are increasing demands to develop new manufacturing approaches that will allow us to deliver vaccines more quickly, in larger volumes with greater quality and to do all this more costeffectively. The requirement for specialized manufacturing capabilities and regulatory experience are important. Certain level of infrastructure and expertise will be required for safe, effective manufacturing, and not all countries may be able to achieve that now. Identification of suitable antigens, adjuvants, and delivery methods.

12 Technology knowledge owned by few major accounts Analytical assays with low throughput Complex impact of process on product Vaccine manufacturing technologies are changing, creating a push to produce newer products. Market uncertainties are high, especially for those vaccines that will be largely used in public-sector programs. Time to clinical approval Limited Analytical tools Analytical challenges during development and production.

13 Challenges In Analytical Characterization The difficulty of characterizing complex biological products such as vaccines makes it especially challenging to ensure that they can be manufactured in a consistent, reproducible, and commercially viable manner with assurance of safety, quality, and efficacy.

14 Traditional Testing Technologies Might Not Be Able To Identify Subtle And Unanticipated Variability. Mass Spectrophotometer (Ms) Based Approaches Have Been Applied Towards Product Characterization As Well As For Routine Monitoring During Commercial Manufacturing. GC MS, HPLC MS etc. MS-based instruments such as Q TOF have further improved sensitivity to understand structural changes in an immunogen Use NMR and SEC-MALLS Study Polysaccharides at the Molecular and atomic levels.

15 Managing Cost consideration-solutions Companies are working rapidly with new combinations-- where they can. Rapid scale-up Improved stability Available regionally Reduced process equipment complexity Reduced facility complexity and cost Faster Construction, Commissioning, and Launch Rapid expansion of capacity Manufacturing cost structure shift to variable costs. Significant reduction in capital equipment costs

16 FINANCING: Success depends on contributions from program, supply and financing GAVI has facilitated the introduction of essential vaccines throughout the least developed countries, such as pentavalent vaccine (DTP-Hib-HepB) in 65 countries. GAVI has not limited itself by handing out vaccines to recipient countries, but is driving co-responsibility through co-funding of vaccines. VACCINE PROCUREMENT ASSURANCE: The procurement strategies need to be designed and managed to increase supplier engagement. Providing Appropriate returns. Creating credible and predictable demand through firm contracting. Working in collarabrative and open fashion with suppliers.

17 REGULATORY PROCEDURES Despite the advances in vaccine manufacturing across the globe, regulatory hurdles still stand in the way of companies seeking to take a candidate product to the clinic and eventually to market. The World Health Organization (WHO) has developed a major role in collaborating with and facilitating knowledgesharing among the NRAs. WHO's prototype GMP guidelines have been adopted by more than 100 countries. Other major regulatory agencies also have mechanisms of supporting product licensure in countries outside their jurisdiction.

18 Further, novel analytical technologies for product characterization need to be put in practice. Newer regulatory initiatives such as quality by design (QbD) and process analytical technology (PAT) need to be implemented for vaccine manufacturing as well. All NRAs need to also follow a process of continuous improvement with respect to their approval process. Tests that are outdated because of developments in technology and advances in understanding should be removed. Timeliness for approval may be an issue for the cases of pandemic vaccines

19 Technology Certain critical vaccines are still manufactured by traditional methods because of lack of suitable technology or lack of incentive for developing improved technology. Example, influenza vaccines are manufactured by methods fundamentally unchanged over several decades. With advances in technology, vaccine manufacturers can have access to a greater range of choices. Traditional vaccines, which are often made through inactivation or crude fractionation of an infectious agent, are now being supplemented by vaccines based on pure proteins

20 A variety of technologies have been used to develop successful vaccines. Technologies include live attenuated bacteria and viruses such as Bacillus Calmette-Guérin and measles, mumps, and rubella (MMR); inactivated bacteria and subunits such as whole cell pertussis; proteins and diptheria and tetanus toxiods, recombinant proteins, conjugated polysaccharides, virus-like particles (VLPs) etc. These variety of technologies used in each vaccine can be a challenge to the vaccine manufacturer with respect to standardization of facilities and equipment.

21 Technology Transfer Technology transfer must be considered step by step approach, in the frame work of long term co-operation, with the mutual interest of different partners clearly identified, recognized and respected.

22 Even when technologies are in the public domain or are available for licensing, vaccine development requires considerable expertise. Even for an experienced vaccine producer, transferring production to another building / site is a real challenge. Quality control, and compliance with regulations, are by far the greatest tasks in manufacturing vaccines. Tech transfer can: Accelerate vaccine availability; reduce production costs; allow for sustainable production overtime.

23 Tech transfer could help facilitate access to vaccines to meet global needs. There are minimum conditions for consideration of tech transfer which include * Compliance with GMP standards, * Existence of a strong and independent National local Control Authority. To guarantee success, tech transfer must proceed in phases in a step by step manner.

24 Thanks..