Rotavirus Vaccination Via Oral Thin Film Delivery

Competition Finalist

This entry has been selected as a finalist in the
Disruptive Innovations in Health and Health Care: Solutions People Want competition.

Our innovation is a room temperature stable quick-dissolving oral thin film delivery system for vaccines that will make vaccinations almost as simple as freshening your breath. This delivery system exhibits many advantages not available in current products: improved patient compliance, improved bioavailability, reduction in the costs associated with storage, distribution, handling and administration.

Our present focus is to develop the oral thin film delivery system for rotavirus vaccination in underdeveloped areas, as rotavirus is the leading cause of gastroenteritis infecting virtually every child in the world resulting in severe diarrhea and death in approximately 600,000 children each year. However, this oral thin film delivery system can be adapted for other therapeutics, not just vaccines.

Our oral thin films combined with a stabilized rotavirus vaccine will be a more practical and attractive alternative to current vaccines because of its simpler storage and distribution requirements. For example, cold chain requirements and excess water weight would be eliminated making transportation and storage more manageable and less costly. Furthermore, oral thin films are simpler to administer to infants than traditional vaccination methods: tablets, liquid droplets, injections. Mass immunization becomes much more feasible with a cheaper, easier and potentially more effective method of vaccination.

Current rotavirus vaccines are delivered in liquid form, which is not sufficiently storage stable and difficult to administer to infants. Unfortunately, these liquid vaccines can be easily regurgitate by infants resulting in inadequate dosing. Furthermore, they require relatively large secondary packaging and must be constantly refrigerated to maintain bioactivity, severly significantly increasing costs. Thus, it is uncertain whether these vaccines will reach children of developing areas, where it is needed the most.

About You

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Location

Project Street Address

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Project Country

n/a

Your idea

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Focus of activity

Technology

Year the initiative began (yyyy)

2006

Positioning of your initiative on the mosaic diagram

Which of these barriers is the primary focus of your work?

Complex, expensive medicine

Which of the principles is the primary focus of your work?

Simplify through technology

If you believe some other barrier or principle should be included in the mosaic, please describe it and how it would affect the positioning of your initiative in the mosaic:

This field has not been completed

Name Your Project

Rotavirus Vaccination Via Oral Thin Film Delivery

Describe Your Idea

Our innovation is a room temperature stable quick-dissolving oral thin film delivery system for vaccines that will make vaccinations almost as simple as freshening your breath. This delivery system exhibits many advantages not available in current products: improved patient compliance, improved bioavailability, reduction in the costs associated with storage, distribution, handling and administration.
Our present focus is to develop the oral thin film delivery system for rotavirus vaccination in underdeveloped areas, as rotavirus is the leading cause of gastroenteritis infecting virtually every child in the world resulting in severe diarrhea and death in approximately 600,000 children each year. However, this oral thin film delivery system can be adapted for other therapeutics, not just vaccines.
Our oral thin films combined with a stabilized rotavirus vaccine will be a more practical and attractive alternative to current vaccines because of its simpler storage and distribution requirements. For example, cold chain requirements and excess water weight would be eliminated making transportation and storage more manageable and less costly. Furthermore, oral thin films are simpler to administer to infants than traditional vaccination methods: tablets, liquid droplets, injections. Mass immunization becomes much more feasible with a cheaper, easier and potentially more effective method of vaccination.
Current rotavirus vaccines are delivered in liquid form, which is not sufficiently storage stable and difficult to administer to infants. Unfortunately, these liquid vaccines can be easily regurgitate by infants resulting in inadequate dosing. Furthermore, they require relatively large secondary packaging and must be constantly refrigerated to maintain bioactivity, severly significantly increasing costs. Thus, it is uncertain whether these vaccines will reach children of developing areas, where it is needed the most.

Innovation

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Define the innovation

Our innovation is a room temperature stable quick-dissolving oral thin film delivery system for vaccines that will make vaccinations almost as simple as freshening your breath. This delivery system exhibits many advantages not available in current products: improved patient compliance, improved bioavailability, reduction in the costs associated with storage, distribution, handling and administration.

Our present focus is to develop the oral thin film delivery system for rotavirus vaccination in underdeveloped areas, as rotavirus is the leading cause of gastroenteritis infecting virtually every child in the world resulting in severe diarrhea and death in approximately 600,000 children each year. However, this oral thin film delivery system can be adapted for other therapeutics, not just vaccines.

Our oral thin films combined with a stabilized rotavirus vaccine will be a more practical and attractive alternative to current vaccines because of its simpler storage and distribution requirements. For example, cold chain requirements and excess water weight would be eliminated making transportation and storage more manageable and less costly. Furthermore, oral thin films are simpler to administer to infants than traditional vaccination methods: tablets, liquid droplets, injections. Mass immunization becomes much more feasible with a cheaper, easier and potentially more effective method of vaccination.

Current rotavirus vaccines are delivered in liquid form, which is not sufficiently storage stable and difficult to administer to infants. Unfortunately, these liquid vaccines can be easily regurgitate by infants resulting in inadequate dosing. Furthermore, they require relatively large secondary packaging and must be constantly refrigerated to maintain bioactivity, severly significantly increasing costs. Thus, it is uncertain whether these vaccines will reach children of developing areas, where it is needed the most.

Context for Disruption:

Mass immunization programs have been slowed due to high overhead costs and complexities associated with traditional vaccine delivery methods. These include expensive cold-chain restricted storage & distribution, complex & inconvenient delivery systems leading to complicated administration, low patient compliance, and medical waste. In particular, underdeveloped areas are at a disadvantage due to the limited availability of clean water sources and trained healthcare personnel needed to administer the drug, poor sanitation conditions and lack of adequate storage facilities to store vaccines. Furthermore, traditional vaccination methods are impractical for populations who need it most. For example, infants will have difficulty swallowing tablets, while other methods requiring accessory items such as needles can cause additional complications.

Our candidate disruptive innovation is a technology to stabilize complex therapeutics for storage at room temperature conditions combined with an oral quick-dissolving thin film system (e.g. Listerine breath strips), both of which will facilitate mass immunization. An oral thin film would be easily distributed in a light, small volume package without the excess water weight and the need for refrigeration. Accessory materials would not be necessary as the film can simply be stored, placed on the tongue and quickly dissolved by saliva. Such easy, intuitive dosing obviates the need for trained healthcare personnel.

Our present focus is to develop the thin film delivery system for rotavirus vaccination, as rotavirus is the leading cause of gastroenteritis infecting every child in the world. However, this oral thin film delivery system can be adapted for other therapeutics, not just vaccines for use in all nations. It will lower the major barriers to mass distribution, leading to increased vaccine coverage. Thus, it has the potential to transform the way all vaccines and complex biopharmaceuticals are delivered across the globe.

Delivery Model

We have currently established relationships with PATH (Program for Appropriate Technology in Health, Seattle WA), Bill and Melinda Gates Foundation, and the World Health Organization (WHO) aimed at providing adequate healthcare to the people of the world. These international health organizations have been serving as important catalysts in advancing the development of vaccines and their use in developing world countries. In some instances, they are also involved in procurement and distribution of vaccines purchased from other pharmaceutical manufacturers for distribution in developing countries. Our collaboration with these non-governmental organizations (NGOs) is an important conduit so that our innovation reaches the target population. In the developed world markets, we intend to form commercial partnerships with larger pharmaceutical development partners who have existing sales, marketing, and distribution infrastructures necessary to implement the vaccines using typical vaccine distribution channels.

Our oral thin film technology would avoid major barriers to reach the customer such as storage and distribution; light-weight and compact thin films allow for reduced costs for shipping offering a strong purchasing incentive to international health organizations. Furthermore, our group is the first to stabilize a dry-form rotavirus vaccine at higher temperatures for long periods, further reducing storage costs. Finally, the manufacturing of the oral thin film system and the stabilization of rotavirus vaccines are cheap and easily scaled up. Thus, our technology would be preferentially adopted to replace current oral liquid dosing forms, allowing us to gain a large portion of the international immunization market. While our technology is not yet available, our future market success will be measured by the percentage of dosing forms currently used that is replaced by our delivery system.

Key Operational Partnerships

Our unique rotavirus vaccine system was developed as a collaborative effort between the Johns Hopkins University, School of Engineering and Aridis Pharmaceuticals. Aridis specializes in formulation technology to stabilize pharmaceutical products and thereby simplifying storage and handling. They have developed a stable rotavirus vaccine that can withstand harsh fabrication procedures and can be stored for long periods in dry-form and at high temperatures. The thin film developed at Hopkins is also aimed to simplify pharmaceutical distribution and administration. By combining these two novel technologies, a superior and unique vaccination system was produced, which could supplant all current oral vaccination methods.

Our established relationship with PATH is critical for getting our product to the infants in need. Within PATH, the Advancing Rotavirus Vaccine Development program exclusively aims to bring rotavirus vaccines to the poorest areas. PATH has partnered with Aridis and other companies including developing world vaccine manufacturers (e.g. one in India, one in China, and one in Brazil), which has been key to the development and manufacture of the vaccine in advance of conducting clinical trials. Other global organizations such as the WHO, the Global Alliance for Vaccines and Immunization (GAVI) and US Centers for Disease Control and Prevention will be involved in purchasing and distributing the vaccine.

Impact

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Financial Model

The financial model governing our innovation is common to many if not all biopharmaceuticals. The initial stages of product development are very resource intensive with no income being generated for at least seven years, which is the typical time required to complete preclinical and clinical testing and obtain marketing approval from the appropriate regulatory authorities. Once marketing approval is obtained, earned income from product sales will be used to offset the cost of manufacturing, sales and marketing, general and administrative (G&A) expenses and any further post marketing studies that are required. The percentage of income that will be allocated to ongoing expenses versus profit will depend on the markets being served, i.e., the economics in a developing world will be significantly different than in the U.S. In the developing world, we anticipate that most of the earned income will be allocated to ongoing expenses with a small fraction (1-5%) retained as profit.

What is your annual operating budget?

1.00

What are your current sources of revenue? (please list any sources that are foundation grants)

Aridis currently receives all of its funding from grants or research collaborations. Our current grants include:

NIH Bioterrorism - Small Business Innovation Research (SBIR) - $100,0000 (2 yrs)
NIH Advanced Technology – Small Business Technology Transfer (STTR) - $600,000 (2 yrs)
PATH Vaccine Solutions (part of larger grant from Bill and Melinda Gates Foundation) - $1.9M (3 years)

We receive funding through the following organizations to continue improving our technology:
National Collegiate Inventors and Innovators Alliance – $16,000
Bill and Melinda Gates Foundation - $2 million

Effectiveness

Although, our innovation has yet to reach our target population as a final commercial product, the collaborative success between Johns Hopkins students and Aridis Pharmaceuticals has gained much popularity in the public domain (e.g. Newsweek and FOXNews ). This initial success has served as an additional stimulus to the Hopkins faculty and administrators to encourage their students to work on projects that can have a real world impact on public health. PATH and the Bill and Melinda Gates Foundation have initiated discussions with us to examine the feasibility of implementing this delivery system for the rotavirus vaccine as well as expanding its applications to other needed vaccines such as typhoid, cholera and shigella.

Perhaps more important is the impact of our advanced vaccine delivery system on those organizations (Gates, WHO, UNICEF, GAVI) focused on the rapid deployment of new vaccines into developing countries. This has required a rethinking of the costs of vaccination to include not only the cost of the vaccine itself, but also the cost of storage, distribution, and administration. Traditional thinking emphasized implementation costs primarily from a cost of goods perspective, thus providing a disincentive to introduce new vaccine technologies that require new manufacturing equipment and potentially adding to the cost of manufacturing. Consequently, there has been a lack of new and potentially disruptive innovations in vaccines, particularly in the developing world. However, the cost of storage, distribution, handling, administration and device disposal often are more expensive than the cost of manufacturing. Our innovation is an alternative that may have marginally higher manufacturing costs than traditional delivery systems, but implementing mass vaccination programs with the Aridis technology will be more cost effective and will reach more people in the most remote locations.

Which element of the program proved itself most effective?

Our innovation heavily relies on formulation and processing techniques to create a dry-form rotavirus vaccine stable at high temperatures. Without this innovation, the manufacturing of a dry oral thin film would not be possible. The stabilization of therapeutics into dry powders to eliminate excess water weight and prolong shelf life has been a major movement in the pharmaceutical industry for many years. We have been able to show stabilization of different strains of live-attenuated rotaviruses at temperatures higher than 110 degrees Fahrenheit for several months. The stabilization of a live virus in these conditions is almost unprecedented and has been the most promising discovery that could revolutionize all vaccination efforts. This stable form is an effective design that will permit large amounts of the vaccine to be stored and used in third world nations where cold-chain storage is expensive, unreliable and impractical.

Number of clients in the last year?

Although we have yet to produce and commercialize our rotavirus vaccine, we have been approached by other pharmaceutical companies and research groups interested in using our stabilization technology and thin film delivery system as a vehicle for their therapeutics. We have been in discussions with the Gates Foundation, PATH, OneWorld Health organizations, as well as the WHO in implementing this delivery system for developing world needs.

What is the potential demand?

The advantages of convenience and room temperature stability associated with our quick dissolving thin film delivery system can be broadly used. The thin film system is applicable to all oral vaccines and oral protein based therapeutic drugs, as well as biopharmaceuticals that can be converted to the oral route. The impact on vaccines could be transformational for infectious diseases such as shigellosis and rotaviral gastroenteritis which combined cause over 1 million deaths in children every year in the developing world.

Considering rotavirus alone, the demand for any vaccine will likely be high since all children by the age of five will have been infected by rotavirus and many children in third world countries will die. Currently, it is recommended that all new born infants in the U.S. be given rotavirus vaccine and it is highly likely that most of the world will follow this recommendation. It is estimated that the required annual worldwide rotavirus vaccine doses will be greater than 400 million. Although current vaccines exist on the global market, a majority of children in need still do not receive them. Without a new vaccine, it is likely that many will not receive a vaccination, both because of supply limitations and the difficulty of getting a sufficient number of doses into an already limited cold chain.

It has been estimated that the rotavirus vaccine market will be worth $2.5 billion by 2010, primarily driven by high demand for rotavirus vaccines in the developed world. The support for immunization of millions of new infants is to prevent the hospitalization cost burden, which are estimated to be one billion dollars per year in the U.S. Due to the inherent ease of use advantages in our rotavirus vaccine, the adoption of our system over current vaccines would allow us to capture market share and supply the necessary vaccines.

Scaling up Strategy

Although we have an established formulation to stabilize rotavirus in dry stable form as well as the oral thin delivery system, each component can be further improved by in vivo animal studies to demonstrate its efficacy and safety. We will also conduct process development studies to scale up rotavirus thin films production to clinical trial material manufacturing scale. The manufacturing process is relatively simple and well developed by a number of companies. We have an existing partnership with one such manufacturer who has commercial scale GMP thin film manufacturing facility and who are willing to take on manufacturing of our vaccine on thin films.

Year 2 & 3 of the funding period will involve initial phase 1 study comparing the safety of a single dose of the stabilized vaccine to the unstabilized vaccine in adults. If the vaccines have similar safety profiles, we will proceed by the end of year 3 to Phase 2 clinical testing of the stabilized vaccine in young children (2-5 years) followed by testing the stabilized vaccine administered to young infants. It is estimated that preclinical and phase 1 and 2 clinical testing can be completed within a total of 2.5 years. The associated clinical trial costs will be partially supported by the funding being requested in the current RWJ grant with the remaining from the PATH/Gates Foundations, which we have existing partnership agreement. Our year 1 to year 3 plan will advance rotavirus vaccine development through the feasibility stage where larger pharmaceutical companies would be more likely to engage in commercial partnership and complete late stage development and marketing.

Additionally, by year 3, we would have already initiated development and process scale up of the thin film technology for our proprietary shigella vaccine. This work will further validate our unique thin film delivery approach for oral vaccines.

Stage of the initiative:

0

Expansion plan:

Since both vaccine stabilization and oral thin film production were designed to be easily scaled-up, large scale processing techniques and equipment already exist and require minimal engineering. The expansion plan relies on forging a partnership agreement with a large pharmaceutical company with the necessary R&D, quality control, regulatory, and manufacturing infrastructure because the costs to build a dedicated manufacturing facility and the costs to complete large scale safety testing of the vaccine are beyond what typical venture capital firms would invest. Alternatively, production of large scale manufacturing can be done by existing vaccine manufacturers from within the developing world countries such as those in India and China. The Gates and PATH or WHO organizations are expected to play a major role in facilitating such manufacturing arrangements.

Although the demand for a practical rotavirus vaccine is very high, our innovation must be adopted by health organizations. Despite anticipated regulatory approval, new technologies are poorly adopted due to skepticism. Thus it is important to maintain close relations with international health organizations.

After the rotavirus initiative, we intend to expand the oral thin film delivery concept to other therapeutics. This will require making the thin film delivery system versatile enough to accommodate other therapeutics such as antibodies, peptides, enzymes, molecular compounds, and other vaccines.

Origin of the Initiative

The idea to use an oral thin film for rotavirus immunization was conceived through a collaborative effort between Johns Hopkins University and Aridis Pharmaceuticals. Aridis aims to create dry-form stabilized vaccines that can sustain high temperatures, so that vaccines may be easily stored and distributed thus improving mass immunization efforts. Upon Aridis’ successful formulation of a stabilized rotavirus vaccine, they sought for a delivery vehicle from Hopkins to complement their vaccine to evade the major barriers to mass distribution, especially to third world nations. Hopkins students began synthesizing advanced oral thin film systems containing more functionality than the typical films used for breath-freshening. While both Hopkins and Aridis continue to work closely, many more hurdles exist before the thin film vaccine can reach the children in need.

This Entry is about (Issues)

Sustainability

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What are your two main challenges to finance the growth of your initiative

The main challenges centers around the perception by the venture capital community of financial, regulatory, and liability risks associated with bringing vaccine products, which are typically of low profit margins, to the market. It is exceedingly difficult to attract private financings of products associated with developing world markets, even those that exhibit impacting properties such as room temperature stability.

The production of the live-attenuated virus vaccine in larger clinical grade quantities is a significant financial challenge as facilities to support production of such biologics are inherently expensive. While the materials contained in the actual delivery system are inexpensive and readily available, the required clinical GMP scale processing equipment would contribute to the high costs of establishing an initial manufacturing facility. Furthermore, financially supporting the regulatory approval process for the vaccine design, manufacturing process, and preclinical and Phase 1 clinical testing would account for a large percentage of total costs to expand and bring our innovation closer to market.

How did you hear about this contest and what is your main incentive to participate?

A colleague informed us about the “Disruptive Innovations in Health and Healthcare” contest. We are primarily interested in Robert Wood Johnson Foundation's (RWJF) Pioneer Portfolio and its potential to support our endeavors to bring our technology to market.

The Story

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Do you have an annual financial statement?

Yes. The fiscal year for Aridis ends with the calendar year, so the last financial statement is for December 31, 2006. The revenue for Aridis is currently generated from a combination of grants and research collaborations, which has grown 3-4 fold over the last several years. A detailed financial statement is available upon request.

Do you currently have an annual financial statement that tracks profit/loss?

Yes. As noted above, Aridis’ revenue is generated from grants and research collaborations and therefore, we are not operating at a profit at this point. A detailed profit and loss statement is available upon request.

Please describe the amount (and/or type) of funding you need to implement your initiative, at year 1 and at year 5.

As indicated above:

Time Period Activities Supported Cost
Year 1: formulation, delivery device,
feasibility studies in animal models $0.75M

Year 2,3,4 develop methods, preclinical tox testing,
produce 1 clinical lot, obtain reg. approval
initiate phase 1 clinical testing $2.75M

Year 5: completing clinical testing $1.5M

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372 weeks ago Rotavirus Vaccination Via Oral Thin Film Delivery has been chosen as a finalist in Disruptive Innovations in Health and Health Care: Solutions People Want.