An Alternative to the Scale-up and Distribution of Pandemic Influenza Vaccine - With baculovirus-based production in disposable equipment, vaccine can be available 10 to 12 weeks after an outbreak. -

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An Alternative to the Scale-up and Distribution of Pandemic Influenza Vaccine
With baculovirus-based production in disposable equipment, vaccine can be available 10 to 12 weeks after an outbreak.


BioPharm International Supplements


Abstract

An influenza pandemic is a global health risk and many solutions are being developed to attempt to address this serious threat. Vaccination is thought to be a preferred solution, although access to a timely and sufficient supply of vaccine against a new emerging pandemic strain is inadequate in every country around the world. A new approach makes it possible to provide vaccine within 10 to 12 weeks of identification of a new viral strain, with an exact match to the wild-type influenza strain, by using disposables-based manufacturing facilities that can be built more quickly and cheaply than traditional vaccines plants.

The Current State of Preparedness


Virus-like particles (VLPs) mimic a natural virus in size, structure and surface proteins, but do not have the nuclear material necessary for infection. They trigger an immune response as if a natural infection takes place. (Novavax, Inc.)
The threat of an influenza pandemic is well recognized. Many thought leaders in the field believe it is a matter of when, not if, a pandemic event will occur. The threat has triggered emergency preparedness efforts in many developed countries and the result has been the purchase of multiple medical countermeasures including stockpiles of medical supplies (e.g., masks, gloves), antiviral drugs (e.g., Tamiflu), and the development and stockpiling of vaccines against multiple prepandemic strains of the H5N1 influenza virus (e.g., A/Vietnam, A/Indonesia, A/Anhui). Because the total supply and cross-reactivity of these stockpiled vaccines is insufficient for mass immunization, adjuvants are also stockpiled, to stretch the available antigen supply and to improve the cross-reactivity of the vaccines we can make today.

As a result of this government-sponsored procurement and development of these medical countermeasures, there is clearly an improved state of preparedness today in some specific countries, particularly the US. However, vulnerabilities remain even in the best-prepared countries, and the majority of the global population remains unprotected. No country has a supply of vaccine for a novel influenza strain (e.g., H2, H7, H9), as the focus of development efforts to date has been on various strains of H5N1. No country has a sufficient supply of vaccine without adjuvants, and the adjuvants have not been proven safe in large-scale clinical studies. Most countries do not have influenza manufacturing capabilities within their national borders, and because borders will close on the declaration of a pandemic to control the spread of disease, vaccine distribution will also be hindered. In addition, it will be politically difficult to ship precious vaccine out of a country until all citizens are protected. In the end, most countries would be left without a supply of pandemic vaccine.

The Challenges of Ensuring Sufficient Supply

Today, the vast majority of influenza vaccines are made by growing the target influenza virus in fertile chicken eggs. The eggs are infected with the virus, the virus is allowed to grow for several days, and then the virus is removed from the egg, purified, inactivated, and treated with detergent to remove most egg and influenza proteins other than the hemagglutinin (HA) protein. (Antibody to HA from immunization will neutralize a similar virus on infection and is thereby correlated with protection from disease risk).

Newer methods are being developed to replace the chicken egg with a cell line developed from various mammalian species, although the purification and inactivation are managed in a similar manner.

The cost of developing new vaccine production capacity by traditional means is prohibitively expensive. New facilities in the US have been reported to cost $150 million for large-scale egg-based (100 million doses/season) and to $600 million for mammalian cell–based (50 million doses/season) facilities. These high costs have resulted in large centralized facilities in developed countries where the market value is high, with excess supply being exported to other markets.

In addition, the capacity needed for a rapid and complete pandemic response is far greater than the seasonal influenza vaccine demand. Building capacity for the pandemic need would result in overcapacity for seasonal needs. Such new capacity would be severely under-utilized, or the market for seasonal vaccine would be overserved, lowering prices and margins and hence diminishing the financial returns required to build and maintain the operational infrastructure for manufacturing under current good manufacturing practices (CGMPs). This may already be the case in the US, where new facility projects (e.g., Solvay's cell culture plant) are being shelved because of poor economics, even with government cost-sharing for new facilities.

Many governments are aware of these problems and the need to create supply within their borders. However, the initial high capital requirements for traditional approaches have left them with a list of expensive alternatives that are difficult to justify given the uncertainty of the pandemic need. Likewise, a facility built to react to a pandemic event would only be effective if it were in a constant state of readiness for production, because equipment needs to be exercised and maintained, and people must be trained. This state of readiness can be accomplished only by making other products in the facility and then switching to pandemic flu vaccine production when needed. The best fit would be seasonal influenza production for the local market, but this has important implications for global influenza vaccine oversupply, competition, and the utilization of capital, as the facility would likely not be well suited for other vaccines made by traditional means.


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