To succeed in a pandemic flu outbreak, the biopharmaceutical industry must unite, disregard proprietary and competitive issues,
and forge a preparedness plan to ensure adequate vaccines. A business continuity plan is essential. Such a plan must address
three key areas: maximum tolerable disruption period, recovery-time objective, and process resilience. Technical and regulatory
hurdles must be overcome, in part through the pursuit of new vaccines, including those that use cell-culture and recombinant
manufacturing techniques. An effective pandemic preparedness plan would involve manufacturing scale-up, production optimization,
and shared capacity among organizations.
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During the last few years, efforts to develop a preparedness plan for an avian flu pandemic have galvanized the world community.
Though health experts worldwide may feel relatively well positioned to detect such an outbreak early, support international
efforts to contain it in its earliest stages, and limit its spread, the reality is that its impact could be devastating. As
the world shifts its focus away from other potentially catastrophic outbreaks such as severe acute respiratory syndrome (SARS),
we cannot drop our guard against any pandemic.
The real challenge in preparing for a pandemic outbreak involves putting in place a process by which the biopharmaceutical
industry can respond quickly and effectively. The obstacles normally associated with vaccine production are exacerbated in
a pandemic. If the industry is to ensure public safety, tasks such as indentifying the strain rapidly, compressing vaccine-development
and process-development timelines, and translating global regulatory standards must be executed flawlessly. To meet the expectations
of the global community, the industry must invest heavily in developing a well-defined business continuity plan that goes
beyond normal business continuity and includes the task-compression activities required in response to a pandemic.
A History of Pandemics
A brief overview of the past emphasizes the magnitude of the current challenge. The initial outbreak of the Spanish flu was
recorded as early as 1918, and this pandemic is generally considered the most lethal of the 20th century. The outbreak began
simultaneously in France, Sierra Leone, and the United States, and it swept around the globe. The World Health Organization
(WHO) estimates that during the Spanish flu's lifecycle, nearly 25% of the world's population fell ill (approximately 500
million people), with an estimated fatality rate of 40 million people. The Spanish flu was just one of several flu pandemics
in the United States in the last century.1 Table 1 summarizes the various types of viral strains and the impact of each on US population. In each case, the pandemic
was caused by a different subtype of the influenza A virus.
Table 1. Viral strains and their impact. Spanish Flu affected nearly 25% of the world population.
Influenza viruses are characterized as type A, B, or C. Table 2 summarizes the attributes of each of the three types. The
key challenge in pre-paring a vaccine to combat these three involves influenza A's ability to morph as it develops. This attribute
is called "antigenic shift" and "antigenic drift."
Table 2. Attributes of the three viral strains—influenza type A, B, and C.
The first of these changes in the virus, antigenic drift, is a minor modification in an antigen on the surface of a pathogenic
micro-organism. This circumstance is typically the result of natural selection, in which the virus mixes with a partially
immune population. Immunization against the original virus may provide some partial protection against the modified virus,
but an epidemic could result if the situation is left unchecked.
The second of these alterations, antigenic shift, is a more lethal and abrupt change in antigenic composition. For example,
the hemagglutinin (H) or neuraminidase (N) spikes from a human influenza virus could be replaced with a spike from a nonhuman
animal, or an adaptive mutation could result in a major antigenic change. This type of change is called "re-assortment." In
re-assortment, humans can become the "mixing bowl" in which a non-human virus strain, such as an avian strain, can mix or
re-assort with a human influenza strain, resulting in a new strain that is immuno-logically unique, readily trans-missible,
and consequently, much more effective as a human patho-gen. The 1918 Spanish flu virus began as an avian flu, and then it
mixed with a human influenza virus to form the H1N1 influenza A virus subtype that attacked a quarter of the world's population.
Pandemic preparedness activity is currently focused on the H5N1 influenza A virus subtype, a bird-adapted strain, which is
known as avian flu. To date, the H5N1 avian flu virus has been found in birds in 48 countries, and in pigs in China, felines
in Thailand, and civets in Vietnam. When the first fatalities were recorded from the outbreak of avian flu, the US Centers
for Disease Control and Prevention (CDC) estimated the fatality rate worldwide could range from 80 million to 100 million
people if a pandemic outbreak were to occur. Since 2002, more than 385 cases and 243 deaths have been reported from the avian
flu virus.2 Because of its ability to mutate and to be rapidly transmitted, the global community has focused on this virus.