Flu vaccines

Stephen Tuck is Vice President of Biopharmaceutical Development at Dynavax Technologies in Berkeley, California. He has over 14 years of experience in pharmaceutical chemistry. He was involved in the development of Fluad adju-vated flu vaccine as well as various subunit vaccines, adjuvants, vaccine conjugates, and protein therapeutics. He earned his B.Sc. and Ph.D. degrees from Imperial College, University of London, United Kingdom. 

After a suspected case of the 1918 Spanish flu vims (which, in a global pandemic during World War I, affected half the world s population and killed almost 25 million people in 18 months) was identified in 1976, Congress passed the National Swine Flu Immunization Program, releasing manufacturers from the liability, so that a flu vaccine... 

Competition is a powerful constraint on manufacturing costs. Historically, sponsors have used contracts to purchase a fixed quantity of drugs as an incentive to build new manufacturing capacity. Examples include polio and, more recently, bird flu vaccine (Maurer 2005). Competition is also a powerful way to constrain manufacturing costs once production begins. By far the simplest strategy is for pay-as-you-go sponsors to put drug compounds in the public domain so that anyone can manufacture them. ... 

Judged in terms of the relationship of benefit to cost, vaccines are among the most socially valuable public health investments (U.S. Centers for Disease Control and Prevention [CDC] 1999 Stratton, Durch, and Lawrence 2000)d In spite of some recent successes, such as increases in immunization rates in the United States (CDC 2002a, b, 2003), substantial structural and financial problems remain. In particular, the United States has recently experienced unprecedented shortages in 8 of the 11 routine childhood vaccines (Georges et al. 2003). Flu vaccine shortages were experienced in 2000-2002 and 2004 (Cohen 2002 Enserink 2004 Institute of Medicine 2004). 

Vaccination is recommended for elderly people particularly those with heart, lung or kidney disease. Flu vaccination has to be repeated before each winter because of the possible changes in virus types. 

Another new adjuvant used in a flu vaccine in Europe is called as MF59, which is a submicron oil in water emulsion containing squalene as the oil phase. This adjuvant emulsion is safe and nontoxic for use in humans and has been tested in several million subjects (13-16). The vaccine formulation contains MF59 (FLUAD) , which is a licensed product in Europe and has been shown to be safe and well tolerated in patients over the last seven years. 

Several other diseases exist which can destroy the myelin sheath. Many are a result of viral infections or the body s immune response to a bacterial infection. Guillain-Barre syndrome causes numbness and paralysis starting at the extremities radiating into the trunk of the body where it can cause complete respiratory collapse. Guillain-Barre has occurred in senior citizens who have been given flu vaccinations. The virus used in the vaccination may be attenuated (diminished in virility but not "killed") and still be capable of causing an infection. 

Other vaccines available are those for influenza(flu), pneumonia (lifetime immunity), rabies, cholera, smallpox, typhus, typhoid, and Rocky Mountain spotted fever. Some vaccines can cause adverse effects especially to small children or the elderly. Flu vaccine has been implicated in the onset of a condition known as Guillain-Barre syndrome, a polyneuritis which can lead to anything from mild pain and weakness in the extremities to paralysis. These symptoms can last from a few weeks to a few months. 

In general, there are three types of stock to consider. Cycle stock is the regular inventory that is needed to fulfill orders. Buffer, or safety, stock is additional inventory that is needed in case of a supply or demand fluctuation. Anticipatory, or speculative, stock is inventory that is kept on hand because of expected future demand or expected price increase (e.g., flu vaccine in the fall and winter months). Buying anticipatory stock is risky, and therefore, pharmacists usually do not carry much anticipatory stock and place higher markups on such anticipatory stock. These types of stock are important to consider when deciding how much to order and when to order (Silbiger, 1999). 

Billions of doses of vaccines were safely administered over the last century to millions of infants, children, and adults [1,4], Vaccine-associated adverse events were nevertheless identified in a minority of patients. Many of the adverse events were directly related to the vaccine others as in the case of MMR have not been substantiated with data but still cause considerable public unease [1], One documented case is that of vaccination with a formalin-inactivated respiratory syncytial virus (RSV) that, when given prophylactically, caused enhanced disease after exposure to the virus and resulted in the death of some children [1,4,5], An increased incidence of Guillain-Barre syndrome appeared to be associated with a swine flu vaccine that was tested in humans in the late 1970s [1,6]. Guillain-Barre syndrome has also been associated with other vaccines including those for polio, measles, and hepatitis B [6]. 

Making the influenza vaccine is a highly seasonal business, and when the virus strain of the year is identified one needs the production apparatus to produce 20 to 100 million doses of this relatively simple and cheap viral vaccine. When the strain is mistakenly identified as it was in the 2003-2004 season, there is no time to regear. One has to hope for some cross-reactivity of the immune response to the vaccine with the real virus. Much depends on a good flu vaccine or drug today when the population s average age is high and heart and respiratory disease are prevalent. While influenza is serious in most patients, it can be lethal in those who are compromised by age and heart or respiratory disease. The flu is a big health concern and big business. 

Influenza vaccine viruses are propagated in embryonated chicken eggs. The virus-containing extra-embryonic fluid is harvested, purified, and inactivated with formalin. Inactivated flu vaccine is produced either as whole virus vaccine or ether-disrupted split or subunit preparations. However, many other new or modified influenza vaccines are already available or are expected to appear in the near future, for example vaccines containing new adjuvants, live attenuated vaccines, and vaccines administered by alternative routes. 

Case reports of complications temporarily connected with the administration of flu vaccine have been... 

Examination of new cases of multiple sclerosis among the 45 million swine flu vaccine recipients indicated no excess over the expected frequencies. Inactivated swine flu vaccine did not influence the onset or exacerbation of the disease (33). 

In a study of serum concentrations of the anticonvulsants phenytoin, phenobarbital, and carbamazepine, before and after mentally retarded patients received flu vaccine, the... 

After influenza immunization there was a reduction in blood theophylline concentrations in patients and healthy volunteers (58). The authors concluded that flu vaccine may influence the pharmacokinetics of several drugs, and a second group found that theophylline oxidation was significantly reduced at 1 day, but not at 7 days, after immunization (57). However, others did not confirm these effects (55,59). The lack of a clinical interaction with theophylline has also been confirmed by a report of the US Immunization Practices Advisory Committee (9). 

Kurland LT, Molgaard CA, Kurland EM, Wiederholt WC, Kirkpatrick JW. Swine flu vaccine and multiple sclerosis. JAMA 1984 251(20) 2672-5. 

Relate the need for medications to a child s past experiences with the illness. For example, if child is being recalcitrant about receiving immunization against influenza, the pharmacist might use a probe such as, Do you remember the yucky flu you had last year Would you like to avoid that this year This approach can help the child remember previous bouts of the flu as an awful-feeling illness. The child then can understand the need to prevent the illness by receiving the flu vaccination. 

Currently, there are many examples of cell processing in the industrial environment using tangential flow filtration. To illustrate the breadth of microbial types which may be processed by this technology, we will discuss three applications which have been in routine operation under production conditions. The applications include cell/growth medium separations directly from fermentors (Escherichia coli and Mycoplasma species) and the concentration/washing of influenza virus used in the production of flu vaccines. 

Guillain-Barrb syndrome was particularly associated with swine flu vaccine in 1976. It has rarely been associated with other vaccines — tetanus toxoid, BCG, rabies, smallpox, mumps, rubella, hepatitis B, diphtheria, and polio (Wraith et al., 2003). 

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