indicated for individuals at high risk of exposure to B. anthracis spores such as veterinarians, laboratory workers, and others whose occupation may involve handling potentially infected animals or other contaminated materials.” This labeled indication has not changed from the original, which was developed in view of the plausible exposures at the time of licensure of the vaccine and was supported by field and observational studies of animal product processors.

The subsequent weaponization of B. anthracis, however, changed for DoD the definition of the groups identified as “high-risk persons” to include not only veterinarians but also members of the armed services who were or who might be deployed to areas near countries where B. anthracis had been weaponized. As a result of the recent bioterrorist release of anthrax spores through the U.S. mail system, the definition of “high-risk persons” may be expanded further to include other occupational groups. The population receiving AVA has thus become considerably wider than that anticipated at the time of original licensure.

Meanwhile, the supply of the currently licensed vaccine had been limited by manufacturing difficulties, which have now been overcome. As mentioned above and as discussed in more detail in Chapter 7, the AVA manufacturing facility and the AVA production process have both been the subject of numerous FDA citations and responses. Indeed, the manufacturer undertook a thorough renovation of its manufacturing facility starting in 1998 and modernized several aspects of the production process. These modifications, although certainly intended to improve the overall process of vaccine production, are still changes. Changes in facilities or processes, however, can result in changes in the product, and FDA is responsible for monitoring those changes (see Chapter 7).

Noting the possibility that these changes may affect the final AVA product does not mean that the changes are necessarily bad; in this case they are surely improvements. On the basis of the information provided in presentations and in papers from both BioPort and FDA, the committee notes that modifications were undertaken to incorporate more modern technology into the manufacturing process and to increase assurance of the consistency of the final product (e.g., in the concentration of protective antigen), which still remains a relatively crude vaccine by current standards.

Although greater assurance of product consistency will result from the modifications of the manufacturing facility and the production process that have been undertaken by BioPort and certified by FDA, the levels of immunogenicity, safety, and stability of the postrenovation AVA product must be characterized empirically, as the committee recommends below. The committee emphasizes that the surveillance methods recommended below are the same as those that would be expected for any widely used vaccine and are not unique to AVA.

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