Aerosols challenge

Verification of the microbial retention efficiency of the membrane filters may be undertaken using either Hquid or aerosol challenge tests. A Hquid challenge test is more stringent. Furthermore, this test can provide retention information for process conditions such as extreme moisture after sterilization or air entrained with water drops. A Hquid challenge is performed using a protocol similar to that described for Hquid filtration. 

Yeadon, M. and Payne, A.N. (1989). Ozone-induced bronchial hyperreactivity to histamine and ovalbumin in sensitised guinea-p differences between intravenous and aerosol challenge. Eur. Resp. J. 2, 2995. 

Static aerosol challenge Expose sealed containers to periodic challenge by generating aerosol containing the challenge organism... 

The second IND vaccine, C-85, has been tested but not licensed for humans. It is prepared by formalin-inactivation of the TC-83 strain (see above). The vaccine is not used for the primary immunization, but rather to boost non-responders to TC-83. The required regimen for this vaccine is to administer 0.5 mL subcutaneously at two to four week intervals for up to three inoculations or until an antibody response is measured. Booster shots are required for the C-84 vaccine, and it does not protect rodents from an aerosol challenge. 

Jemski, J. (1961a). Aerosol challenge of guinea pigs, parenterally immunized with botulinum toxoid, with type D botulinum toxin disseminated by the Hartman fixture at 75°F and 50... 

Pollowing verification of the proper velocities, the HEPA filter should be aerosol-challenged in accordance with industry standards. " " Because this challenge is based upon the effectiveness of the filter in retaining aerosols, the upstream concentration of test aerosol should be verified before commencing this test and should not be assumed to be adequate, regardless of the circumstances. 

There are two general approaches, wet tests and aerosol challenge tests. Wet tests consider penetration of microorganisms in liquid suspension into sealed containers usually previously filled with sterile medium. The basic assumption is that the most vulnerable route for penetration of liquid filled containers by microorganisms is in the event of a continuous liquid film or bridge forming between the outside and the inside of a container. Aerosol challenge tests are less critical than wet tests and should be applied only when total exclusion of moisture from the containment system can be ensured by secondary barriers. 

Likewise, a formalin-treated abrin toxoid vaccine was shown to reduce lethality in rats exposed to a supralethal aerosol challenge with toxin the abrin toxoid delayed the onset of pulmonary toxicity, but could not prevent significant lung damage (Griffiths et al., 1995b). 

Passive pretreatment of animals with an aerosolized cocktail of polyclonal antiserum offered some protection against lung lesions in an aerosol challenge model (Poll et al., 1996). Comparable levels of protection could be obtained by stimulating secretory antibodies through mucosal immunization (Yan et al., 1996 Griffiths et al., 1997, 1998, 1999). 

Kende, M., Yan, C., Hewetson, J., Frick, M.A., Rill, W.L. and Tammariello, R. (2002) Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge. Vaccine, 20, 1681-1691. 

Gas niters may be evaluated prior to use by the same methods used for liquid filters (see Section 111 below), allowing that they can be effectively dried out and sterilized without loss of the qualities being tested. Alternatively they may be evaluated by exposure to particles in a gas stream, for instance by the sodium name test, which is also used for HEPA filters. Microbiological tests have to be considered in a somewhat different light. Leahy and Gabler 71 describe an aerosol challenge test of 10 Ps. diminuta bacteria per mL over a four-day period as an appropriate manufacturer s validation test. It would not be practical for routine use. 

B. Microbiological Aerosol Challenge Tests in. Physical Evaluation of Maintenance of Sterility... 

Experimental evidence58 has demonstrated that treatment with antibiotics beginning 1 day after exposure to a lethal aerosol challenge with anthrax spores can provide significant protection against death. All three drugs used in this study—ciprofloxacin, doxycycline, and penicillin—were effec-... 

There have been no controlled clinical trials in humans of the efficacy of the currently licensed U.S. vaccine. This vaccine has been extensively tested in animals and has protected guinea pigs against both an intramuscular6061 and an aerosol challenge.59 The licensed vaccine has also been shown to protect rhesus monkeys against an aerosol challenge.5868... 

Ivins BE, Fellows PF, Pitt MLM, et al. Efficacy of a standard human anthrax vaccine against Bacillus anthracis aerosol challenge in rhesus monkeys. Salisbury Med Bull Suppl. 1996 87(suppl) 125-126. 

Pitt MLM, Estep JE, Welkos SL, Friedlander AM. Efficacy of killed whole-cell vaccine against a lethal aerosol challenge of plague in rodents. Annual meeting, American Society for Microbiology 1994 Las Vegas, Nev. Abstract E-45. 

Vaccines to prevent tularemia have included those made from killed, whole cells and live, attenuated strains. A whole-cell, killed vaccine was developed by L. Foshay and associates94 in the 1930s, but proved to be of limited efficacy. Experimental studies24 done with human volunteers showed that this vaccine reduced the frequency of systemic symptoms but did not prevent the local lesion after intracutaneous challenge. Additional studies25 with aerosol challenge in humans showed that the killed vaccine neither prevented nor modified the disease. 

In animals, TC-83 vaccination will protect hamsters from a lethal VEE subcutaneous or aerosol challenge,137 although up to 20% of hamsters may die of reactions to the vaccine.95 165 Subcutaneous immunization of monkeys98 with the vaccine produces (a) neutralizing antibody responses in serum and (b) protection from virulent VEE virus delivered by peripheral or intranasal challenge. However, TC-83 provides only partial protection against... 

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