oversight

Summary of GAO's Findings on the Safety and Efficacy of the Anthrax Vaccine

Published by the Government Accountability Office on 1999-11-04.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

United States General Accounting    Office                                                 National Security and
Washington, DC 20548                                                            International      Affairs Division



           B-284044

          November     4, 1999

          The Honorable Steve Buyer
          Chairman, Subcommittee on Military Personnel
          Committee on Armed Services
          House of Representatives

          Subject:        Summary      of GAO’s Findinas on the Safetv and Efficacv of the Anthrax
                          Vaccine

           Dear Mr. Chairman:

          Concerns have been raised about the Department of Defense’s (DOD) anthrax
          immunization program since DOD began vaccinating its 2.4 million active duty and
          reserve members in 1998. At your request, we are providing you with information we
          have previously reported concerning (1) the need for a six-shot regimen and annual
          booster shots, (2) the long- and short-term safety of the vaccine, (3) the efficacy of
          the vaccine and (4) the extent to which problems the Food and Drug Administration
          (FDA) found in the vaccine production facility in Michigan could compromise the
          safety, efficacy, and quality of the vaccine.’ We are also providing for you the three
          testimonies that are the source of the information we are providing you today.

           BACKGROUND

          The original anthrax vaccine was developed in the 1950s and was first produced on
          a large scale by the Merck Pharmaceutical Corporation.      In 1962, a study was
          published on the safety and efficacy of the Merck vaccine against cutaneous anthrax
          in wool mill workers. Later, the Michigan Department of Public Health took over as
          the vaccine’s producer but the manufacturing process, the strain, and the ingredients
          differed from the Merck vaccine. This changed vaccine, which is the vaccine
          currently being given to U.S. military personnel, was licensed in 1970 by the Division
          of Biologics Standards, National Institutes of Health. FDA is currently responsible
          for licensing new vaccines and ensuring vaccine safety.




          ’ Medical Readiness: Safety and Efficacy of the Anthrax Vaccine (GAO/T-NSIAD-99-148, Apr. 29,1999);
          Medical Readiness: Issues Concerning    Anthrax Vaccine (GAO/T-NSIAD-99-226,  July 21, 1999); and
          Anthrax Vaccine: Safety and Efficacy Issues (GAO/T-NSLAD-0043, Oct. 12,1999).


          Page 1                              GAO/NSIAD-00-MR     Safety and Efficacy of the Anthrax Vaccine
B-384044

As of July 1999, more than 315,000 service members had received at least one
dose of the vaccine. Initial immunization consists of three shots given at 0, 2, and 4
weeks followed by three additional shots given at 6, 12, and 18 months.

SUMMARY       OF OUR KEY FINDINGS

Our work has identified that data on the current immunization schedule and the
vaccine’s safety and efficacy is limited in some areas. Moreover, FDA has identified
some deficiencies concerning the manufacturer’s controls over the vaccine’s quality.
DOD and the company that purchased the vaccine production facility in 1998 have
several efforts planned or underway to address these issues.

Data on the Need For Six Shots and Annual Boosters Are Unavailable

 No studies have been done to determine the optimum number of doses of the
anthrax vaccine. A three-dose regimen was used initially for the original vaccine
based on a regimen developed using animals in the early 1950s. However, the
number of doses was increased to six after three people who received three doses
of the vaccine became infected. The licensed vaccine adopted this schedule and
DOD has followed this regimen. Although annual boosters are required, the need
for annual booster shots has not been evaluated.

Lorw-term     and Short-term       Safetv of the Vaccine

The long-term safety of the licensed vaccine has not been studied.                However,     DOD
is designing studies to examine the vaccine’s long-term effects.

With regard to short-term safety, according to FDA officials, data from two studies
conducted prior to licensing of the current anthrax vaccine are difficult to interpret
since one study used the original vaccine, and part of the study population in the
other study had already received the original vaccine.

Post-licensing data on safety are limited because only a limited number of doses-
about 68,000-were     distributed by the manufacturer from 1974 through 1989. Also
FDA did not establish its Vaccine Adverse Event Reporting System (VAERS) until
1990. This system, which DOD uses, alerts FDA and the Centers for Disease
Control to increases in adverse events. 2 However, it is a passive surveillance
system, which means that FDA and the Centers for Disease Control must rely on
vaccine recipients or their health care providers to report any adverse events after
receiving the vaccine. Studies show that adverse events are reported significantly
less frequently with passive surveillance systems than they would be in an active
system where vaccine recipients are monitored to find out if they had any adverse
effects.


2Clinical events reported to a passive surveillance system such as FDA’s are usually termed adverse
events rather than adverse reactions because there is usually insufficient evidence that the vaccine,
rather than other health conditions, caused the reported events.


Page 2                             GAO/NSIAD-00-54R     Safety and Efficacy of the Anthrax Vaccine
DOD has recently conducted two studies using active monitoring where DOD
personnel contacted the vaccine recipients directly to find out if they had any
adverse reactions. Data from these studies, conducted in 1998 and 1999, showed
that a higher proportion of women reported both local and systemic reactions to the
vaccine than their male counterparts.      In addition, data from one of the studies
showed that more than twice the proportion of women reported that they missed one
or more duty shifts after their vaccinations than did males.

Vaccine    Efficacy

A study on the efficacy of the original vaccine concluded that it provided protection to
humans against anthrax penetrating the skin but did not provide sufficient data to
determine its effectiveness against anthrax that was inhaled. Beginning in the late
1980’s, DOD began studying the efficacy of the licensed anthrax vaccine on
animals, using guinea pigs, rabbits, and monkeys. All of these studies support the
view that in these animals, the licensed vaccine can protect against exposure to
some but not all strains of anthrax either by inoculation or inhalation. It is clear,
however, that animal species differ in their susceptibility. Studies of guinea pigs
show that some anthrax strains are more or less resistant to vaccines for humans
but are protected by the live spore veterinary vaccine.

Research using monkeys showed for the first time that monkeys could be protected
against aerosol exposure. However, several studies have shown no direct
comparison of immunity in humans to that in monkeys. DOD officials recognize that
correlating the results of animal studies to humans is necessary and told us that
DOD is planning research in this area. DOD also plans to develop a second
generation anthrax vaccine, and as part of this effort, it will need to address whether
strains of deliberately engineered or naturally occurring anthrax can overcome the
protective immunity of such a vaccine.

Problems     with the Vaccine   Manufacturinq    Process

With regard to the manufacturing process, it is important to note that the quality of a
vaccine is closely linked to its manufacturing process, which must be rigorously
controlled to ensure that batches of vaccines produced on different occasions are of
consistent quality. Accordingly, vaccine production is highly regulated to ensure that
the products are of consistent quality and safe and effective for the purpose(s) for
which regulatory approval was granted. Until 1993, FDA inspectors did not inspect
the Michigan Department of Public Health facility where the anthrax vaccine was
made. According to FDA, access was not granted because its inspectors had not
been vaccinated against anthrax. DOD conducted inspections, however, and
identified deficiencies during a March 1992 inspection.

FDA’s inspections of the vaccine production facility in 1996 and 1998 found a
number of deficiencies. The deficiencies that FDA identified in its February 1998
inspection fall broadly into two categories: those that might affect only one or a
limited number of batches that were produced and those that could compromise the


Page 3                          GAODWAD-00-54R   Safety and Efficacy   of the Anthrax   Vaccine
safety and efficacy of any or all batches. In 1998, the manufacturer shut down the
facility for renovation. A new company, which purchased the facility in mid-1998, is
addressing the issues identified by FDA.

If you need additional information on these issues, please call me on (202) 512-3652
or Dr. Sushi1 Sharma, Assistant Director, on (202) 512-3460.

Sincerely yours,




Kwai-C heung C han
Director, Special Studies and Evaluations




(713057)



Page 4                        GAON3AD-W54R    Safety and Effkacy of the Anthrax Vaccine
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