Member of Congress
November 3, 1999
The Honorable Jane E Henney, M.D., Commissioner
Food and Drug Administration
14-71 Parklawn Building, 5600 Fishers Lane
Rockville, Maryland 20857
Dear Dr. Henney:
We are writing to express our serious concerns regarding
the pending license supplement application of BioPort to produce
the anthrax vaccine. We strongly urge that each of the items contained
in the letter be fully addressed and a response provided to us
prior to the approval of BioPort's license supplement application.
As you are aware, in 1997 the Department of Defense mandated the
implementation of a force-wide Anthrax Vaccine Immunization Program
(AVIP). Since the announcement of this plan to inoculate all 2.4
million members of our Armed Services, FDA documented deficiencies
in the manufacturing process have caused widespread and persistent
concerns regarding the safety of the vaccine.
Of particular concern is that despite the licensure of the anthrax
vaccine in 1970, 23 years passed before your agency physically
inspected the anthrax-specific portion of the manufacturing facility.
In testimony before the House Government Reform Committee, Dr.
Zoori, the Director of FDA's Center for Biologics Evaluation and
Research, indicated that two inspections of the production facilities
in 1997 and 1998 revealed significant deviations from the Federal
Food, Drug, and Cosmetic Act, FDA's regulations, and the standards
in the Michigan Biological Product Institute (MBPB license. Inspection
reports of the production facilities following its purchase by
BioPort revealed some progress but many remaining deviations.
In large part, the significant ongoing deviations prompted the
company to close the facility for remodeling rather than face
the likelihood of FDA revoking their license.
Given the documented deviations from approved practices in the
manufacturing process, it is imperative that the FDA follow it's
own prescribed regimen of thorough testing for purity, potency,
identity, and sterility. As a prerequisite for approval of the
license supplement, the testing must reveal lot-to-lot consistency
for the vaccine. Included within the testing requirements, the
FDA must ensure lot-to-lot consistency for the antigen level.
FDA mandated lot-to-lot consistency will ensure we can accurately
measure the efficacy of the vaccine. The lack of clinical data
detailing the relationship between antigen levels and the amount
of protection provided argues strongly for greater vaccine consistency
data so correlates of immunity can be studied. In that regard,
please provide information on the status of FDA's request of BioPort
to characterize the vaccine. Any failure to characterize the vaccine
must preclude the approval of the license supplement application.
We also urge that the FDA place the anthrax vaccine back under
Investigational New Drag (IND) status. As Dr. Zoon testified before
the Government Reform Committee, the MBPI vaccine was licensed
for use by a liraired population of individuals at risk for coetaneous
exposure to anthrax through infected animals or animal products.
The December 13, 1985 Federal Register and the FDA approved package
inserts indicate: "Since the risk of exposure to anthrax
infection in the general population is slight, routine immunization
is not recommended." However, the Department of Defense,
in its implementation of the AVIP, is performing a large-scale
inoculation for protection against inhalation anthrax. The scope
of the vaccination program and the form of exposure anticipated
by DoD were not addressed in the initial license. A March 13,
I997, letter from Dr. Michael Friedman, FDA Lead Deputy Commissioner,
to Stephen Joseph, then Assistant Secretary of Defense for Health
Affairs, acknowledged the "paucity of data regarding the
effectiveness of the anthrax vaccine for prevention of inhalation
anthrax." This lack of significant data strongly suggests
the need for further study under IND status.
Additionally, the data submitted for Iicensure of initial vaccine
did not include scientifically valid support for the current dosing
structure, GAO stated that no studies have been conducted to determine
the optimum number of doses of the anthrax vaccine. Although annual
boosters are recommended, the need for a six-shot regimen and
annual booster shots has not been evaluated. There is also no
clinical data to accurately conclude that the prescribed regimen
provides a consistent level &protective antigen to be efficacious
against inhalation anthrax. A September 29, 1999 letter from Dr.
Zoon to Dr. Sue Bailey, the Assistant Secretary &Defense for
Health Affairs indicated that there is lack of data on the impact
of deviations from the approved vaccine regimen. Prior to the
approval of the license supplement application, the FDA must scientifically
verify the clinical data supporting the six-dose regimen. We would
like to be apprised of FDA's plans to accomplish this goal and
be provided the clinical data supporting the correlation between
the dosage and anti-body levels.
We are also requesting the status of FDA's proposed rule regarding
the use of animal data to support claims of human efficacy. Human
efficacy information for the current license and the license supplement
application is based overwhelmingly upon the application of data
from animal anthrax vaccinations and exposure. However, there
have been great discrepancies between various animal models regarding
the efficacy of the anthrax vaccine. We acknowledge and support
the moral argument against human testing to determine the efficacy
of the vaccine. At the same time, we must ensure there is a scientifically
verifiable extrapolation from animal data that can be applied
to humans. It is our understanding the proposed rule would attempt
to establish protocols to provide that information. If that rule
has not been approved, we would like to know the FDA's plans to
resolve the discrepancies in the results of the animal models.
If the rule has been approved we would like to receive information
on FDA's plans to ensure the license supplement data is in accordance
with the rule. We would also like the clinical data to supporting
the extrapolation of the animal models to humans. These steps
must be taken prior to the approval of the license supplement
application.
Further, it is our understanding that the Department of Defense
acting in conjunction with BioPort has a pending IND application
to approve a reduced shot regimen. We are not challenging the
approval of the IND application for the reduced shot course. However,
we are greatly concerned with current DoD policy of deploying
individuals to threat areas after three injections of the anthrax
vaccine and claiming the same individual is 90 percent protected.
In a September 29 letter to Dr. Bailey, Dr. Zoon reiterated congressional
concerns that the Department of Defense is not following the shot
regimen. The Department's inability to follow the shot regimen
for large numbers of its personnel, and its policy of deployment
to described threat areas prior to completion of the shot regimen,
have the net effect of implememting an IND study on the majority
of the 2.4 million members of the Armed Forces without the benefit
and protection of informed consent. If FDA approves the pending
IND application under these conditions, all personnel receiving
the vaccine must be allowed to do so by informed consent. Failure
to do so would feed claims of government sanctioned experimentation
on our military personnel. Please provide a status report and
regular updates on the pending IND application and of FDA's plan
to address this potential inconsistency.
We are also concerned about reported re-dating or re-labeling
of current vaccine stock. As you are aware, the current facility
has not produced licensed vaccine since early 1998. However there
are numerous reports that BioPort, acting through the Department
of Defense, has re-dated a number of vaccine lots or vials to
allow their continued use. It is our understanding that the re-dating
of a vaccine by a manufacturer beyond the expiration is a violation
under the Federal Food, Drug, and Cosmetic Act. If that is the
case, no amount of supplemental testing can avoid the legal obligation
to prevent the lots from being used. It is within FDA's legal
authority to ensure this has not occurred and if it has, take
appropriate action. We would like to know how many lots of that
anthrax vaccine or vaccine doses have been re-dated and the identification
of those lots. We are also requesting the status of quarantined
lots and lots that have not yet passed supplemental testing.
We have been informed that BioPort is currently producing consistency
or at-risk lots for testing. Please provide the number of consistency
lots that have been produced and the current status of those lots
in the production cycle. Please also update us on the agency's
plans for the consistency lots should FDA not approve the license
supplement application. Please provide information on the characterization
of each of the consistency lots produced by BioPort since the
company's closure for remodeling.
Should you have any questions regarding this letter, please do
not hesitate to contact us or any member of our staffs. Please
provide this information by November 18. Thank you for your consideration
of these serious matters. We look forward to your prompt reply.
Sincerely,
Walter B. Jones
Member of Congress
Dan Burton
Member of Congress
Christopher Shays
Member of Congress
Benjamin Gilman
Member of Congress
Last revised: March 2000