DEPARTMENT  OF THE  NAVY 

B O A R D   F O R   C O R R E C T I O N   O F   N A V A L   R E C O R D S  

2  N A V Y   A N N E X  

W A S H I N G T O N   D C   2 0 3 7 0 - 5 1 0 0  

ELP 
Docket No. 7985-00 
5 April 2002 

This is in reference to your application for correction of your 
naval record pursuant to the provisions of Title 10, United 
States Code, Section 1552. 

A three-member panel of the Board for Correction of Navy Records, 
sitting in executive session, considered your application on 
3 April 2002.  Your allegations of error and injustice were 
reviewed in accordance with administrative regulations and 
procedures applicable to the proceedings of this Board. 
Documentary material considered by the Board consisted of your 
application, together with all material submitted in support 
thereof, your naval record and applicable statutes, regulations 
and policies.  In addition, the Board considered the advisory 
opinions furnished by the Occupational Medical Specialty Leader 
for the Navy Surgeon General, dated 1 August 2001, and the Deputy 
Director of the Criminal Law Division in the Office of the Judge 
Advocate General, dated 29 November 2001, copies of which are 
attached. 

After careful and conscientious consideration of the entire 
record, the Board found that the evidence submitted was 
insufficient to establish the existence of probable material 
error or injustice.  In this connection the Board substantially 
concurred with the comments contained in the advisory opinions. 

The Board found that you served continuously on active duty 
after your graduation from the U.S. Naval Academy in May of 1997. 
While assigned to USS LAKE ERIE  (CG 70), you submitted two 
requests for waivers from the Department of Defense  (DOD) Anthrax 
Vaccination Immunization Program  (AVIP).  Both requests were 
denied. 

On 24 August 1999, you officially refused to submit to the 
AVIP by signing an administrative remarks (page 13) entry to that 
effect.  As a result, on 12 September 1999, you received 
nonjildi c i  a1  pilni shment  (N,TP)  for v i  nl a t i  on  of Arti PI  e  92 of the 

Uniform Code of Military Justice (UCMJ) for failure to obey a 
lawful order to take the anthrax vaccination.  You were awarded a 
punitive letter of reprimand.  Your appeal of that NJP was 
denied. 

You also were awarded NJP on 24 October 1999 for disrespect to 
your commanding officer by sending an inappropriate e-mail, 
conduct unbecoming an officer, and failure to obey a lawful 
order.  On appeal, this NJP and the 30 days of restriction for 
disrespect toward the commanding officer were upheld.  The two 
other charges and an oral reprimand were set aside. 

On 10 December 1999, you submitted an unqualified resignation and 
requested an honorable discharge.  This request was denied, and 
on 24 April 2000 the Chief of Naval Personnel (CNP) advised the 
Secretary of the Navy you were recommended for separation as a 
probationary officer with a general discharge.  CNP also 
recommended recoupment of $38,812 in advanced educational funds 
received at the U. S. Naval Academy.  The Assistant Secretary of 
the Navy  (Manpower and Reserve Affairs) approved the general 
discharge and directed recoupment.  On 26 May 2000 you were 
separated with a general discharge due to misconduct. 

The Board first considered your contentions that the order to 
submit to the AVIP was unlawful since it was inconsistent with 
existing Federal laws and regulations; the AVIP is not sanctioned 
by law, but only by military order; and administration of the 
anthrax vaccine was prejudicial to your health.  The.Board also 
considered your contentions that 10 U.S.C.5 2005 does not 
authorize recoupment of educational expenses if a policy decision 
prevents an individual from completing his military obligation; 
refusal to submit to the AVIP does not meet the definition of 
misconduct as defined in U.S. V Gears, 835 F.  Supp.1093 (N.D. 
Ind. 1993); recoupment may only be sought if the failure to 
fulfill a service obligation was voluntary or was due to 
misconduct; and such action is unfair in your case since the 
midshipmen involved in cheating and sex scandals in 1993 and 1995 
were not subjected to recoupment. 

The Board took particular notice of the arguments in the legal 
memorandum prepared by two Air Force Reserve judge advocates who 
contend that orders requiring service members to submit to 
anthrax vaccinations are illegal because they contradict the 
terms expressed in Presidential Executive Order 13139 and 10 
U.S.C. §  1107 as well as the letter to the Secretary of Defense, 
signed by 36 members of Congress, requesting immediate suspension 
of the AVIP; the Committee on Government Reform Report titled, 
"The Department of Defense Anthrax Vaccine Immunization Program: 
Unproven Force Protectionw; and the bills that were introduced in 

Congress to suspend the AVIP to provide for additional study, and 
to make the program voluntary for all service members. 

The Board noted that despite all of the material you cite, the 
AVIP was not and has not been suspended, and no evidence has been 
submitted to s'how that Congress enacted any legislation 
supporting your position.  Additionally, federal case law clearly 
shows that orders to submit to an anthrax vaccination are lawful. 
Ponder v. Stone, 54 M.J. 613, 616-17 (N.M.Ct.Crim.App. 2000); 
United States v. Washinaton, 54 M.J. 935, 940 (A.F.Ct.Crim App. 
2001); OvNeil v Secretary of the Navv, 76 F. Supp.2d 641, 645 
(W.D. Pa. 1999).  Furthermore, Secretary of Navy Instruction 
6230.4 of 24 April 1998, which implemented the Navy's AVIP, 
states that the anthrax vaccine is a FDA-licensed product and not 
an "Investigative New Drugvv, requiring informed consent for its 
administration.  Accordingly under the provisions of this 
directive, mandatory anthrax immunization is proper and those who 
refuse the vaccine are subject to disciplinary action.  Clearly, 
the AVIP is intended to be a force-wide protective measure 
against a biological anthrax agent, which is the primary 
biological weapons threat against U.S. Naval forces. 

The Board then considered the documentation detailing your 
request for a medical waiver of the anthrax vaccine, the two 
nonjudicial punishments and appeals, your request for redress of 
injuries, and other documentation detailing the circumstances 
which led to your discharge.  There appears to be no merit to 
your assertion that taking the anthrax vaccination was 
prejudicial to your health based on a chronic bronchial 
condition.  The Bureau of Medicine and Surgery  (BUMED) thoroughly 
and thoughtfully reviewed the arguments in your waiver request 
and found no justification for approving a medical wavier. 

Since you were discharged by reason of misconduct, specifically, 
the two NJPs, proportional recoupment was proper and appropriate 
in accordance with 10 U.S.C.§ 2005.  The Board was well aware 
that certain midshipman involved in various scandals in 1993 and 
1995 have had their academy debts forgiven.  However, their cases 
are not similar to yours.  The Board believed your misconduct as 
a commissioned officer was especially serious in view of its 
potential adverse impact on good order and discipline of the 
command.  The Board concluded that given the two NJPs, discharge 
by reason of misconduct was proper and appropriate.  The Board 
further concluded that you were fortunate to receive a general 
discharge, since your record of misconduct could have resulted in 
processing for separation under other than honorable conditions. 

Accordingly, your application has been denied.  The names and 
votes of the members of the panel will be furnished upon request. 

It is regretted that the circumstances of your case are such 
that favorable action cannot be taken.  You are entitled to have 
the Board reconsider its decision upon submission of new and 
material evidence or other matter not previously considered by 
the Board. In this regard, it is important to keep in mind that a 
presumption of regularity attaches to all official records. 
Consequently, when applying for a correction of an official naval 
record, the burden is on the applicant to demonstrate the 
existence of probable material error or injustice. 

Sincerely, 

W. DEAN PFEIFFER 
Executive Director 

I 

Enclosures 

1  Auq  01 

From:  Occupational Medlcine Specialty Leader 
To : 

C h a ~  rman, Board  tor  ('or I  ei-t ion of  Naval  lie cord^^ 

Ref 

1 .   As  requested ln  refercnc-c3 ~ d ) ,   h a v e   r c v l  ewed  l  ]I(> 
documentation  forwarded  111 thl:, cdse.  Thc~ f 01 l o w ~ n c ~  r ~ : , l x  II',P-" t 
your questlo~~s are provided. 

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vacclne  1s , i   h l s t o r v   = i f  
,i  sc.vel  c 
anthrax  vat( In?.  T~inltatlon~ i 
vacclnatio~ ~~iclld(> ~ I V P  ~ n f c ( '  
lrnniune  s u p p ~  essl 111;  ox  pregnanc , . 
condl tlons that would preclude adnll nlstratlo~l of anthrax vac-clne. 
Speclflcally, anthrax vacclne tan be  safely admlnlstered  to 
indlvlduals wlth asthma or chronlc bronchltls  (or chranlc 
bronchial  ~llness). Based on my  revlew of the record, thls member 
did not have a medical condition that would preclude 
administration of anthrax vaccine. 

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b .   Have  t h e r e   been  any  medical  developments  s i n c e  

P e t i t i o n e r ' s   waiver  r e q u e s t   was  denied  t h a t   would  warrant  granting 
t h e   r e l i e f   he  s e e k s ?  

No. 

c .   Any  o t h e r   comments  you  b e l i e v e   may  be  p e r t i n e n t   t o   t h i s  

c a s e   and  P e t i t i o n e r ' s   medical  c o n t e n t i o n s   a r e   also s o l i c i t  ed,.. 

There have been additional studies of anthrax vaccine safety 

since the time that Petitioner's  waiver request was denied by 
reference  ( b ) .   While  research is continuing in this area, studies 

DEPARTMENT OF THE N A V Y  

OFFICE O F  T H E  J U D G E  A D V O C A T E   G E N E R A L  

W A S H I N G T O N  N A V Y   Y A R D  

1 3 2 2  P A T T E R S O N  A V E N U E  S E   S U I T E  3000 

W A S H I N G T O N   DC  20374-5066 

Rct' 

(a) B('NK  Irr  Docker  No. 7985-00 (w/encl) 
(b) 21  U.S.('.  3  355 (2001) 
(c)  SECNAVINST 6230.4 of 29 Apr~l 1998 
(d) DoD  Information  About the Anthrax  Vaccine and tlic Anthrax Vacc~lic I1ii1nu111/at1on 

f'rogram  (AVIP) of  1 5  Aug 200 1 

1:ncl 

( 1  )  Lt  ('01 

, USAFR and Maj  Smith, IJSAFK legal niernor,indurii 
1 ? 139 of 30 Sep 00 

1icfi.r-cncc. ( a )  I - C ~ ~ I C S ~ S  

1 
-USN, 
upgrade of his discharge and waiver of the action to recoup his "academy  debt"  for  I'aililrc  to 
fulfill his service obligation due to misconduct. 

0 15- IO-85'X (Petitioner) to corrcct  his naira1 record.  I'crit~oncr I-quests an 

C ' O I I I I I I ~ I I ~ S  and  ~ - ~ c o ~ i i ~ i i e n d a t ~ o ~ i  

0 1 1  the petltioli ol'c~\-lI~is~yi 

2.  BACKGROUND:  Petitioner was on continuous active duty from his graduation  from the 
U.S.  Naval Academy in May of 1997 until his separation with a General discharge on 26 May 
2000.  While assigned to USS LAKE ERIE (CG 70), Petitioner submitted two requests for 
waivers from the Department of Defense Anthrax Vaccination Immunization Program (AVIP). 
Both rcqllests were denied.  On 24 August  1999, Pctitioncr officially rcfkcti to submit to the 
AVIP by signing a page  13 to that effect.  As a result, on 12 September 1999, Petitioner received 
non-judicial punishment (NJP) for violation of Article 92 of the Uniform Code of Military 
Justice (UCMJ) for failure to obey a lawful order to take the anthrax vaccination.  He was 
awarded a punitive letter of reprimand.  Petitioner's  appeal of that NJP was denied.  Petitioner 
also was awarded NJP on 24 October for separate offenses.  On appeal, the second NJP and the 
30 days restriction awarded for Violation of UCMJ Article 89, disrespect toward his 
Commanding Officer, were upheld.  Two other charges and an oral reprimand were set asfde. 

On  10 December  1999, Petitioner submitted an unqualified resignation and requested an 

honorable discharge.  His request was denied, and on 24 April 2000, the Chief of Naval 
Personnel advised the Secretary of the Navy that the Petitioner was recommended for separation 
from the Naval service as a probationary officer with a General (under honorable conditions) 

discharge, and that  $38,8 12 in advanced educational funds received  at the U.S. Naval  Academy 
be recouped.  The Assistant  Secretary of the Navy (Manpower and Reserve Affairs) approved 
the General discharge.  On 26 May 2000, Petitioner was separated with a General discharge duc 
to misconduct. 

T  DISCUSSION:  l'hc  sole qucst~on in  rlic subject  request  1s  \vllcthcr rhc  Pctitio~lcr's 
Con~niandins Officer issucd a  lawful o d e s  for I'ctitioncr  to submit  to tllc AVII',  spcc~ lical I!, 
whether the ordcr was consistent with existing federal laws and  regulations.  'l'hc P c r ~ r ~ o ~ ~ e r  
c~lcs 
enclosure ( 1 )  as Justification \vhy the ordcr \ifas not  la\vfuI.  Tllc authors of tllc IIIC'IIHII ;111dt1111 
conclude that ordcrs to submit to the AVII'  arc unla\vful  because: 

thcy contradict the express terns of I'residcntial  Executi\rc 01-dcr 
13 139 and  l o  U.S.C Sec. 1  107 (1999). Because the anthrax vacclnc 
is being used  in  a manner inconsistent with both  its original  licensing 
and  for a purpose  for which  i t  has never been  tested, the vaccine  1s 
properly considered an  Investigational New  Drug under Food and 
Drug Administration (FDA) regulations and court decisions.  Both 
the executive Order and the statute mandate that informed consent 
is a prerequisite to all vaccinations with an  Invcstigational  New 
Drug.  It  is undisputed  that senlice members arc not  giving their 
infoniied consent to the \,accination process. 

The basic premise of'thc memorandum  in  I~nclosure ( 1  ) is incor-rcct. Although  Executi\,c 

Order  13 139, Enclosure (2), does require infoniied consent'  for administration of "Investigative 
New Drugs"  (IND), the anthrax vaccine as utilized  by DOD is not experimental, and not an IND. 
The definition of IND, i.e., "drugs  intended solely for investigational  use by experts qualified by 
scientific training and experience to investigate the safety and effectiveness of drugs," can be 
found in subsection (i) of Reference (b).  In addition, the Navy's  implementing instruction in 
reference (c) states that the anthrax vaccine is a FDA-licensed product and not an IND requiring 
informed consent for its administration. 

An  FDA approved drug in use for years may in essence become new again and require 

IND testing if it is to be put to an unapproved  use, that is a use not listed on the label as its 
approved intended purpose.  As outlined in Enclosure (3), the question of whether DOD's use of 
the anthrax vaccine as prophylaxis against inhalation anthrax constituted an unapproved 
application was raised with the FDA, the agency solely responsible for making such a 
determination.  On November 3,  1999, Congressional Representatives wrote the FDA proposing 
the vaccine be considered experimental and that IND testing be carried out.  In Enclosurq3), the 
FDA found no basis for the challenge and refuted the misconception that the vaccine's license 
only covers use "by  a limited population of individuals at risk for cutaneous exposure to 
anthrax."  The FDA also expressly concluded that "use  of the vaccine for protection against both 

I  There arc certain circumstances under  10 U.S.C. 1107(f) where the President may waive the informed consent 
rrquircnlent for the adminishtion of an investigational drug to a  mcmbcr of the Anned I;orccs in counection with 
the member's participation in a particular military operation. 

cutaneous and inl~alation anthrax exposure is not  inconsistent with the labeling."  (Enclosure (3)) 
Accordingly, the anthrax  vaccine is not  considered an IND, and informed consent  is not  required 
of service menlbers before requiring them to submit to vaccination. The Navy-Marine Coqx 
Court of Criniinal  Appeals (NMCCA) considered and rejected  a similar argun~ent in Potrtlct. 1 -  
Sfotlc. 54 M..I. 0 13 (N.M.Cl.Crini.App. 2000). 

Scr\.ice mcnibers \vho disobey a lawful order to take antliras 
vaccination  are subject to administrative or disciplinary actions. 
'T'llere is no  DoDwidc policy directing a specific disposition when 
a Service Member refuses a lawful military order.  Rather, local 
military commanders apply the principles  in  the Unifomi Code 
of Military Justice (UCMJ) and the guidance in the Manual  for 
Courts Martial and Service regulations  that apply to all cases 
involving refusal to obey a lawful order. 

According to  Reference (c), anthrax  inimunization  is mandatory within  the Departnient of the 
Navy and those refusing the vaccine are subject  to disciplinary action.  The Navy  Marine Corps 
Court of Criniinal  Appeals has affirmed  the lawfulness of an order to submit to anthrax 
vaccination  in Porider  11. Srorlc.,  54 M.J. 6 13 (N.M.Ct.Crini.App. 2000) and  U~iitctl . S t c ~ t ( ~  
1,. 
Boltori, No. 20000 102 1  (N. h4.(.'t.Crim.App.)(unpublislied 16 Nov  2001 ). 

4.  RECOMMENDATION:  While the effectiveness and propriety of the AVIP may be subject 
to continued public debate, the validity of a military commander's order designed to "promote or 
safeguard the morale, discipline and usefulness of members of a command and (that is) directly 
connected with the maintenance of good order in the service" does not rest on public consensus 
or a service member's  consent (see UCMJ Article 90 and MCM 2000, para.  14.c.(2)(a)(iii)). The 
order given to the Petitioner to submit to anthrax vaccinations was consistent with Federal law 
and pertinent implementing regulations, properly related to a valid military purpose, and 
arrordingly, w ~ r  I~wful. A subordinate who discrheys swh an order does so at his own peril. 
Based on the foregoing analysis, I respectfully recommend that Petitioner's  requests be denied. 

Fgd 

christ 

. L. 

L C M ,  JAG Corps, U.S. Navy 

2 This paper, as well as other information on the AVIP program are available on the official DoD website at 
http://www.anthrax.osd.mil. 

lln~dentified Defensc Department  Spokesman at  Ilepar-tmerlt o f  Ilefense 
("DoD")  Background  Briefing on the Anthrax Vaccine, August 5 ,  1999. 

Arc orders cur-r-ently being given to members of'the U.S. Armed  I-or-ces to sulmit to  anthrax 
vaccinations consistent with  federal law'? 

II. 

Orders cur-rently beir~g given to rllenlbcr-s of tlle  linited States Armcd  For-ces to suhmit to  a~itllr-as 
vaccinations arc illegal because they contradict the express terms of Presidential Executive Ordc~ 
13 139 and  10 U.S.C. tj  1 107 (1 999).  Because the anthrax vaccine is being used in a manner 
inconsistent with both its original licensing and for a purpose for which it has never been tested, 
the vaccine is properly considered an Investigational New Drug under Food and Drug 
Administration ("FDA")  regulations and federal court decisions.  Both the Executive Order and 
the statute mandate that informed consent is a prerequisite to all vaccinations with an 
Investigational New Drug.  It is undisputed that service members are not giving their informed 
consent to the vaccination process. 

111.  ANALYSIS: 

Introduction 

Members of the Armed Forces of the United States are currently being vaccinated against 
anthrax (Bacillus anthracis), a relatively common, spore-forming soil bacterium that can cause 
death within  1-6 days of exposure to a lethal dose.  Anthrax is postulated as a likely biologrcal 
warfare (B W) agent becaae it is relatively easy to synthesize, exists naturally as spores that are 
readily dispersed in the atmosphere and because a variety of second and third world nations are 
known to have at least attempted to create B W versions of the disease.  &g Atch.  I, Excerpt of 
Dept. of Defense Background Briefing p.  1 3 (August 5, 1999). 
There are ~sessentidly two wnys to medicnlly counter ~otl~rax--BW - ~ntibiotics nnd vnccines 
Antibiotics must be administered shortly before or after anthrax exposure to be effective. 

Antibiotics cannot prcvcnt a lethal  infection o ~ ~ c c  
Vaccines, o n  (hc other hand, can be administercd  ycars before exposure, arc tl~eorcl~cally 
cflcctivc as long as tllc victinl  has enough immunity to neutralize the hac~llus, ~
 
f
1101  p r o v ~ d e  (he kind  of logistics problcrns nssocintcd  with  long-term, fonvill-d storage of' 
i~rltibiot ics 

the anthrax spore has produced  slgns ot'illness. 

gener-ally do 
~

t

The sole production  Sacili~y L'or anthrax  vaccine was origi~lally owned by the M~chigm 
Department of Public Ilealth ("MDPIH").  In the mid  1990s the facility was sold  lo  ii  corposatio~l 
known  as Michigan  Biologic Products, Inc. ("MBPI"). 
group o f  investors heading up a company called  Bioport, Inc. 

In September  1998, MBI'I  was sold to a 

MDPI-I obtained approval  for the anthrax vaccine in  1970 from the Nat~onal Institute of IIealth 
("NIH")  Bureau of Biologics.  This was some two years before efficacy and safety data were 
required  by the FDA for drug approval and licensing.  Long-term safety data for the vaccine was 
not supplied with  the original  licensc application  and  none has cvcr been  supplied t o  the FDA. 
In addition, tile vaccine now being produced b y   MBPI's  successor, Biopor-t, is produced under- a 
different procedure and is apparently chemically diffcrcmt  from the o r - ~ g ~ r l ~ l  
\.accirw alymwcd b y  
the NII-I. 

. 

. 

The license to produce antl~rax vaccine was onginally the property of MDI'I-l atld later, MBI'I 
and Bioport.  'The  original license for the anthrax vaccine reflects its use in agricultural and 
veterinary settings as a protection against cutaneous (skin) contact anthrax.  See Atch. 2, Antllrax 
Vaccine Adsorbed, various package inserts, Michigan Dept. of Pub. Health, 1978.  The vaccine 
has never been licensed as a prophylaxis against airborne anthrax, the most likely BW variant. 

The Anthrax Vaccine Used By  DoD Is An  Investi~ational New  Drug 

The key to understanding why current Defense Department policy is illegal is the recognition 
that the anthrax vaccine as currently used by DoD is properly characterized under FDA 
regulations as an "Investigational New Drug"  ("IND").  The vaccine (hereafter referred to as 
"AVA"  for "anthrax  vaccine adsorbed")  was originally approved only for protection against 
cutaneous anthrax.  However, it is undisputed that the DoD vaccination program is aimed at 
protecting vaccine recipients fiom pulmonarv, or airborne, anthrax.  In addition, the DoD 
vaccination regimen differs from the regimen originally approved by the NIH. 

- 

These substantive changes in the way the vaccine is used and the purpose for which it is used 
render the vaccine an IND under current federal law.  As an MD, the vaccine may not be 
administered to service members without their informed consent,  as directed by President 
Clinton's  Executive Order 13 139 and 10 U.S.C. 5  1 107.  Accordingly, orders to military 
personnel to submit to the vaccine without their consent are per se violative of a direct order 
finm the Prwident in his role as Co~nrrmndet-in-Chief. 

. 

Investigational Ncw  Drug Status. 

I t  is clear that the tcnn "invcst~gational" drugs also ernbraces so-called "ric*\v"  (11-ugs , I >   clc.1ilic.d 
by  the FDA itself'.  See 2 1  C.1-.R. 5  3 12.3(b) (cited in EO  13 139).  The de1ermination of \vhat is a 
"new"  drug for purposes of FDA regulatory coverage (and coverage under EO  13 139) llirlges on 
a variety o f  factors.  A drug is "new",  even if it has been in use for years, i'f  there is a  proposed 
change in the target use of the product, a change in  the formula, dilution of the drug, n  clia~lgc in 
its route of administration, or even repackaging of the drug product. 
generally  \4'liat  Is A 
"New  Drug"  Within the Meaning of 4  201(p) of the Federal Drug and Cosmetic Act,  I33 ALIi 
Fed  229 (1999), and cases cited  therein. 

Court decisioris reinforce F D A ' s  interpretatio~l. For exalnplc, in Iloffi~~ar~ 
485 F.2d  132 (3d Cir.  1973) the cou1-1 held that marketing a drug that  had  becri  appro~.ccl 1)s t
FDA for the treatment of malaria as suitable for use in treating lupus caused  the alread), 
approved drug to be considered  a "new"  drug, at  least as far as the lupus treatment  w ~ s  
concerned.  Similarly, in U.S. v. Articles of Drug, etc., 442 F. Supp.  1236 (S.D.N.Y. 1978) thc 
court found that a drug may be considered "new"  if there is a change in the dosage, or method or- 
duration of administration or application, or other condition of use prescribed, recommended or 
suggested in the labeling of such drug, despite the fact that the drug had previously had been 
approved, albeit with a different dosage and for a different purpose. 

\..  S I C I - ~ ~ I I I ~  
l

III-LI~:,II~C.. 

l ~  

In addition, dnigs thnt are not arlequntdy tc-qtcrl are also considcr ed "new" and investil;i~~it~n;tl, 
regardless o f  usage.  In U.S.  v. Articles of Drug Consisting of the follow in^:  5906 Boxes, 745 
F.2d 105 (I st Cir.  1984) the court found that a nausea-suppressing drug was a "new"  drug in the 
absence o f  substantial evidence that it was recognized by experts as safe and effective.  The court 
defined "substantial  evidence"  to mean consisting of adequate and well-controlled  investigations, 
including clinical investigations conducted by experts.  T h e  court noted that substantial evidence 
that a drug is generally recognized by experts as safe and effective means adequate and well- 
controlled investigations including clinical investigations conducted by experts. 

-. 

It  is important to note that the FDA approval is not a prerequisite for use by a medical practitioner or the 

I 
DoD. Thc FDA regulates the manufacturer in the marketing of drugs, vaccines and devicxs, not the use OF the 
products.  In hct, the FDA docs not have jurisdiction to regulate the adminisVation of the AVA.  It is commonplace 
in the practice of medicine for physicians to make use of drugs and devices that do not bear FDA approval. &a 
391 F. Supp. 697 sffd. 532 F.2d 708 (9th CU. 1978); J'allev  v.  Danck Mdml Inc., 
FM: V.  Simeon Mmt. Corn, 
179 F3d 154 (4th Cir.  1999); In m: O r t h d i c  Bone Screw Products Liabilitv Utiaation, 159 F.3d 817 (3d Cir. 
1998). 

Finally, In  U.S.  v .  I 
safe and effective as used  in  thc I'crsian  Gulf.  The vaccine should tlweforc ly 
considered  investi~ational wlicn used as a protection anainst biological warfa~c. 
(emphasis added). 

U.S. Senate Committee on Veterans'  Affairs Report at  14 (December 8, 1994) (citations omitted). 

4 
DoD has produced two letters that it relies on in an effort to show that the AVA is not an IND when used 
for inhalation anthrax.  The first is a letter from Dr. Michael Friedman to former DoD ASDMA Dr. Joseph, dated 
March 13, 1997.  The scc-md letter was writrctl to Reprcstntative L>an Burtot) by FDA Associate Commissioner 
Melinda Plaisicr on November 26,  1999.  Both letters are circumspect in their assessment of the status of the AVA 
as an W, but indicate that the AVA is not investigational.  However, such letters have absolutely no effect on the 
legal status of the AVA.  FDA regulations specifically note that 

a statement made or advice provided by an FDA employee constitutes an 
advisory opinion only if it is issued in writing under this Section.  A statement or 
advice given by an FDA employee orally, or given in writing but not under this 
Section or Q 10.90 is an informal communication that represents the best 
judgment of that employee at that time but does not constitute an advisory 
opinion, docs not necessarily represent the formal position of the FDA, and does 
not bind or otherwise obligate or commit the agency to the views expressed. 

21 CFR 9  10.85(k). 

Neither o f  the letters refcrcnctd by DoD were issued pursuant to  the above Section.  They do not bind the agency, 
they do not carry the weight of law and they cannot constitute a chmgt in the bgal slatus of the AVA from an IND 
to something else. 

((1) 

Content of Not~ce. - 'l'he notice required under subscct~orl (a)(]) 
shall include the following: 

Clear notice that  the drug being adminlstcl-ed is all 
investigational new drug or a drug unapproved  for i ~ s  
applied  use. 

1nfi)rn)ation regarding the possible sidc effects oSt11e 
investigational new drug or- drug unapproved  for its applied 
use, including any known side effects possible as a result of 
the interaction of such drug with other drugs or treatments 
being administered to the members receiving such drug. 

(e) 

Limitation and Waiver. - (I) In the case of the administration of 
an investigational new drug or a dr,ug u r ~ n p ~ m w ~ d  
for  its applied 
use to a member ofthe armed forces in connection with the 
member's participation in a particular military operation, the 
requirement that the member provide prior consent to receive the 
drug in accordance wiih the prior consent requirement imposed 
under section 505(i)(4) of the Federal Food, Drug, and Cosmetic 
Act (21 US. C 355(i)(4)) may be waived only by the Presiden~ 
The President may grant such a waiver only if the President -.- 

,  determines, in writing, that obtaining consent - 

(1) 

(2) 

(3) 

is not feasible; 

is contrary to the best interests of the member; or 

is not in the int'cr-csrs of national security. 

See,.  2.  Administration ot'l~lvestigat~onal New  Dr-ugs to  h4cnll~cr- 
of the Amled  Forces.  ( a )  The Secretary of Defense (Secretnry) 
shall collect intelligence on potential  Ilcalth threats that might be 
cilcountered  ill  an  area ofopcrations.  ' 1 1 ~  Secretary shall work 
together with  the Secretary of Health and  Human  Services to 
ensure appropriate countermeasures are developed.  IVire~r tire 
Secretary  corrsiders ail  irrvestigatiorral new drug or a drrtg 
rt rr aj)j)ro~vdfor its irr terrded rrse  (ill vestigatiotml clrrrg) to 
reprcscrrt tJ~e most appropriate corrntermeaslrre, it sir all bcl 
sfrrdied tlr ro~,glr .scierrti/ically based rcsenrclr  and dcvelopt~rcrrt 
pt~otoc.ol.s to dcfcrrrlinc wlietJrer it is safe arrd effective f i r  its 
itrfc~~cic~ci 
rr.%cf.  (b) I t  is the expectation that the United  States 
(io\~cm~ncn[ will  administer products approved  for their intcndcd 

111 tllc 

by  tllc  1-ood and Drug Ael~nirlistr-ation (1:I)A).  I~o~veves, 
cvcnt that  the Secretnry considers a product  to represent the most 
appr-opriate countermeasure  for diseases endemic to the area of 
operations or to protect against possible chemical, biological, or- 
radiological  weapons, but the product has not yet been approved 
by the FDA for its intended use, the product may, under certain 
circumstances and strict controls, be administered to provide 
potential protection for the health and well-being of deployed 
military personnel in order to ensure the success of the military 
opcrdion.  The yr-o~risiuns of 2 1 CFR I'WI  3 12 wtllaill the FDA 
requirements for investigational new drugs. 

Sec. 3.  Infonned Consent Requirements and Waiver Provisions. 

(a) 

. 

Before adnrinisterirzg an investigational drug to ,menrbers of the 
Arnzed Forces, the Department of Defense (DoD) must obtain 
informed consent from  each individual unless the Secreta2 cart 
justfi to the President a need for  a waiver of informed con&~rt in 
accordance with 10 U S .  C 11070.  Waivers of informed corrsent 
will be granted only when absolutely necessary. 

(emphasis added). 
In addition, the provisions of 21 C.F.R.  $g 50,3 12 (Octobq 5,  1999) support both the federal 
statute and the Executive Order by specifically noting situations where the informed consent 
requirements may be waived.  Echoing 10 U.S.C. 5  1 107, the Regulations note that only the 

I'residcnt  o i  the Un~ted States may  waive the infbnned conscnt requircrncnts mandnted  by 
Executivc Ordcr atid  fcderal law.  Waiver is allowed only if one of three prcconditiolis is met 
obtaining infornlcd corlsenl is not  lcasiblc; if obtaining informed conscnt is contrary to  the \lest 
interests of (Ile rccil~ient; or  11' ~nfonncd consent is contrary  to  national sccur~ty ~ntercsts. .l'\lc. 
I'resident  Ilils yet  I O  ~ s s u c  a n y  sllcll \v;~ivcrs, o r  even initiate action to do st-, rcyarding rllc A\!.;\ 

11 

CLINICAL lNV1~STIGA'I'IONS I N  MEDICAL IA appr-o\~ed 
dl-ugs ... in  a manner not provided  for in  the FDA approved  indications.  Using FIIA 
approved drugs, devices or radiopharmaceuticals  for therapeutic effects that arc widely 
reported  and are generally accepted within the scope of normal medical practice, does not 
constitute clinical investigation or research in the sense of this instruction. 

AN  medications or devices will be used within the FDA approved indications for  the 
drug . .. 

3.1.3.  'l'he Investigator must avoid all unnecessary physical or mental discomfort to 
human subjects, by planning for adequate facilities and making proper research 
preparations.  Studies are not permitted if there is significant possibility that the subject 
could suffer disease, injury, or death.  The investigator must: Conduct an evaluation of 
the subject before the study begins and record the results. 

3.1.6.  Before a subject is permitted to give consent, the investigator or associate 
investigator must accurately explain the investigation in language the sutyect can-.. 
understand.  Thifaplanation must be made apart of the informed consent documenl. 

3.1.6.1.  The informed consent document should contain, in addition to the components 
identified  in 32 CFR 2 19, the following statements: 
Any medical misadventure or unanticipated medical event will be brought immediately to 
the attention of the subject, or the subject's guardiaxi or next of kin, if the subject is not 

9 d 

3 .  1 .7.2. The tnvcstigator- or- associate inves[igator- gives the adwcc that  limll~ tllc l,as~s 
for the irifomied consent.  This individual must sign thc consent  fomi in  the presence of 
the same witness. 

3  1.7.3. Sip1 or reproduce  tlle consent  (iocumcnt  in  at Icast  t0u1 copies 

Terms 

111 formed  Consent: 
Informed Consent Process.  The informed consent process is intended to give a subject all 
the information that he or she reasonably would want about a study; to ensure that the 
subject understands this information; and to give the subject an opportunity to agree or 
decline toparticipate in the study.  The process provides for interaction between the 
investigator and the subject. 

-. Ifr vestigational Drugs or Devices--Drugs or devices that are not FDA approved for 
marketing.  These include drugs or devices for  which the FDA has provided  either a 
notice of exenrption as an hrvestigational New Drug (IND), or an Investigational 
Device Exemption (IDE), as appropriate ... 

. 

- - .  

2.  Additional Information.  If you will be using investigational drugs or devices, the 
following additional information is required: 

a.  The drug or device to be used, including the trade and generic name and the 

manufacturer. 

b.  If rhe drug or device is f;DA approsled, but it. will be used ouuide of its approved 
labeling, lndicale that this is an trinvestigational usew and give rationale (for cwample, 

5 .   Use of Investigatlonnl Dr-ugs. II'tlie ~nvestigation conccrns hutnan studres of'treatrlicr,r 
or diagnostic procedures involving the use of medications or radiopl~am~aceuticals not 
approved by the FDA, include the approved  IND number and the following information 
about the investigational  drug. 

5 

(enipliasis added). 

. ..if thc military is  ili(cres1ed in using a vaccine tirile scliedulc 
different  from  the cur~ently licensed schedule for a mass 
vaccination effort, then infonned consent  would appropr-iate.. . 

The same holds true, presumably, for the military's  use of a vaccine for a purpose different from 
the original licensing, as well as using a different route to administer the vaccine.. ..a fact most 
recently recognized by the Army in a November  1997 briefing. Atch.  13. 

It is abundantly clear that failure to get informed consent from Armed Forces'  members prior to 
the administration of the AVA, an MD, violates  federal law and supporting regulations, 
Presidential Order, and, in the case of the Air Force, service regulations.  An order to submit to 
the DoD'anthrax vaccination program, as it  is currently constructed, is therefore illegal. 

The DoD Vaccination Propram May Violate International Law 

The AVA program is experimental under FDA regulations. 

. 

In Atch.  8, Unproven Force Protection, at 72, Congress said plainly: 

Note Chat  the A H  is completely consistent with FDA defitions as to what compromises an CND.  Of 

s 
p a k u l a r  rw tc  is  d1c  t c x ~  idttdiyir~g mi "invarigational use" - we Oursidc of approved lakllng, rou tc of 
.dminisQtion,  higher dose kvel, or treatment of anothtx condition not approved by the FDA. Obviously, even 
under Air FORX regulations, the AVA is an DID requiring consent from the sewice member prior to its application. 

Use ol'tllc anthrax vaccine for force protection  against biologicnl 
wilrtirc should be corlsidcrcd esperirttetrtal and undcrtakcn old y 
pursuant  to  FDA rcgulatioris goveniing ~rlvestigational testing for ;I 
new  ~ndlcntion. (cmphiis~s added) 

< 
The samc corlclilsioll was reached  in  ill1 October  1999 CiAO r-cpo11 entitled, hfc~rlicol I~c~rrdirre~.~.~: 
DoD  Faces Clrnllcrrgc.s irr  Irrrplertrerrlirrg Its Ar11lrrtr.v I'accirre  Irrrrrr rtrlizcrliorr I'rwgr-c~rrr, 1)  S .  
Atcli.  14. ?lie GAO reltcratcd that the effectiveness of the AVA against inllalational antlwax 111 
humans has not  becn  proven as it ~i~orrld be rrrretlricrrl to corrdrrct srrclr  slrrriics orr  Irrr/rrrr~r.s. ' l ' l ~  
rcport  continued, noting that while some studies had  proven that the vaccine was effective in 
animals no valid scientific evidence exists to link the results of animal studies to proof of 
efficacy  i l l  Ilun~rrris. 

'T'lie most  significant i~idictmelit o f  DoD's repeated  assurances that tl~e A V A  I S  elIbctl\~c agair~sl 
weaponizcd a n t h r a x   is coritair~cd in a  March  13, 1907 letter  from  h4icllncl  A .  I : I . I c ~ I ~ ~ ; I I ~ ,  
Lead  Deputy ('oliiniissioner,  Food and D r u ~  Administration, Dcpartrncnt 01'1  lcnltli : ~ n d  Iluriiall 
Services (Atcll. 15) which plainly said: 

h4.11 . 

Even more troubling to the AVA program is the statement in 21  C.F.R. Part 3 12.3(b) that an 
experiment is any use of a drug except for the use of a marketed drug in the course of medical 
practice.  Clearly, as evidenced by the 1996 investigational new drug application and the failure 
to show its effectiveness, the AVA is investigational only and has never been licensed for 
marketing by the FDA:  The AVA is, therefore, experimental and its use falls within the ambit of 
both the Nuremberg Code, Atch.  16 and  50 U.S.C. 5 1 S2Oa. and 50 U.S.C. $1520a, Atch. 17. 
Both proscribe, inter aha, the inoculation of military members with the AVA without their prior 
expressed and informed consent. 

Nuremberg Code 

The Nuremberg Code provides assurance that human beings will not be used as unwilling 
subjects of chemical or biological experimentation without their specific and informed consent. 
The Code arose as part of the trials Karl Brandt and others at Nuremberg for crimes againit 
humanity committed in their roles as the Nazi high command. 

It is indisputable that such international law is an integral part of United States domestic law, via 
treaties, executive agreements and customary international law.  Paauete Habana, 175 U.S.  677 
(1900).  And, it is equally well grounded that the Nureruberg Code is a part of our domestic law. 
S c e  dissmi, Gibbons, Circuit Judgc, JdTw v. United  Sratcs, IGG3 F. 2d 1226 (3d. Cir., 1981) (Per 
the Nuremberg Code, ''The  international consensus against involuntary human experimentation 

: 

IS clcar;" Scc also, Annas, GJ., Protecting Soldiers from  Friertdly Fire:  Thc (hrr.vcrrrr 
Rcquirerrrcrrrfor  (Jsitrg Irr~v.stigational Drugs nrtd  I'accirres  irr  Corrthnf, 24  An1  J 
245-260 ( 1 W8), Atell.  I8 

1 . ~ \ v  S:  Mctl 

50 U.S.C. g1520a. 

The pinciples oftlic Nurclnbcrg  Codc are codified in  50 U.S.C. 91520a (which also p~.olirblts 
the Department of Ilefense from conducting a grand-scale experiment of tlie A V A  drug on its 
members). 

(a)  1'1-ohib~tvd a c t ~ v ~ t i ~ b  
'I'he  Sccrctary 01'I)ctknsc  may 11ot conduct (directly or by conlr-act) 
( I )   any lest or experiment involving the use of a chernical 
agent or biological agent on a civilian population; or 
(2)  any other testing of a chemical agent or biological agent 
o n  human subjects. 

(b)  Exceptions 
Subject to subsections (c), (d), and (e) of this section, the prohibition in subsection 
(a)  of this scdion does not apply to a test or experiment carried out for any of the 
following purposes: 
(1)  Any peaceful purpose that is related  to a medical, 
therapeutic, pharmaceutical, agricultural, industrial, or 
research activity. 
(2)  Any purpose that  is directly related  to  protection  against  toxic chemicals or 
- 
biological weapons and agents. 
(3)  Any law enforcement purpose, including any purpose related to riot control 

(c)  l n  formed  consent required 
The  Secretary  of  Defense  may  conduct  a  test  or  upcrirmrrt  described  in 
subsection  @)  of  this  section  only  if informed  consent  to  the  testing  was 
obtained from  each  human subject  in advance  of  the testing on  that subject. 
feimph~4s nddcd). 

1. 

Bioport or other suitable contractor secures a full FDA license and approval  f o r  

marketing of AVA as a prophylaxis against pulmonary anthrax (Note: the DoD is presently 
seeking a change to those FDA regulations to allow animal surrogate testing, vice the present 
requirement for two studies, in humans, to prove safety and efficacy. Atch.  19); 

2. 

The Surgeon General designs and implements a scientifically and medically valid 

and appropriate adverse reaction reporting system for service members presently suffering 
reactions to the AVA; and 

3 .  

The DoD Inspector General, together with the Veterans Administration, openly 
investigates and reports on all adverse reactions involving Air Force members past and present, 
to date. 

-. 

Such a response would cyre the current aura of illegality that surrounds the anthrax program 
orders as well as provide a mechanism for accounting for the variety of reactions that may or 
may not be related to the vaccine.  It is undeniable that certain units have been hit hard by what 
appear to be adverse vaccine reactions.  The situation needs to be fully investigated by competent 
authorities in an environment free from political pressure to approve the program.  The proposed 
steps will result in a better and efficacious vaccine, and will allow the Air Force to properly deal 

Source  All Sources > Federal Legal - " S  > Execul~ve Branch Mater~als > Executive Orders 0 

Terms  executive order 131 39  (Ed11 Search) 

C-  Select for  FOCUS TM  or  Dellvery 

6 4  FR  54175,  ' 

frtDERAL  REGISTER 

Vol  64,  No  192 

P r c s ~ d e n t ~ a l  Documents 

PRESIDENT OF  THC  UNITED STATES 

Executive Order  1 3 1 3 9  o f  S e p t e m b e r  30,  1999 

Title 3  - 

The President 

I m p r o v i n g  Health Protection of M i l i t a r y  Personnel Participating i n  Particular 

Military Operations 

Part  I V  

D A T E :  T u e s d a y ,   O c t o l ~ e r  5, 1995 

By the authority vested in me as President by the Constitution and the laws of the United 
States of America,  including section  1107 of title  10,  United States Code,  and in order to 
provide the best health protection to military personnel participating in particular military 
operations,  it is hereby ordered as  follows: 

Section  1. Policy.  Military personnel deployed in particular military operations could 
potentially be exposed to a range of chemical,  biological,  and radiological weapons as well as 
diseases  endem~c t o  an area  of operations.  I t  is the policy of the United States Government 
to  provide our  military  personnel with safe  and effective vaccines,  antidotes,  and treatments 
that will  negate or  minimize the effects of these  health threats. 

Sec.  2.  Administration of  Investigational New Drugs to Members of the Armed  Forces. 

(a)  The Secretary of Defense (Secretary) shall collect intelligence on potential health threats 
that might be encountered In an area of operations. The Secretary shall work together with 
the Secretary of Health and Human Services t o  ensure appropriate countermeasures are 
developed.  When the Secretary conslders an Investigational new drug or a drug unapproved 

, 

4 

for Its intended use (~nvestigational drug) to represent the most appropriate countermeasure, 
it shall be studied through scientifically  based research and development  protocols to 
determine whether  it is safe and effective  for  its intended use. 

(b) It  is the expectation that  the United States Government will adniinlster  products 
approved for  thelr  intended use by the Food and  Drug Adrn~n~stratlon 
event that the  Secretary  considers a product to  represent  the most appropriate 
countermeasure  for  dlseases endemlc  to the area  of operations or to protect against  possrble 
chemrcal,  brological,  or  radrological weapons,  but the  product  has not yet  been approved  by 
the FDA  for  rts Intended use,  the  product  may,  under certain circumstances  and strrct 
controls,  be admrnistered  to provide  potentral protect~on for  the  health and well-l~cing o f  
deployed military personnel in order  to ensure  the success  of  the  military operati?!i  Tlic 
provlslons of  2 1  CFR  Part  3 1 2  contain the  FDA  requ~rements for  investrgational nc>w drug\ 

(FDA). However,  in the 

Sec.  3  Informed Consent  Requ~rements and  Wa~ver Provisions 

(a) Before adniinistering  an investrgational drug to  members of the Armed  Forcec,, the 
Department of  Defense (DoD) must obtain  rnformed consent from each  rndrvidual unless the 
Secretary can justrfy  to the  President  a need for a waiver  of informed consent  In accordance 
wlth  10 U S.C  1107(f). Waivers  of Informed consent  will  be granted only  when absolutely 
necessary 

(b) I n  accordance  wrth  10 U  S  C  1107(f), the  President  may walve  the  Informed consent 
requirement for  the admrnistration  of a n  investigat~onal drug to a member of the Armed 
Forces  in connection  with the  member's participation In a partrcular mrlitary  operation,  upon 
written  determination  by  I h e  Prt.s~dent that  obtarn~ng consent 

( 1 )  is  not feasible; 

( 2 )  IS  contrar-y to  the  best  ~ntert>sts of the  member;  or. 

(3) is  not in the interests of  national secur~ty. [*54176] 

(c)  I n  making a determination to waive  the  informed consent requirement on a ground 
described  in subsection ( b ) ( l )  or (b)(2) of this section,  the President is required by law to 
apply the standards and criteria set forth in the relevant FDA regulations,  2 1  CFR  50.23(d). 
In determining a waiver  based on subsection (b)(3)  of this section,  the President will also 
consider the standards and criteria of the relevant FDA regulations. 

(d) The Secretary  may request that the President waive the informed consent requirement 
with respect to the administration of an investigational drug. The Secretary  may not delegate 
the authority to make this waiver  request. At a minimum, the waiver  request shall contain: 

(1) A  full description of the threat,  including the potential for exposure.  I f  the threat is a 
chemical,  biological,  or radiological weapon,  the waiver request shall contain an analysis of 
the probability the weapon will  be used,  the method o r  methods of delivery,  and the likely 
magnitude of its affect on an exposed individual. 

-.. 

(2) Documentation that the Secretary  has complied with 2 1  CFR  50.23(d).  This 
documentation shall  include: 

(A)  A  statement that certifies and a written justification that documents that each of the 
criteria and standards set forth in 2 1  CFR  50.23(d)  has been met;  or 

(B) If the Secretary finds it highly impracticable t o  certify that the criteria and standards set 
forth In 21 CFR  50.23(d)  have been fully m e t  because dolng so would slgnltkantly lmpalr the 

Secretary's ability  to carry out the particular mllltary  mlssion,  a wrltten ~ u s t ~ f ~ c a t l o r l  
that 
documents which criteria and standards  have or have not been met, explains the reasons for 
failing t o  meet any of the criteria and standards,  and provides additional justification  why  a 
waiver  should be granted solely  in the interests of national security. 

( 3 )  Any  add~tional information pertinent  to the Secretary's determination, ~ncludlng the 
mlnutes of the  Inst~tutional Rev~ew Board's (IRB) dellberations and the  IRB members' vot~nq 
record 

( e )  The  Secrctary  shall develop  the waiver  request  in consultat~on wrtll  the  f-DA 

( f )  The  Secretdry shall submit  tlie waiver  request  to the Pres~derlt and  provide  J  ~ O P Y  
t o  
Cornrn~ss~oner of  the  FDA  (Cornmlss~oner) 

(g) The Cornmlss~oner shall exped~t~ously review the walver  request and certlfy to  the 
Assstant  to the  Pres~dent for  Nat~onal Secur~ty Affa~rs (APNSA)  and the Assrstant  to  thc 
Pres~dent for  Sc~ence and Technology  (APST) whether  the standards  and c r ~ t e r ~ a  of the 
relevant FDA regulat~ons have been adequately addressed  and whether  the  ~nvest~gatlonal 
new drug protocol may proceed subject to a declslon  by the Presldent on the Informed 
consent waiver request.  FDA shall  base  ~ t s  declsion on,  and the c e r t ~ f ~ c a t ~ o n  
shall Include an 
analys~s descrrblng,  the extent  and strength of the evldence  on the safety  and effectlvenes5 
of the  ~ n v e s t ~ g a t ~ o n a l  
durlng the  m ~ l ~ t a r y  operat~on 

new drug  In relat~on to the  med~cal r ~ s k  that could  be encountered 

(h) The APNSA  and APST  w ~ l l  prepare a joint  advisory  oplnlon as  to whether  t t i e  ivaiver of 
Informed consent  should be granted  and w ~ l l  forward  ~ t ,  along  with  the  i.:,jlvcr 
request  anti 
the  FDA  cert~ficat~on 

to the Presldent 

(I) The  Pres~dent wrll  approve or  deny  ttie  waiver  request  and wrll  prov~di- ivr Itten iict~ficatlorl 
of the decis~on to the Secretary and the  Coniniiss~oner  [*54177] 

Sec.  4.  Requ~red Act~on After  Wawer  IS  Issued. (a) Follow~ng a Pres~dent~al warver  under  10 
U.S.C.  1107(f), the  DoD off~ces responsible  for  ~rnplementing the waiver,  DoD's Offlce of the 
Inspector General,  and the FDA, consistent w ~ t h  its regulatory  role,  will conduct an ongolng 
review and monitoring to assess adherence to the standards and cr~teria under 21 CFR  50.23 
(d)  and this order.  The responsible DoD offices shall also adhere to any periodic reporting 
requirements specified  by the President a t  the time of the waiver  approval.  The Secretary 
shall submit the findings t o  the President and provide a copy to the Commissioner. 

(b) The Secretary shall,  as soon as practicable,  make the congressional notifications required 
b y  1 0  U.S.C.  1107(f)(2)(8). 

(c) The Secretary shall,  as soon as practicable and consistent with classification 
requirements,  issue a public notice in the Federal Register describing each waiver of informed 
consent determination and a summary of the most updated scientific information on the 
products used,  as well as other information the President determines  is appropriate. 

(d) The waiver will expire at the end of  1 year  (or an alternative time period  not to exceed  1 
year,  specified by the President at the time o f  approval),  or when the Secretary informs the 
President that the particular military operation creating the need for the use of the 
investigational drug has ended,  whichever  is earlier. The President may revoke the waiver 
based o n  changed circumstances or for any other reason.  I f  the Secretary seeks to renew a 
waiver prior t o  its expiration,  the.Secretary must submit t o  the President an updated request, 
specifically  Identifying any new Information available relevant to the standards and criteria 
under 21 CFR 50.23(d).  To request t o  renew a waiver,  the Secretary must satisfy the criteria 
for a waiver as described in section 3 of this order. 

-.. 

(e) The Secretary  shall notify the  President and the Commissioner  if the threat countered by 
the investigational drug changes significantly  or if significant  new information on the 
investigational drug is received. 

for  M ~ l ~ t a r y  Personnel.  (a) The  DoD shall  prov~de ongolng  tralnlng and health 

Sec  5  T r a ~ n ~ n g  
rlsk communlcatlon on the  requ~rements of  uslng an ~nvestigat~onal drug In support  of a 
r n ~ l ~ t a r y  operat~on to all m ~ l ~ t a r y  personnel,  ~ncludlng those In leadersh~p poslt~ons, dur~ng 
chern~cal and  b~olog~cal warfare  defense t r a ~ n ~ n g  and other training, as  appropriate  Th~s 
ongolng  t r a ~ n ~ n g  and health r ~ s k  conirnun~cat~on shall  Include general ~nforrnat~orl about  1 0  
U  S  C  1107 and  21 CFR  50.23(d) 

(b)  I f  the  Presldent grants a walver  under  10 U S.C. 1107(f), the  DoD shall provide trair-i~ng 
to all m ~ l ~ t a r y  personnel conducting the  walver  protocol and health r ~ s k  cornrnun~cat~on 
m ~ l ~ t a r y  personnel recelvlng the speclflc  ~ n v e s t ~ g a t ~ o n a l  
use. 

to  all 
drug to  bepdmin~stered prlor to  ~ t s  

( c )  The  Secretary shall  s u b m ~ t  the t r a ~ n ~ n g  and  health rlsk  commun~cat~on plans  as  part of 
the  ~ n v e s t ~ g a t ~ o n a l  
and health risk commun~cat~on shall Include at a mlnlmum: 

new drug  protocol subrniss~on to the FDA  and the  revlewlng IRB. Tra~n~ng 

(1) The  bas~s for  any  determ~nat~on by the  Presldent  that  Informed consent  IS  not or  may  not 
be  feas~ble; 

( 2 )  The  means for  track~ng use and adverse  effects  of  the  invest~gat~onal d!-ug; 

( 3 )  The  benef~ts and r ~ s k s  of  u5rng the  ~ n v e s t ~ g a t ~ o n a l  

drug;  and 

( 4 )  A  statement  that  the  ~ n v e s t ~ g a t ~ o n a l  
intended use). 

drug  I S   not approved  (or not approved for the 

(d) The  DoD shall  keep operational commanders  informed of the overall requlrernents of 
successful  protocol execution and their  role,  with the support of medical personnel,  In 
ensuring successful execution of the  protocol. 

Sec.  6.  Scope.  (a) This order applies to the consideration and Presidential approval of a 
waiver o f  informed consent under  10 U.S.C.  1107 and does not apply to other FDA 
regulations.  [*54178] 

(b) This order is  intended only to improve the internal management of the Federal 
Government.  Nothing contained in this order shall create any right or benefit,  substantive or 
procedural,  enforceable by any party against the United States,  its agencies or 
instrumentalities,  its officers or employees,  o r  any other person. 

S WILLIAM  J.  CLINTON 

THE  WHITE  HOUSE, 

September  30,  1999. [FR  Doc. 99-26078  Filed  10-4-99; 8:45 am] 

Billing code 3195-01-P 

food m n d  o w  C L d n r h h h ~ o ,  
Ra3xila MO W l

 

The Hono~able Dan Burton 
Houac  of  K n p r c s t u ~ t a t i v e ~  
Waehrngton,  P . C .  

1001s 

3xm.k  y o u   f o r   your  F n t a r e ~ t  i n   the  anthrax  vaccine. 
~ h L s  i o  
in reaponse  t o  your  letter dated  Novearber  3 ,   1999, c o - o r g m d  
by  three  of  your  colleagues, to Dr. 
Comaiasianer  of  t h e   Food  and  Drug 
~ g t n c y ) .  You  raised  a number of  iasuae related  t o   t h e   pending 
license supplernant  application of BioPort  Corporation to 
produce  the  anthrax  vaccine.  Ms. 
has had o e ~ s r a l  converaatlam  rich H r .  
staff,  on  Novembu:  12 and N u v d r
6 t 6 t u s   of  this  re8ponse-  RB  waa  txpluined  to U r
respame  prmvrdcd  M o w  is based  on  i n f o r m a t i a n   available  under 
thc hreedom  of  Information Act  (POIA) and  FDA hnplernenthg 
rtgulatronc. 

 17, 1999, concerning the 

Dn  nt of rrry  s t a f f  

ot your 

or  t h e  

,

 the 

.

6

FDA has  inspscted  t h i a   facility on  many  occasians 
identifying  a number  of  defieienciee 

AB  you knou,  BioPort  Corporation,  (previously k m  ac  MFchigan 
Department  of Public  H e a l t h   or Midngan  Biologics P r d u c t s  
Institute),  holcb  a  license to mbnufacture Anthrax  V a c c i n e  
Adsorbed. 
during  the paet  decade, 
r w i r i n g   correction.  Your  statement that the  anthrax  vaccine- 
upecif ic  portion of  the manufacturing  f acilf ty uas  not 
physically  inspected  in 23 year& is not accurate.  A  review  of 
inspection reports  froar  1972 to 1998  ahowe  tbat Pnthrax  Vaccine 
Maorbed  was  covered as  part  of the i n q e c t i o n  on 12 separate 
occasions either  by  record  review,  obervation  of  araaufactuking 
areas  or  interviews  w i t h   engineering and  manufacturing staff. 
Thi 
Dr. 
and 
Subcommittee on National Security, Veterans  AEf air8 and 
International Relations, on April  2 9 ,   1 9 9 9 -  
Nembcrs 
i n s p e c t i a m   for the  anthrax  vaccine  prior  to 1996. 

contained in the  writtan testimony of 
Director,  Canter  for Biologics  Evaluation 
before  the Colmrittee  on Government Reform, 

questions, D r .  w also atated  that FDA  d i d   conduct 

I n   reeponse t o  

Page  2  - The  Honorable Dan  Burton 

~

t

 

~

be  consistently manufactured to 

Hanufacturera may  release l o t o   of  product only 

FDA agree6  that products  a
meet  specifications prior  to  product  approval.  FDA r e v i e w   Q c o  
include  pmduct  characterization.  .Because  of tha c q l e x  
manufacturing procass  for  m o t   biological  products, each  lot  of 
t h e   p d u c t  undergoes  thorough  teatiq  for purity, potency,  and 
s t e r i l i t y .  
a f t e r   teotlng  lo documented.  FDA  m y  require lot  aamplee.md 
protocols showing reeults of applicable t e a t e   to be @ m i t t e d  
for revieu  and  poeeible  teetFng by  the  Agancy .  ~ h c  anthrax 
vaccine  m~rmfactured by BioPort  is subject  to lot releaoc, 
under which a manufacturer  may  aot  diotribute  a  l o t   of product 
until (ZBW  releaws  it.  The  lot  release program  i a   part  of 
FDA's  multi-part etrategy  that  helps  assure  biological  product 
safety by  providing  a  quality  control  check  on product 
~ c i

icatlons .- 

f

 

8ha  d i d   mt  s t a t e   that  the  anthrax  vacciac  i6  indicated 

Dr.  ZoonOs teetimony kmfore  t b  C o d c t e e  on Covarnmant  Reform 
on October  12,  1999,  etated  t h a t   t h e   indrcation  ic  baeed  an 
r i o k .  
only  for  individuals at  r i n k   for cutaeeoua  a c p o u r e   to anthrax, 
nor  that the w e  is  for a  *limitedm population. 
~ h n  labeling 
for the anthrax vaccine p d c t  is eacloead.  Tba  labeling  for 
Anthrax Vaccine  Adeorbcd does not  mention  route of exposure 
( e  - g.,  cutaneous) , per ee.  Uee  of  the vaccine  for pmtection 
againat  both  cutmeom  and  inhalatian anthrax axpomre  is  not 
inconsistent  with  tht  lebeling  for Anthrax Vaccine Absorbed. 

m

?ht  term  'paucity  of  data,'  used  in  the 1997,  l c t t c ~  to 
Dr.  Stephen Joseph,  then  Assistant  Secretary  of  Defense far 
 Dr. Xicbael A-  Friedman, then FDA Lead 
H e a r t h  Affairs,  f
Deputy  Comaimioner,  is used  to &ecxFbe  the ralatively  few 
reported caaee  of  inhalation anthrax  in the  efficacy trial. 
Requiring the anthrax v a ~ i n e  to be rctuxned to an 
imfeatigational new  drug  (IHDI  fitatus  will aot generate  wrc 
human efficacy data,  as inhalation anthrax in huraa~ is not 
umenable to atudy,  due  to the Low incidence and sporadlc 
occurrence of disease  in natural  oettings.  ~t ehourd  be noted 
that in the  United States,  in this  century,  only  10 human cases 
of  ;inhalation  anthrax  have been reported  ( 8 r a a .  P. S .  
Inhalation anthrax.  &m  N YAcad  Sci 353~83-93t 1980).  This low 
incidence of aaturally &curring  inhalation anthrax  since 
introduction of  the vaccine makes  it  irapossible  t o   duplicate the 
findings in the Bradman  and the Centers for  D i ~ e a e e  Ccx~trol and 
Prevention (CDC)  sunreillance data of  the 1950'5  to early  1970 V .  
In the past  eeveral years,  the Department  of  Defense (Do) 

.. 

Page  3  -  The   ono or able  Dan Burton 
In  thc past  acvcral yeare, 
 ha^  concluded  that  the .threat of  iological  attack i o   great 
enough that  troops  should  be connidered  part  af the high-riek 
population for which thia vaccine is an appropriate 
w a e   provided  to 
prophylactic  u m a m .  
Chairman  Dan  Burton,  in a reaponee to an August  11,  1999. 
letter  eccking  Mormation  on vaccines.)  you  m y  vish  t o  
contact  DOD  to diocueo  i t a   r i e k   asaeorrment. 

the  "8" rtment  of  Defcmc 

(Thio  info-tion 

(DODI 

There  is preeently no basis for concludrng  that  the anthrax ' .  
vaccina,  a  licandtd p&t, 
labeling,  shoqld be  wed  pursuant  to an  IND application or, as 
requeeted  In your  l e t t a r ,   that  FIU  'place  the anthrax  vaccine 
back  under fND status.' 

uhen  used in accordance with  currcnc 

the cursent  Anthrax  Vaccine 

0 ,   2  an8  4  we&; 

Thin t r i a l  wan  a single-blinded, well- 

is  a  mirrperception  that  ao clinical or  scientific  s t u d i e o  

%re 
have  been conducted  to m q ~ ~ r t  
Meorbed-doeq  schEdule.  me currently licensed  anthrsx  vaccine 
administration  schedule was  w e d   in  the  Brachum  efficacy t r i a l  
and  CDC  m. 
The  E l r w  ct (11. trial  wa6  used  to support  ttu?  liceneure of 
tho  anthrax  vaccine. 
controlkd trial.  canducred  in  fwr  W t e d  Stat-  textile  mills 
p r o c e e e h g   iaxprted  goat  hair  with an \ergoaed, eusceptible, 
suptrviccd  population.g  The  avurage  incidence of  anthrax  prior 
t o   the study  una  1.2  catrse  par  100 employsea per y&*r.  Tbe dose 
adminiatration s d m i u l e  uaa  tht  aama  as the ~ z r e a t l y  I icewed 
vaccine  dose  administration  achedule; 
6, 12, 
and  1 8  mantha,  followed thercaf ter  by annual h e t e n .   of  tbe 
1,249 m i 1 1  wnrkers,  909  individuals  pattidpated  in the 
contmllcd  part  of t h e .  9Cudy.  ~ndidx%als ubo received  neither 
vaccine nor place. earotd  as an ztmtaccinated  obeuvatiadal 
wcurred  during  the  trial : 
control.  A  total of 26: anthrax 
21 cutaneous  cases  and If iva inhalation cases  (four fatal.) . Of  ' 
theee  26  cases,  three  (dl cutitneou)  occp~red Ln  anthrax  vaccine 
recipients.  One arre oCcurred after  trro  dootd,  m e  m e  . o c m c d  
13  mcwths  after the  thi*  dose  (fourth dose  not  given),  and  one 
caet  occwred  five ((~lflths after  the third dose.  Five case8  of 
inhalation anthrax occurred at  one  site  (thc Hanchater, 
New  Hamprrhire  goat  hair; processing. plant)  during  the t r i a l .   TWO 
of  the inhalation caeca r  were  in the placebo  gioup, and  three 
inhalation cases  were  ih the  unvaccinated group.  m  csaas  of 
inhulatiorr  an- 

o c c k e d  in  mtbrux  raccfna  recipi~nts. 

Page  4  -  The  Honorable Dan Burton 
The  efficacy level of  9 2 . 5   p e r c a t ,   a8  presented  in  the  major 
publication of tba efficacy trial (Bra-, 
evaluation  of  a human anthrax  vaccina.  Am  J Public Haalrh. 
521632-645)  includes  anthrax  casee  in  the  vacclne  and  placebo 
groups and  is  ~t  limited  to cutaneous anthrax cases. 
efficacy  of  the anthrax  vaccine  in this  strrdy  vat3  calculated t o  
be  9 2 . 5   percent.  This  calculation  (92.5  percant)  i 6   samctimco 
errorieouely  presented  as  the  vaccine  efficacy a g a i n s t   c u t a n m n  
anthrax. 

et. al.,  1962 F i e l d  

. . 

Following tbc  1957 trial and  t h e   five caaca of inhalatlm  anthrax 
in  placebo  and  urrvacdnsted  individuale,  the  Icanchester, 
New H a m p h i r e   goat  hair praccseing  plant ~ c c h a t e d  all crnployceo 
against  anthrax  (starting  in December  1957) .  The case  rate i n  
t h l ~  plant  f e l l   from 6.2  case6  per  year prior  to 1957 to 0 . 4  
caeca per  year  from D e c W  1957 to June  1966, the latter 
In July 1966, an etployee 
cozuiating  of  four cutanecm  caee5. 
(unvaccixmted)  of an adjacent  facility  (mttal  fabricator  shop) 
died  frorn  inhalation anthrax.  The source of  the  agent  was 
thought to be  the  adjacent  goat  bair  processing plant.  ~n a 
follow-up investigation by CDC  (January 30 - February 6 ,   190), 
envfrurmrtntal  sampling  of both  f a c i l i t i c o   identified  8 .  m t k s c i o  
inhalation anthrax  (LPForce PH et a1 . :  Epidcmiolqic  atudy  of a 
fatal case of inhalation anthrax.  Arch  E m d m n   Health  18:798- 
805,  1969). 

Under W C  JXD,  approximately  16,000 doeeo of the vaccine were 
acfministared  to approximately  7,000  study participant8 w h o   were 
at risk for anth~ax. These doses  n r e  administered according 
to thc  Bame  aix-dose schedule that  ia  the  appraved  dosing 
schedule t6day - 

individuals,  m e  case after  one  dose of vaccine 

huthermore,  in cDc surveillance .data (1962-1974), 27  caees  of 
anthrax  occurred  in. ' a t - r i s k g   induetrial  e t e t i n g a :   24  casca  in 
~ ~ ~ ~ c c i n a t e d  
and  t w o   cases after  tm  doses  of hraccine.  No caeee  of anthrax 
were rap0rted.h individuals who  received  d l  six dosss  of 
anthrax  vacciae . 
It  is  intereating  to note that (332  mlicatbm,  Bfosdfety  in 
Microbiological and Eiomcdi cal  LaboraCorle~  Edition (1999), 
states that  laboratory  aesociated  caees  of anthrax  have  mt 
been  reported  in the United States  since t&  late 19506  uhea  the 
human anthrax  vaccine uae  introduced.  Before  that  date,  numerous 
casee  of  laborator  associated anthrax,  occurring primarily a t  
- 
facilities  conducting  anthrax  research, were  reported. 

Page 5 - The  Honorable Dan  Burton 

e w  w a s   initiated in order  to asstss  thc 

including  vaccines  that  had  been  licensed  prior  t o  

The  Public Health Service  Act,  under which  blologLcals  such ao 
v a c c h e   were  licenaad  in  1 9 7 0 ,   r e q u i r   evidence of  s a f e t y ,  
purity  and  potency.  After  the Division  of  Biologic Standards 
wae  transfcrrcd from  ths Natioaal  I n s t i t u t e e   of Health t o   PM, 
expert panela  w e r e   s e s i w  t o   review  Fnformation  un  biological 
products, 
the  transfer.  The  d
eafety,  effectivaneea  md  labeling  of products  licensed p r i o r  
to July  1,  1972.  Baaed  q m ~  
the A c M s a r y   Review Panel recormnendcd  that  ararketing  of  Anthrax 
Vaccine  Adeorbad marmfactured by Kichiqan Department  of  P u b l i c  
Health be  a l l o m d   to continue  hued upon  substantial  evidence 
of  safety  and effectiveness  of the product. 
The safety data 
from CDC  IM),  at3  well  86  the efficacy data  from the Brbchman 
et .&I. trial,  and CDC eurveillanca data  (1962-1974) from 
'at-rhkn  induntrial  s e t t i n g e   were  the basis  for  these 
These  findings w e r e   published  in the  Federal 
f-. 
Reqister of  December  13,  l9O5. 

their  r e v i e w   of  available data, 

Purtbennore,  data  frwrn  a  well-conu-olled  nronkey  study has 
bcamz  available since  tha  t i m e   of  tb4 1985 Panel  report. 
efficacy  of  the  Anthrax  Vaccine  Iuborbed  licensed  for  u e  i n  
humam  a l s o   wan  cested  fn rheeue  rnonkeya  challenged by  m 
aeroeol of v i r u l e n t   B a c ~ l l u o  anthracfs apores.  The data  f r c m  
this study suggeeto vaccine efficacy against  inhalation 
anthrax.  It sbould  be noted  that mcnkeya  are quite  cimilar  to 
humma  with  regard  to t;he  clinical course  and p a t h l o g i c a l  
finding13  following inhalation  anthrax. 

7 % ~  

Whila  theee studiee cannot  prove  that the vaccine  would  be  100 
percent  effective in  a  :terroritit  or  wartime situation, they  are 
the only k n m  data  on :pre-acpaeurc protection  currently 
available against inhalation anthrax. 

In the September  29,  1999, letter to Dr 
Secretary a£ Defuree  Health  Affaire,  B@ 
Director,  CBER,  otaced ;ia the  f h l  paragraph,  We  reiterate 
our  previous  statement jmade  to DOD an Deceaher  16,  1997,  that 
FDA  approval  of  the anthrax vaccine is based