[House Hearing, 108 Congress]
[From the U.S. Government Publishing Office]




 PREVENTING ANOTHER SV40 TRAGEDY: ARE TODAY'S VACCINE SAFETY PROTOCOLS 
                               EFFECTIVE?

=======================================================================

                                HEARING

                               before the

               SUBCOMMITTEE ON HUMAN RIGHTS AND WELLNESS

                                 of the

                              COMMITTEE ON
                           GOVERNMENT REFORM

                        HOUSE OF REPRESENTATIVES

                      ONE HUNDRED EIGHTH CONGRESS

                             FIRST SESSION

                               __________

                           NOVEMBER 13, 2003

                               __________

                           Serial No. 108-127

                               __________

       Printed for the use of the Committee on Government Reform


  Available via the World Wide Web: http://www.gpo.gov/congress/house
                      http://www.house.gov/reform


                                 ______

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                            WASHINGTON : 2003
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                     COMMITTEE ON GOVERNMENT REFORM

                     TOM DAVIS, Virginia, Chairman
DAN BURTON, Indiana                  HENRY A. WAXMAN, California
CHRISTOPHER SHAYS, Connecticut       TOM LANTOS, California
ILEANA ROS-LEHTINEN, Florida         MAJOR R. OWENS, New York
JOHN M. McHUGH, New York             EDOLPHUS TOWNS, New York
JOHN L. MICA, Florida                PAUL E. KANJORSKI, Pennsylvania
MARK E. SOUDER, Indiana              CAROLYN B. MALONEY, New York
STEVEN C. LaTOURETTE, Ohio           ELIJAH E. CUMMINGS, Maryland
DOUG OSE, California                 DENNIS J. KUCINICH, Ohio
RON LEWIS, Kentucky                  DANNY K. DAVIS, Illinois
JO ANN DAVIS, Virginia               JOHN F. TIERNEY, Massachusetts
TODD RUSSELL PLATTS, Pennsylvania    WM. LACY CLAY, Missouri
CHRIS CANNON, Utah                   DIANE E. WATSON, California
ADAM H. PUTNAM, Florida              STEPHEN F. LYNCH, Massachusetts
EDWARD L. SCHROCK, Virginia          CHRIS VAN HOLLEN, Maryland
JOHN J. DUNCAN, Jr., Tennessee       LINDA T. SANCHEZ, California
JOHN SULLIVAN, Oklahoma              C.A. ``DUTCH'' RUPPERSBERGER, 
NATHAN DEAL, Georgia                     Maryland
CANDICE S. MILLER, Michigan          ELEANOR HOLMES NORTON, District of 
TIM MURPHY, Pennsylvania                 Columbia
MICHAEL R. TURNER, Ohio              JIM COOPER, Tennessee
JOHN R. CARTER, Texas                CHRIS BELL, Texas
WILLIAM J. JANKLOW, South Dakota                 ------
MARSHA BLACKBURN, Tennessee          BERNARD SANDERS, Vermont 
                                         (Independent)

                       Peter Sirh, Staff Director
                 Melissa Wojciak, Deputy Staff Director
                      Rob Borden, Parliamentarian
                       Teresa Austin, Chief Clerk
              Philip M. Schiliro, Minority Staff Director

               Subcommittee on Human Rights and Wellness

                     DAN BURTON, Indiana, Chairman
CHRIS CANNON, Utah                   DIANE E. WATSON, California
CHRISTOPHER SHAYS, Connecticut       BERNARD SANDERS, Vermont 
ILEANA ROS-LEHTINEN, Florida             (Independent)
                                     ELIJAH E. CUMMINGS, Maryland

                               Ex Officio

TOM DAVIS, Virginia                  HENRY A. WAXMAN, California
                      Mark Walker, Chief of Staff
                Mindi Walker, Professional Staff Member
                        Danielle Perraut, Clerk
                   Richard Butcher, Minority Counsel


                            C O N T E N T S

                              ----------                              
                                                                   Page
Hearing held on November 13, 2003................................     1
Statement of:
    Egan, Dr. William, Acting Director, Office of Vaccines 
      Research and Review, U.S. Food and Drug Administration; and 
      Dr. Robert Hoover, Director, Epidemiology and Genetics, 
      National Cancer Institute, accompanied by Dr. May Wong, 
      Program Director, Division of Cancer Biology, National 
      Cancer Institute...........................................    10
Letters, statements, etc., submitted for the record by:
    Burton, Hon. Dan, a Representative in Congress from the State 
      of Indiana, prepared statement of..........................     4
    Cummings, Hon. Elijah E., a Representative in Congress from 
      the State of Maryland, prepared statement of...............    61
    Egan, Dr. William, Acting Director, Office of Vaccines 
      Research and Review, U.S. Food and Drug Administration, 
      prepared statement of......................................    13
    Hoover, Dr. Robert, Director, Epidemiology and Genetics, 
      National Cancer Institute:
        Letter dated January 16, 2004............................    46
        Prepared statement of....................................    26

 
 PREVENTING ANOTHER SV40 TRAGEDY: ARE TODAY'S VACCINE SAFETY PROTOCOLS 
                               EFFECTIVE?

                              ----------                              


                      THURSDAY, NOVEMBER 13, 2003

                  House of Representatives,
         Subcommittee on Human Rights and Wellness,
                            Committee on Government Reform,
                                                    Washington, DC.
    The subcommittee met, pursuant to notice, at 2 p.m., in 
room 2154, Rayburn House Office Building, Hon. Dan Burton 
(chairman of the subcommittee) presiding.
    Present: Representatives Burton and Davis.
    Staff present: Mark Walker, chief of staff; Mindi Walker 
and Brian Fauls, professional staff members; Nick Mutton, press 
secretary; Danielle Perraut, clerk; Richard Butcher, minority 
counsel; and Jean Gosa, minority assistant clerk.
    Mr. Burton. Good afternoon. A quorum being present, the 
Subcommittee on Human Rights and Wellness will come to order 
and I ask unanimous consent that all Members and witnesses' 
written and opening statements be included in the record, and 
without objection so ordered.
    I ask unanimous consent that all articles, exhibits and 
extraneous or tabular material referred to be included in the 
record. Without objection so ordered.
    Today the subcommittee is holding the second in a series of 
hearings examining the aftermath of the tragedy of SV40 
contamination of America's poliovirus vaccine supply in the 
1950's and early 1960's. During the first half of the 20th 
century, polio struck down hundreds of thousands of people 
leaving many paralyzed, and I knew some of those people, some 
in iron lung machines and killing many thousands of others.
    The worst year for the disease in the United States was 
1952, when more than 57,000 polio cases were reported and at 
least 300,000 or 3,000 of those individuals died.
    Following the licensure of the Salk polio vaccine in 1955, 
the incidence of the disease fell dramatically. The disease was 
further reduced by the advent of the Sabin oral polio vaccine 
in 1961. In fact, the last cases of paralytic polio from 
natural poliovirus in the United States were in 1979 and the 
most recent case from outside the United States occurred in 
1993. Today polio has virtually been eliminated from the United 
States and the entire Western Hemisphere, although it remains a 
threat in some developing countries.
    There can be little doubt that the invention of the vaccine 
immunization to protect children and adults from infectious 
diseases, as demonstrated by the success of the anti-polio 
campaign, was one of the greatest public health achievements of 
the 20th century. Nobody takes issue with that. In fact 
immunization as a tool against disease in general has been so 
successful that it has now become almost commonplace to use it 
against even relative minor diseases such as human influenza.
    As a society we have been so confident in the power of 
vaccines that we even create government mandates requiring 
vaccinations be administered before admitting individuals to 
daycare, public schools, college or the military. But what we 
perhaps tend to forget is that immunization is very different 
than administering a medicine to combat an active illness in a 
person. Instead of curing a disease, vaccines instead introduce 
a potentially disease causing agent into an otherwise healthy 
body in order to stimulate an immune response. Thus, there are 
always risks associated with taking any vaccine, and I think 
most people realize that.
    In some cases vaccines have been known to cause the very 
disease they were created to prevent. But the risk can be 
greater still. In the earliest days of the polio vaccine 
production, laboratory tests were not sophisticated enough to 
detect the presence of what became known as Simian Virus 40 
[SV40]. At least 26 other Simian contaminants were detected and 
eliminated. But SV40 slipped past quality control testing 
procedures and into the vaccine pool, potentially infecting 
millions of Americans.
    Soon after its discovery, scientists also learned that SV40 
could cause cancerous tumors in hamsters. So in society's zeal 
to combat one disease we as a society potentially risked 
exposing millions of Americans to another deadly disease.
    As the subcommittee learned at our last SV polio hearing on 
September 10th, we are still trying to uncover the true health 
impact of the SV40 contaminated polio vaccines. For four 
decades Federal Government officials have insisted that there 
is no evidence that SV40 is harmful to humans or that polio 
vaccines produced after 1963 were contaminated with SV40. But 
in recent years dozens of scientific studies have found the 
virus in a steadily increasing number of rare brain bone and 
lung related tumors, the very same malignant cancers that SV40 
caused in lab animals.
    The subcommittee's previous hearings in September examined 
the intense debate raging within the scientific community 
between government scientists who claim that SV40 has had no 
effect on the human population and independent researchers from 
across the globe who believe SV40 is a human carcinogen.
    What the government witnesses testified to at the last 
previous subcommittee hearing raised serious concerns about the 
National Cancer Institute's handling of research related to the 
presence of SV40 in human tumors. The subcommittee subsequently 
asked NCI to provide written clarification regarding several 
issues of concern to our investigation.
    Today we have invited representatives from the NCI to 
reappear before the subcommittee in the hope that they might 
better explain and clarify the apparent inconsistencies in the 
research being supported by the NCI's Division of Cancer 
Epidemiology and Genetics regarding the relationship of SV40 to 
contaminated polio vaccines. In September we also heard from 
Mr. Stanley Kops, a Philadelphia based attorney, regarding 
allegations that at least one polio vaccine manufacturer may 
have knowingly shipped contaminated vaccine lots after the 
FDA's 1961 SV40 screening regime was implemented and that not 
only did said manufacturer not submit vaccine safety tests to 
the FDA as required, but the FDA regulators failed to hold the 
manufacturer responsible for their failure to comply.
    In response to these allegations, the subcommittee has 
invited representatives from the FDA and several vaccine 
manufacturers to present evidence that supports compliance with 
safe manufacturing protocols and the assertion that all polio 
vaccines have been, are and will continue to be SV40 free. 
Regrettably none of the vaccine manufacturing companies chose 
to attend today's hearing. And because of the mandatory nature 
and risk associated with all human vaccines, government health 
agencies have a special duty to exercise the utmost care and 
the approval, administration and post-administration 
surveillance of vaccines.
    The government must always err on the side of caution in 
this worthy public health endeavor and to do anything less is a 
breach of the public trust.
    This subcommittee will continue to pursue the historic 
truth in this matter to either reaffirm or, if necessary, 
rebuild the public's confidence in vaccines specifically and 
our public health service in general.
    I look forward to hearing from our witnesses this 
afternoon. I think my colleague might have some quick questions 
she might like to submit for the record. She is in California 
because we are in recess.
    [The prepared statement of Hon. Dan Burton follows:]

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    Mr. Burton. We have the chairman of the full committee with 
us. Do you have any questions?
    Mr. Tom Davis. No comments.
    Mr. Burton. No comments? Thank you.
    With that, would the witnesses please stand and be sworn?
    Our witnesses today for the record are Dr. William Egan, 
Acting Director of the Office of Vaccines Research and Review, 
U.S. Food and Drug Administration; Dr. Robert Hoover, Director 
of Epidemiology and Biostatistics Program from the Division of 
Cancer Epidemiology and Genetics at the National Cancer 
Institute. And our other panel I think did not respond. So we 
will continue to ask them to be here. And hopefully we will get 
them here in the future.
    [Witnesses sworn.]
    Mr. Burton. Dr. Egan, do you or any of your colleagues have 
an opening statement?
    Mr. Egan. I do, sir.
    Mr. Burton. OK, Dr. Egan, proceed.

  STATEMENTS OF DR. WILLIAM EGAN, ACTING DIRECTOR, OFFICE OF 
       VACCINES RESEARCH AND REVIEW, U.S. FOOD AND DRUG 
 ADMINISTRATION; AND DR. ROBERT HOOVER, DIRECTOR, EPIDEMIOLOGY 
AND GENETICS, NATIONAL CANCER INSTITUTE, ACCOMPANIED BY DR. MAY 
 WONG, PROGRAM DIRECTOR, DIVISION OF CANCER BIOLOGY, NATIONAL 
                        CANCER INSTITUTE

    Mr. Egan. Thank you, Mr. Chairman and members of the 
committee. I am William Egan, Acting Director of Vaccines 
Research and Review at FDA's Center for Biological Evaluation 
and Research. Thank you for the opportunity to testify today.
    The availability of vaccines has been one of the most 
significant public health achievements of the 20th century. 
Many of us can recall the devastation caused by diseases such 
as polio in a time when children survived in iron lungs or 
walked only with the help of leg braces and crutches. The polio 
vaccine and other childhood vaccines have likely saved more 
lives and prevented more illnesses than any other medical 
intervention.
    Unfortunately, a significant number of the early poliovirus 
vaccine lots were contaminated with a previously unknown viral 
agent designated Simian Virus 40 [SV40]. A tissue culture 
procedure to detect SV40 was developed and officials at the 
Public Health Service's Division of Biological Standards 
notified poliovirus vaccine manufacturers that vaccine lots 
would be released for distribution only if test results for 
SV40 were negative. This requirement was also codified in 
Federal regulations.
    Nevertheless, before SV40 was recognized as a problem and 
tests were in place, millions were vaccinated with poliovirus 
vaccines that contained SV40. Since this unfortunate event 4 
decades ago FDA has required that manufacturers perform routine 
testing for poliovirus vaccines to demonstrate the absence of 
SV40.
    Studies in the 1960's showed that SV40 could produce 
certain cancers in newborn hamsters. More recent studies 
reported finding SV40 genes in several types of human tumors. A 
report by the Institute of Medicine, which reviewed this area 
last year, concluded, ``The evidence is inadequate to accept or 
reject the causal relationship between SV40 containing polio 
vaccines and cancers.''
    For several reasons, including: Because some researchers 
questioned whether the tissue culture tests are sufficiently 
sensitive to detect low levels of SV40. FDA researchers 
developed a highly sensitive test based on the preliminary 
chain reaction technology, or PCR technology, to probe for the 
presence of SV40 DNA. When a random sample of oral polio 
vaccines manufactured between 1972 and 1996 were tested by this 
PCR technology, no SV40 DNA was found in any of the 30 vaccine 
model pools or 30 trivalent vaccine samples that were tested. 
FDA published these results in 2000.
    Like all vaccines, the poliovirus vaccine must meet 
stringent standards for safety and effectiveness. Vaccines are 
different from most drugs in several respects, and achieving 
the highest quality and manufacturing is especially challenging 
and critical.
    First, vaccines are often produced from or use living cells 
and organisms as well as complex growth materials derived from 
living sources. Thus, the potential for contamination is higher 
than for most drugs, and quality and purity is carefully 
monitored.
    Second, the production of most vaccines requires growing 
and purifying the immunizing agents from living cells. Growth 
conditions are complex and subtle changes in materials in the 
process itself, in temperature or other conditions can affect 
vaccine safety, effectiveness or both.
    Third, in light of these differences, we utilize the 
mechanism of lot release review to monitor the quality and 
potency of the final vaccine before manufacturers can 
distribute their product.
    Finally, unlike most drugs, which are provided to people to 
treat an existing illness, most vaccines are administered to 
large numbers of healthy people to prevent infectious disease. 
Therefore, even very rare adverse events are a concern and 
generally are not viewed as acceptable if they can be 
prevented.
    With this in mind, FDA's efforts to ensure safety and 
effectiveness begin early in the pre-approval process and 
continue throughout the post-approval process. As a part of 
this process manufacturers must meet the standards established 
in FDA regulations, including current good manufacturing 
practices [CGMPs].
    FDA also uses inspection and surveillance both before and 
after granting a license to help assure conformity with current 
good manufacturing practices and standards in the 
manufacturer's license. Once we license a vaccine, the agency 
continues to monitor product safety and effectiveness.
    FDA may also perform targeted inspections when, for 
example, there are changes to the manufacturing process, 
facility or equipment or other significant events.
    Finally, when safety concerns arise FDA promptly responds 
to address these concerns.
    In closing, Mr. Chairman, although scientists have not 
reached consensus on the potential risks posed by SV40 and 
whether it may
contribute to causing some types of tumors in humans, the one 
thing we all agree on is that poliovirus vaccine has provided 
an enormous public health benefit and has practically 
eradicated this horrible disease.
    I am happy to answer your questions. Thank you.
    [The prepared statement of Mr. Egan follows:]

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    Mr. Burton. Thank you, Dr. Egan.
    Dr. Hoover.
    Dr. Hoover. I am Robert Hoover, a physician epidemiologist, 
currently Director of the Epidemiology and Biostatistics 
Program. Accompanying me today is my colleague, Dr. May Wong, a 
Program Director from NCI's Division of Biology, and we are 
pleased to be here, particularly since NCI has historically 
been and continues to be responsible for a substantial 
proportion of the research into the role of Simian Virus 40 in 
carcinogenesis.
    Both my written and oral comments will be brief since NCI 
did submit substantial testimony last September.
    For several decades the NCI has been supporting research 
directed at understanding SV40 carcinogenesis in several areas. 
Most of this support has been in the area of laboratory studies 
of molecular virology and carcinogenesis, and other efforts 
have been focused in epidemiology.
    In the past decade multiple investigations from independent 
laboratories have identified SV40 in tumor samples, as you 
mentioned, from mesotheliomas, brain tumors, osteosarcomas, and 
non-Hodgkins lymphoma.
    Some research groups have described unique characteristics 
of these SV40 DNA sequences and the detection of viral proteins 
and tumors, both of which argue against the laboratory 
contamination as an explanation. However, when detected, SV40 
appears to be present in very low amounts, which has 
complicated our understanding of what this detection means. 
Additionally, using the same highly sensitive molecular 
techniques, other research groups have not detected SV40 in the 
same tumor types.
    Recognizing some of the difficulties and limitations of 
current approaches, the Institute of Medicine recommended the 
development of and use of sensitive and specific standardized 
techniques for SV40 detection. Meanwhile, those who have found 
evidence of SV40 infection in human tumors have also begun the 
more difficult task of attempting to discern whether this 
infection actually plays a role in the development of these 
cancers.
    The other line of scientific inquiry is provided by 
epidemiologic studies which examine the relationship between 
SV40 and exposure or infection and the risk of cancer in human 
populations. To date most of these studies have relied on large 
population-based cancer registries, such as NCI's SEER program 
or the Danish Cancer Registry, to examine the incidence of 
cancer in people who had a high probability of receiving SV40 
contaminated polio vaccine as children.
    Up through the 1990's these studies have failed to detect 
evidence of an increased risk of those cancers suggested by the 
molecular biology work, indicating that it is unlikely that 
there is an epidemic of these cancers that might be attributed 
to SV40 contaminated polio vaccine. Nonetheless, as pointed out 
by the Institute of Medicine, it has not been possible in these 
studies to be certain which individual persons were actually 
infected through receipt of contaminated vaccines.
    Thus, to answer the question of whether there is any 
increased risk and, if so, of what magnitude of cancer from 
such exposure will require more epidemiologic research, using 
specific data on exposure for individuals. Some attempts have 
been made to do this by testing for antibodies to SV40 and 
cancer cases and controls. To date these studies have not 
indicated an increased risk for those with such antibodies. 
However, because of limitations in our current technologies, 
these studies cannot be considered definitive. Here again the 
development of accurate tests for SV40 infection, in this 
instance serologic tests called for by the Institute of 
Medicine, will facilitate future epidemiologic research on the 
question of whether SV40 causes cancer.
    In summary, we agree with the Institute of Medicine that 
the evidence is inadequate to accept or reject a causal 
relationship between SV40 containing polio vaccines and cancer. 
At the moment there is no consensus in the scientific community 
on whether SV40 causes cancer in humans. When working at the 
cutting edge of science this situation is neither unusual nor 
surprising. Different disciplines and different groups using a 
variety of approaches and techniques frequently come up with 
contrasting results. Indeed, it is in pursuing the scientific 
answers for such differences that our knowledge is enhanced and 
we are able to move the science forward.
    At NCI we are committed to the support and conduct of the 
scientific research that will lead to the needed answers. We 
are particularly optimistic that improved tools for the 
detection of SV40 infection can be developed and thus allow the 
power of molecular virology to be combined with the rigor of 
the epidemiologic method in addressing these important 
questions.
    And I would be happy to take your questions.
    [The prepared statement of Dr. Hoover follows:]

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    Mr. Burton. Thank you very much. Dr. May Wong, do you have 
a comment you would like to make?
    Dr. Wong. No.
    Mr. Burton. OK. Thank you. If you would like to answer--
help answer these questions, we can move that mic back and 
forth.
    We have had a number of parents before my committee over 
the last 4 or 5 years whose children had medulla blastoma and 
died, and many of those feel that SV40 could have been the 
culprit, could have been passed on through the parent to the 
child. We had one case where the father, I think, ultimately 
died as well of cancer. So those things are kind of heart 
rending. That's one of the reasons why we are very aggressive 
in trying to get the answers to these questions.
    We also have a former employee of one of our government 
research agencies that provided an awful lot of information on 
this. I am not at liberty to give his name out right now. But 
as you read, I am sure, your agency as you went through the 
questions in our letter knew that didn't come out of my brain. 
And so we are very anxious to get accurate answers and I know 
you want to be as accurate as possible. We don't have a lot of 
media here today or anything, but I hope that we will be able 
to get as many accurate answers as possible because this is an 
issue that, like some of the others we have raised, is not 
going to go away, you know, as long as I can hold these 
hearings.
    Dr. Hoover, you are not specifically an expert on SV40, is 
that correct?
    Dr. Hoover. That is correct.
    Mr. Burton. What is your area of expertise?
    Dr. Hoover. Epidemiologic methods. I've studied a variety 
of tumors and exposures over my career, applying the 
epidemiologic method to that.
    Mr. Burton. You're familiar with the subcommittee's recent 
exchange and correspondence with the NCI regarding the SV40 
research, is that correct?
    Dr. Hoover. Yes, I am.
    Mr. Burton. Do you have any idea why the National Cancer 
Institute did not send somebody who has expertise in SV40?
    Dr. Hoover. Well, I'm responsible for the program that does 
viral epidemiology. I'm the program director and that branch is 
under my direction, so----
    Mr. Burton. Yes, sir. Do you have under your jurisdiction 
people who have expertise in SV40?
    Dr. Hoover. Correct.
    Mr. Burton. Why didn't we have one of those come as well?
    Dr. Hoover. We sent one last time when it looked like you 
were asking for a more global view, or whatever, of the 
science.
    Mr. Burton. Well, we may want to ask them to come back in 
the future if we don't get, you know, all the questions 
answered.
    In its November 7, 2003 response to this subcommittee the 
National Cancer Institute claims that the NCI fact sheet on 
SV40 presents a balanced view of the current research 
surrounding the connection between SV40 and human cancer. For 
example, the NCI fact sheet states that the Institute of 
Medicine issued a report in October 2002 which concluded that 
the scientific evidence was insufficient, I think you mentioned 
that today, to prove or disprove the theory that exposure to 
poliovirus vaccine contaminated with SV40 resulted in cancer in 
humans. As I said, I think you stated that a while ago.
    Do you agree that the fact sheet represents or presents a 
balanced view of the current research surrounding the 
connection between SV40 and human cancer?
    Dr. Hoover. Well, we thought that since it gave evidence 
and pointed out the conflicts and the only conclusion reached 
didn't reach its own independent conclusion--the only 
conclusion reached was the Institute of Medicine's conclusion 
with a link to the Institute of Medicine's Web site--we thought 
it was reasonably balanced, but as Dr. Von Eschenbach wrote to 
you and as you're probably aware from the controversy over our 
fact sheet on abortion and breast cancer in the past year, 
whenever anyone asks us to review a fact sheet, any responsible 
body or person, we do it, and Dr. Von Eschenbach has asked that 
fact sheet be reviewed for its balance.
    Mr. Burton. So what you're saying is that you think it is a 
balanced view?
    Dr. Hoover. I thought it was a reasonable view, but it 
could stand to be reviewed again.
    Mr. Burton. The NCI fact sheet was last reviewed in April 
2003, well after the IOM report was issued in October 2002. 
That's correct, isn't it?
    Dr. Hoover. That's correct.
    Mr. Burton. Is it true that the IOM report concluded that 
the scientific evidence was inadequate to prove or disprove the 
theory because the epidemiological studies like those conducted 
by the NCI were too flawed to be scientifically useful?
    Dr. Hoover. That was part of their--the reason for their 
conclusion, yes.
    Mr. Burton. Is it true that the IOM report concludes that 
the biological evidence is strong that SV40 is a transforming 
or cancer causing virus?
    Dr. Hoover. That is correct.
    Mr. Burton. Is it true that the IOM report concludes that 
the biological evidence is of moderate strength that SV40 
exposure could lead to cancer in humans under natural 
conditions?
    Dr. Hoover. That is correct.
    Mr. Burton. Is it true that the IOM report concludes that 
the biological evidence is of moderate strength that SV40 
exposure from the polio vaccines is related to SV40 infection 
in humans?
    Dr. Hoover. That is correct.
    Mr. Burton. Why does the NCI Web site omit these 
conclusions from its discussion of the IOM report?
    Dr. Hoover. The Web site is intended to give information to 
the general public about issues concerning cancer, and the 
bottom line issue in SV40 is does it cause cancer in human 
populations. And the bottom line conclusion of the Institute of 
Medicine's report was it is unknown at this point, the science 
is not adequate to either rule it in or rule it out. And that 
was what we tried to convey and presented some of the 
contrasting information on either side. We did also provide a 
link to the IOM site itself on our site so that people could go 
directly to it.
    Mr. Burton. The American people would like to have, 
especially in the Internet age, as much information as possible 
when they're talking about vaccinations of their children and 
themselves, and so you omit this from your Web site. And we had 
a similar answer from the NCI, not the NCI but the FDA, on 
whether or not the mercury in the vaccinations which has a 
cumulative effect in the body, in the brain, could cause 
neurological problems such as autism in children and possibly 
contributed to Alzheimer's in adults. And I can't understand 
why they don't put on the Web sites, you know, that this is one 
of the things that has not been proven or disproven so that 
people can at least have that information that there's a 
possibility that cancer is caused by SV40, and that there's a 
possibility, very strong, and from scientists around the world, 
on these vaccinations that I talked about from FDA that contain 
mercury that they could cause neurological problems. And I 
can't understand why we don't put on the Web sites that kind of 
information.
    Dr. Hoover. Well, I think we did try to indicate that there 
is the possibility they could cause cancer. That was the whole 
reason for the Web site and the presentation of some of the 
evidence that has been produced to raise that question and 
included the conclusion of the IOM report which indicated that 
it couldn't rule it out, and also the link to the IOM Web site 
for those who wanted more detailed information so they could 
click and go there.
    But as I mentioned, we review these all the time when 
someone thinks that they don't reflect the appropriate balance 
or the appropriate summary, and we will review them and I will 
certainly include in that your recommendation that the other 
conclusions of the IOM report be considered for inclusion.
    Mr. Burton. Thank you. I appreciate that. You know, in the 
questions you answered just a minute ago, those epidemiological 
studies that were conducted by NCI, according to the IOM 
report, were too flawed to be scientifically useful and you 
said that's true, that is what the IOM report----
    Dr. Hoover. Too flawed to be scientifically useful to 
determine whether or not SV40 causes cancer in humans or not. 
They are useful, those kinds of studies are useful to frame the 
risk, if there is one. And that's why I mentioned in my written 
and my oral testimony that it--by not seeing any impact on the 
rates in the general population among those age groups that 
were most likely to have received the contaminated vaccine does 
rule out an epidemic, the classic ones we have seen for tobacco 
related diseases, estrogen and endometrial cancer, AIDS, AIDS 
virus and Kaposi's sarcoma. All of those show up because they 
are so widespread and they are so strong. They all show up 
pretty readily in these kinds of epidemiologic investigations. 
So we didn't see that.
    It does not, however, give you the kind of power that other 
kinds of epidemiology do, when you can actually identify people 
who have been infected and people who haven't and look at their 
cancer experience or look at people who have cancer and 
evidence of infection in them and people that don't. Those are 
so-called analytic epidemiologic studies, much more powerful. 
Those are the ones that people use to support or not support 
carcinogenesis for a particular agent. Those actually, we agree 
with the Institute of Medicine, those can't be done to the best 
of our abilities at this point because the measurement 
techniques are not good enough to do that, to validly identify 
everybody who got infected and those that didn't. But we 
actually are, as I mentioned, very enthusiastic that with 
modern molecular technology and all of the research that's 
going on that we will actually get those tools in the very near 
future and be able to do something about it.
    Mr. Burton. That's good. The epidemic of various forms of 
cancer that we see in the United States would lead one to 
believe that there's some major causes and since SV40 was shown 
to be a carcinogenic in laboratory hamsters, it seems that 
you'd want to make sure that people had some idea. I'm not 
concerned so much about the liability that the pharmaceutical 
companies might have unknowingly incurred because we protect 
them legislatively in most cases. But the American people I 
just think need as much information as possible so that they 
can deal with these problems.
    Dr. Hoover. I agree.
    Mr. Burton. You know I've had people before the committee 
who almost blame themselves for their children's brain cancers 
or their wife's breast cancer. And of course my wife, as you 
know, died from cancers. And it would mentally relieve them of 
some of this if they thought that there was a cause that you 
could point to.
    Dr. Hoover. I agree with you thoroughly, and I believe that 
we need to focus on identifying causes and we need to focus on 
this particular one. When I have been taking care of patients, 
the most difficult time I had was dealing with children who had 
cancer. Children aren't supposed to get cancers, and there's no 
more driving force in my life than those observations and those 
feelings to try and identify causes of cancer.
    Mr. Burton. Well, I appreciate that and I do hope that we 
will be able to get more information on the Web sites.
    Also from the November 7, 2003 response to the 
subcommittee, NCI states that in light of a body of evidence 
which demonstrates that there may be some SV40 in some rare 
human tumors, NCI will review the fact sheet. Is that an 
admission by NCI that SV40 is in fact present in human tumors?
    Dr. Hoover. There is certainly a large body of evidence out 
there indicating that it is.
    Mr. Burton. Well, if so, what evidence has come to light 
since April that convinced the NCI of that fact?
    Dr. Hoover. I think NCI has always been convinced that 
there's a large body of evidence and certainly growing all the 
time that there is SV40. We support most of that research 
actually and--of the people who have identified it. There are 
problems interpreting it because we get this wide range of 
estimates from 3 percent to 90 percent and not everybody that 
looks for it can find it. But those are probably not to be 
unexpected in using new technologies and sort of working, as I 
mentioned, working at the cutting edge. I think we can, with 
time and with more people getting involved in the field, sort 
out those issues and those concerns.
    Mr. Burton. What explanation or theory does the NCI offer 
for SV40 being present in human tumors? I mean, how did it get 
in these tumors?
    Dr. Hoover. That's a very good question, and I don't think 
we know. The only relevant exposures that we know of or the 
only exposures we know of happening in this population has been 
through contaminated vaccine. There are places in the world 
where people have pretty close contact with the monkeys that 
are infected with the virus, so perhaps in those locales they 
can get it in an epizootic kind of sense. But----
    Mr. Burton. Here in the United States we don't have a lot 
of people coming in contact with monkeys.
    Dr. Hoover. No, we don't. If there are, I think as the 
Institute of Medicine pointed out, once the techniques for 
measurement get better, they actually think one of the first 
things we should do is go back to tumors that occurred in the 
40's and early 50's and test them to see if there's evidence of 
SV40 in them.
    Mr. Burton. Before the vaccines were used.
    Dr. Hoover. Before the vaccines.
    Mr. Burton. Well, was the SV40--was monkey tissue used in 
other vaccines?
    Dr. Hoover. Not that I know of. This was their attempt to 
see----
    Mr. Burton. OK. Was SV40 found in other areas other than 
the monkeys and the vaccine that came from the monkey tissues?
    Dr. Hoover. Right now the only host that I know of--I'm not 
an expert in this area--is the monkeys. But we don't--there's a 
lot we don't know about infectious diseases and whether there 
might be another source of SV40 infection out there that we 
don't know about now I think is what the Institute of Medicine 
was concerned that aspect be pursued too, that perhaps this 
virus or a very, very highly related virus molecularly may 
actually come from somewhere else as well.
    Mr. Burton. Come on. You don't believe that. I mean, you're 
a very--I'm sure you're a very dedicated scientist and doctor. 
But if it's only in the monkey and the monkey tissue is used to 
make the vaccine and you know of no other place that SV40 comes 
from and people in the United States have SV40 and cancerous 
tumors, deductive reasoning would lead you to believe that it 
came from the vaccination unless somebody's got a bunch of 
monkeys running around their house.
    Dr. Hoover. That seems to be the most likely explanation. 
But we also agreed with the Institute of Medicine report that 
indicated that we should make sure of that by looking at 
tissues from people who couldn't have been exposed to that--by 
that route to see whether I agree with that.
    Mr. Burton. So there really is no explanation from the NCI 
on SV40 being in humans?
    Dr. Hoover. Other than from contaminated polio vaccines and 
in other parts of the world the contact with monkeys, no, we 
don't have another.
    Mr. Burton. Well, you know as bright as everybody is over 
there I would think that they'd come to the conclusion before 
going back to pre-1950 vaccinations and other things that the 
SV40 was the culprit. But----
    Dr. Hoover. Me personally, and a lot of us, have been 
burned too many times by thinking we know something without the 
data to prove it and so we are generally in the business of 
going out and finding the data to demonstrate that. And I think 
that's what the Institute of Medicine wanted to do.
    Mr. Burton. Well, parents of kids who died from medulla 
blastoma, I think would like to know if there's a strong 
possibility that the SV40 was the cause. And if there's no 
other avenue that we know of, I think the parents should at 
least have that kind of information. It would allay some of the 
pain that they've gone through. I mean, you know, to say well, 
we don't know, when you know the only source that's known to 
man is the monkey and the virus that was in the--and the polio 
vaccine, to just keep saying we don't know, I think is--I think 
maybe you should reframe that and say it's probable, it's 
probable that the vaccine caused it. You've got an out there. 
But----
    Dr. Hoover. Well, I think it's probable that SV40 
contamination of vaccine is responsible for infection in the 
U.S. population. The significance of the SV40 in the tumors has 
yet to be determined and I'm sure all the molecular scientists 
who are working night and day on that issue, the issue of is 
that because they get to find the virus in the tumors is the 
virus related to that tumor, that's another question and that 
is the hardest question of all to answer.
    Mr. Burton. You know, I would think there would be a major, 
major scientific research project.
    Dr. Hoover. It is.
    Mr. Burton. Well, I hope so, because my gosh, all the 
people that are dying of cancer, my wife, people who are 
suffering from breast cancer, medulla blastoma, all these 
people, all these various kinds of cancer that 25 years ago you 
never saw or very rarely saw, you'd think that if you thought 
the culprit might be SV40 that all hell would break loose to 
get the research done so that we might stop it in the future if 
we can or find a cure that might negate SV40 from killing 
somebody.
    Dr. Hoover. I think that's why, I know, Dr. Wong's program 
is funding probably about $9 million worth of research a year 
in SV40 molecular virology.
    Mr. Burton. Nine million?
    Dr. Hoover. Yes.
    Mr. Burton. How much money does our health agency get over 
there? NCI, how much do you get over there?
    Dr. Hoover. You'll have to tell me. I know what our own 
budget is. Several billion.
    Mr. Burton. Several billion?
    Dr. Hoover. Right.
    Mr. Burton. Several billion, and the culprit for cancer in 
many cases may be SV40 and you're dedicating $9 million to this 
project?
    Dr. Hoover. There are very many candidates for what may 
cause cancer in human population, an extremely large number, 
and we try to keep a balanced portfolio to investigate 
everything for which there is a likelihood.
    Mr. Burton. I know, Dr. Hoover, but here you know probably 
this is, and very strongly possibly, this could be a culprit 
because you've found it in cancerous tumors in human beings and 
it seems to me that you know it was in laboratory animals. You 
know it's showing up in human cancers. It seems that this would 
be a top priority and would get more money than $9 million out 
of a multi-billion dollar appropriation.
    Dr. Hoover. Well, I'm not the one that makes those 
decisions, but the people who send in grants do. One of the 
problems in making headway in any area where you think you have 
something that's worth investigating is do you have the tools 
available to you to make--to get the answer. And that's what 
the grant mechanism is supposed to determine when people send 
in grants and tell their ideas to the study section. People 
decide, OK, who's got the best tools to answer this question? I 
think we need better tools in the area of viral carcinogens.
    Mr. Burton. Could I ask your associate, Dr. May Wong, a 
question?
    Dr. Hoover. Sure.
    Mr. Burton. And this may put you on the spot. Put the mic 
real close to you. This may put you on the spot and I don't 
want to do that. I mean we're here today not to beat up on 
anybody. I have been accused of that in the past. I see you 
smiling a little bit there. What we want to do is get the facts 
out and try to do something constructive about the possible 
cause of cancer.
    Would additional funding be helpful?
    Dr. Wong. Yeah. I really agree with you. I think we do need 
additional research funds. Unfortunately, I guess under the 
current fiscal environment, you know, we're obligated with so 
many different areas of research not just on SV40, but other 
things, but in terms of SV40, yes, I do agree, I think maybe 
you or the Congress can set aside or appropriate, you know.
    Mr. Burton. You mean dedicate a certain amount of money?
    Dr. Wong. Dedicate a certain amount of funds.
    Mr. Burton. How much money do you think--and I know this is 
a tough one. How much money do you think would be necessary to 
do--you don't want to do overkill, but an adequate job of 
investigating this?
    Dr. Wong. No. No. We have been really actually thinking 
about this problem quite a long time and I think what is also 
lacking is that cross-discipline area, you know, the 
collaborations between, like, from our part is mostly the 
molecular virologists, molecular biologists. We need to really 
collaborate and work with other parts of disciplines such as 
epidemiologists. Currently that's not being really done. That's 
why we have a lot of confusion in the area.
    Mr. Burton. Well, what I would like to have from you----
    Dr. Wong. Is a dollar figure?
    Mr. Burton. No, no, not just a dollar figure. And Dr. 
Hoover, could you give this subcommittee a recommendation on 
how you could come to a conclusion, if possible, quicker? I 
mean, she's saying that there needs to be a cross-pollination 
between researchers in order to find out, you know, if this is 
a culprit and ultimately lead to maybe some kind of a cure or, 
like AIDS, maybe a way to prolong life without stopping the 
AIDS. You see what I mean? And if we could get from you some 
kind of a statement that would say--tell us how that cross-
pollination should take place, in addition to, and in the 
letter, or recommendation, in addition to the amount of money 
you think is necessary for additional research, I would be very 
happy to go to the appropriators and to the authorizing 
committees and write a letter directly to your superiors at the 
agency saying this is what our subcommittee found should be 
done. I don't want to jeopardize you by going to your superiors 
and saying, hey, you guys aren't doing your job and here's 
what's recommended, but I think it would be helpful if we in 
Congress knew what your recommendation is so we could convey 
that to the authorizers, appropriators and the people at the 
top of the agencies. Could you do that for us?
    Dr. Wong. Yeah, I think we can go back and discuss amongst 
each other, you know, what is the best approach and then get 
back with you.
    Mr. Burton. We'd like to do that because then maybe we can 
help you get that approach. We'd like to do that. OK.
    What explanation or theory does the NCI offer for SV40--
well, you've already answered that question. You don't really 
have an answer yet, although you think it's likely that it's 
from the SV40.
    Who are the experts who will review this fact sheet for 
accuracy and balance?
    Dr. Hoover. That's up to Dr. von Eschenbach. The fact 
sheets are run out of his office, and it's done in different 
ways for different times. For the abortion and breast cancer 
fact sheet it ended up being an entire conference of experts 
from all over the world. That's rarely needed at that level to 
respond. But I'm sure he will make a wise decision about who 
needs to----
    Mr. Burton. Well, the experts have been picked, have they 
not, to review that fact sheet?
    Dr. Hoover. I don't know.
    Mr. Burton. Well, could we make a request here today, and 
I'd like to put that in writing, that we have a list of the 
experts that are reviewing that fact sheet for accuracy and 
balance?
    Dr. Hoover. Sure.
    Mr. Burton. But you don't know right now?
    Dr. Hoover. I don't know.
    Mr. Burton. What are the NCI procedures for public and 
outside comment on the fact sheet?
    Dr. Hoover. Well, as I mentioned, people--most of the fact 
sheets that involve--I shouldn't say most. Many of the fact 
sheets, when they're developed, are also passed through our 
consumer panel, the cancer advocacy groups that are represented 
at NCI at the initial stage. Second, when someone has a concern 
about our fact sheet, and they e-mail us or they phone us, 
almost always if it's a responsible question or a responsible 
concern, it ends up in some sort of a review at some level.
    Mr. Burton. One of the principal studies cited by NCI 
refuting the contention that SV40 is in fact present in human 
cancer tumors was a multi-laboratory study conducted by Dr. 
Strickler and Dr. Shaw and published in 2001. In 2002, excerpts 
from a sworn deposition by Dr. Shaw were published in the 
journal Anti-Cancer Research. Those excerpts indicated that Dr. 
Shaw was under contract from several pharmaceutical companies 
to assist them in litigation against patients with SV40 
positive tumors. Dr. Strickler and Dr. Shaw published a 
rebuttal in the journal Anti-Cancer Research in 2003. The 
subcommittee understands that several NCI scientists sit on the 
editorial board of Anti-Cancer Research. When we asked about 
their apparent conflict of interest in our letter to NCI dated 
October 10, 2003, NCI replied via a footnote that they were 
unaware of Dr. Shaw's purported relationship with the 
pharmaceutical industry until we mentioned the issue in our 
letter.
    When Dr. Shaw or any scientists signs a contract with NCI 
to conduct research either as grantee or subgrantee, are they 
required to disclose their conflicts of interest?
    Dr. Hoover. I think the--testifying as an expert witness, I 
don't believe it is asked of grantees or contractees, but I 
could stand to be corrected if----
    Mr. Burton. You know, that's something that needs to be 
corrected.
    Dr. Hoover. No, no, it's not. It is not.
    Mr. Burton. You know that needs to be changed. You know we 
had the advisory committees that approve or recommend to the 
FDA the approval of a vaccination to be put in the market. We 
investigated and found that there was at least one incident, I 
believe several, where people on those advisory committees had 
stock in companies that were making the very same product. And 
that is definitely going to, in many cases, skew somebody's 
judgment and is a conflict of interest.
    And the thing that bothers me about--I think it was a 
retrovirus. What was that--RotaShield, the RotaShield 
vaccination. One of the people, I think it might have been even 
the chairman of the advisory committee, had stock in a company 
that was going to make that RotaShield vaccine, at least one of 
them, and they approved it even though a lot of the members 
weren't there. And the FDA went ahead with it. And the FDA 
always--we have found no cases where the FDA doesn't approve 
the recommendation of the advisory panels, and they put it in 
the market. At least one child died and several others were 
injured severely by the vaccination and it was withdrawn 11 
months later. Now, that is tragic. If there's a conflict of 
interest in any of these areas, it must be known because if 
not, you're liable to put things into the marketplace and into 
people's bodies simply because of money, and that shouldn't 
happen.
    Dr. Hoover. That's not my area of expertise, but I have 
just two comments to make. As you know, if you work for the 
government, you have to fill out all those forms about what 
stocks you hold and those rules have never been applied to 
grantees. My guess is that if you suggest applying those rules 
to grantees that there would be a very large outcry from the 
academic community that this is something that they don't 
believe is necessary. But if that's what you want to suggest, I 
can----
    Mr. Burton. Well, let me interrupt you just a second, Dr. 
Hoover, and I apologize for this. Dr. Shaw, he gets paid to 
testify, and his testimony carries a lot of weight because of 
his expertise, and he had a conflict of interest. Don't you 
think that's something that could skew a report that's very, 
very important?
    Dr. Hoover. I personally don't. I'm sure that----
    Mr. Burton. You don't think so?
    Dr. Hoover. I'm sure that in these same cases the people 
who have found SV40 in tumors have also probably testified as 
expert witnesses because they are experts. And I actually don't 
believe that influences the science. One of the great things 
about working in the scientific field is that nothing is ever 
done based on one person's study or one person's research. The 
sine qua non in science is that it has to be replicated and it 
has to be replicated multiple times by different people working 
in different circumstances. So it is usually readily apparent 
if someone found something that cannot be replicated, came to a 
finding that can't be supported, it becomes readily apparent 
and it doesn't get disseminated. So I think there's actually--
the way science operates, it operates in a way which 
irregardless of the personalities involved, guards against----
    Mr. Burton. Dr. Hoover, you're a very bright fellow. 
There's an old saying. Money talks and baloney walks. I'm being 
nice about that comment. The RotaShield virus vaccine I talked 
about, it was evident, and there were--the man on the advisory 
committee who had a conflict of interest stood to make a lot of 
money out of that.
    Dr. Hoover. It's possible that being on an advisory 
committee--and I know that FDA advisory committees require 
people to list conflicts of interest. I'm talking about doing 
research.
    Mr. Burton. OK. Well, even doing research----
    Dr. Hoover. Doing and publishing your research.
    Mr. Burton. I think it's important that there be 
disclosure, and I don't know that would be a discouragement. 
You might have to get another expert or scientist who doesn't 
have a conflict in that general area. But it seems to me when 
you're talking about something as important as SV40 and the way 
our scientific community and our agencies view it, that you'd 
want to make sure that the person doesn't have a skewed point 
of view because of financial interests.
    How did NCI not know about this conflict until our letter 
dated October 10 if several NCI scientists sit on the editorial 
board of the Anti-Cancer Research? Because it isn't required?
    Dr. Hoover. That's correct.
    Mr. Burton. OK. So just simply because it isn't required?
    Dr. Hoover. Right.
    Mr. Burton. What is NCI planning to do to address this 
issue in the future, or is it NCI's position that such 
conflicts of interest are not serious? I think you've answered 
that. You don't think it's a serious problem?
    Dr. Hoover. I don't think this is a serious problem. I 
believe that we can have conflicts in science that are most 
often the results of the science and not because of 
incompetence or venality on the part of the investigators.
    Mr. Burton. Or money?
    Dr. Hoover. Or money, that the weight of the scientific 
evidence is based on multiple people finding the same thing, 
and the consistency of the evidence, and we have plenty of 
safeguards. I think there's--if we ruled out everybody who gave 
expert testimony in some of these tort cases, my guess is--and 
we ruled out giving money to them from the Cancer Institute of 
Research that we would lose many of the most valuable 
researchers to both sides of the controversy, and I think that 
would be a shame.
    Mr. Burton. The Strickler-Shaw study was originally 
submitted to Anti-Cancer Research, one of the preeminent cancer 
journals, for publication but was rejected; is that correct?
    Dr. Hoover. I don't know. That's probably true. It could be 
true, I don't know.
    Mr. Burton. Well, it was correct. It is correct. Can you 
explain why a journal would reject a paper of that type?
    Dr. Hoover. A whole variety of reasons. I think I've--
probably half the papers I've published have been rejected by 
one first. You usually shoot high to get a paper into a very 
high visibility journal because it's good for your career. 
They're the most competitive journals or the ones that can 
choose from many things and they may make a priority decision 
that this isn't of high enough interest for them to publish in 
their journal.
    Mr. Burton. Well, we also understand that five coauthors of 
the study disassociated themselves from the paper's 
conclusions, including Dr. Janet Butel, who actually wrote the 
last version of the manuscript. Is that correct?
    Dr. Hoover. Yes, it is.
    Mr. Burton. Is it common for coauthors to disassociate 
themselves from their own work?
    Dr. Hoover. No, it is not.
    Mr. Burton. Well, why is that? It's not common?
    Dr. Hoover. It's not common.
    Mr. Burton. Given the controversy surrounding this study, 
is it appropriate for the NCI to continue to use this material 
as the basis for the assertion that SV40 is not present in 
human tumors?
    Dr. Hoover. I don't think we make that assertion. We say 
that study is one that didn't find it; and there's, as you 
mention, a whole body of studies out there that don't.
    Mr. Burton. Are there other studies that say that SV40 was 
not found in human tumors?
    Dr. Hoover. There are maybe 10 to 13 that don't find them 
in some of the identified tumors. But for that particular 
article they submitted a letter to the editor pointing out 
their concerns, and Dr. Strickler responded. That is in the--
published in the journal; and I believe that evidence makes it 
possible for people to read the article, read the concern, read 
the response, and come to their own conclusion of how 
scientists can come to their own conclusion about what it is, 
about whether the study would be credible and worth 
considering.
    Mr. Burton. The October 2002, Institute of Medicine report 
on SV40 contamination of the polio vaccine recommended that the 
Federal Government develop sensitive and specific serologic 
tests for SV40. Since it's now been over a year ago that the 
IOM issued the report, what steps has the NCI taken to 
implement this recommendation?
    Dr. Hoover. I do know there are people who are attempting 
to develop new serologic tests using viruslike particles and 
that Hopkins is one, and you probably know more about it than 
I?
    Ms. Wong. Gee, Denise Galloway at Seattle and Bob Garcia, 
in collaboration with the city, who's with Dr. Shah's group at 
Hopkins, they are trying to develop a serological assay, but, 
unfortunately, I think there are problems. They could not 
detect anything. One possibility is that SV40 cross-reacts with 
these human poliomaviruses, J, C, B and K, so that might mask 
the detection. So I know several groups are attempting to 
further develop this or use other immunological assays to try 
to see if they can develop a more sensitive way to detect SV40.
    Mr. Burton. So the NCI is taking steps right now to 
implement that recommendation?
    Ms. Wong. Well, unfortunately----
    Mr. Burton. No, no.
    Ms. Wong. Oh, OK.
    Mr. Burton. Is the NCI taking steps to implement that 
recommendation?
    Ms. Wong. Well, we're funding it indirectly, let's say. 
We're not directly funding that work.
    Mr. Burton. Why not?
    Ms. Wong. Well, because--one reason is they haven't come in 
with a proposal to request for money. That's usually the normal 
route of how we fund applications, is people have this idea, 
they come in, it gets peer-reviewed, and if this did well and 
was with----
    Mr. Burton. Well, pardon me for interrupting----
    Ms. Wong. Right.
    Mr. Burton [continuing]. But what we're trying to find out 
is what steps the NCI has taken to implement that 
recommendation. Have they let people know this is something 
that they're interested in?
    Ms. Wong. Yes.
    Mr. Burton. Because the IOM in October of last year 
indicated, over a year ago, that those tests should be taken.
    Ms. Wong. Well, at least, I know, through communications, 
not through any funding mechanism, we have our grantee--so-
called extramural investigators are aware that this is what 
needs to be done in the community and this is a high priority. 
Unfortunately, we are not currently funding any of those 
studies.
    Mr. Burton. Well, it's been reported over a year ago, and 
it doesn't appear that there's real concern over there if over 
a year later they still haven't taken steps to implement the 
report.
    Dr. Hoover. I think what May was trying to say was that 
when august bodies make recommendations people that have good 
ideas in this area usually immediately submit grants, because 
they know--in fact, they reference the recommendation; and 
study sections who review that take that quite seriously 
because this is recommended in the field. And people who are 
out there, who are--who do this for a living--so, usually, when 
you don't get a sudden flood of good grant requests, it means 
that no one actually has a very good idea right now about how 
to do it better.
    I suspect what's going to happen--I suspect that with all 
the improvement in molecular science that's going on weekly, if 
not daily, that somebody will come across a method that they 
think they can apply to this; and I would guess that the grant 
would come in almost immediately.
    Mr. Burton. Do you publish on the Internet or through 
medical journals that this is something that you want to see 
NCI do? I just wonder how many researchers even know that this 
is something----
    Ms. Wong. Well, last year I had published a workshop 
report. In that workshop report one specific topic was on SV40, 
and we did recommend one for future studies in development was 
to develop more sensitive assays, and that could be in the 
workshop report. But, other than that, I don't think there's 
any.
    Mr. Burton. Do you think we also need an agreement on 
methodologies between intramural and extramural research so 
when examining the link between cancer and SV40 all the 
researchers and scientists will accept the findings once 
they're completed?
    Dr. Hoover. I think that the ideal would be to find methods 
that are robust enough that everyone can use them and everyone 
can get the same answer when they use them. That's been the 
history of when we advance.
    Cervical cancer field's a good example. Back in the early 
1980's, it was Dr. zur Hausen and others developed papilloma 
virus in the vast majority of cervical cancers, maybe 80, 90 
percent. The next question was, well, how does that compare in 
different populations and how does it compare to people who 
don't have cervical cancer?
    The first study that was done was to look at the--at 
something called block analysis, which was considered the gold 
standard, and looked at it in multiple labs and found there was 
no consistency--people couldn't replicate each other very 
well--and probably explained why some of the studies in 
humans--in human populations were giving conflicting results.
    Shortly thereafter, two new assays were developed, PCR-
based and a hybrid-capture-based assay, that, when used by 
multiple people, everybody got the same answer; and it 
catapulted that research forward. So now we, in fact, know that 
papilloma virus is the major cause of certain invasive cervical 
cancers. So as the field advances and as techniques get better 
what we try to find is a technique that everyone can use and 
end up getting the same answer and, hopefully, that's the right 
answer, that's the valid answer, as well.
    Mr. Burton. So I presume that's a yes.
    OK. The October 2002, Institute of Medicine report on SV40 
contamination of the polio vaccine recommended that the Federal 
Government develop sensitive and specific serologic tests for 
SV40. Since it's now been over a year ago that the IOM--oh, 
excuse me. I'm getting punchy here. The IOM report also 
recommended the development and use of sensitive and specific 
standardized techniques for SV40 detection. What steps has the 
NCI taken to implement that recommendation?
    Dr. Hoover. Once again, that would probably be done through 
the molecular virology community; and I'm unaware of what new 
efforts are going on.
    Mr. Burton. If you don't have that answer, can you submit 
that to me?
    Ms. Wong. Yeah.
    Mr. Burton. I mean, can you find that out?
    Ms. Wong. Yeah, we can get back with you later.
    Mr. Burton. We want to find out if there are sensitive and 
specific standardized techniques for detection, and I'd like to 
know if they've implemented that recommendation, and, if not, 
why they haven't and when they intend to do so. Can we get that 
information from you?
    Dr. Hoover. Sure can.
    Mr. Burton. Thank you.
    [The information referred to follows:]

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    Mr. Burton. The IOM report further recommended that no 
additional epidemiological studies be performed because of the 
uncertainty of knowing which individuals were exposed to SV40 
made interpretation of the data problematic.
    The IOM report was issued in October 2002. Yet, in 2003, 
the NCI released a new epidemiological study based on data from 
Denmark. Was this study begun before or after the IOM released 
its recommendation, the Denmark study?
    Dr. Hoover. Yeah, that was certainly begun before; and that 
was actually presented to the IOM committee. They asked for 
people to come who had unpublished information; and we 
presented that plus two others, actually, another one that was 
published in December as well. So they had that body of 
knowledge in hand when they made their recommendation.
    Mr. Burton. Can you confirm that NCI has no other 
epidemiologic studies currently in the works?
    Dr. Hoover. We have none of the kind that the Institute of 
Medicine was concerned about, following populations where you 
can't identify who's been exposed to vaccine, who hasn't.
    Mr. Burton. Should peer review data protocols be agreed to 
before further studies are funded and released?
    Ms. Wong. I'm sorry?
    Mr. Burton. Should peer review data protocols be agreed to 
before further studies are funded and released?
    Ms. Wong. No, peer review should also be reviewed, and they 
are.
    Mr. Burton. Excuse me just 1 second.
    I think you can relax for a little bit. Now I get to go to 
Dr. Egan.
    The U.S. Food and Drug Administration first learned about 
SV40 problem with the polio vaccine in 1960, is that correct?
    Mr. Egan. That's correct.
    Mr. Burton. Starting in 1961, the FDA stipulated that no 
lots of polio myelitis vaccine would be released in the absence 
of negative results of a valid tissue culture for SV40; that's 
correct?
    Mr. Egan. That's correct, sir.
    Mr. Burton. Prior to the requirement, millions of Americans 
were vaccinated with SV40 contaminated polio vaccines; that's 
correct?
    Mr. Egan. That's correct.
    Mr. Burton. Once the FDA released there was a problem with 
the polio vaccine, did the agency issue any type of recall?
    Mr. Egan. No, they did not, sir.
    Mr. Burton. Why?
    Mr. Egan. OK. Well, at this time this would have been the 
Division of Biological Standards at the National Institutes of 
Health. At that time they took this question about recall or 
leaving material on the market to the Polio Myelitis Vaccine 
Committee, their advisory committee to the NIH; and the 
committee weighed the risks and benefits, the risks of polio, 
the risks of not having the polio vaccine virus out there and 
the potential risk that might result from SV40 and they 
concluded that, on balance, from the risk benefit analysis, 
that it was much better to leave the vaccine on the market and 
not to recall it.
    Mr. Burton. Once the FDA released there was a problem with 
the polio vaccine, did the agency ever issue a notice to 
health-care providers not to use contaminated vaccine, even 
though it wasn't recalled?
    Mr. Egan. Yeah, I do not have any knowledge of that, sir.
    Mr. Burton. Can you find out for me?
    Mr. Egan. I will try, sir.
    Mr. Burton. Because I know, since I was a child, at that 
time, everybody was very concerned about polio. We knew about 
iron lungs and all that sort of thing, and our parents wouldn't 
even let us get around water outside or flies or anything.
    Mr. Egan. I shared the exact same experience. I was 12 
years old when the vaccine came out.
    Mr. Burton. I understand that. But when they found out the 
SV40 was a possible cause of cancer in the hamsters, couldn't 
the--I mean, there was other ways to make the vaccine other 
than using that contaminated SV40 vaccine; wasn't there?
    Mr. Egan. I'm not aware of another method that was known at 
that time. But once the issue came to the fore, the FDA--the 
Division of Biological Standards did require that all vaccine 
be free of SV40, that it be tested for SV40, each lot of 
vaccine be tested for SV40, be found free of SV40 prior to 
release to market.
    Mr. Burton. I think we know the answer to this question 
from Dr. Hoosier, but SV40, if it was discovered in a major 
vaccine today, what would the FDA's response be and how would 
it differ from your response in the 1960's?
    Mr. Egan. If SV40 was found in the vaccine today?
    Mr. Burton. It would not be put on the market?
    Mr. Egan. It would not be put on the market, no, sir.
    Mr. Burton. FDA testing from the 1972 to 1976 polio vaccine 
questions I'd like to ask you next.
    In your testimony, you mentioned that the FDA has tested 
live supplies of polio vaccine between 1972 and 1976 and that 
you found them free of SV40; is that correct?
    Mr. Egan. That's correct.
    Mr. Burton. The subcommittee understands that the FDA 
tested no samples prior to 1972 because no pre-1972 samples of 
the polio vaccine still exist; is that correct?
    Mr. Egan. They were not in our possession. I don't know 
whether they exist or not, but the retention samples that we 
had went back to 1972.
    Mr. Burton. Well, would any of the laboratories that had 
produced the vaccine have that?
    Mr. Egan. I don't know what their retention policies are. 
They might.
    Mr. Burton. Could that be requested from them so that we 
could be testing those?
    Mr. Egan. Yes, I'll do that.
    Mr. Burton. So, since you didn't have any of that, the FDA 
has no way to independently test if the polio vaccine was SV40-
free from 1955 to 1972; that's correct?
    Mr. Egan. Well, that's correct. Certainly the vaccine--many 
of the lots of vaccine from 1955 through the early 1960's was 
certainly contaminated. I don't think there's any question 
about that.
    Mr. Burton. That it was left on the market.
    How about up to 1972?
    Mr. Egan. That vaccine was tested for SV40 and found to be 
free.
    Mr. Burton. But the vaccine that contained the SV40 was 
still on the market, was it not, in 1972, or was it?
    Mr. Egan. It should not have been.
    Mr. Burton. Should have been exhausted by then?
    Mr. Egan. Exhausted. I'll have to look at what the 
expiration dating period was, but it was probably no more than 
a year or 2, couple of years----
    Mr. Burton. OK.
    Mr. Egan [continuing]. And everything released after 1961 
would have been SV40 free, found to be SV40 free, so----
    Mr. Burton. If after 1961 you required the vaccines to be 
SV40 free, why didn't they recall the vaccines that were 
contaminated before that?
    Mr. Egan. OK. Again, that was the--I was not there at those 
discussions, but my understanding is that the--they had 
discussions of the risks of polio versus----
    Mr. Burton. I understand, but----
    Mr. Egan. Yes.
    Mr. Burton. I'm sorry to interrupt. Go ahead.
    Mr. Egan. That in determining--in going over those risk-of-
benefit determinations, they felt it was better to leave the 
market--leave the vaccine on the market to prevent polio, 
rather than withdraw it, which would have resulted in a 
shortage.
    Mr. Burton. I know, but I'm saying if there's a vaccine 
that is SV40-free coming on the market, is being produced, you 
still have contaminated vaccine in the marketplace. Why didn't 
they recall what was left at that time? Why run the risk of 
infecting additional people when you have an SV40-free vaccine?
    Mr. Egan. I mean, I could only, you know, speculate, not 
being there, but----
    Mr. Burton. Could you check?
    Mr. Egan [continuing]. I think there was an issue of supply 
of vaccine, how much would be available. But I mean that's 
speculation.
    Mr. Burton. Could you check for the record and give us an 
answer to that? Because it seems to me that the manufacturers 
would move pretty quickly to jam up supply of free SV40 vaccine 
as quickly as possible; and if that's the case, they would 
have--it seems to me our health agencies would have said, let's 
get this contaminated vaccine off the market.
    I understand the rationale about weighing it and saying do 
we want to stop polio or run the risk of possible cancer down 
the road. I can understand that rationale if you don't have the 
alternatives. But once you have the alternative why would you 
keep that out there? That's what I would like you to answer, if 
you could.
    Let me get back to the pre-1972. So the FDA had no way to 
independently test whether the polio vaccine was SV40 free from 
1955 to 1957; is that correct? They had no way to test it?
    Mr. Egan. No, they were testing after 1960 or 1961. It was 
the period in between----
    Mr. Burton. 1955 and 1960.
    Mr. Egan. 1955 and 1961 where it was unsuspected. Because 
the virus didn't harm, you know, kill the cells in which it was 
growing.
    Mr. Burton. Excuse me, just 1 second.
    My right arm here indicated that they were getting SV40 
polio vaccine off--not off the market but produced after 1961, 
but he tells me that there was no test to test the vaccine up 
to 1972; is that correct?
    I'm going to let you ask this question. I want to make sure 
I get this correct for the record.
    Mr. Fauls. I think you've already answered the first 
question, is that you--when studies first came out that showed 
SV40 in cancerous tumors, FDA went back and tested all of the 
samples it had of polio vaccine in its possession, which only 
went back to 1972, to verify again those were free of SV40. 
That's correct?
    Mr. Egan. One minor change. We tested a sampling of the 
retention samples that we had. We tested 30 monopools, and we 
tested 30 trivalent vaccine lots. It wasn't 100 percent.
    Mr. Fauls. So you didn't test 100 percent of all the lots 
produced from, say, 1961 to 1972 or what you had in your 
possession?
    Mr. Egan. No, what we had in our possession were a number 
of lots that were kept in as retention samples that represented 
lots that were manufactured between 1972 and 1996. Of them, we 
chose the large sampling, which was 60 samples in total; and 
each and every one of those was negative to a highly sensitive 
chain reaction, preliminary chain reaction testing methodology 
that we developed. We did not have any samples that predated 
1972 in our possession.
    Mr. Fauls. OK.
    Mr. Egan. But there was, for every lot of vaccine, lot 
release testing from 1961 onward; and this was the tissue-
culture-based testing.
    Mr. Burton. So in the absence of this independent testing, 
the possibility existed that pre-1972 polio vaccine could have 
been contaminated with SV40; is that correct?
    Mr. Egan. I do not believe so, because each lot of vaccine 
was tested in the tissue culture test, which is rather 
rigorous, testing in sub-culturing, looking for a cytopathic 
effect in the African green monkey tissue, and this was done 
for every lot of vaccine since 1961.
    Mr. Burton. But the FDA doesn't have any samples of the 
vaccine that was manufactured prior to 1972; is that correct?
    Mr. Egan. No, we did not have any in our possession. If we 
did, we would have gone back further.
    Mr. Burton. The samples that were tested by the FDA were 
under--were they under the FDA's supervision since their 
manufacturer was supplied by individual manufacturers at the 
FDA's request in 1996?
    Mr. Egan. I'm sorry. I don't understand the question? Would 
you mind repeating it?
    Mr. Burton. I'm going to let you ask that question.
    Mr. Fauls. OK, sir. Very good.
    The question gets at--and I think you answered this 
earlier--that the samples that you tested back to 1972 were in 
the FDA's possession; is that correct?
    Mr. Egan. That's correct.
    Mr. Fauls. OK, so you have a clear chain of custody of 
those samples so that you know that they were, in fact, 
produced in 1972 and they weren't--they weren't, say, produced 
in 1996 specifically because you were going to do some 
retesting?
    Mr. Egan. It's a different office within the--within FDA 
that handles these, but they come in. They're logged in and 
then stored in the freezer.
    Mr. Fauls. OK, but since the time of the manufacturer 
they've been stored there?
    Mr. Egan. Yes. Whenever the samples are submitted, along 
with the lot release protocol, every lot of vaccine that's 
released to market must be released by FDA before the 
manufacturer can send it out. What they will send in to the FDA 
after they've manufactured a lot is a lot release protocol that 
contains all of the testing that was done so this can be 
reviewed by FDA scientists to see whether it's satisfactory or 
not. The manufacturer, at the time that they send in this 
protocol, will also send in physical samples in the event that 
FDA wishes to do any testing on that lot, so they're sent in 
prior to the release of the vaccine by FDA.
    Mr. Fauls. And stored at FDA?
    Mr. Egan. And stored at FDA.
    Mr. Burton. And they're still there in frozen status?
    Mr. Egan. Yes.
    Mr. Burton. And you have documentation to verify that the 
vaccine was actually produced when the manufacturer said it was 
produced?
    Mr. Egan. Well, it would come in----
    Mr. Burton. Come in with it?
    Mr. Egan [continuing]. With the lot release protocol at 
that time. So the vaccine that was manufactured, for example, 
in 1982 would--that vaccine would come in with the lot release 
program.
    Mr. Burton. What we're trying to get at is something that 
was produced in 1972 is there as a 1972 product and not 
something that was manufactured later in 1994?
    Mr. Egan. No.
    Mr. Burton. OK. Thank you.
    Mr. Egan. No, that would not be an issue.
    Mr. Burton. Has the FDA required the polio vaccine 
manufacturers to produce results showing that their seed stocks 
are SV40 free?
    Mr. Egan. The two vaccines that are currently in use--you 
know, we've switched, a number of years back, to IPV--and the 
two major IPV's that are in use at the moment----
    Mr. Burton. Are SV40 free.
    Mr. Egan. They're SV40 free, but the manufacturers also 
demonstrated that the seeds that are used to produce the 
vaccine are SV40 free by PCR technology, and I'm referring to 
the recently licensed Pediarix and the Ipol.
    Mr. Burton. So the manufacturers are required to submit 
their polio vaccine lots to a 14-day tissue culture procedure 
to test for the presence of SV40?
    Mr. Egan. OK, the procedure that I think--I think the 
procedure that you're referring to is, for example, the one 
that was in the Code of Federal Regulations. If I look at the 
one, for example, for OPV, they hold the seed--they hold the 
part of the production for a number of days--I forget how many 
it is, exactly--and then there are two subcultures of 14 days 
and 14 days. So from the beginning to the end of that entire 
process with the control production cells is about 50 days.
    For the part of the harvest with the monkeys just prior to 
the inoculation with polio virus, they also hold those cells 
and then subculture them for one or two periods of--I think 
it's one period of 14 days. They observe the cultures in 14 
days. Then there's a third one with the actual harvest itself 
where they neutralize the polio virus with specific anti-sera 
and then culture and subculture again. So they are actually 
three very--three independent sets of cultures and subcultures 
that go out for, you know, 28 plus days.
    Mr. Burton. So that would be considered three independent 
tests?
    Mr. Egan. They're independent tests in the sense that 
they're done on different parts of the process, yes. They are 
not independent in the sense--they're independent tests, yes. 
They are coming from the same tissues, though. I would be happy 
to outline that for you.
    Mr. Burton. My counsel says that your original answer was 
they are not part of the same test.
    Mr. Egan. They are three independent tests on the same 
monkey kidney cells. Yes, they are three independent--they are 
independent tests. For clarity, I would be happy to submit to 
you what is done.
    Mr. Burton. I wish you would do that.
    Mr. Egan. Sure.
    Mr. Burton. I think that might help.
    Mr. Egan. I think we can diagram that.
    Mr. Burton. Like I said, we have somebody who used to be--
work on this in the health department of the government, and we 
want to, you know, discuss this with them in some detail.
    Mr. Egan. It's very, very complicated and hard to 
understand.
    Mr. Burton. That's why we go to an expert. You folks tell 
us, and then we talk to them to find out if there is additional 
information we need.
    Mr. Egan. Sure.
    Mr. Burton. So we appreciate that.
    Well, I think this is important. There's evidently one 
scientist who claims to have discovered a second strain of SV40 
that takes longer than the 14 days to develop in the culture 
testing. You said that you actually go beyond the 14 days?
    Mr. Egan. That's correct.
    Mr. Burton. If a polio vaccine lot fails that 14-day test 
and the subsequent tests that are part of the testing process, 
does the manufacturer automatically destroy it or can they 
attempt to clean the vaccine and retest it for SV40?
    Mr. Egan. I will double-check this, but my understanding is 
that if SV40 is in the vaccine they are not permitted to clean 
it up.
    Mr. Burton. If they want to get rid of it, they destroy it.
    Mr. Egan. Yes, if SV40's in the vaccine, yes.
    Mr. Burton. Can you double-check that for us?
    Mr. Egan. Yeah, but that's my interpretation, my 
understanding.
    Mr. Burton. Well, one of the accusations against one of the 
major drug manufacturers of the product is that they went back 
and scrubbed it and used the same vaccine, so we'd like to 
check that if you could for us.
    Mr. Egan. Yeah, I'd be very happy to. I do not believe 
that's allowed.
    Mr. Burton. Would you know if they did that?
    Mr. Egan. It would have to be part of the manufacturing 
record, yes. Any reprocessing----
    Mr. Burton. One of the accusations we have been told is 
that they--that this rescrubbing process did take place. Could 
that have been done without the FDA's knowledge?
    Mr. Egan. Anything is possible. The only reprocessing that 
I'm aware of is related to the viral inactivation, and that's 
described in the CFR.
    Mr. Burton. OK.
    Mr. Egan. That's the polio virus inactivation.
    Mr. Burton. I guess if we were to find out that a 
manufacturer did clean and retest they'd be subject to 
penalties by the FDA, severe penalties; wouldn't they?
    Mr. Egan. I cannot really respond to the compliance side of 
that, what those penalties would be.
    Mr. Burton. Is there any way we can find out what those 
penalties would be if that was the case?
    Mr. Egan. Yes.
    Mr. Burton. So you will let us know the maximum penalty for 
violating those regulations. And the manufacturers are required 
to, by the FDA, to keep records on all testing of vaccine prior 
to releasing it to the public; that's correct?
    Mr. Egan. Yes. I believe that they are required to keep 
those records for--it's either 5 years or 10 years after the 
date of manufacture. I don't know--I think it is one of those. 
They are required to keep them for either 5 or 10 years after 
the date of manufacture. We're going to have to look it up and 
get back to you on the exact length of time they're required to 
keep them.
    Mr. Burton. I appreciate that.
    Are experimental monkeys ever allowed to be used as donor 
tissue for vaccine growth cultures?
    Mr. Egan. Monkeys that had been used in experiments?
    Mr. Burton. Mm-hmm.
    Mr. Egan. No.
    Mr. Burton. I guess that's another accusation that's been 
made, and we'd like to verify that, and we would probably--you 
would have to go to the manufacturer to get that information; 
would you not? How would the FDA know about that?
    In 1986, I think it was Wyeth-Lederle wrote to the FDA, 
talking about a herd of monkeys that they had, that they wanted 
to, I guess, reuse. Can you see if there's any correspondence 
or any information on that we can get about that?
    Mr. Egan. 1986 was reuse of monkeys from Wyeth?
    Mr. Burton. Wyeth Lederle material, yeah. I presume that if 
that was done that also would be subject to review and penalty 
by the FDA, if they were doing that?
    Mr. Egan. Again, I'll have to check this, but I think that 
the Code of Federal Regulations states that monkeys that had 
previously been used in some fashion----
    Mr. Burton. Can't be.
    Mr. Egan [continuing]. Cannot be used.
    Mr. Burton. Well, you will let us know the maximum penalty 
of what it would be if it did occur?
    Mr. Egan. Well, yeah. I won't personally, but I'll ask the 
compliance, yes.
    Mr. Burton. Thank you.
    Mr. Egan. Because I don't know that part of this.
    Mr. Burton. How often does the FDA conduct site visits to 
inspect vaccine manufacturing facilities?
    Mr. Egan. Those are generally biennial.
    Mr. Burton. Biennial?
    Mr. Egan. Yes, sir.
    Mr. Burton. Every 2 years?
    Mr. Egan. Yes, sir.
    Mr. Burton. Are they usually announced or not announced?
    Mr. Egan. They are at least now unannounced. I don't know 
if in the past what the policy was, but they're unannounced.
    Mr. Burton. Is there any way we can find out what the 
policy has been and what it is now?
    Mr. Egan. Yes.
    Mr. Burton. And when it was changed?
    Mr. Egan. Yes.
    Mr. Burton. Thank you.
    How often does the FDA review their regulations to be sure 
they conform to the most current good manufacturing processes? 
I presume you do that periodically; don't you? Review your 
regulations to make sure that----
    Mr. Egan. Well, the current good manufacturing practices 
regulations that exist are, let me say, more philosophical. 
They state how things should work as opposed to what exactly 
everything is. For example, like a housing code may say you 
have to use exactly this kind of wire, you know, in a co-axial 
cable. It doesn't say that. It says that, you know, records 
must be maintained, personnel must be trained, etc., and that 
this is constantly evolving.
    Mr. Burton. So it's a flexible approach?
    Mr. Egan. It's a flexible system.
    Mr. Burton. But records are kept?
    Mr. Egan. Oh, yes.
    Mr. Burton. OK.
    How often are the FDA inspectors retrained in inspecting 
for good manufacturing practices or are they retrained? I mean, 
you know, if you're an insurance man or a lawyer or real estate 
guy, a lot of the professions, they have an educational 
process, because they have that for the inspectors.
    Mr. Egan. Yeah. The inspectors for good manufacturing 
practices facilities and inspections, these are actually done 
by a different part of the agency than the Office of Vaccines, 
so I'll have to get back to you on that answer, but I believe 
that they are given training in the beginning and that there's 
continual updating.
    Mr. Burton. Continuing education?
    Mr. Egan. Continuing education.
    Mr. Burton. Well, if we could get that, that would be 
helpful.
    If a manufacturer is found to be in violation of FDA 
regulations, what can the agency do to the manufacturer? Can 
they close them down or penalize them? What do they do?
    Mr. Egan. I'll have to get the lawyers to----
    Mr. Burton. OK.
    Mr. Egan [continuing]. To give you exactly what those are, 
but we can certainly suspend or revoke the license.
    Mr. Burton. I did know we were talking about the 
vaccination for anthrax, and the major manufacturer was shut 
down for a while because of some problems like that. We'd just 
like to know what the rule of--that you follow to deal with 
that.
    Has the FDA ever taken any action against any of the FDA's 
licensed polio vaccine manufacturers? If you don't know----
    Mr. Egan. I don't know.
    Mr. Burton. OK.
    In May 2000, the FDA's Public Health Service and the Center 
for Biological Study and Evaluation held an advisory board 
meeting to review vaccines and other biologically related 
agents. At the board meeting, advisory board Chairman Harry 
Greenberg admitted that there's no way to ensure absolute 
purity in the vaccine manufacturing process. Is that a pretty 
accurate statement?
    Mr. Egan. Yes.
    Mr. Burton. Chairman Greenberg also stated there was no way 
possible to eliminate all infectious adventitious agents, which 
SV40 would be one example of. Is that a correct statement as 
well?
    Mr. Egan. Well, you know, if we want to talk about, you 
know, adventitious agents' molecules, ensuring that something 
is out to the last possible molecule or the last, you know, 
virion is essentially impossible.
    What one does is, you know, as the case with SV40 for the 
best available technology, that the materials are negative to 
that testing. It's impossible to go beyond the limits of 
scientific testing.
    Mr. Burton. I will guess this is a tough question----
    Mr. Egan. And the same, for example, if you had, you know, 
water and you wanted to say that the lead content of water must 
be, you know, approved, that there isn't one single lead 
molecule in the entire reservoir. It's impossible.
    Mr. Burton. Well, has the FDA ever established a threshold 
level for contamination for vaccines? I mean, is there a 
maximum level of contamination that you would accept or is that 
a flexible thing? Is that a judgment call?
    Mr. Egan. Right. It would be flexible, depending on the 
situation, vaccine materials.
    Mr. Burton. That's the way it sounds when SV40 was first 
found.
    Mr. Egan. With SV40, when it was first found they developed 
very sensitive tissue culture tests that were developed, and 
the answer was that there could be no SV40 demonstrated by that 
testing.
    Mr. Burton. So they were almost 100 percent sure there was 
no SV40 in those?
    Mr. Egan. We can make estimates of what the most could have 
been, there would have been, and it's very small.
    Mr. Burton. Is there some kind of standard that you're 
considering developing that would set a minimum level 
acceptable for these contaminants or can you do that?
    Mr. Egan. For SV40?
    Mr. Burton. No, for any kind of a contaminant.
    Mr. Egan. Well, I mean, we certainly have, you know, 
standards for a lot of things. For example, the amount of 
residual DNA in vaccines or in biological products, you know, 
cannot be above a certain number of picograms. So these 
standards are developed and used all the time.
    Mr. Burton. The bottom line is you can't be 100 percent 
free of contamination, you can't guarantee that, just do the 
best you can?
    Mr. Egan. Yes, sir.
    Mr. Burton. OK. Thank you.
    What else do we have? Anything else?
    We're almost finished here, and I appreciate your patience.
    Mr. Egan. You're very welcome, sir. This is a very 
important issue.
    Mr. Burton. It is, it is, and you know there's lawsuits 
pending on some of these issues.
    Mr. Egan. Yes, I'm aware of that.
    Mr. Burton. There are people who worked at the health 
agencies who take issue with some of the statements I've 
admitted, and we just wanted to make sure we clear it up.
    Mr. Egan. We have disagreements all the time.
    Mr. Burton. The IOM's SV40 report issued in October 2002--
and this is a question for any of you--recommended that the 
appropriate Federal agencies develop a vaccine contamination, 
prevention, and response plan. The plan should identify the 
steps already in place of those that need to be developed to 
prevent contamination of vaccines and to respond to concerns 
about possible contamination. The plan should include 
strategies for routine assessment of vaccine for possible 
contamination, notification of public health officials, health 
care providers and the public if contamination occurs, 
identification of recipients of contaminated vaccine and 
surveillance and research to assess health outcomes associated 
with contamination. What have either of you or your two 
agencies done to implement that recommendation?
    Mr. Egan. That's being handled by the National Vaccine 
Program Office and specifically something known as the 
Interagency Group within that office, which has representatives 
from each of the Federal agencies that's involved with 
vaccines. So that plan is--that part of the recommendation of 
the IOM is handled by the National Vaccine Program Office.
    Mr. Burton. How far advanced is that plan; do you know?
    Mr. Egan. I'm not the representative to it, so I don't 
know.
    Mr. Burton. Do we need to request that information from 
them or could you request it for us?
    Mr. Egan. I can ask the initial vaccine program where they 
stand on that program.
    Mr. Burton. The last thing is, also, it's important--if a 
plan is developed, is there a communication program that's 
being formulated to inform the public and medical practitioners 
about it?
    Mr. Egan. That should be part of the plan. I think that is 
part of the recommendation of the IOM.
    Mr. Burton. OK.
    Mr. Egan. And I certainly concur with that.
    Mr. Burton. We'd like to know about that, as well.
    Is there anything else we need, right now?
    I want to thank you very, very much for your patience. I'm 
sure we'll be talking in the future, but you're very helpful, 
and we appreciate it.
    I would really like to get from the two of you, you know, a 
proposal or whatever you want to call it that would help in 
getting additional funding and the cross-pollination of the 
agency so that we could maybe get to the conclusion a little 
bit quicker on cancer.
    OK, hey, thanks a lot. We appreciate it.
    Mr. Egan. You're very welcome, Mr. Chairman.
    Mr. Burton. We stand adjourned.
    [Whereupon, at 4:45 p.m., the subcommittee was adjourned.]
    [The prepared statement of Hon. Elijah E. Cummings 
follows:]

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