UNITED STATES OF AMERICA

BEFORE THE FOOD AND DRUG ADMINISTRATION

DEPARTMENT OF HEALTH AND HUMAN SERVICES

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:

In the Matter of: :

:

Enrofloxacin for Poultry: Withdrawal : FDA DOCKET NO.

of Approval of Bayer Corporation\'s : 00N-1571

New Animal Drug Application (NADA) :

140-828 (Baytril) :

:

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Monday, April 28, 2003

The hearing in the above-entitled matter commenced at 9:03 a.m.,
pursuant to notice.

BEFORE:

DANIEL J. DAVIDSON

Administrative Law Judge

APPEARANCES:

On behalf of the Center for

Veterinary Medicine (CVM):

NADINE R. STEINBERG, ESQ.

ROBERT M. SPILLER, JR., ESQ.

CANDACE C. AMBROSE, ESQ.

CLAUDIA J. ZUCKERMAN, ESQ.

U.S. Food and Drug Administration

Department of Health and Human Services

Office of the General Counsel

Office of the Chief Counsel

5600 Fishers Lane, GCF-1

Rockville, Maryland 20857

\(301\) 827-5050

On behalf of Respondent Bayer Corporation:

GREGORY A. KRAUSS, ESQ.

ROBERT B. NICHOLAS, ESQ.

McDermott, Will & Emery

600 13th Street, N.W.

Washington, D.C. 20005-3096

\(202\) 756-8263

On behalf of the Animal Health Institute:

KENT McCLURE, ESQ.

1325 G Street, N.W., Suite 700

Washington, D.C. 20005

Also present:

Dennis D. Copeland, D.V.M., Director

Stewardship - Government/Industry Relations

Research & Development

Bayer HealthCare Animal Health Division

Bayer HealthCare LLC

P.O. Box 390

Shawnee Mission, Kansas 66201-0390

\(913\) 268-2522

C O N T E N T S

WITNESSES: DIRECT CROSS REDIRECT RECROSS

Linda Tollefson 21 23 170 178

BAYER CORP. EXHIBITS: MARKED RECEIVED

B-1929 - Draft Testimony Dr.

Cray 3-18-03 93 (Withdrawn)

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P R O C E E D I N G S

(9:03 a.m.)

JUDGE DAVIDSON: Come to order. On the record.

By the Orders of April 10, 2002 and April 15, 2003, this hearing for the
purposes of cross examination was set to begin at this time and place in
FDA Docket Number 00N-1571, Enrofloxacin for Poultry: Withdrawal of
Approval of New Animal Drug Application (NADA) 140-828.

Counsel, in announcing your appearances, please state your name, your
address, the capacity in which you appear, and whether you have been
admitted to practice before the bar or bars of any of these United
States.

Who appears for the Center for Veterinary Medicine?

MS. STEINBERG: Nadine Steinberg. The address is 5600 Fishers Land,
Rockville, Maryland 20857. I appear on behalf of the Center for
Veterinary Medicine and I\'m admitted in the District of Columbia.

MR. SPILLER: I\'m Robert Spiller. My address is the same as Ms.
Steinberg\'s. I\'m also appearing for the Center for Veterinary
Medicine, and I\'m admitted to the bar of the Commonwealth of Virginia.

JUDGE DAVIDSON: Okay.

MS. AMBROSE: Candace C. Ambrose. My address is the same as Nadine\'s.
I\'m also counsel for CVM, and I\'m admitted to the bar of the State of
Maryland.

MS. ZUCKERMAN: I\'m Claudia Zuckerman. My address is the same as Ms.
Steinberg\'s. I\'m also counsel for the Center for Veterinary Medicine
and I\'m admitted to the bar in Maryland.

MR. KRAUSS: Your Honor, Gregory Krauss on behalf of Respondent Bayer
Corporation.

JUDGE DAVIDSON: You didn\'t me a chance to even ask.

MR. KRAUSS: I\'m sorry, Your Honor.

(Laughter.)

JUDGE DAVIDSON: Who appears for Bayer Corporation?

MR. KRAUSS: Your Honor, Gregory Krauss on behalf of Bayer Corporation.
My address is 600 13th Street, Northwest, Washington, D.C. 20005. I\'m
admitted to the bars of the States of Maryland, New Jersey,
Pennsylvania, and the District of Columbia.

MR. NICHOLAS: Your Honor, I\'m Robert Nicholas. I appear on behalf of
Bayer, the same address as Mr. Krauss. I\'m admitted to the bars of
Massachusetts and the District of Columbia.

JUDGE DAVIDSON: Is there someone here for the Animal Health Institute?

MR. McCLURE: Yes, Your Honor. My name is Kent McClure. My address is
1325 G Street, Suite 700, Washington, D.C. 20005. I\'m admitted to the
bars of the District of Columbia and Texas, and I might add, Your Honor,
that I meant no disrespect by not wearing a tie today. I have a broken
arm and can\'t ‑‑

JUDGE DAVIDSON: That\'s why we didn\'t give you a desk.

(Laughter.)

JUDGE DAVIDSON: Are there any other appearances?

(No response.)

JUDGE DAVIDSON: Hearing none, let\'s move on to preliminary matters.
I\'ll let you go first with the preliminary matters. Ms. Ambrose.

MS. AMBROSE: Yes, Your Honor. I have one preliminary matter. I ask that
I be excused from appearing on time this afternoon after the lunch
break. I have a conference call scheduled with one of the witnesses who
was to appear on cross examination during the lunch hour, and I\'ll
return to the courtroom as soon as the call is over.

JUDGE DAVIDSON: Well, I\'ll conditionally authorize that, but we may be
talking some more about that before we get into actually cross examining
the witnesses.

Anything else?

MS. ZUCKERMAN: Your Honor?

JUDGE DAVIDSON: Yes, Ms. Zuckerman.

MS. ZUCKERMAN: At this time, the Center for Veterinary Medicine requests
reinstatement of certain testimony and exhibits into the evidentiary
record that were stricken from the evidentiary record but remain in the
administrative record pursuant to Your Honor\'s Order dated March 3,
2003.

The March 3rd Order stated:

\"The Respondent\'s motion to strike testimony and exhibits set forth in
Appendix D thereto relating to the Sentinel County study is granted
solely for the reason that relevant information requested by the
Respondent was not furnished by the Center for Veterinary Medicine (CVM)
in a timely manner.\"

The Footnote 3 at the end of that sentence reads:

\"The ruling is without prejudice to the resubmission of the testimony
and exhibits at the oral phase of this hearing.\"

CVM seeks reinstatement into the evidentiary record of the following
exhibits and related testimony that were part of Appendix D referred to
in the March 3rd Order.

Exhibit B-589, which is the Patent article, describes ‑‑

JUDGE DAVIDSON: I\'m sorry, say that again, the exhibit number.

MS. ZUCKERMAN: The Exhibit number is B ‑‑

JUDGE DAVIDSON: B.

MS. ZUCKERMAN: ‑‑ as in Bayer ‑‑

JUDGE DAVIDSON: Okay.

MS. ZUCKERMAN: ‑‑ 589, and I have copies if Your Honor ‑‑

JUDGE DAVIDSON: That\'s all right. Let\'s get them all listed first.

MS. ZUCKERMAN: B-589 is the Patent article describing the Sentinel
County study methods;

Exhibit G, as in government, 624, which is the Ten-over article
describing the Sentinel County susceptibility test results; and

Parts of the testimony of CVM witness Fred Angulo, Exhibit G-1452 at
Page 14, Lines 2 through 20 and Lines 38 through 46, which discuss the
methods and the test results of the Sentinel County study.

Any concerns regarding Bayer\'s timely access to documents that are
related to the Sentinel County study have now been mooted, for two
reasons.

First, on January 27, 2003, Bayer received additional Sentinel County
related information, a study protocol, and a patient questionnaire that
it sought from CDC pursuant to a Freedom of Information Act request. By
now, Bayer has had sufficient time, about three months, to review the
protocol and questionnaire.

Second, CVM is seeking reinstatement into the evidentiary record of only
a portion of the exhibits and testimony that relate to the Sentinel
County study. CVM is limiting it request to cover only information
relating to the susceptibility test results from the study.

In other words, CVM is not requesting reinstatement of interview-related
data on risk factors and duration of illness that were also generated as
part of the Sentinel County study and that were stricken from the
evidentiary record by the March 3rd Order.

As a result of CVM\'s narrow request, the patient questionnaire that
Bayer received from CDC on January 27th is irrelevant to the exhibits
and testimony CVM now seeks to resubmit.

With the exception of the study protocol that Bayer received from CDC in
January, the relevant Sentinel County information has been in Bayer\'s
possession since at least November 2002.

Bayer has had an electronic copy of the susceptibility test results of
CDC since November, and in addition, the Patent article, B-589, and the
Ten-over article, G-624, were contained in the parties\' original
12-A(5) submissions.

Finally, although CVM witnesses, in addition to Dr. Angulo, testify in
their written direct testimonies to the susceptibility test results of
the Sentinel County study, CVM is seeking reinstatement of testimony
only from Dr. Angulo, who is scheduled for cross examination on
Wednesday.

Therefore, to the extent that Bayer is entitled to cross examination on
testimony related to the test results from the Sentinel County study,
Bayer will still have the opportunity to conduct such cross examination.

Therefore, CVM respectfully requests that Your Honor reinstate into the
evidentiary record B-589, G-624, and G-1452, Page 14, Lines 1 through 20
and Lines 38 through 46.

Thank you, Your Honor.

JUDGE DAVIDSON: You don\'t have a chair?

MR. KRAUSS: I\'m fine, Your Honor.

JUDGE DAVIDSON: I know you are, but I\'m not. If you want to go back
about 20 years ‑‑

MR. KRAUSS: Thank you, Your Honor.

JUDGE DAVIDSON: ‑‑ you want to go back about 20 years to a hearing we
had on something called Catherabol, I removed somebody from the hearing
because he insisted on standing up when I wanted him to sit down.

MR. KRAUSS: Your Honor, I\'m happy to sit down.

(Laughter.)

JUDGE DAVIDSON: All right. Do you care to respond?

MR. NICHOLAS: I would, Your Honor.

JUDGE DAVIDSON: Okay.

MR. NICHOLAS: We would oppose that motion.

We\'ve had a great deal of difficulty, as you know, obtaining
information from CDC and/or CVM with respect to the Sentinel County
study.

It\'s true that we did receive additional information in early January
from CDC. However, we have a pending FOIA appeal with respect to
additional information for that study, which we have not received a
reply to, notwithstanding many phone calls to CDC, and great efforts on
our part to obtain all of the information relevant to that study so we
could make a judgment with respect to the credibility of that study and
the background of that study.

So we would oppose it, Your Honor, because we do not have all the
information, even as of this day.

JUDGE DAVIDSON: Well, I\'d like to see what\'s in the protocol, because
based on what you\'ve, both sides, presented to me when I was faced with
this minor task of dealing with 600 pages of motions to strike and
replies, all I saw was that they didn\'t furnish you a protocol. Since
you didn\'t have it, I couldn\'t expect you to show me what was in it.

I still haven\'t seen it, so I don\'t know whether it\'s something that
would interfere ‑‑ that\'s why I struck the exhibit, because, and
related material, because I had no way of knowing what was kept from
you.

Until I find out what it was ‑‑ and you\'ve received it as of January
27th, so you must now have a copy of it.

MR. NICHOLAS: Well, we\'ve received the protocol, Your Honor.

JUDGE DAVIDSON: Yeah, and that was ‑‑

MR. NICHOLAS: But there are other many other things that we\'ve asked
for with respect to that, sir.

JUDGE DAVIDSON: Well, I understand that\'s a lot of things you\'ve asked
for, a lot of things you haven\'t gotten, and a lot of information that
supposedly has come to me hasn\'t come to me.

I\'m not criticizing anybody in particular, but from time to time, I
would get e-mails saying that something was faxed to me, and I never got
it, and I think I mentioned that to you on the last telephone
conversation we had, group conversations.

I\'m not ready to rule on this until I see what\'s involved. If I know,
if I can see ‑‑ the basis for striking the exhibit in the first place,
as I said in my Order, was the fact that they hadn\'t furnished you with
what I considered to be important, if not vital information, being the
protocol.

Now, if I see the protocol and I don\'t think that that has that much of
an impact on whether or not you could adequately understand the exhibit,
then I might change my mind, but I haven\'t seen the protocol, so I
still don\'t know where I am on this.

So I\'m not ruling until I see it. No one has bothered to give it to me.
It may be filed in the file somewhere, but that doesn\'t help me.
There\'s a lot of stuff in this file that I\'ll admit I haven\'t looked
at, and until it gets in the evidentiary record, I won\'t look at it.

MR. NICHOLAS: Your Honor, if I may, I\'d like to request permission to
respond to this motion tomorrow morning.

We will go back and be able to provide you a list of what we have not
received from CVM or CDC, and so when you have the protocol, you\'ll
have an opportunity to look at these other materials as well, and make a
judgment with respect to whether Bayer has been prejudiced in its
ability to examine this material.

JUDGE DAVIDSON: Sounds like a very reasonable way to proceed.

MR. NICHOLAS: Thank you, Your Honor.

JUDGE DAVIDSON: Okay. Any other preliminary matters?

MS. STEINBERG: No, Your Honor.

JUDGE DAVIDSON: Well, I have a couple. Let\'s see.

First of all, after I went home on Friday, apparently somebody dropped
this at my door, a motion from CVM to supplement the 1285 and enter
Exhibit 1801 into evidentiary record.

Now, by rule, you have 10 days to respond to that. Are you ready to
respond at all at this point, or not? I\'m not making you respond.

MR. NICHOLAS: Your Honor, we are preparing the response. We did get that
letter from Mr. Foster from CDC. It represents, in our view, a one-sided
tale, as one might expect, and we are going to present the Court with a
full opportunity to understand the circumstances surrounding that.

Additionally, with respect to the documentation that we have received by
CDC, we have gone back, and I am prepared to represent in that motion
that much of the analysis that\'s contained in the witness\'s testimony
to Bayer is accurate and based upon data that was provided by CDC, but
we will address this fully. We don\'t expect to wait the 10 days, but we
just got this late Friday afternoon.

In addition, Your Honor, I would say that we have a motion that we will
be filing today that will ask to add several recent articles to the
documents.

JUDGE DAVIDSON: Do you have additional copies of this motion?

MS. STEINBERG: We have one copy.

JUDGE DAVIDSON: Well, before we finish today, I\'d like you to provide
one to the court reporter.

MS. STEINBERG: Certainly, Your Honor.

JUDGE DAVIDSON: I\'m going to allow it into the 1285 and reserve
judgment on whether it goes into the evidentiary record or not, so that
you don\'t have to deal with the 1285 aspect in your response.

Additionally, which witnesses is this going to refer to? Are we going to
need a response earlier than the 10 days?

MS. STEINBERG: No, Your Honor, I don\'t think that we will.

JUDGE DAVIDSON: Okay. I have one more preliminary matter. It\'s a
wonderful schedule you sent me, but I don\'t love it.

What used to be three hours is now four hours. What was two hours is now
four hours. What was two hours original request is now three hours. With
Dr. Kassenborg, what was three hours is now four hours ‑‑ and so on.

Now, I don\'t understand why your original good faith estimate was
increased to show additional time. I also don\'t understand why I have a
three-hour witness based on your latest estimate on May 5th and a
witness who\'s supposed to take two hours tomorrow.

If I\'m going to go to the trouble to put this thing on and come down
here, I\'d like to work. We could do both of those in one day for sure,
and maybe some others.

I don\'t know whether you realize it or not, but I do require ‑‑ you\'ve
had enough time to prepare for cross examination.

I require cross examination to be succinct and to move along and not to
have a lot of delays involved in one question to the next question, and
I do limit any redirect to what was brought up on cross and I limit,
obviously, the cross to what was in direct. I\'ve got an awful lot of
direct, I realize.

So, I don\'t know the schedule of your witnesses. I don\'t know which
ones are here or are not here at this present time, but I would like to
do some consolidating to shorten this, work, you know, full days, and
get this down to where we don\'t have to spend the entire time waiting
for the next witness to come in tomorrow.

All right, go ahead, Ms. Steinberg.

MS. STEINBERG: I would ask that, at least for today, we keep the witness
schedule as originally set. Our witness that is scheduled to appear
tomorrow was not told to come today because ‑‑

JUDGE DAVIDSON: Oh, I understand that part. I issued the order the way
you sent it in, but I want to make changes starting from today on.

MS. STEINBERG: Thank you, Your Honor.

JUDGE DAVIDSON: Have we got any proposals to that, or do you need a
recess to talk with opposing counsel, or do you have to check with your
witnesses, or what\'s the story?

MS. STEINBERG: I believe we do need to check with our witnesses and make
sure they\'ll be available here in Rockville. A lot of them, several of
them are out-of-town witnesses.

JUDGE DAVIDSON: I understand.

MS. STEINBERG: We can do that now or get back to you after the lunch
recess.

JUDGE DAVIDSON: I think that would be fine, after the luncheon recess.

All right. That\'s all I have of a preliminary nature. Are we ready for
our first witness?

MS. STEINBERG: We are, Your Honor.

(The witness was sworn by Judge Davidson.)

JUDGE DAVIDSON: Please be seated, give your full name and address to the
reporter, and then ‑‑

THE WITNESS: My name is Linda Tollefson. That\'s T-o-l-l-e-f-s-o-n.

Address is 7519 Standish Place, Rockville, Maryland 20855.

Whereupon,

LINDA TOLLEFSON

was called as a witness and, having been first duly sworn, was examined
and testified as follows:

DIRECT EXAMINATION

BY MS. STEINBERG:

Q Dr. Tollefson, can you state your position for the record?

A Yes. I\'m deputy director of the Center for Veterinary Medicine in
FDA.

MS. STEINBERG: Your Honor, may I have permission to show the witness a
document, Exhibit G-1478?

JUDGE DAVIDSON: That\'s her testimony?

MS. STEINBERG: Yes.

JUDGE DAVIDSON: Of course.

BY MS. STEINBERG:

Q Dr. Tollefson, could you please identify this? A Yes. It\'s the
written direct testimony of mine.

Q Can you turn to Page 20? Is that a photocopy of your signature that
appears on the original?

A Yes, it is.

Q Since you submitted, since you signed and submitted that testimony, is
there anything ‑‑ have you had a chance to review the testimony?

A Yes.

Q Is there anything in the testimony that you need to correct,
typographical errors or other errors?

A Yes, there are two issues. The first is on Page 8, the paragraph
that\'s numbered 18, and specifically, it\'s Lines 36 to 38. That\'s a
mistake.

That statement now reads: \"The 2001 data on Campylobacter isolates has
not been available.\" That should be 2002. 2001 is available and is
actually in the table attached to my testimony.

Q Thank you. Is there anything else?

A Yes, there is. There\'s one other thing. It\'s Page 10, the last
sentence, and it\'s on the top of that page, the paragraph that ends on
the top of that page.

It\'s the end of Paragraph 21, and I\'m speaking to Campylobacter jejuni
and coli, and identification of those, and I say ‑‑ I talk about
nalidixic acid and fluoroquinolone, and the statement reads:

\"This is because resistance develops first in nalidixic acid.\" That is
actually not correct for Campylobacter. It\'s pretty much simultaneous.

Q Thank you. Are there any other corrections that you\'d like to make?

A No, that\'s all.

MS. STEINBERG: Thank you. Your Honor, Dr. Tollefson is ready for cross
examination.

JUDGE DAVIDSON: Okay.

MR. KRAUSS: Thank you, Your Honor. Gregory Krauss on behalf of Bayer
Corporation.

CROSS EXAMINATION

BY MR. KRAUSS:

Q Good morning, Dr. Tollefson.

A Good morning.

Q I\'m Greg Krauss and I\'m going to conduct your cross examination
today. We\'ve already established that you\'ve submitted testimony in
this case.

You are the deputy director for the Center for Veterinary Medicine; is
that right?

A Yes.

Q You\'re also assistant surgeon general in the Public Health Service?

A Correct.

Q Ms. Steinberg showed you your testimony and if you\'ll ‑‑ you have a
copy of that; isn\'t that right?

A Yes.

Q If you would take a look at Page 20, I think we\'ve already
established this, but that\'s your signature; isn\'t that right?

A Correct.

Q You signed it on or about December 6, 2002?

A Correct.

Q When you signed it, you made a declaration that it was true and
correct under penalty of perjury, right?

A Yes.

Q Dr. Tollefson, did you draft your testimony yourself?

A Yes.

Q All of it?

A Yes.

Q Let me just explore your professional background a little bit, please.

A Mm-hmm.

Q You\'re a veterinarian?

A Yes, I am.

Q Do you have a Master\'s in Public Health?

A Correct.

Q And your Master\'s in Public Health emphasized epidemiology?

A Yes.

Q And biostatistics?

A Correct.

Q In your testimony, you describe yourself as a veterinary
epidemiologist. Is that right?

A Yes.

Q Your testimony also states that the majority of your career in the
Public Health Service has been focused on food safety issues; is that
right?

A That\'s correct.

Q Dr. Tollefson, you\'re not a medical doctor?

A No, I\'m not.

Q You do not have any advanced degrees in microbiology, do you?

A No, I do not.

Q You do not have any advanced degrees in veterinary microbiology, do
you?

A No, I do not.

Q You do not have a Ph.D. in epidemiology, do you?

A No.

Q You are not a poultry veterinarian, are you?

A No.

Q You are not a Diplomate of the American College of Poultry
Veterinarians, are you?

A No.

Q You\'re not a member of the American Association of Avian
Pathologists, are you?

A No.

Q You are one of the designers of the National Anti-Microbial Resistance
Monitoring System, right?

A Yes.

Q That\'s known a NARMS?

A Correct.

Q Now, the Notice of Opportunity for Hearing in this matter was filed on
October 31, 2000; isn\'t that right?

A That\'s correct.

Q And at that time, you were the director of surveillance and
compliance; is that right?

A Yes.

Q Did you have a role in the decision to file the NOOH?

A Yes, I did.

Q What was your role?

A I guess I was one of the proponents that the time had come to file the
NOOH, and I wrote the first draft.

Q Did you review data in coming to the decision that the time had come,
as you say?

A Yes.

Q What data did you review?

A A number of ‑‑ a number of different sources of information.

One was the historical record for how we decided to approve Cerofloxacin
and Enrofloxacin for use in poultry.

I reviewed the transcript of the Joint Veterinary Medical and
Anti-Infective Drugs Advisory Committee meeting that took place in May
of 1994.

I reviewed the National Anti-Microbial Resistance Monitoring System
data.

I reviewed the Kirk Smith study.

I reviewed a number of published literature studies, also some U.K. data
that had been coming out around that same time.

I reviewed the Campylobacter Risk Assessment that we were ‑‑ that was
still in draft.

I don\'t think that\'s an exhaustive list, but it\'s a general ‑‑

Q Okay. And your testimony states that:

\"Taken as a whole, the evidence requires the Center for Veterinary
Medicine to act to stop the poultry use of fluoroquinolones; isn\'t that
right?

A That\'s correct.

Q Now, Dr. Tollefson, would you agree that this case is about whether
Baytril use in chickens and turkeys is causing resistant Campylobacter
infections in humans?

A Yes, I think that\'s simplistic. I would say it\'s about whether
fluoroquinolone resistance develops in Campylobacter in poultry and
whether those Campylobacter are retained in the carcass, are transferred
to humans through a food safety or a food consumption or a handling
issue, and cause resistant infections in humans, correct.

Q Okay. So the ultimate question is whether, through that chain of
events, use of fluoroquinolones in poultry is resulting in resistant
Campylobacter infections in humans; isn\'t that right?

A Yes.

Q We agree, don\'t we, that Baytril is used for prescription use only?

A Correct.

Q And it\'s not used in any way for growth promotion?

A Correct.

Q It\'s only used to treat infections in the birds?

A I would disagree with that. The reason that I disagree with that is
that the drug is administered in drinking water to a group of chickens.
Some of those chickens are ill and have an infection. Others do not.

Q Okay. Well, we can get into that, Dr. Tollefson.

A Okay.

Q You would agree with me that Baytril is not prescribed to treat
Campylobacter, right?

A Correct.

Q It\'s for, in chickens, E. coli infections, right?

A Right.

Q And in turkeys for E. coli infections and for Pasteurella multocida?

A Mm-hmm.

Q In terms of Campylobacter infections in humans, and even resistant
infections in humans, for the most part, the disease consequence is
diarrhea, right?

A Campylobacteriosis in humans causes diarrhea, causes cramping. Yes, I
would say for the most part it\'s a diarrheal illness.

Q So, just to put this into perspective here, you know, sometimes in FDA
proceedings we\'re talking about, you know, cancer risk. We\'re not
talking about cancer risk here, are we?

A No, we\'re not.

Q Sometimes in FDA proceedings, we\'re talking about a birth defect risk
or something like that. We\'re not talking about that here, right?

A No.

Q We\'re talking about a diarrhea risk, right?

A We\'re talking about a risk of an adverse health event.

Q Now, your testimony states that you\'ve examined the data and
evidence, and we went through what you looked at and said it wasn\'t an
exhaustive list, right?

A Right.

Q But what you did look at, you looked at, as you say, as a public
health official, right, as a veterinarian, right?

A Mm-hmm.

Q And as an epidemiologist; isn\'t that right?

A Yes, that\'s right.

Q In your review of the evidence, in addition to what you\'ve already
testified that you looked at, did you also look at, in general,
literature on food-borne illnesses?

A Yes.

Q Did you also look at the 1998-1999 Centers for Disease Control and
Prevention Campylobacter Case Control Study?

A Yes.

Q You\'re familiar with that study?

A I\'m familiar with it. I\'m not intimately familiar with it.

Q Now, Dr. Tollefson, I do not have a background in epidemiology, and
you do, so I\'d like to establish with you some terms.

A Okay.

Q Epidemiological terms, if you will.

A Sure.

Q As an epidemiologist, would you agree that an incidence rate for a
disease consists of the number of cases over a defined period of time in
a defined population?

A It\'s the number of new cases over a defined period of time in a
defined population.

Q So it\'s the number of new cases of whatever the incident case,
whatever it is you\'re looking at, the number of new cases ‑‑

A New cases, correct.

Q ‑‑ over a defined period of time ‑‑

A Correct.

Q ‑‑ in a defined population?

A Right. The other is prevalence.

Q Right. A prevalence, correct me if I\'m wrong, is a snapshot in time
of who may have the ‑‑

MS. STEINBERG: Objection.

MR. KRAUSS: Do you have an objection?

MS. STEINBERG: Yeah. Counsel is testifying.

JUDGE DAVIDSON: Overruled. I\'ll allow it. Go ahead.

MR. KRAUSS: Thank you, Your Honor.

BY MR. KRAUSS:

Q A prevalence rate would be a snapshot in time looking at a population,
what\'s the level of disease in that population at that moment, right?

A Correct. It\'s the number of existing cases is an easier way to think
of it.

Q Okay. Thank you.

A Mm-hmm.

Q Would you agree with me that for food-borne illnesses, incidence rates
are often recorded as the number of cases per 100,000 per year?

A It depends on the organism. Yes, sometimes it\'s 10,000, sometimes
it\'s 100,000. Sure. That\'s a rate.

Q Right. We\'re talking about incidence rates?

A Right.

Q Annual incidence rates are used by epidemiologists, aren\'t they?

A Mm-hmm.

Q And they\'re used to examine trends of disease incidence over time,
aren\'t they?

A Correct.

Q Let me shift gears and go into another epidemiological term, please.

A Okay.

Q As an epidemiologist, would you agree that confounding ‑‑ are you
familiar with that term?

A Yes.

Q Would you agree that confounding is the distortion of an
exposure/disease association by the effect of some third factor?

A No. That\'s a frequently misused term. Confounding has to affect both
the disease and the exposure, not just one.

I\'m probably not being clear enough here, but ask your question again.

Q Are you familiar with the book, Field Epidemiology by Gregg?

A No.

Q There\'s a definition in the book, which I\'d be happy to show you if
you want to see it, that states that confounding is the distortion of an
exposure/disease association by the effect of some third factor.

A Okay. I\'d like to see the definition. In general, a confounding
variable has to have an effect on both the exposure and the disease,
which makes it very unique. There aren\'t that many confounding
variables.

If you\'re talking of confounding in more of a use of the term in
general English, I would agree with you. Okay?

Q Okay.

A Let me look at the definition ‑‑

Q I\'d be happy to show it to you, Dr. Tollefson.

For the record, this is Field Epidemiology by Greg, 2d Edition, Page
157.

A Okay.

(The witness examined the document.)

JUDGE DAVIDSON: Do I get to see it, too?

MS. STEINBERG: And also, I would like to know, Your Honor, if this is an
exhibit, and if so, what the exhibit number is?

MR. KRAUSS: Portions of this book, including this page, are in the
record.

MS. STEINBERG: And the exhibit number?

MR. KRAUSS: B-1912, attached to the Feldman testimony.

MS. STEINBERG: Thank you.

THE WITNESS: After that statement, he goes on to explain it, which is a
better definition.

BY MR. KRAUSS:

Q Good, because I wanted to go into the explanation.

A Okay.

Q So if you could clarify it, it would be great.

A A third factor in any association may be a confounder and distort the
exposure/disease association if it is, two things: associated with the
outcome independent of the exposure ‑‑ that is, even in the non-exposed
group ‑‑ okay, so the outcome being the disease in this case; and
associated with the exposure but not be a consequence of it.

So yes, I would agree with this whole definition.

Q Okay. Well, perhaps the confusion was that I split it up, then you
took care of part of my outline by doing what you just did. Thank you.

A Mm-hmm.

Q So with what you said, let me make sure I have this right here, the
third factor would be a confounder if the third factor is associated
with the outcome ‑‑

A Correct.

Q ‑‑ independent of exposure?

A Right.

Q Or, the third factor is associated with the exposure but not a
consequence of the exposure?

A No. It\'s and, not or.

Q It has to be both?

A It has to be both.

MS. STEINBERG: Your Honor, may Mr. Krauss please give the book with the
definition to Dr. Tollefson?

JUDGE DAVIDSON: I thought he did already.

MS. STEINBERG: He\'s asking questions about it without her being able to
look at it.

MR. KRAUSS: I\'m happy to do that, Your Honor.

JUDGE DAVIDSON: Certainly.

BY MR. KRAUSS:

Q So it\'s got to be both, in your opinion?

A It\'s got to be both. Yeah. He says that, too.

Q Okay. Thank you. Like I said, I\'m not an epidemiologist.

A Yeah.

Q So, Dr. Tollefson, just as an example, there\'s an example here in the
Gregg book where they go through the death rate, the mortality rate in
Arizona versus Alaska.

A Okay.

Q And the death rate in Arizona is 7.9 deaths per 1,000 and in Alaska
it\'s 3.9 deaths per 1,000, so on its face, it looks like there\'s a
higher risk of death ‑‑

A It\'s an age adjustment.

Q Well, that\'s the point.

A That\'s right.

Q Yeah, that\'s exactly the point.

MS. STEINBERG: Your Honor, can Dr. Tollefson be provided a copy of the
book with the example Mr. Krauss is referring to?

MR. KRAUSS: I would be happy to.

MS. STEINBERG: Thank you.

MR. KRAUSS: Once again, we\'re on Page 157.

MS. STEINBERG: Mr. Krauss, do you have another copy of the book?

MR. KRAUSS: No. It\'s in the record, B-1912, attached to Feldman\'s
testimony.

THE WITNESS: So it\'s a crude mortality rate.

BY MR. KRAUSS:

Q Right, right, without adjustment. But on its face, it would look like
you would have a higher risk of death in Arizona than in Alaska, but age
is associated with mortality.

A Correct.

Q The older you are, the greater the chance of dying, and, as it
happens, age is associated with where you live. More people are older
living in Arizona than in Alaska; isn\'t that right?

A Right.

Q So in that instance, age is a confounder, right?

A Correct.

Q And you have to correct for age?

A Right, and you can do that a number of ways.

Q Okay. Good.

A Okay.

Q Now, Dr. Tollefson, one of the things that you testified that you
looked at in this case is the study by Dr. Smith?

A Kirk Smith, right.

Q Kirk Smith.

A Of Minnesota, right.

Q Right. One of the things that Dr. Smith finds in that study, one of
his findings is that he believes there is a longer duration of illness
associated with a resistant Campylobacteriosis case compared to a
susceptible Campylobacteriosis case ‑‑

MS. STEINBERG: Your Honor ‑‑

BY MR. KRAUSS:

Q ‑‑ and here, we\'re talking about ‑‑

MS. STEINBERG: ‑‑ I have an objection to the form of the question.

JUDGE DAVIDSON: Well, let him finish the question first, then you can
object. Are you finished?

MR. KRAUSS: No, Your Honor.

JUDGE DAVIDSON: Okay. Go ahead.

MR. KRAUSS: I may have to start over.

BY MR. KRAUSS:

Q In the Smith study, one of the things he finds and reports on is an
association between having a resistant ‑‑ fluoroquinolone resistant
Campylobacter infection associated with the longer duration of illness
compared to a susceptible, fluoroquinolone susceptible Campylobacter
infection; isn\'t that right?

JUDGE DAVIDSON: Is there a problem?

MS. STEINBERG: Yes, Your Honor. I object to the form of the question.
Mr. Krauss is describing what\'s in the study and should be providing a
copy of the study to the witness.

JUDGE DAVIDSON: That\'s understandable, but the witness didn\'t seem to
have a problem with it. Have you got a copy for her?

MR. KRAUSS: I believe I may. We will find one, Your Honor.

JUDGE DAVIDSON: While we\'re waiting, I\'d like to remind you that I
know you like to see the same thing in the record over and over and over
again, but a couple of times you\'ve asked the question, you\'ve gotten
the answer, and then you\'ve repeated the answer for the record. And I
trust the reporter. You don\'t have to do that.

MR. KRAUSS: Okay, Your Honor. Thank you.

(Pause.)

JUDGE DAVIDSON: Are you looking for something that\'s in the record?

MR. KRAUSS: No ‑‑ yes, Your Honor. It\'s G-589, and counsel for CVM
requested that we provide the witness a copy ‑‑

JUDGE DAVIDSON: G-589?

MR. KRAUSS: Yes, Your Honor.

I\'m afraid this is going to be a little bit anti-climactic, but if they
want her to have a copy, then she\'s going to have a copy.

THE WITNESS: Thank you. What I recall is that he showed a slight
difference between fluoroquinolone resistant the fluoroquinolone
susceptible, but that was not a big consideration in my review of data
for the NOOH, if that matters.

MR. KRAUSS: Okay.

THE WITNESS: Okay.

BY MR. KRAUSS:

Q In terms of a consequence of a resistant Campylobacter infection, the
Smith report was not a big factor in your ‑‑

A No, the difference between the fluoroquinolone, the days of diarrhea
for the fluoroquinolone resistant infection as compared to a
susceptible, I didn\'t think that was a large part of this study.

Q Okay.

A Okay. That was a question that you asked, whether ‑‑

Q I asked whether it was one of the things that he found, Dr. Tollefson.

A Yeah, and I vaguely remember that yes, it was, but the difference was
not that great, and ‑‑ go ahead.

Q Okay. And did you review any other studies, in coming to your decision
to file the NOOH, that related duration of, longer duration of illness
to a fluoroquinolone resistant infection compared to a fluoroquinolone
susceptible infection?

A No. Most of those studies were published after we began the NOOH. The
Smith study was one of the earliest, and that was 1999. We were writing
the NOOH in early 2000.

Q Right. Well, let me ask you this, on the issue of confounding.

A Uh-uh.

Q If ‑‑ this is an if ‑‑ foreign travel, okay, persons in the study had
undertaken foreign travel.

Okay, foreign travel is associated with both resistant
Campylobacteriosis and with a longer duration of illness. Would foreign
travel be a confounding variable in that analysis?

A No. The foreign travel isn\'t causing the illness or the duration of
the illness itself, so I would not call it a confounding variable.

You should adjust for foreign travel, but it\'s not the foreign travel
itself, it\'s not the act of traveling that\'s causing either one of
those, so I guess I would not call it a confounder.

Q Even though it would be associated with the exposure but not a
consequence of the exposure?

A Okay, yes. It would be ‑‑ so if the person traveled to a foreign
country and got the infection there, then it would be associated with
the travel, but not a consequence of the actual travel. Yes, that\'s
what I\'m saying. And the outcome is not the infection, but the
duration.

I still, I don\'t see how the travel itself affects the outcome.

Q What I\'m saying is if you have a case control study, and you\'ve got
persons in your study who have had foreign travel, and they also have a
longer duration of illness, and they also have a resistant infection, in
that instance, if statistically, when you do your analysis, the foreign
travel is associated with both the resistant infection and with the
longer duration, wouldn\'t that be a confounder?

A I guess what I\'m objecting to is that it isn\'t associated with both.
I don\'t see how it can be.

Q It\'s a hypothetical, Dr. Tollefson.

A It\'s a hypothetical. Okay. If it\'s a hypothetical, then, yes, it
would be a confounder.

Q Okay. I\'m going to approach and take that.

A Okay.

Q Thank you.

A If the travel in some way gave you the illness.

Q Now, Dr. Tollefson, your career, as you said, is focused on food
safety issues, right?

A Correct.

Q You make an effort to keep current on literature discussing causes of
food-borne illness in the United States, don\'t you?

A Yes.

Q In doing so, are you familiar with the Centers for Disease Control and
Prevention MMWR Reports on the Incidence of Food-Borne Illness?

A Yes.

Q Would you agree that CDC MMWR Reports on the Incidence of Food-Borne
Illness are reliable?

A Yes.

Q Now, your written direct testimony ‑‑ and you have that with you at
the stand, right?

A Right, mm-hmm.

Q ‑‑ on Page 3, states: \"A recent reliable publication estimates 5,000
deaths and 76 million food-borne illnesses annually in the United
States.\" Isn\'t that right?

A Right, the Mead, et al. article.

Q Right. And that recent reliable publication that you refer to is
Mead\'s 1999 article?

A Right.

Q And that\'s G-410 in the record?

A Correct.

Q Now, that 76 million food-borne illnesses, that\'s not all
Campylobacter, is it?

A No, no. Not at all.

Q In fact, in the Mead report, don\'t they estimate Campylobacter to be
approximately 2.4 million cases?

A Correct.

Q So ‑‑

A And it\'s actually less than that, now.

Q Yes. We\'re going to get to that. Thank you.

So for Campylobacter, 2.4 million out of 76 million, we\'re talking
about something like 3 percent?

A Correct. The 76 million, however, most of those are of unknown source.

Q Right.

A And some of them are viral. Campylobacter is an important bacterial
cause of food-borne illness.

Q Right. But Mead\'s estimates, from what they can estimate versus the
total, it\'s about 3 percent; would you agree with that?

A Yeah, I would agree with that. That\'s ‑‑ Mead\'s article, or efforts,
were the last time that CDC has tried to do this in such an extensive
way. That\'s why it\'s frequently cited.

Q But isn\'t it true that for pathogens under active surveillance in the
Mead article, he used data from 1996 to 1997 in making his estimates?

A Right, he did.

Q Now, as someone who keeps current in the food safety literature, are
you aware that in April of 2002, CDC publicly reported that during the
period 1996 to 2001 the estimated incidence of infection with food-borne
pathogens has decreased?

A Yes.

MR. KRAUSS: In fact, I\'m going to hand you Government Exhibit G-1791.
Your Honor, I have an extra copy, if you would like it.

JUDGE DAVIDSON: I got it.

(The witness examined the document.)

BY MR. KRAUSS:

Q Dr. Tollefson, do you recognize this to be that report we just talked
about?

A Mm-hmm.

Q This report states, does it not, that, from the period 1996 to 2001,
the estimated incidence of food-borne Campylobacter infections decreased
27 percent?

A That\'s correct.

Q And as you testified earlier, that previous prediction of, or estimate
of 2.4 million has been changed, and now CDC says that
Campylobacteriosis is less than 2.4 million, right?

A Right.

Q In fact, there\'s evidence in the record that says it\'s 1.4 million?

A About 1.4, that\'s correct.

Q Okay.

A Mm-hmm. There\'s a newer one, actually, for 2002.

Q And Campylobacter has gone down again, hasn\'t it?

A No, actually, it went slightly up, but not much.

Q In the exhibit that I handed you, the overall incidence as of April
2002, the overall incidence of Campylobacter infections was lower than
the overall incidence of food-borne Salmonella infections; isn\'t that
true?

A Yes, and that\'s still true. Campylobacter is now second. This is
based on the Food Net data.

Q Right, based on the Food Net data, and in fact, it\'s based on Food
Net data from 1996 to 2001, right?

A Right.

Q You would agree with me, wouldn\'t you, that a report using data from
1996 to 2001 would contain more recent data than one using just data
from 1996 to 1997; isn\'t that right?

A That\'s right, but the Mead, et al. article gives peer review that
morbidity, mortality ‑‑ well, it goes through a clearance process within
CDC, and actually FDA also, but it\'s not quite as ‑‑ it\'s ‑‑ I don\'t
want to call it preliminary, but it\'s somewhat preliminary, in the
effort to get it out as soon as they can.

Q Right.

A Which is why I think a lot of people rely on the Mead article.

Q Well, your written direct testimony states that Campylobacter has been
cited as the most common known cause of food-borne illness in the United
States, right?

A That\'s true.

Q And that is based on a 1992 article, right?

A Yes. It\'s probably ‑‑ yeah, it\'s TOPES article, 1992?

Q Right. But as of 2001, and even as you said, as we sit here today,
it\'s no longer true that Campylobacter is the most common known cause
of food-borne illness in the United States, right?

A I would agree with that. However, it\'s still a very important cause
of food-borne illness.

Q But at the time you finalized your testimony ‑‑

A No, no, wait a minute. I said Campylobacter has been cited as the most
common cause of food-borne illness. I was trying to establish that it\'s
an important cause.

Q Well ‑‑

A It\'s in the section on background on anti-microbial resistance.

Q Dr. Tollefson, before 1492, the world had been cited to be flat, and
we now know that not to be true, right?

A I don\'t see the relevance.

Q Your testimony says Campylobacter has been cited as one of the most
important causes ‑‑

A As the most common known cause.

Q ‑‑ or as the most common known cause, and on the date of your
testimony, that was no longer true, was it?

A Correct. That\'s correct.

Q Let me turn your attention to the 1998-1999 CDC Campylobacter case
control study. Now, you testified that you looked at that, okay?

A Mm-hmm.

Q Do you recall what aspects of that you looked at?

A I looked at aspects of it that were used for the Campylobacter risk
assessment.

Q Let me hand you an exhibit. This is G-1452, Attachment Number 3. This
is attached to Dr. Angulo\'s testimony, and if I\'m not mistaken, it has
an independent G-number, but I can\'t bring it ‑‑ is it 1488, maybe, do
you know?

A No, it\'s 1452, Attachment Number 3.

Q Right. Well, what I\'m saying is, I think it has its own number now,
because it\'s ‑‑ it\'s not important. We\'ll use this one.

A Okay.

Q Thank you. Do you recognize this report, Dr. Tollefson?

A Yes. That\'s an attachment to the exhibit. I didn\'t see it ahead of
time. I recognize it as an attachment to Fred Angulo\'s testimony.

Q Okay. And this is a study by ‑‑

A It\'s a draft publication, manuscript.

Q Right. As of the time the testimony was filed in December of 2002, it
was still in draft, right?

A Correct.

Q Isn\'t it true that data from this study on the risk factors of
Campylobacteriosis was presented as early as July 2000?

A I don\'t know. That makes sense. We had that data of ruse in that risk
assessment, July ‑‑

Q I\'m going to hand you what\'s Exhibit B-27. It\'s an abstract by
Freedman, et al.

A Okay.

Q Do you recognize that?

A I don\'t, but it looks like it\'s a presentation that this manuscript
would be the more detailed report.

Q Based on looking at Exhibit B-27, if you look at the citation at the
end in particular, isn\'t it true that data from the 1998-1999 CDC
Campylobacter case control study was presented as early as July 2000?

A Yes, I would have to assume that\'s true. This is ‑‑ it doesn\'t say
where it was presented, but it says \"Food Net Presentation.\" It also
says Campylobacter is the most common cause of bacterial gastroenteritis
in the United States.

Q That was before the 2002 article came out; isn\'t that right?

A 2001.

Q April 2002, reporting on ‑‑

A Right.

Q ‑‑ data for 2001, right?

A Sure.

Q Now, you testified earlier that you were familiar with the CDC case
control study in relation to its data for the risk assessment.

A Mm-hmm.

Q Am I characterizing your testimony correctly?

A That\'s correct.

Q Isn\'t it true that one of the things that the CVM risk assessment
does is calculate what fraction of Campylobacteriosis cases in the
country are associated with poultry, as one of the steps along the way?

A Yes. It attempts to do a fraction of the total cases.

Q For the record, there\'s an agreed finding of fact in this case,
Bayer\'s finding of fact B-593, well, Bayer 593, that states that the
CVM BOSE risk assessment model relies, to calculate attributable
fractions ‑‑ let me restart it and just read it directly as it is.

\"The data that the CVM BOSE risk assessment model relies on to
calculate attributable fractions came from two studies from the 1980s,
Harris et al. and Deming et al.\" Then there\'s some citations.

A Right, that\'s correct.

Q And that\'s your understanding?

A Yes.

Q So for calculating the attributable fraction, what portion of
Campylobacteriosis is attributable to chicken, relied on these studies
from the 1980s ‑‑

A That\'s true.

Q ‑‑ and it didn\'t rely on the 1998-1999 Campylobacter Case Control
Study for that ‑‑

A Piece.

Q ‑‑ piece.

A Right. That\'s true. And I think we took the average of those two, or
something ‑‑

Q You say the average of those two. You\'re talking about Deming and
Harris?

A Right.

Q Are you familiar with the Deming and Harris studies?

A Vaguely.

Q You would agree with me, wouldn\'t you, that they\'re from the 1980s?

A Yes.

Q And you would agree with me, wouldn\'t you, that the data from the
1998-1999 Campylobacter case control study is more recent than the
Deming study, right?

A Right.

Q And it\'s more recent than the Harris study?

A Yes.

Q Now, Dr. Tollefson, as someone with a background in epidemiology and
biostatistics, do you have an understanding of what a matched odds ratio
is?

A Yes. Yes, in a matched case control study ‑‑

Q Correct.

A ‑‑ is that what you mean? Okay.

Q Right.

A Right.

Q What is your understanding of what a matched odds ratio is?

A Well, the ‑‑ an odds ration in a case control study is the odds of the
cases having the disease to the odds of the controls having the disease.
A matched case control study is usually where the controls are matched
to the cases on the other risk factors.

Q In a matched case control study, the matched odds ratio less than
equal to 1.0 has some import, doesn\'t it?

A If it\'s less than or equal to 1.0, it means that it\'s not ‑‑ it\'s
not a risk factor ‑‑

Q Would you agree with ‑‑

A ‑‑ 1.0 being null.

Q Right. If it\'s 1.0, the cases are as likely as the controls ‑‑

A Controls.

Q ‑‑ to, after having the exposure, to have the outcome.

A Right.

Q Okay. And with a matched odds ratio of less than or equal to 1, isn\'t
it true that that means that the exposure is associated with a reduced
risk of the disease?

A Sometimes. Sometimes it\'s termed as a protective factor, but it
usually ‑‑ most epidemiologists don\'t put that much credit in it.

Q Now, as someone with a background in epidemiology and biostatistics,
do you know what a P value is, Dr. Tollefson?

A Yes.

Q What\'s a P value?

A It\'s the probability of that result having occurred. There\'s usually
like a, if it\'s a P value of less than .05, it means that 95 percent of
the time that finding would not have occurred by chance, so it wouldn\'t
have been a spurious finding, for example.

Q So you would agree with me that a P value less than or equal to 0.05
is statistically significant?

A The 95 percent confidence level, yes.

Q And that\'s what FDA typically uses in that, right?

A I think so, yes.

Q For a P value of less than or equal to 0.01, that would be even more
statistically significant compared to 0.05, right?

A Correct.

Q In the exhibit that I gave you, which is by Dr. Freedman, which is
G-1452, Attachment 3, isn\'t it true that eating poultry meat at home
was associated with a lower risk of illness?

A Yes, and that was statistically significant.

Q If you would turn, please, to Page 98 of Exhibit 1452 ‑‑ and by 98,
I\'m using the upper right-hand corner number.

A I know.

Q Okay.

A Okay.

MS. STEINBERG: Can you repeat those page numbers?

MR. KRAUSS: 98, Nadine. It\'s in the upper right-hand corner.

MS. STEINBERG: Okay.

BY MR. KRAUSS:

Q Dr. Tollefson, this is a table of exposures, among other things,
matched odds ratios and P values, isn\'t it?

A Right, it is.

Q And this come from the 1998-1999 Campylobacter Case Control Study?

A Right.

Q If you would now turn to Page 99, it doesn\'t have that table heading,
if you look down the list, you see \"8 - Chicken prepared at home\" as
one of the exposures?

A Yes.

Q And the matched odds ratio is 0.5?

A Correct.

Q And the P value is 0.01?

A Correct.

Q That would mean, wouldn\'t it, that in this study, persons who ate
chicken prepared at home were less likely to be a Campylobacteriosis
case?

A Yes, that\'s true.

Q In fact, isn\'t it true that persons who did not eat chicken prepared
at home were more likely to be a Campylobacteriosis case than persons
who did eat chicken at home?

A The converse isn\'t ‑‑ no. The converse, you really can\'t say that,
unless they actually examine it, because you\'re looking at a number of
different exposures.

You could say that it\'s statistically significantly associated with a
decreased risk. Could you say that the cases ‑‑ say it again, please.
I\'m sorry. Ask the question again.

Q Right. Based on this finding in the Freedman analysis, isn\'t it true
that persons who did not eat chicken prepared at home were more likely
to be a Campylobacteriosis case than persons who did eat chicken at
home?

A I can\'t answer that. What ‑‑ you can go through the different
exposures and you can associate it, associate the level of significance
with each one of these. A lot of the chicken eaten at a restaurant, for
example, has a high association of illness.

You can\'t say that a person who didn\'t eat chicken prepared at home
had a less ‑‑ you can\'t say that. They didn\'t ask that question.

Q But wouldn\'t that have been the control, in doing the match between a
case and a control?

A So that ‑‑

Q Persons who did not eat chicken ‑‑

A Did not eat the chicken ‑‑

Q ‑‑ prepared at home were more likely to be a Campylobacteriosis case
than persons who did eat chicken at home.

A So you\'re just doing a logical converse of what the study found. I
guess I\'d have to say yes.

Q Dr. Tollefson, if you would look at that same table, the fourth one
down, \"Ate turkey prepared at home,\" the matched odds ratio is 0.6 and
the P value is less than 0.01?

A Yes.

Q Do you see that?

A Yes.

Q So in the Freedman analysis, isn\'t it true that persons who did not
eat turkey prepared at home were more likely to be a Campylobacteriosis
case than persons who did eat turkey at home?

A As an epidemiologist, I would phrase it the other way.

Q Tell me how you would phrase it.

A I would say that people who ate turkey prepared at home were less
likely to be a Campylobacteriosis candidate.

Q Compared to persons who did not?

A Eat turkey prepared at home, yes.

Q Okay.

A Yes.

Q There\'s other risk factors here, or exposures here, under \"Kitchen
and food handling practices.\" Do you see those, Dr. Tollefson?

A Mm-hmm.

Q For example, the first one, \"Had raw chicken in home refrigerator.\"

A Yes.

Q Would you agree with me that the matched odds ratio is 0.7?

A Yes.

Q And that the P value is less than 0.01?

A Yes. I\'d also note that almost everybody had raw chicken in a home
refrigerator.

Q Okay.

A It\'s only a few more ‑‑ go ahead.

Q Okay. And given that the matched odds ratio is less than 1.0 and that
the P value is less than 0.01, wouldn\'t it be true that persons who had
raw chicken in their home refrigerator were less likely to be a
Campylobacteriosis case compared to persons who did not have raw chicken
in their home refrigerator?

A Yes ‑‑ yes, and the difference is statistically significant, but it\'s
barely, just from eyeballing it.

Q P value of less than 0.01, right?

A Right.

Q Dr. Tollefson, if you\'ll continue down the list, do you see the one
that says, \"Touched raw chickens\"?

A Yes.

Q It has a matched odds ratio, does it not, of 0.06?

A Yes.

Q And a P value of less than 0.01?

A It\'s 0.6, not 0.06.

Q Thank you.

A And yes, the P value is less than .01.

Q So would you agree with me that, based on the Freedman analysis,
persons in the case control study who touched raw chicken were less
likely to be a Campylobacteriosis case than persons who did not touch
raw chicken?

A Yes.

Q I\'m just going to do one more of these.

If you would look at the very last one in the list, and I\'m sorry, the
very last one in the list of \"Kitchen and Food Handling Practices.\"

It says, \"Chicken that was prepared at home required cutting while
raw.\" Do you see that?

A Right. Mm-hmm.

Q That has a matched odds ratio, does it not, of 0.5?

A Yes.

Q And a P value of 0.01?

A Yes.

Q So based on Freedman\'s study, isn\'t it true that persons who ‑‑ for
persons who had chicken that was prepared at home that required cutting
while raw, those people were less likely to be a Campylobacteriosis case
than persons who did not have chicken that was prepared at home that was
required to be cut while raw?

A Yes.

Q The findings we just discussed, those were all statistically
significant?

A Correct.

Q Dr. Tollefson, let me turn your attention to Page 2 of your testimony,
Paragraph 4. Do you see, towards the bottom of Page 2, a sentence that
starts with, \"Resistance traits\"?

A Yes.

Q And your testimony states: \"Resistance traits may be passed to human
pathogenic bacteria by mechanisms that allow the exchange of bacteria\'s
genetic material.\"

A Correct.

Q That\'s your testimony?

A Under \"Background on Anti-Microbial Resistance,\" yes.

Q Are you aware of the fact that in this case the parties stipulated, in
Joint Stipulation Number 10, \"The parties do not have any facts or data
demonstrating horizontal gene transfer for fluoroquinolone resistance in
Campylobacter\"?

A That\'s correct.

Q The parties also stipulated, in Joint Stipulation Number 40, \" The
horizontal transfer of genes conferring fluoroquinolone resistance in
Campylobacter has not been demonstrated\"?

A That\'s true.

Q Do you agree that was stipulated?

A Yeah, I agree.

Q Okay. And not only do you agree that was stipulated, you agree that
that\'s true?

A That\'s true.

Q What this means is that fluoroquinolone resistance cannot be
transferred from one existing Campylobacter to another existing
Campylobacter through genetic exchange?

A Correct. That\'s correct. It\'s not plasma mediated.

Q Right. And it also means, does it not, that fluoroquinolone resistance
from Campylobacter cannot be transferred to some other non-Campylobacter
bacteria through transfer of genetic material?

A Correct.

Q So when you say in your testimony, your testimony about resistance
traits passing by exchange of genetic material, that\'s not relevant to
Campylobacter, is it?

A That\'s correct, it\'s not.

Q Dr. Tollefson, if you\'ll turn to Page 3 of your written direct
testimony, you refer to certain \"classic studies.\"

A Yes.

Q Do you see that?

A Yes.

Q Those studies are Homberg, G-285; Spika, G-702; Taket; Conan Talkes,
B-252; and Edgar and Bivey.

A Uh-huh.

MR. KRAUSS: Now, I didn\'t kill another tree by making lots of copies of
these. Let me just show these to your counsel, and then I want to ask
you about them.

(Pause.)

MR. KRAUSS: Now, let me approach.

BY MR. KRAUSS:

Q Let me ask you first about Homberg, G-285, here. That\'s relates to
Salmonella and not Campylobacter; isn\'t that right?

A Right, mm-hmm.

Q Let me ask you about G-702.

A That\'s Campylobacter.

Q That\'s not even an article by Spika, is it?

A No. The Spika article is ‑‑ they got the wrong exhibit ‑‑ is an
article about Salmonella.

Q And the Taket article that you referenced, that has not been submitted
to the docket, has it? There\'s no B or G number?

A I don\'t know.

Q And ‑‑

A It\'s in the 1285. Whether or not it\'s in the docket, that\'s
different.

Q Well, if it\'s in the 1285, it would be in the docket, but maybe not
in evidence?

A Okay.

Q All right. And the B-252, Conan Talkes article, this relates to
Salmonella and not Campylobacter, right?

A Correct.

Q And the Edgar and Bivey article has not been submitted to the docket,
right?

A Correct.

Q Dr. Tollefson, let me turn your attention to the joint advisory
committee meeting that you referenced. I believe you testified that you
were aware of the transcript from this committee meeting?

A Mm-hmm.

Q Your testimony at Page 4 states: \"FDA held a Joint Veterinary
Medicine and Anti-Infective Drugs Advisory Committee meeting in May 1994
to discuss the specific issue of approval of fluoroquinolones for use in
poultry. There was\" ‑‑

A That\'s not quite right. I just noticed that.

Q I\'m sorry. Am I reading it wrong?

A No, no, no. That\'s what I said, but it was actually for use in
food-producing animals.

Q Oh, so it wasn\'t specific to poultry?

A Uh-uh. No. I\'m sorry. I just noticed that.

Q So your testimony is wrong here?

A It\'s wrong. It should be food-producing animals in general.

Q Okay. In any event, your conclusion drawn in your testimony is that
there was no clear consensus among committee members as to whether
fluoroquinolones should be used in food-producing animals. That\'s your
testimony, right?

A That\'s correct.

Q Okay.

A There was agreement that fluoroquinolones are useful in animal
medicine, that there\'s no clear consensus that they should be ‑‑
there\'s a lot of discussion about whether or not they should be
approved in food-producing animals.

Q Well, in coming to your conclusion that there was no clear consensus,
did you review the transcript?

A Yes, I was there, first of all, and I reviewed the transcript, and I
actually talked to some of the numbers in the committee.

Q The transcript is the official record, right?

A Correct.

Q And the transcript is in evidence?

A Yes, that\'s true.

Q And it was a public meeting?

A Right.

Q And in the official record, the transcript, which I also reviewed,
isn\'t it true that not a single member on record in the transcript of
the joint advisory committee took the position that fluoroquinolones
should not be used in food-producing animals?

A Two members ‑‑ it may be semantics. It may be how you interpret that.
But two members felt that additional study should be done on, and more
extensive evaluation of the benefits in animals versus the risk to
humans.

So they didn\'t ‑‑ they did not say they should not be approved, but
they weren\'t asked that question. Okay?

Q Well, isn\'t it true that in the transcript, at least nine of the
committee members affirmatively state there is a need for
fluoroquinolones in food-producing animals?

MS. STEINBERG: Your Honor, if Mr. Krauss is going to ask the witness
about what is in the transcript, he needs to provide a copy to the
witness, and I might also add that the transcript speaks for itself ‑‑

JUDGE DAVIDSON: Yes, I think it does. It\'s in the record, isn\'t it?

MR. KRAUSS: Yes, Your Honor.

JUDGE DAVIDSON: Let me see it, and ask your question.

MR. KRAUSS: And just for the record, on this particular exhibit, the
sticker page numbers are not in order, in order to make the transcript
page numbers bed in order.

THE WITNESS: Yes. I would agree that I think most of the members said
that there is a need for fluoroquinolones in animals, in food animals.

BY MR. KRAUSS:

Q And not a single member, in response to the members saying there\'s a
need, stood up and said, \"No, there\'s not a need\"?

A I agree with that.

JUDGE DAVIDSON: Again?

THE WITNESS: Again.

JUDGE DAVIDSON: She\'s agreeing for the second time.

MR. KRAUSS: Thank you, Your Honor.

BY MR. KRAUSS:

Q Now, let me turn your attention to NARMS.

A Okay.

Q You\'re one of the designers of NARMS, right?

A Yes.

Q And planning for NARMS began in 1995; isn\'t that right?

A Planning for what we now know as NARMS began in 1995. We actually
started planning a resistance monitoring system a couple of years before
that.

Q But your testimony at Page 2, Line 19, says planning for NARMS began
in 1995?

A Correct.

Q And that was before the approval of Baytril, right?

A Correct.

Q And NARMS became operational in January 1996?

A Right.

Q That was also before Baytril was approved, right?

A Correct.

Q The NARMS system monitors resistance in food-borne enteric bacteria,
right?

A Correct.

Q There is a human component and then an animal component?

A And a retail meat component.

Q The retail meat component wasn\'t added until 2001, right?

A Correct.

Q When NARMS became operational in January 1996, in terms of the
susceptibility testing of enteric bacteria, Campylobacter was not
included, right?

A No, only Salmonella.

Q Campylobacter was not added to the human arm of NARMS until 1997,
right?

A Correct.

Q And Campylobacter was not added to the animal arm of NARMS until 1998,
right?

A Correct.

Q Now, let me ask you about, you have some testimony about speciating C.
jejuni and C. coli, right?

A Okay. Right.

Q I\'m going to need to use a whiteboard here. Again, not only am I not
an epidemiologist, I\'m not a microbiologist, so I don\'t understand
something here, and I want to clarify it.

A That\'s fine. It\'s very confusing.

Q I agree. If I understand the speciation issue correctly, NARMS will
collect Campylobacter isolates ‑‑ and here I\'m talking about both
aspects of NARMS, human and poultry. In general, NARMS collects all
Campylobacters. It doesn\'t ‑‑ if someone\'s got Campylobacteriosis, at
first, they don\'t know what species of Campylobacter it is; isn\'t that
right?

A Correct. Okay.

Q Okay.

A Okay.

Q And then, so you start off with all Campy. Do you mind if I use the
abbreviation Campy for Campylobacter?

A No, not at all.

Q And NARMS wants to distinguish between Campylobacter jejuni and
Campylobacter coli and the other thermophilic Campylobacters; isn\'t
that right?

A It\'s not NARMS on the animal side. It\'s FSIS.

Q Okay.

A Okay?

Q Okay.

A On the human side, I could say yes, those around NARMS partners.

Q Okay.

A Okay, but ‑‑

Q But you\'d agree ‑‑

A ‑‑ distinction.

Q ‑‑ with me that somewhere in the NARMS ‑‑

A Yes, we definitely speciate the Campylobacter organisms, yes.

Q Okay.

A Okay?

Q So we were kind of stepping all over each other here for a minute. Let
me just make sure I\'ve got this right.

Somewhere in the NARMS process, on both arms of NARMS ‑‑

A Yes.

Q ‑‑ there is an attempt made to speciate between Campylobacter jejuni
and coli versus the other ‑‑

A Other thermophilic Campylobacters, okay.

Q Okay.

A Yes.

Q And the way that that was traditionally done ‑‑ I know it changed in
2001, or after 2001 ‑‑ but ‑‑

A Go ahead.

Q ‑‑ the process that was used to speciate was using nalidixic acid and
cephalothin; isn\'t that right? A No. No. That\'s not correct. As early
as 1987, it was known that using nalidixic acid in the media to
differentiate coli and jejuni was an error, that it was not wise,
because of the increasing resistance to quinolones.

For some reason, FSIS continued to use that in their isolation
procedures to find Campylobacter. The human arm never used that
procedure.

Q Okay.

A Okay?

Q So I\'m now going to limit this discussion to ‑‑

A The animal? That\'s easier. That\'s easier. Yeah.

Q ‑‑ the animal part of NARMS. Okay.

A Okay. So yes, you\'re right. For the animal part of NARMS, until 2001,
they were using nalidixic acid, susceptibility to nalidixic acid and
resistance to cephalothin as identification of jejuni and coli.

Q Okay.

A That\'s not the right way to do it.

Q Okay.

A Okay?

Q But nevertheless, NARMS was doing it?

A Yes. But no ‑‑ no. FSIS was doing it.

Q Okay.

A We didn\'t know that.

Q Okay. FSIS was doing it?

A Yes.

Q Okay. And so FSIS would get Campylobacter isolates in and they would
have all Campy, and they would use nalidixic acid to speciate between
the jejuni and coli on the one hand, and others ‑‑

A Yes.

Q ‑‑ primarily lori?

A Yeah, any.

Q Others?

A There\'s a couple others.

Q Okay. And also cephalothin, right?

A Yes.

Q I\'m just going to say \"C\" for that. Okay? Now, in ‑‑

A Resistance to that, yes.

Q Right. So in the process, there\'s a split, and these over here, the
jejuni and coli, they\'re determined to be jejuni and coli because they
are susceptible to nalidixic acid ‑‑

A Correct.

Q ‑‑ and resistant to cephalothin, right?

A Yes.

Q And that\'s how you determine that\'s jejuni and coli?

A That\'s not how I determined it, that\'s how FSIS determined it.

Q That\'s how FSIS determined it. Okay. And then, after this process,
these same isolates are tested ‑‑

A Okay. Now, all the isolates are sent, then, to Paula. The jejuni and
coli, those are sent to ARS Laboratory in Athens, Georgia.

Q Okay.

A FSIS does not do any susceptibility testing.

Q Okay.

A Okay.

Q So when you say Paula, you mean Dr. Paula Fedorka-Cray?

A Right. Correct.

Q And you\'re saying when they ‑‑ when those isolates arrive at FSIS on
the poultry arm of NARMS, they\'ve already gone through this process?

A Yes, they have, until 2001.

Q Right.

A Okay.

Q And now, the jejuni and coli isolates that arrive to Dr.
Fedorka-Cray\'s lab have already been determined through this process to
be susceptible to nalidixic acid, right?

A Yes. It\'s somewhat of a screening test. They use a disk to select the
colony, so it\'s not 100 percent in either case, the susceptibility to
nalidixic acid and the resistance to cephalothin, but it\'s the majority
of them.

Q So it\'s not 100 percent, so what you\'re saying is when the isolates
are then chosen to be nalidixic acid susceptible, it\'s not 100 percent,
some of them might be resistant?

A Correct.

Q But they\'re called C. jejuni or C. coli?

A Correct.

Q And then all of these isolates have already been determined to be
jejuni ‑‑

JUDGE DAVIDSON: Excuse me, Mr. Krauss. You\'re playing fast and loose
with my record.

MR. KRAUSS: I\'m sorry.

JUDGE DAVIDSON: I mean, I know you\'re doing, and I understand and I
appreciate the aid that you\'re using there, but when you say \"these
isolates,\" \"this process,\" the record doesn\'t show what you\'re
talking about, even though I see what you\'re talking about and the
witness sees what you\'re talking about.

I don\'t like to delay this any more than you do, but if you have to
explain it again, you know, you have to go through and name the process
you\'re talking about. Otherwise, the record is not going to show it.

MR. KRAUSS: I appreciate it, Your Honor. Thank you. So I\'m going to get
rid of the theses and thoses and thats.

BY MR. KRAUSS:

Q In the speciation process, using nalidixic acid as development, the
jejuni and coli isolates have already been determined to be susceptible
to nalidixic acid. That\'s why they are determined to be jejuni and
coli, right?

A That\'s correct.

Q And then these isolates are sent to, on the poultry side now, sent to
Dr. Paula Cray\'s laboratory ‑‑

A Yes.

Q ‑‑ for susceptibility testing?

A Right, and ‑‑

Q And they ‑‑

A ‑‑ they re-identify them as being jejuni or coli, but not ‑‑

Q Using some other method?

A Right, exactly. Yeah.

Q But they\'ve already been determined to be susceptible to nalidixic
acid?

A Yes.

Q These jejuni and coli?

A Correct.

Q And then, susceptibility testing is performed in the laboratory of Dr.
Paula Fedorka-Cray, and some of these isolates are then determined to be
resistant to nalidixic acid ‑‑

A Mm-hmm.

Q ‑‑ and some are also determined to be resistant to Cipro ‑‑

A Right.

Q ‑‑ even though they already have been determined to be susceptible to
nalidixic acid, right?

A Right. The procedure isn\'t 100 percent.

Q Now, still talking about NARMS here, Dr. Tollefson, you weren\'t the
only designer of NARMS, right?

A No.

Q In fact, Dr. Frederick Angulo from CDC was one of the designers, too?

A Yes.

Q And his role related primarily to the human arm of NARMS, right?

A Correct.

MR. KRAUSS: I don\'t even know if he\'s in the room, Your Honor, but
I\'m going to ask this.

BY MR. KRAUSS:

Q You respect him as a scientist, don\'t you?

A Yes.

Q He submitted testimony in this matter?

A Mm-hmm. Yes, he did.

Q And Dr. Paula Fedorka-Cray of USDA was also one of the designers of
NARMS, isn\'t that right?

A Yes.

Q She\'s a veterinary microbiologist, right?

A She\'s a microbiologist, she\'s not a veterinarian. Is that what she
calls herself? That\'s fine. I don\'t ‑‑ she works with animal isolates.

Q Okay. So she\'s a microbiologist?

A Correct.

Q And she works with animal isolates?

A Yes.

Q She has a Ph.D., doesn\'t she?

A Yes, she does.

Q And her role was mainly with the animal arm of NARMS; isn\'t that
right?

A Correct.

Q You testified that your testimony is based in part on your knowledge
and experience as a co-author with Dr. Fedorka-Cray on several abstracts
and papers; isn\'t that right?

A Yeah, that\'s right.

Q And you respect Dr. Fedorka-Cray as a scientist, don\'t you?

A Yes.

Q Now, Dr. Fedorka-Cray did not submit testimony in this matter, did
she?

A No, she did not.

Q She was originally on CVM\'s witness list, wasn\'t she?

A Yes.

Q She was?

A Yes.

MS. STEINBERG: Objection, Your Honor.

JUDGE DAVIDSON: Yes?

MS. STEINBERG: What relevance does it have who was on our witness list?

JUDGE DAVIDSON: Well, I assume he\'s going to get to it sooner or later,
but let him go for now.

MR. KRAUSS: I\'ll get to it now, Your Honor.

JUDGE DAVIDSON: Okay.

BY MR. KRAUSS:

Q Now, Dr. Tollefson, are you aware that Dr. Fedorka-Cray completed a
draft of testimony for this hearing?

MS. STEINBERG: Objection, Your Honor. Relevance.

JUDGE DAVIDSON: Overruled. Go ahead.

BY MR. KRAUSS:

Q Do you want me to repeat the question?

A No. She completed several drafts. We went back and forth drafting
testimony. I actually wrote them first ‑‑

Q Okay.

A ‑‑ based on things that she had told me orally and things that we had
done in abstracts and so on, as I said in testimony.

Q Okay.

A Yes. So we worked on testimony together.

Q And at some point in time, she had what was referred to as a completed
draft?

A She ‑‑ the way I recall it, she thought ‑‑ she felt it was completed.
We disagreed. She had added another paragraph that we thought wasn\'t
relevant; and time ran out.

So we put most of what Paula was going to testify in mine.

Q Right.

A It has do with a lot of this stuff.

Q Right. And you reviewed the completed draft of Dr. Cray\'s testimony;
isn\'t that right?

A I wouldn\'t call it reviewed it.

Q You reviewed drafts?

A Yes, definitely, I reviewed drafts.

MR. KRAUSS: Let me hand you ‑‑ first counsel, and then you ‑‑ would you
take a look at this, please?

The first page ‑‑ Your Honor, let me hand her the copy.

THE WITNESS: (Examining) Yes, this is one of the drafts that I remember.

BY MR. KRAUSS:

Q You reviewed this draft?

MS. STEINBERG: Objection, Your Honor.

JUDGE DAVIDSON: Okay.

MS. STEINBERG: This document was not mailed to us.

JUDGE DAVIDSON: I understand that.

MS. STEINBERG: It\'s not in the record.

JUDGE DAVIDSON: I assume if it has some relevance, it will be moved into
evidence.

MR. KRAUSS: It will, Your Honor.

BY MR. KRAUSS:

Q In fact, Dr. Tollefson, you testified that you recognized this
document?

A Yes.

Q And you recognize this to be a draft of testimony prepared by Dr.
Fedorka-Cray?

A Right, but we objected that not everything in here was factual.

Q Okay. We\'ll get into that.

A Okay. Okay.

Q Do you have any reason to believe that the draft, what\'s referred to
as \"Completed Draft Testimony\" that\'s attached to the cover letter,
do you have any reason to believe that it\'s not a true and accurate
copy of Dr. Paula Fedorka-Cray\'s completed draft testimony that you
reviewed at some point in time?

A We never had anything marked \"Completed Draft,\" so I couldn\'t ‑‑ I
really can\'t ‑‑ I don\'t know, because I don\'t know, word-for word ‑‑

Q But you reviewed drafts along the way?

A Yes, I did. I never saw this with \"Completed Draft\" stamped on it,
but it looks, in general, sort of the penultimate draft, because we
objected in one particular paragraph and some minor things.

MR. KRAUSS: Okay. Your Honor, we would move this document into evidence.

JUDGE DAVIDSON: Do you have a number?

MS. STEINBERG: Your Honor, we object.

JUDGE DAVIDSON: They haven\'t given me a number yet.

MR. KRAUSS: Your Honor, it would be B-1929.

(Bayer Exhibit No. B-1929 was marked for identification.)

MS. STEINBERG: We object. This is a non-witness statement.

JUDGE DAVIDSON: Well, I\'m going to reserve ruling on it\'s admission
into evidence. It will go into the 1285 file, until I hear more what
we\'re talking about.

MR. KRAUSS: Okay.

JUDGE DAVIDSON: Because obviously, if there\'s something in here you
think is of evidentiary nature, you have to get Dr. Cray to testify. If
you think it\'s just something that you\'re going to use with respect to
Dr. Tollefson\'s testimony, then I\'ll allow it. You know, that\'s the
difference. Okay

MR. KRAUSS: Okay. Thank you, Your Honor.

BY MR. KRAUSS:

Q Now, would you agree with me that ‑‑ I think you testified that you
drafted portions of this completed draft testimony?

A Mm-hmm.

Q Would you agree that the subject matters covered in Dr.
Fedorka-Cray\'s completed draft testimony were incorporated into Pages 9
to 12, and in particular, Paragraphs 20 to 29, of your testimony?

Take your time to look at your testimony.

A Yes, that\'s correct. Some of it was from Carolyn Minnick\'s and
Geraldine Ransom\'s testimony, from which I then, in order to help Dr.
Cray with time constraints, drafted and sent to her, she looked at it,
and saw it.

So I don\'t know if everything in here, from 20 to 29, was primarily Dr.
Cray\'s.

Q Would it help you to have a comparison between your Paragraphs 29 to
29 and Dr. Cray\'s completed draft testimony?

A Well, the problem is that I\'m not saying who wrote the first ‑‑ you
know, who put in what. I would say that most of what is in here, from
Paragraphs 21 through 29, are in Paula\'s area. I\'d say that. Okay?

Q Okay.

A FSIS and AR ‑‑ the USDA portion of NARMS.

Q Now, portions of Dr. Fedorka-Cray\'s completed draft testimony
reference certain phenomena that she and others performing Campylobacter
susceptibility testing were experiencing, and she raised questions about
the accuracy of the poultry NARMS results; isn\'t that right?

MS. STEINBERG: Objection, Your Honor.

JUDGE DAVIDSON: Okay. What are you putting it in for? Remember, that\'s
what I said before. If you\'re trying to get this in the record as
evidence, I got to have ‑‑

MR. KRAUSS: Your Honor, for right now, I\'ll withdraw my motion to move
it into evidence, and I\'m just going to use the document with the
witness.

JUDGE DAVIDSON: All right. But you realize, my ruling means that you\'re
talking about whether this witness\'s testimony is going to be affected
by what was in this document as opposed to whether or not this is going
to be on the record as evidence.

MR. KRAUSS: I understand that, Your Honor.

JUDGE DAVIDSON: Okay. Thank you.

MR. KRAUSS: Your Honor, I withdraw my motion without prejudice.

JUDGE DAVIDSON: I understand, counsel.

BY MR. KRAUSS:

Q Now, let me re-ask my question, since it got interrupted.

Isn\'t it true that portions of Dr. Paula Fedorka-Cray\'s completed
draft testimony referenced certain phenomena that she and others
performing Campylobacter susceptibility testing were experiencing and
that raised questions about the accuracy of the poultry NARMS results?

MS. STEINBERG: Your Honor, objection to the form of the question.
There\'s no evidence that this is the completed testimony, completed
draft testimony.

JUDGE DAVIDSON: I think we can solve that problem, if you stop referring
to it as the completed draft testimony. It is in 1285 as Exhibit B-1929,
and you just use that ‑‑

MR. KRAUSS: No, Your Honor, I did not make that representation. It is
not in the docket as D-1929.

JUDGE DAVIDSON: It is now.

MR. KRAUSS: Oh, it is now. Thank you.

JUDGE DAVIDSON: As B-1929, so if you stop referring to it as completed
draft testimony, you\'ll obviate the necessity for objections from the
other side.

MR. KRAUSS: Thank you, Your Honor.

JUDGE DAVIDSON: Okay.

THE WITNESS: Okay, but I\'ve got another objection, as well, that\'s
more technical.

You\'re asking two questions. Let me answer the first part, did she have
this paragraph that talked about phenomena in isolating Campylobacter.

And that\'s the paragraph we objected to, because our laboratory at FDA
did not have that problem. The CDC food-borne disease laboratory did not
have that problem. Many other laboratories that deal with Campylobacter
do not have the problem. So we objected to her statement about \"and
others.\"

Now, your second part of your question was, doesn\'t that invalidate the
animal NARMS data.

BY MR. KRAUSS:

Q Well, that wasn\'t my question. My question was, didn\'t she raise
questions about the accuracy of the poultry NARMS results?

A Okay. And my answer to that is, I consider this, as an epidemiologist
and a person used to reviewing data, as a much more minor issue than the
issue with the nalidixic acid susceptible isolates only coming from Dr.
Cray\'s lab.

So in my mind, questions were raised about the animal ‑‑ poultry
isolates from NARMS before this testimony was ever drafted.

Q Okay.

A Okay?

Q When you used the word \"this,\" you had the same problem I had
earlier ‑‑

A Yeah, right.

Q ‑‑ you were pointing to something in the document, and we don\'t know
what that is for the record.

You apparently ‑‑ there\'s two issues. There\'s the \"this\" and
there\'s the speciation. What was the \"this\"?

A Dr. Cray had said that she has problems in her laboratory with
aggregation of colonies and mixed cultures, and those are two different
issues, but the one, the mixed culture issue, we think is not really a
problem. Most infections are due to a mixture of organisms.

For example, if somebody has a fluoroquinolone resistant Campylobacter
infection, it doesn\'t mean that all of their Campylobacter are
resistant, by any means. They will have a mixed infection of susceptible
and resistant. Okay? So we didn\'t think of that as a phenomenon.

And then the issue of aggregation, other people, other laboratories have
not had that problem, so we did not want to introduce that into her
testimony as a major item. I mean, we just didn\'t agree with it.

Q What do you understand ‑‑

A Our microbiologists did not agree with it.

Q What do your understanding the aggregation issue to be?

A Well, when she talks about aggregation of isolates, she was thinking
that it meant ‑‑ Dr. Cray was thinking that it means that you can\'t
speciate the isolates very easily, and that you can\'t susceptibility
test them very easily.

Susceptibility testing of isolates is a probability issue. Okay?
There\'s a certain number resistant, there\'s a certain number
susceptible. Which isolate you pick from the plate has more to do with
whether or not it\'s going to show up resistant or susceptible, until
that resistance reaches something greater than 50 percent, right, as a
prevalence.

So it\'s always ‑‑ we\'re sort of always underestimating resistance, if
you will, until resistance becomes so common that your limit of
protections are no longer there, so the aggregation issue, I just
didn\'t think it was an issue at all, and our microbiologists didn\'t,
either.

Q And who is that?

A Doctors Dave White, Pat McDermott, and Bob Walker. So we objected. We
did not want to keep that in the testimony.

Q But isn\'t it true that Dr. Fedorka-Cray, on the susceptibility to
nalidixic acid issue, was prepared to testify in this case:

\"Thus, by use of susceptibility to nalidixic acid as a criteria for
selection, isolates would have been expected to be susceptible to
nalidixic acid and therefore also susceptible to fluoroquinolones.
However, a percentage of the isolates were resistant to nalidixic acid
with additional fluoroquinolone resistance observed for some of the
isolates.

\"This suggested that either sensitivity was not absolute as defined by
clinical laboratory standards or that other phenomena were occurring.\"

MS. STEINBERG: Objection, Your Honor.

JUDGE DAVIDSON: Sustained. You\'re reading into the record testimony
that is long, and convoluted, and may or may not have been received in
evidence in this case if I had a chance to rule on it, but the witness,
the person you\'re trying to get the testimony in from is not here, not
before me, and this witness can say yes, she was prepared to testify to
that, but she doesn\'t have to answer, as far as I\'m concerned.

Move on.

MR. KRAUSS: Okay, Your Honor. Please allow me to approach it one
different way here?

JUDGE DAVIDSON: Go ahead.

MR. KRAUSS: The witness has already testified that she had reviewed ‑‑

JUDGE DAVIDSON: I understand.

MR. KRAUSS: ‑‑ some drafts.

JUDGE DAVIDSON: But you\'re still going in an area which is putting
stuff in the record which I can\'t rely on, because I don\'t have this
witness in front of me. She\'s not subject to cross examination.

You\'re trying to back-door, and get stuff on this record which doesn\'t
help, so you\'re wasting our time with it unless you think you\'ve got
something really important here, as I said before, as it reflects on
this witness\'s testimony only; and yet you read a long passage of what
she was prepared to testify to, and I believe that\'s contrary to what
my ruling was.

MR. KRAUSS: Thank you, Your Honor.

JUDGE DAVIDSON: Okay.

BY MR. KRAUSS:

Q When you reviewed Dr. Fedorka-Cray\'s draft testimonies, like you
testified that you did, was there information in the draft testimony
relating to the speciation of Campylobacter isolates with nalidixic
acid?

A Yes.

Q And ‑‑

A This.

Q Right.

A Yes.

Q And did that testimony that you reviewed, the draft, did it say that,
based on your recollection, did it raise an issue as to whether
sensitivity was absolute or not?

MS. STEINBERG: Objection, Your Honor.

JUDGE DAVIDSON: Sustained. You\'re still doing the same thing. I can\'t
help what she said or didn\'t say, but it\'s not before me.

If you want to get this witness to change her testimony or alter it in
some way based on what that says, fine, but you\'re already asked her
that and she said she didn\'t agree with it, so I don\'t know ‑‑ move on
to something else, please.

MR. KRAUSS: Thank you, Your Honor.

BY MR. KRAUSS:

Q Dr. Tollefson, let me turn your attention to Table, the table in your
testimony on Page 12.

A Mm-hmm. In Paragraph 29.

Q Right. Now, this table relates to poultry NARMS, doesn\'t it?

A Correct, only poultry NARMS.

Q Now, at the beginning of your testimony when you were being questioned
by Ms. Steinberg, you made a correction to your testimony regarding the
2001 poultry NARMS?

A Correct.

Q And you say that that has been published?

A Yes, it has, in abstracts and presentations. What I changed was on
Page 8, because I said that 2001 data were not available yet, but it\'s
really 2002, which is repeated in the table.

Q Yes.

A Not yet available, not published.

Q Okay. So the 2001 data are available, right?

A Yes.

Q But they\'re not published?

A Well, it depends on what you mean. Dr. Cray has presented at meetings
on that data, so they\'re public, and they\'re also ‑‑ they\'ve been
confirmed. They\'re not preliminary. Okay?

NARMS works on a calendar year system, so now we\'re in April 2003, all
the 2002 isolates have been received, possibly not all susceptibility
tested; but then we go back and check and, you know, make corrections,
and so on. Then, that data is available in the reported audit.

So I\'m not sure what you\'re asking. Published in a peer review
journal, I don\'t believe so.

Q Let me clarify.

A Okay.

Q Isn\'t it true that, for other years, for the animal isolates, the
veterinary isolates from NARMS, there\'s a final ‑‑

A Report.

Q ‑‑ report?

A Yes.

Q And that gets disseminated?

A Right, it\'s on our web site.

Q Right. And that\'s disseminated as a final report?

A Right.

Q That has not happened to the 2001 poultry NARMS for Campylobacter;
isn\'t that right?

A That\'s correct.

Q Now, looking at your table, isn\'t it true that over the time period
1998 to 2001, there were changes in the sources of the whole carcass
rinsates used to collect Campylobacter isolates?

A Yes.

Q And isn\'t it true that over the time period 1998 to 2001, different
geographic areas were represented in the poultry NARMS sample?

A No, we actually don\'t know that.

Q Well, for example, in 2001, isn\'t it true that the isolates were from
the eastern lab only?

A Yes, but that doesn\'t represent poultry slaughtered in the eastern
part of the country. FSIS has three labs, but what they receive is based
on their load.

Q Okay.

A So they could be getting isolates from all over the country, and they
do get isolates from all over the country.

Q Looking at your table, comparing 2000 to 2001, isn\'t it true that the
sources of isolates from 2000 were different than the sources of
isolates in 2001?

A Not really, not enough to make a difference. The sources are all from
the FSIS regulated, federally regulated slaughter plants.

What we had available in \'98, \'99, and 2000 were programs where FSIS
was actually looking at Campylobacter. It\'s the same kinds of chickens
as are in their Salmonella program. Okay.

So what happened is once they stopped looking specifically at
Campylobacter, we had to use their Salmonella program chickens, but
they\'re the same chickens. I mean, it\'s all the chickens going through
the federally inspected slaughter plants.

Q Have you done a comparison between the sources of chickens from the
broilers nationwide young chicken study and FSIS chicken monitoring
program that was the source of the 2000 isolates and the Salmonella
program rinsates, eastern lab only, that was the source of the 2001
isolates?

A What we had in 2000 were not just the broilers. We also had the whole
chicken laundry program, so it was everything. Okay?

Q Right.

A Okay. And then in 2001, the Salmonella program rinsates are
everything, potentially everything. What we actually receive, we don\'t
know.

Q My question was whether anybody did a comparison study between the
sources for the 2000 and the sources for the 2001?

A All right. Let me answer it another way. Our sources of isolates come
from federally inspected slaughter plants, which is Food Safety and
Inspection Service of USDA. We do not know where, like which plant is
sending in which isolate from what kind of chicken. We don\'t know.
That\'s all blinded. We do not have that information.

The reason we, FDA, consider it a valid sample is simply because of the
numbers. We get ‑‑ all the Salmonella rinsates that they\'re doing have
an equal probability of coming into the NARMS program, if that explains
it better, but we couldn\'t do a comparison, because we don\'t know.

Q Okay. And now you\'ve answered my question.

A All right. Thank you. I\'m sorry.

Q Nobody did such a comparison?

A No. No. That\'s not possible.

JUDGE DAVIDSON: Excuse me, Mr. Krauss. The witness has been on for over
an hour-and-a-half, and since we just had some exodus from attorneys, I
think maybe it\'s time for a break, if it\'s okay with you. If you want
to ask a few more questions, first, find a convenient, place, that\'ll
be okay.

MR. KRAUSS: I\'m happy to break here, Your Honor.

JUDGE DAVIDSON: All right. We\'ll take a 10-minute recess.

(A brief recess was taken.)

JUDGE DAVIDSON: Counsel for Bayer is not here at the moment, but I had a
question directed to counsel for CVM which is procedural in nature.

There was a reference made to G-589, and what I need to know, since I
think somebody is not giving me all the information I need, not from
your standpoint, but from ‑‑ come on in. It\'s all right. No problem.
We\'re just talking about G-589. I want to know whether it\'s in
evidence or not in evidence.

MS. STEINBERG: It is in evidence.

JUDGE DAVIDSON: That\'s what I was afraid of. The people who did my
disks here so that I could follow along ‑‑

MS. STEINBERG: Would you like a copy of it? I have a copy.

JUDGE DAVIDSON: That will be fine. Thank you. But I\'ve got to get
another disk made up here, because they didn\'t do what I asked them to
do.

While you were out, we decided that the case doesn\'t have to go on
anymore.

(Laughter.)

MR. KRAUSS: Who says prayers can\'t be answered, Your Honor?

JUDGE DAVIDSON: No, I was just talking about ‑‑ we\'re on the record ‑‑
I was just talking about the fact that the disks that were prepared for
me by the dockets people didn\'t include all of the evidence that I
asked them to, so I\'m going to have to get some changes on that.

So you\'ll have to bear with me when you refer to things that are on the
record, and you have to tell me whether it\'s in evidence or just in the
1285 when you\'re referring to it, and you have to give me an
opportunity to try and find it someplace.

MR. KRAUSS: Okay, Your Honor.

JUDGE DAVIDSON: Because I had asked them to give me a disk that showed
all of the evidentiary record with the strikes, and what they gave me
was just everything from my Order with motions to strike, so there\'s a
lot of stuff not here.

Okay. Proceed.

MR. KRAUSS: Thank you, Your Honor.

BY MR. KRAUSS:

Q Dr. Tollefson, returning now to the table at Page 12 of your
testimony, you\'re looking at the year 2000 and the year 2001, in
particular.

In the year 2000, the isolates were speciated using nalidixic acid and
cephalothin, right?

A Mm-hmm, yeah.

Q And that was not done in 2001, right?

A Correct.

Q Let me turn your attention to Page 19 of your testimony, in particular
Lines 23 and 24. It refers to fluoroquinolone resistance among
Campylobacter found on chicken and turkey carcasses from the animal arm
of NARMS prior to 2001. Do you see that testimony?

A Mm-hmm.

Q Isn\'t it true that the animal arm of NARMS did not test
fluoroquinolone resistance among Campylobacter found on turkey carcasses
before 2001?

A (Examining) It must be true. We must have had turkey from epidemiology
studies. Yes, you\'re correct. That\'s a mistake.

Q Your testimony here is not correct?

A It\'s not correct.

Q Dr. Tollefson, turning to the human arm of NARMS, if you will, your
testimony states that one of the goals and objectives of NARMS is to
provide descriptive data on the extent and temporal trends of
anti-microbial susceptibility in enteric organisms from the human and
animal populations.

A Right.

Q Is that right?

A That\'s correct.

Q Now, would you agree with me that NARMS could not establish causal
trends?

A NARMS alone cannot establish causal trends.

Q Now, focusing on the human arm of NARMS, NARMS ‑‑ the human of NARMS
does not collect any data, other than maybe age and a patient ID, from
Campylobacter patients who submit their stool samples; isn\'t that
right?

A Correct. There\'s limited demographic information.

Q And that limited demographic information does not include, for
example, whether the patient who is submitting their sample may have
used a fluoroquinolone or any other antibiotic before they submitted
their sample, right?

A Correct.

Q So published reports from NARMS that report the percent of human
isolates that are fluoroquinolone resistant, human Campylobacter
isolates that are fluoroquinolone resistant, those numbers don\'t
exclude patients who may have taken an antibiotic or ‑‑ fluoroquinolone
or any antibiotic ‑‑ before they submitted their sample?

A That\'s correct.

Q And that limited demographic information also does not include whether
the person who\'s submitting their stool sample and then the
Campylobacter isolates for susceptibility testing may have undertaken
foreign travel prior to submitting, or prior to getting their
Campylobacter infection; is that right?

A Correct.

Q So published reports from NARMS regarding the percent of Campylobacter
isolates that are fluoroquinolone resistant includes persons who got
their Campylobacter infection through foreign travel?

A We don\'t know that. First of all ‑‑

Q You can\'t exclude them, because you don\'t collect the data; isn\'t
that right?

A I don\'t believe you get Campylobacter infections by foreign travel.
You get it from ‑‑ they may have been traveling in the week before
showing signs of Campylobacteriosis. It\'s true, we do not exclude those
people from NARMS. There\'s no ‑‑ it\'s a public health surveillance
system. There\'s no way to exclude them.

Q So, for example, NARMS would not exclude isolates from persons who had
traveled to, say, Mexico, prior to having their Campylobacter infection?

A Correct.

Q And it wouldn\'t exclude persons that may have traveled to Spain
before they came down with their Campylobacter infection?

A Correct.

Q They wouldn\'t exclude ‑‑

MS. STEINBERG: Objection.

JUDGE DAVIDSON: That\'s enough. It wouldn\'t exclude any of them.

MR. KRAUSS: Thank you, Your Honor.

(Laughter.)

BY MR. KRAUSS:

Q In fact, isn\'t it true that NARMS doesn\'t collect any data that
would allow for determination of the source of the Campylobacter
infection?

A Correct. It\'s simply a surveillance system.

Q Now, in your testimony you testified that in 2003, all 50 states and
three local health departments will participate in NARMS?

A That\'s correct, as of now.

Q That\'s not true for Campylobacter monitoring, is it?

A No. Campylobacter is very difficult and unique, and you should use Dr.
Angulo\'s testimony for that.

Q Okay.

A Which I think I referred to when I talked about Campylobacter. It
changes, year to year.

Q Okay. So when you testified that for most of the period relevant to
the hearing on fluoroquinolones 27 state and local public health
departments representing 63 percent of the U.S. population submitted
isolates to the CDC for inclusion in NARMS, that wasn\'t referring to
Campylobacter monitoring?

A No, that\'s in general. Campylobacter is a small part of NARMS.

Q Right. So you\'re not suggesting for the purposes of this hearing that
27 states representing 63 percent of the population were submitting
Campylobacter isolates?

A No. For Campylobacter participating public health laboratories. See
written direct testimony of Dr. Angulo, farther down in the paragraph.

Q Right. But I wanted to talk about your testimony.

A Mm-hmm. That\'s fine.

Q Now, from ‑‑ you have a list on Page 7 of participating states that
participate in NARMS, right?

A Correct.

Q Now, Hawaii didn\'t submit any Campylobacter isolates from 1996 to
2001, did they?

A No.

Q And neither did Kansas?

A I don\'t think so. I\'d have to look at Fred\'s testimony.

Q Louisiana didn\'t submit any, did they?

A No, I don\'t think so.

Q Maine didn\'t?

A I\'m telling you, I\'m going to have to look at Dr. Angulo\'s
testimony to see which states were participating in NARMS over those
years.

Q Okay.

A Which states were participating for Campylobacter in NARMS over those
years.

Q Okay.

A They did change each year.

Q Let me short-circuit this a little bit so Judge Davidson will be
happy.

Isn\'t it true that for all the time that NARMS has been collecting
human Campylobacter isolates, it collected from, at most, nine states
and not 27?

A Yes, that\'s true. Sentinel Laboratories within the states.

Q Let me turn your attention to the human NARMS sampling scheme.

A Okay.

Q Now, according to your testimony, for Campylobacter, participating
public health laboratories select and forward the first Campylobacter
jejuni or Campylobacter coli isolate received in each laboratory each
week to CDC for susceptibility testing; is that right?

A Yes. That\'s what they send to CDC.

Q And the sampling scheme is different for other enteric pathogens that
NARMS monitors, isn\'t it?

A Oh, yeah, absolutely. Campylobacter is much more expensive.

Q How does the fact that Campylobacter is much more expensive impact the
sampling scheme?

A Well, we needed to limit the number of Campylobacter isolates that we
could do in NARMS because of the cost per isolate, if you will. Think of
it that way.

Q So for Campylobacter monitoring through human NARMS ‑‑

A Right.

Q ‑‑ the sampling scheme is limited?

A It\'s limited, right. Now, Campylobacter also, not all states isolate
that organism, which is another reason why we only do some of them.

Q The most it\'s ever been is nine?

A Yeah, and it probably won\'t be more than that.

Q For non-typoid Salmonella, NARMS, participating NARMS public health
laboratories select every 10th isolate, right?

A For Salmonella typing, correct.

Q I thought it was non-typing.

A No. No. Where are you?

Q Page 7 of 20, Line 26.

A Oh, okay. Right.

Q It\'s non-typing?

A Right. Now, that\'s ‑‑ okay. For most of the time that was true. It\'s
not true anymore. It\'s changing.

Q Okay.

A But if you\'re going to compare it to Campylobacter ‑‑ is that what
you\'re trying to do?

Q Yes.

A Yes. It was every 10th.

Q Okay. And for Shigella, participating public health laboratories that
are participating in NARMS, sent every 10th Shigella, right?

A Correct.

Q And for E. coli 157, they sent every fifth isolate, right?

A Right.

Q So ‑‑ and for Campylobacter, it\'s the first of the week, right? One
week?

A Right.

Q So for a participating public health laboratory, let\'s say that
laboratory gets 100 isolates in a week of Salmonella, it would send 10
for susceptibility testing in NARMS?

A It would send 10 to CDC, correct. They not all be susceptibility
testing.

Q They would send 10?

A Right.

Q To CDC?

A Right.

Q And that same lab, if in a given week it receives 100 Campylobacter
isolates, in that one week, it would send one isolate for susceptibility
testing ‑‑

A Correct.

Q ‑‑ is that right?

A That\'s correct.

Q And so in that example, for the Salmonella, every one of the isolates
that\'s sent represents 10 other isolates, right?

A Right.

Q And in the Campylobacter example, that one isolate would represent 100
isolates, right?

A That\'s correct, in that hypothetical example.

Q Right. And then, in that same scenario, if a participating state
laboratory received 50 Salmonella isolates, it would send five, right?

A Mm-hmm.

Q And if it received 50 Campylobacter isolates, it would send one?

A One, in that week.

Q So still, for the Salmonellas, it\'s representing ‑‑ every one isolate
sent represents 10, right? And in this instance, the one isolate from
Campylobacter represents 50, right?

A That\'s right.

Q Going the other way, let\'s say that a participating state laboratory
receives 200 Salmonella isolates, it would send 20 for testing, right?

A I agree.

Q And ‑‑

MS. STEINBERG: Your Honor, this line of questioning has been asked ‑‑

JUDGE DAVIDSON: Where are we going with this, Mr. Krauss?

MR. KRAUSS: Your Honor, I\'m trying to demonstrate that the sampling is
not representative in Campylobacter versus ‑‑

JUDGE DAVIDSON: Well, it\'s in the testimony ‑‑ 10, five, one. I mean,
go to your brief. I mean, it\'s here. There\'s no question. If you want
to get from this to somewhere else, fine, but don\'t keep giving me more
examples of ‑‑

MR. KRAUSS: Thank you, Your Honor.

JUDGE DAVIDSON: I think we can all figure what a 10th, 5th, 20th, 20
percent, 10 percent, and 1 percent of the samples, with your example,
but there\'s no need to go through it any more.

MR. KRAUSS: Thank you, Your Honor.

JUDGE DAVIDSON: If you want to draw some conclusion from it, go right
ahead.

BY MR. KRAUSS:

Q Dr. Tollefson, do you agree that the frequency of Campylobacteriosis
in the United States over time in a given year varies, month to month?

A We think so, yes. We think there\'s some kind of seasonal variation.

Q Okay. And in that seasonal variation, would you agree with me that
typically the peak for human Campylobacteriosis is sometime in
July-August time frame?

A Correct.

Q Would you agree with me that there\'s a seasonality to the ‑‑

MS. STEINBERG: Your Honor, objection. This is beyond the scope of Dr.
Tollefson\'s testimony.

THE WITNESS: That\'s true.

JUDGE DAVIDSON: Where are you doing ‑‑

MR. KRAUSS: Your Honor, she\'s ‑‑

JUDGE DAVIDSON: Just tell me where you\'re going, so I\'ll know.

MR. KRAUSS: May I approach?

JUDGE DAVIDSON: Sure.

(Counsel approached the Bench.)

(Counsel conferred with the Judge.)

BY MR. KRAUSS:

Q Dr. Tollefson, would you agree with me that fluoroquinolone resistant
Campylobacter, that there\'s evidence that fluoroquinolone resistant
Campylobacter also varies over time, over the course of a year?

A I don\'t know that.

Q Isn\'t it true that in the study by Kirk Smith, he found a higher
level of fluoroquinolone resistance in the winter months, say January?

A I\'d have to refresh my memory. I think he found more ‑‑

Q I have it here. I\'m sorry, Dr. Tollefson.

A Yeah. Oh, that\'s right, with notes on it.

MS. STEINBERG: Your Honor, I object. Again, it\'s beyond the scope of
the testimony and Dr. Smith\'s exhibit speaks for itself.

JUDGE DAVIDSON: I understand. I\'m going to allow it for a while yet,
because the basis of the witness\'s testimony is the reliability of the
studies. There\'s where he\'s going.

MS. STEINBERG: Thank you, Your Honor.

JUDGE DAVIDSON: We\'ll let it go.

(Pause.)

MR. KRAUSS: Dr. Tollefson, let me approach with our battered copy of Dr.
Smith\'s study; and in particular, I\'m referring to Page 3 of G-589.
This is in evidence, Your Honor.

BY MR. KRAUSS:

Q And if you take a look at the draft that demonstrates, over time,
percentage of resistant isolates ‑‑ would you take a look at that?

A Uh-huh, that it increased over time, by year and by quarter.

Q Do you see that there\'s a peak in every year?

A Yes, and it flows with the total. At the bottom is the total number,
and these are the resistance levels.

Q Right, and the resistance levels, as demonstrated by the draft, on
Page 3, the top draft, Figure 1, doesn\'t it demonstrate a peak in
resistance in a regular pattern at the beginning of every year?

A Yes. I\'m not aware of others ‑‑

Q But you agree that that\'s what this shows?

A Yes.

Q Are you aware that the human NARMS data as reported by quarter shows a
higher level of resistance consistently in the first two quarters,
compared to the last two quarters?

A It generally shows a higher level of resistance, yes, for six months,
same thing. Yes.

Q For Campylobacter?

A For Campylobacter, I agree.

Q So that would be, besides the Smith article, another reference that
resistance in Campylobacter is seasonal; would you agree?

A I guess. Yeah.

Q Now, I think I already asked this, but since I was interrupted, I need
to make sure I did. I\'m sorry.

Didn\'t you agree that, overall, Campylobacteriosis peaks sometime in
the summer?

A Yes.

Q Now, if during the peak in the summer ‑‑ you would agree with me,
wouldn\'t you, that during the summer months, a participating laboratory
collecting NARMS Campylobacter isolates would get more isolates than,
say, in January?

A Probably, yes.

Q Let\'s say in January the lab got 100 isolates and ‑‑ I\'m sorry. In
July, the lab got 100 isolates and in January it got 25 isolates, for
the sake of our discussion.

A Yes.

Q In both instances, if it received those isolates in a week, it would
send one, one isolate, right?

A Correct.

Q And then the human arm of NARMS would get those isolates and include
it in their yearly sample, right?

A Most of them. Sometimes the participating labs send too many, or
whatever.

Q And then, human NARMS typically will get somewhere around 50 isolates
from each participating site, if they\'re sending one a week, right?

A Right.

Q And in those 50 isolates in our example, one might be from the 100 in
July, right?

A That\'s correct.

Q And one might be from the 25 in January, right?

A Yes.

Q And the peak in resistance is in January, right?

A Right, but ‑‑

Q And each of those would be given ‑‑

A Equal weight.

Q Yes.

A That\'s how surveillance systems, what we call surveillance systems
are done. Now ‑‑

Q But you don\'t disagree that that\'s what\'s happening?

A No, I don\'t disagree that it\'s happening. I disagree with the
implication of a large effect.

Q Would you agree that NARMS does not calculate ‑‑ the NARMS program
does not calculate an incidence rate?

A Correct.

Q Let me finish my question, for the record. NARMS does not calculate an
incidence rate of fluoroquinolone resistant Campylobacteriosis in the
United States?

A Correct.

Q All NARMS does is report a percentage of the collected isolates that
it has determined to be resistant, isn\'t that right ‑‑ Campylobacter
isolates?

A Correct. Correct.

Q Now, you\'ve already agreed with me, Dr. Tollefson, that one of the
purposes of NARMS, in your opinion, is to track trends in antibiotic
resistance in enteric pathogens over time; isn\'t that right?

A That\'s correct.

Q And you\'ve agree with me today that annual incidence rates are used
by epidemiologists to examine trends of disease incidence over time,
right?

A Yes, or prevalence ‑‑ or prevalence rates.

Q Right. Both.

A Right.

Q Right. Incidence or prevalence.

A Okay.

Q And you\'ve agreed with me today that CDC MMWR reports on incidence of
food-borne illness are reliable, right?

A Yes.

Q In your opinion, are the annual percentages of fluoroquinolone
resistance in Campylobacter that are reported by human NARMS, are they
representative of the national proportion of Campylobacter cases that
are resistant infections?

A In my opinion, yes.

Q So isn\'t it true that if you assume that human NARMS data are
representative of the national proportion of Campylobacter cases that
are resistant infections, and you use the reliable CDC MMWR data on the
national incidence of Campylobacteriosis, you can calculate an annual
incidence rate of fluoroquinolone resistant Campylobacteriosis cases ‑‑
you don\'t agree?

A No, because, first of all, I want to talk about prevalence, not
incidence. We\'re not talking about incidence here.

MS. STEINBERG: Your Honor ‑‑

THE WITNESS: There\'s only one way to do that.

MS. STEINBERG: Your Honor, the question asked for a statistical
analysis. It\'s beyond the scope of the testimony.

JUDGE DAVIDSON: Well, she\'s already attempting to answer it, so ‑‑ I
mean, you know, you got to get your witness to know that when you
object, she\'s supposed to stop talking. But if she wants to keep
talking, that\'s her business.

MS. STEINBERG: Thank you, Your Honor.

JUDGE DAVIDSON: What was the answer again?

THE WITNESS: Well, we\'re not dealing with incidence rates, or incidence
of fluoroquinolone resistant Campylobacteriosis or anything else.

BY MR. KRAUSS:

Q I thought you said that if NARMS reports 14 percent resistance,
fluoroquinolone resistance in Campylobacter ‑‑

A It\'s not a representation of the incidence rate of fluoroquinolone
resistant NARMS (sic). That\'s what I answered. It is a representation
of the prevalence rate of fluoroquinolone resistant Campylobacteriosis
in the U.S.

Q For that year?

A Okay.

Q Let me make sure I get this right. NARMS reports, let\'s say, 14
percent fluoroquinolone resistance in Campylobacter for a given year.
Okay? Let\'s take that.

A Okay.

Q Would it be your opinion, then, if that\'s the report, and if it\'s
representative of the proportion of Campylobacter cases in the country
that are resistant, that of all the Campylobacter cases in the country,
you tested them all and you\'d have 14 percent resistance?

A Approximately.

Q So isn\'t it true that you can take what you just said would be a
national prevalence of the amount of the amount of fluoroquinolone
resistant Campylobacter cases in a given year and use that with the
incidence rate of all Campylobacteriosis cases in a given year, and
calculate an incidence rate of fluoroquinolone resistant
Campylobacteriosis cases in the country?

MS. STEINBERG: Your Honor, again, it\'s beyond the scope, and I think
that most of that has been asked and answered.

MR. KRAUSS: Your Honor, this witness designed the NARMS system. I\'m
asking her what the ‑‑

JUDGE DAVIDSON: I\'m going to allow it.

THE WITNESS: No. That\'s the answer. No.

BY MR. KRAUSS:

Q Okay. Now let me just ‑‑

JUDGE DAVIDSON: Which you care to explain?

THE WITNESS: Yeah. Can I explain that?

JUDGE DAVIDSON: Absolutely. Go right ahead.

BY MR. KRAUSS:

Q Go ahead and explain.

A NARMS is a public health surveillance system. We designed it so that
it has a good probability of detecting resistance should it exist in
each of these several food-borne pathogens, and it\'s based on
practicality, above all else.

Now, what it\'s capable of doing is, if you believe that Salmonella in
California is no different than Salmonella in Maine ‑‑ Salmonellosis or
Campylobacteriosis or any food-borne disease ‑‑ and we know that it
isn\'t, it\'s based on representative, in general ‑‑ we try to make them
as geographically diverse as possible in the case of Campylobacter. In
the case of everything else, we\'ve got all 50 states represented.

We take a limited number of samples to give us an indication of the
prevalence rate of resistance among these food-borne disease pathogens.

Now, your issues about seasonality and resistance varying with
seasonality is true. We\'ve looked at that, and we think the impact is
very minimal.

That doesn\'t mean that we\'re going to say that in 2001, we got 19
percent fluoroquinolone resistance in Campylobacter in humans, that
it\'s absolutely 19 percent, but it\'s approximately one-fifth, or
approximately 15 percent, or whatever. It\'s not exact. It\'s a public
health surveillance system. Okay.

Q But those are ‑‑ human NARMS does publish what it believes to be a
percentage of all Campylobacteriosis cases in the country in a given
year?

A Right. It\'s an indicator of what\'s out there throughout the U.S.,
yes.

Q Right. Right.

A Okay. But that\'s something, it\'s technically very different from
incidence.

Q Okay. Well ‑‑

A Okay. You need an analytical epidemiology study to determine incidence
rates.

Q It\'s your position, is it not, that if human NARMS for 1997 reports
13 percent fluoroquinolone resistant Campylobacter on the human side of
NARMS, that all of the Campylobacteriosis cases in 1997, of all of them,
13 percent of those, best estimate based on human NARMS, were resistant?

A Were fluoroquinolone resistant.

Q Right.

A Approximately 13 percent, right.

Q Okay. Now, if CDC, in their MMWR reports, report that there\'s 25.2
cases of Campylobacter per 100,000 people in that year, it\'s your
position, is it not, that 13 percent of those, give or take, as good or
as accurate as human NARMS can be, 13 percent of those would be
resistant infections, right?

A Correct.

Q Okay. Dr. Tollefson, if you could look at the two exhibits that I gave
you, G-1791, and the other MMWR exhibit that I gave you, G-748 ‑‑ I gave
that thank you, didn\'t I?

A No, I don\'t have 748.

MR. KRAUSS: All right. My apologies. Your Honor, this is Government
Exhibit 748, and I believe it\'s in evidence.

BY MR. KRAUSS:

Q Now, Dr. Tollefson, if you take a look at G-748, on Page 2, Table 1,
do you see a table that\'s the incidence of diagnosed infections for
pathogens through the Food Net ‑‑

A Yes.

Q ‑‑ surveillance network?

A Right.

Q Okay. And you see the Campylobacter is listed there for \'96, \'97,
\'98, \'99, and 2000, right?

A Yes, right.

Q And these are incidence rates, right?

A Right, but through Food Net.

Q Through Food Net.

A Right.

Q And so CDC has estimated, for example, for 1997, that there were 25.2
cases of Campylobacteriosis per 100,000 people in the United States for
the year 1997?

A Right.

Q From what you testified about earlier, human NARMS, the human side of
NARMS reported 13 percent human resistance, right?

A Right.

Q So isn\'t it true that if, for 1997, the incident rate is 25.2 per
100,000, and NARMS reports 13 percent resistance, it\'s your position
that 13 percent of each of these 25.2 infections would be resistant
infections?

A Approximately, yes.

Q So that would give us a resistant incidence rate, if we multiply 13
percent by 25.2, we\'d get 3.28.

A Okay.

Q Yes?

A I wouldn\'t call it an incidence rate, the problem being that Food Net
is an active surveillance system, that\'s more statistically robust, to
get new cases of disease as they arise in the population. NARMS is not.
The Campylobacter, they\'re all Food Net sites, sometimes. Sometimes
they\'re not. But it\'s a Sentinel Lab system.

I would not call that an incidence rate. I wouldn\'t put my money on
that number. Now, if you\'re asking me is it approximately that, fine.

Q Okay.

A I guess I don\'t know what you\'re trying to get to.

Q Well, just allow me to go through this.

A Okay.

Q So would you agree that, then, for 1997, the good estimate of the
number of fluoroquinolone resistant Campylobacter cases per 100,000
people in the United States that were resistant would be 3.28 per
100,000?

A Okay. Yes.

Q All right. Now, if you\'ll take a look at G-748 for 1998, CDC reports
an overall incidence rate for Campylobacteriosis of 21.4, doesn\'t it?

A Yes.

Q And the human NARMS system reported for 1998 14 percent resistance,
didn\'t it?

A Right.

Q So we could get a good estimate by your testimony, a good estimate of
the number of fluoroquinolone resistant Campylobacter infections per
100,000 people by taking 14 percent of 21.4, couldn\'t we?

A Approximately, yeah.

Q And so that would be 3.0 cases of resistant infection per 100,000?
It\'s actually 2.996, but I founded up.

MS. STEINBERG: Your Honor, objection. The witness shouldn\'t be required
to do a calculation on the stand without a calculator ‑‑

MR. KRAUSS: Your Honor, I\'m handing the witness a calculator.

JUDGE DAVIDSON: No, that\'s all right.

THE WITNESS: It\'s approximate.

JUDGE DAVIDSON: We\'ll let it go for now. If there\'s a problem with the
calculations, you\'ll let me know, I\'m sure.

MR. KRAUSS: Thank you, Your Honor.

BY MR. KRAUSS:

Q For 1999, Dr. Tollefson, if you would take a look at Exhibit G-748,
Page 2, Table 1, CDC reported an overall incidence rate of
Campylobacteriosis in the United States of 17.5 per 100,000, didn\'t
they?

A Yes.

Q And your human NARMS system for 1999 reported a resistance rate of 18
percent, didn\'t it?

A Yes.

Q We could get a good estimate of the number of fluoroquinolone
resistant Campylobacter cases in the United States for 1999 per 100,000
by taking 18 percent of 17.5, couldn\'t we?

A Yes.

Q And that would be 3.15.

A Okay.

Q And if you take a look at Exhibit G-748 for 2000, CDC reported, did
they not, an incidence rate for Campylobacteriosis of 20.1 cases per
100,000?

A Right.

Q And your human NARMS system for the year 2000 reported resistance of
14 percent; isn\'t that right?

A Right.

Q So we could get a good estimate of the level of fluoroquinolone
resistant Campylobacter infections per 100,000 people in the year 2000
by taking 14 percent of 20.1, couldn\'t we?

A Mm-hmm.

Q Yes?

A Yes.

Q And that would give us 2.81, wouldn\'t it?

A Mm-hmm.

Q Yes?

A Yes.

Q Now we\'ll need to move to Exhibit, Government Exhibit 1791, and
there\'s a table on Page 5?

A Yes.

Q In this CDC MMWR report, CDC reports an overall incidence of
Campylobacter in the United States of 13.8 cases per 100,000, doesn\'t
it?

A Yes.

Q Your human NARMS system reports for 2001 resistance of 19 percent,
doesn\'t it?

A Right.

Q We could get a good estimate of the number of fluoroquinolone
resistant Campylobacter cases per 100,000 in the United States in 2001
by multiplying the 19 percent by 13.8, couldn\'t we?

A Yes.

Q That would be 2.62, wouldn\'t it?

A Right.

Q So from 1997 to 2001, the good estimate that we can calculate for the
number of fluoroquinolone resistant Campylobacter infections per 100,000
people in the United States in each of those years, except for 1999,
it\'s gone down, hasn\'t it?

A The rate has gone down.

Q Right.

A Correct.

Q And it\'s gone down from, in 1997, 3.28, to 2001, 2.62, right?

A The rate has gone down, correct.

Q And that rate is a good estimate of the number of ‑‑

JUDGE DAVIDSON: All right, asked and answered.

MR. KRAUSS: Okay. Your Honor, I\'m going to take you at your word that
once we got up to noon and I was at a good place for a break, I\'d take
a break.

JUDGE DAVIDSON: Absolutely. You always take me at my word. What kind of
way is that to talk on the record?

(Laughter.)

JUDGE DAVIDSON: All right. I think an hour is more than enough for
lunch.

MR. KRAUSS: Yes, Your Honor.

JUDGE DAVIDSON: And it\'s now ‑‑ all right. We\'re adjourned ‑‑ I\'ll
give you a little bit more ‑‑ adjourned \'til 1:15.

(Whereupon, at 12:05 p.m., a luncheon recess was taken.)

A F T E R N O O N S E S S I O N

JUDGE DAVIDSON: Come to order. Be seated, please.

Have you found out anything about the witnesses?

MS. STEINBERG: Your Honor, we did have discussion during the lunch
break, and in reliance on the earlier Order, it would be difficult to
produce witnesses on other days than already ordered, and we would
jointly ask that we keep to the Order.

JUDGE DAVIDSON: That order that I issued so long ago, right? Was it last
Friday or Thursday?

MS. STEINBERG: Well, Your Honor, we talked, in order to come up with a
joint proposed schedule, and that schedule accommodates all of the
witnesses\' other obligations.

JUDGE DAVIDSON: Okay. Good enough.

MS. STEINBERG: Thank you.

JUDGE DAVIDSON: Getting a little higher. There\'s still another chair
coming, I think.

(Laughter.)

JUDGE DAVIDSON: Feeling much more confident.

(Laughter.)

JUDGE DAVIDSON: I did want to point out, I forgot earlier, that
somewhere along the line, did either of you, did either side get some
kind of special dispensation from the Commissioner on ignoring my
Orders?

Don\'t get excited. But I\'ve noticed that the last month or so, I\'m
getting motions without draft Orders. People just forget about that.
That\'s a requirement in this proceeding.

MS. STEINBERG: I\'m sorry, Your Honor. I don\'t know if that applies,
but I\'m very sorry ‑‑

JUDGE DAVIDSON: No, you can check. It applies.

MS. STEINBERG: No, I mean ‑‑

(Laughter.)

MS. STEINBERG: I\'m sorry about that.

JUDGE DAVIDSON: And I\'ll add another requirement. See, just because I
have ‑‑ see, before, I had no help. Now, I got part-time help, so you
think you don\'t have to bother. But it has to be in MicroSoft. It has
to be e-mailed to me along with the paper, in MicroSoft. What is that,
Word, MicroSoft Word or something?

MR. SPILLER: Word, as opposed to WordPerfect?

JUDGE DAVIDSON: Right.

MR. SPILLER: Okay.

JUDGE DAVIDSON: So that I can ‑‑ so that if I agree with you, I can just
send it out without having to work on it.

Yes, sir.

MR. NICHOLAS: You know, we\'ve been doing that as a result of the
discussion some time ago. The problem has been that many of the
attachments we don\'t have in electronic form, so we did, in fact, file
a motion this morning to enter into the documented record several
additional articles. That motion was e-mailed to you.

JUDGE DAVIDSON: I saw it.

MR. NICHOLAS: But the ‑‑ usually, we\'ve been delivering,
hand-delivering copies to the Dockets ‑‑

JUDGE DAVIDSON: Right, you have to.

MR. NICHOLAS: So I have a copy for you.

JUDGE DAVIDSON: Oh, thank you.

MR. NICHOLAS: I have given a copy to CVM.

JUDGE DAVIDSON: And the draft order?

MR. NICHOLAS: Yes, there\'s a draft order attached to it, as I believe
there always is, but I could be wrong.

JUDGE DAVIDSON: I think maybe you are; but I could be wrong, too. I tell
everybody I may not always be right, but I\'m never in doubt.

(Laughter.)

JUDGE DAVIDSON: Let\'s proceed.

MR. KRAUSS: Thank you, Your Honor.

BY MR. KRAUSS:

Q Good afternoon, Dr. Tollefson.

A Good afternoon.

Q Referring back to your written direct testimony, there\'s a portion of
the testimony on Page 18 that refers to other effective drugs approved
by CVM, and I believe your testimony is, \"There are other effective
drugs approved by CVM to enable the drug and poultry industries, working
together with veterinarians, to treat each of the diseases and specific
bacteria for which Enrofloxacin was approved in poultry.\"

Is that your testimony?

A Yes, that\'s correct.

Q In fact, in your testimony you refer to a chart that was attached to
CVM\'s responses to interrogatories; isn\'t that right?

A Right.

Q And that was attached to Interrogatory Response Number 87?

A Correct.

Q And you attached that chart to your testimony?

A Yes.

Q I\'ve got a blowup of the chart here.

A Okay.

Q And this is the one from the interrogatory answer, but it would be
identical to the one attached to your testimony.

A Yes, that\'s the same one.

Q Now, we agree, don\'t we, that Baytril is approved to treat E. coli
infections in chickens, right?

A Mm-hmm.

Q And E. coli and Pasteurella multocida infections in turkeys, right?
And, Dr. Tollefson, as a veterinarian, are you aware that the types of
infections that Baytril is used, prescribed to treat can occur in
chickens and turkeys older than one to three days old?

A Yes.

Q In fact, are you familiar with the testimony of some of the
veterinarians that Bayer has ‑‑ the witnesses that Bayer has called and
submitted written direct testimony for?

A Yes.

Q And you\'re aware that there\'s testimony and evidence in the record
that these diseases happen in the growout houses of these chickens and
turkeys, right?

A Yes, sometimes.

Q So these drugs here that are approved for day-old turkeys, for
example, or day-old chickens, that approval wouldn\'t be applicable to
turkeys in the growout house that are older than one to three days old,
would it?

A If they\'re used according to their label, correct.

Q Right. And so the same with the day-old chickens and
one-to-three-day-old turkeys, right, and the one-to-three-day-old
chickens, right?

A Mm-hmm.

Q You\'re aware, are you not, that the parties have stipulated that
individual bird treatment, in other words once the birds are in the
growout house and there\'s 20,000 chickens, it\'s not practical to
individually treat each of the birds?

MS. STEINBERG: Excuse me. Can Mr. Krauss provide a copy of that
information to the witness, and can you let us know what number?

MR. KRAUSS: Thirty-six.

(The witness examined the document.)

MR. KRAUSS: For the record, the stipulation is:

\"For commercially grown broiler chickens and turkeys in the United
States, it is neither feasible nor practical to administer Enrofloxacin
on an individual bird basis.\"

BY MR. KRAUSS:

Q Now, Dr. Tollefson, as a veterinarian, would you agree that, not just
talking about Enrofloxacin, but any drug that would be injected for the
treatment, that that would not be practical to administer on an
individual bird basis to 20,000 chickens in a growout house?

A Yes, I would agree.

Q And the same with turkeys in a growout house?

A Yes.

Q You agree with that?

A Yes, I do.

Q So it wouldn\'t be practical to inject, so these wouldn\'t be
applicable for treatment, right?

A Right.

Q And as a veterinarian ‑‑

JUDGE DAVIDSON: Excuse me. These?

MR. KRAUSS: I\'m sorry.

JUDGE DAVIDSON: I know. It\'s a problem. But see, that\'s not going to
be in the record, that chart.

MR. KRAUSS: It\'s attached to her testimony, Your Honor.

JUDGE DAVIDSON: Right, but the lines you drew through, when you say
\"these,\" it confuses the record.

MR. KRAUSS: I understand. I\'m sorry.

JUDGE DAVIDSON: But I think it\'s pretty clear what you\'re talking
about, so just go ahead. I\'m sorry I said anything.

MR. KRAUSS: Thank you.

BY MR. KRAUSS:

Q Now, Dr. Tollefson, as a veterinarian, are you aware that there\'s a
high degree of tetracycline resistance in E. coli isolates cultured from
poultry?

MS. STEINBERG: Objection, Your Honor. That\'s assuming a fact that\'s no
in evidence. Is there something to point to or lay a foundation?

MR. KRAUSS: Other than the evidence that\'s been submitted to the
record?

MS. STEINBERG: Lay a foundation.

MR. KRAUSS: She\'s a veterinarian. Your Honor, I\'m asking her whether
or not she\'s aware of this.

JUDGE DAVIDSON: All right. She can answer.

THE WITNESS: I know there\'s some resistance. I don\'t really know what.

BY MR. KRAUSS:

Q Have you reviewed the testimony of the veterinarians, the veterinarian
witnesses that Bayer submitted ‑‑ you testified you did review that,
right?

A Yes.

Q Did you review the testimony of Dr. John Glysson?

A Yes.

Q He\'s the acting associate dean of the University of Georgia School of
Veterinary Medicine; is that right?

A Yes.

Q When you reviewed his testimony, do you recall that he testified that
tetracycline treatment of E. coli is usually ineffective or poorly
effective because of widespread resistance to tetracycline among avian
E. coli isolates?

MS. STEINBERG: Your Honor, Dr. Glysson\'s testimony speaks for itself,
and Dr. Tollefson\'s recollection of Dr. Glysson\'s testimony ‑‑

JUDGE DAVIDSON: I\'m going to sustain the objection.

If you want to ask her if she knows about certain things, and does she
agree or disagree, that\'s one thing, but don\'t recite other testimony
of record again and again and again.

She admitted that she\'s aware of some degree of a problem with
tetracycline, as far as resistance is concerned. Now you\'re trying to
get Dr. Glysson\'s testimony on the record again with this witness to
approve it or disapprove it? I don\'t understand.

MR. KRAUSS: Well, she testified that she has reviewed Dr. Glysson\'s
testimony.

JUDGE DAVIDSON: I understand that.

MR. KRAUSS: Okay .

BY MR. KRAUSS:

Q Do you, Dr. Tollefson, do you have any knowledge or evidence that
tetracycline, that there\'s not a high level of tetracycline resistance
in avian E. coli isolates such that tetracycline treatment is
ineffective or poorly effective?

A I don\'t ‑‑ I don\'t know. You\'re asking me if I ‑‑ could you repeat
the question?

Q Do you have any knowledge or evidence that tetracycline ‑‑ that there
are not high levels of tetracycline resistance in avian E. coli isolates
such that tetracycline treatment of E. coli is ineffective or poorly
effective? Do you have any evidence?

A That it isn\'t? That ‑‑ I ‑‑

MS. STEINBERG: Your Honor, I object to the form of the question. There
were a lot of double negatives, and honestly, it\'s confusing.

JUDGE DAVIDSON: All right. She can answer it. She doesn\'t know. Okay.

THE WITNESS: I don\'t know. I don\'t know. Let\'s ‑‑

MR. KRAUSS: You don\'t know.

THE WITNESS: I don\'t know.

JUDGE DAVIDSON: Excuse me.

MR. KRAUSS: I\'m sorry, Your Honor.

JUDGE DAVIDSON: Very important interruption. Off the record.

(A discussion was held off the record.)

JUDGE DAVIDSON: Are we all here? Okay. Back on the record. I apologize
for the interruption.

MR. KRAUSS: That\'s fine, Your Honor.

BY MR. KRAUSS:

Q Dr. Tollefson, you\'ve testified that you\'ve reviewed the testimony
of Dr. Glysson; isn\'t that right?

A Yes, I\'ve read it.

Q Do you have any reason to disbelieve his testimony with regard to
tetracycline resistance in E. coli isolates that he\'s observed?

A What ‑‑ I was somewhat confused by his testimony, because there are
other tetracyclines that would be able to be used under ADUCA, under the
extra-label use laws, so I wasn\'t sure if all the tetracyclines were a
problem or not. I don\'t know that personally, and I did not go into it
in depth.

Q Okay.

A So I can\'t answer that with yes or no.

Q Let me ask you this, Dr. Tollefson. Are you aware that, from your
review of the testimony, that practicing poultry veterinarians in this
case have testified that there are no practical alternatives to Baytril
for treating these diseases of poultry?

A Yes, I know that ‑‑ yes.

Q What drugs are you aware of that are being used by practicing poultry
veterinarians that are practical and effective to treat E. Coli
infections in broilers older than three days old and E. Coli or
Pasteurella multocida infections in turkeys older than three days old?

A I don\'t know.

Q You don\'t know of any drugs?

A No, I don\'t, I don\'t ‑‑ I can\'t answer that question. It\'s not my
area of expertise, and I don\'t know what practicing veterinarians,
poultry veterinarians are doing.

Q But you testified that there are other effective drugs ‑‑

A Right.

Q ‑‑ that can be used?

A Correct.

Q But that was outside your area of expertise?

A No. You asked me do I know what poultry veterinarians are actually
using. I know what has been approved for those specific diseases, which
is what you asked us to answer in Interrogatory Number 87, and I also
know that, under the extra-label use provisions of the Animal Drug Use
Clarification Act, other anti-microbials can be used.

Now, what they\'re actually using, I do not know, and that\'s what you
asked.

Q That\'s what I asked. So that\'s what I\'m asking you ‑‑ approved
drugs and drugs available under ADUCA, do you know of any that are being
used by practicing poultry veterinarians to treat these diseases?

MS. STEINBERG: Your Honor, asked and answered.

JUDGE DAVIDSON: Yes. She said she doesn\'t know what they\'re doing now.
Move on.

MR. KRAUSS: Okay.

BY MR. KRAUSS:

Q Now, Dr. Tollefson, you testified about reviewing the Kirk Smith
study, G-589.

A Mm-hmm.

Q I\'m not going to ask you specifically about the document or anything,
but there was a case control study that he performed, or a case study
that he performed, that ultimately got into that article, G-589. You
agree with that, right? That was the basis of the article?

A Case study?

Q Or case control study?

A I ‑‑ okay. Go on. Go ahead and ask the question.

MS. STEINBERG: Your Honor, can Mr. Krauss provide Dr. Tollefson with a
copy of that?

JUDGE DAVIDSON: He did before.

MR. KRAUSS: Can we go off the record one second?

JUDGE DAVIDSON: Off the record.

(A discussion was held off the record.)

JUDGE DAVIDSON: Back on the record.

MR. KRAUSS: Your Honor, it\'s G-589.

THE WITNESS: Case comparison study, he calls it.

MR. KRAUSS: Okay.

BY MR. KRAUSS:

Q Now, this is a study that you testified that you reviewed as part of
the process of coming to the decision to issue the NOOH, right?

A Mm-hmm.

Q Did FDA audit the study?

A No, we did not.

Q Did FDA review the protocol for the study?

A No. The study took place ahead of time. I mean, it already had taken
‑‑ had already taken place.

Q Okay.

A Okay.

Q Did FDA get the raw data from the study?

A No. We spoke to Kirk Smith about the study and about the possibility
of getting the raw did. We did not. I\'m 90 percent sure we did not get
it.

Q Even though the study had already been performed by the time the NOOH
was issued, did you review the protocol, even though it would have been
after the study was done? Did FDA review the protocol?

A I don\'t recall.

Q And FDA did not get the raw data, right, you said?

A Correct.

Q So you couldn\'t have done any kind of an audit of the raw data?

A No, we did not.

Q Or any kind of an analysis of the raw data, right?

A Correct.

Q Did FDA perform any independent assessment of the validity of the
Smith study?

A By independent, you mean someone other than FDA employees?

Q Did FDA conduct an assessment of the validity of the study?

A I guess that\'s inherent ‑‑ I would answer that that is inherent in
our evaluation of the study.

Q So you evaluated the study?

A Yes.

Q And that was based on what? Based on the paper?

A In talking to Dr. Smith, and actually even before the study, and Dr.
Bender, and so on, the co-ops.

Q So this evaluation that you did didn\'t involve a review of the
protocol and ‑‑

A Well, we did review the protocol. When you asked that question ‑‑ I
mean, we looked at the protocol, we talked about the protocol, we talked
about what they did.

Q Okay. Your evaluation didn\'t involve anything with looking at the raw
data, is that right?

A No, it did not.

Q Was there a written protocol?

A Yes, to my recollection there was a written description of what they
did. I would call that a protocol.

Q And FDA reviewed that as part of the evaluation of the Smith study?

A We discussed it as part of the evaluation of the Smith study, right.
We didn\'t do a written evaluation of it, if that\'s what you\'re
looking for.

Q But you looked at a written protocol? There was a ‑‑

A We met with the authors of this study, and ‑‑ I cannot recall. Okay?

Q Was there a written protocol or not?

A I cannot recall.

Q Did you ever see a written protocol?

A I ‑‑

MS. STEINBERG: Your Honor, asked and answered. He\'s badgering the
witness.

JUDGE DAVIDSON: Sustained.

BY MR. KRAUSS:

Q Now, Dr. Tollefson, let me turn your attention to the CDC
Campylobacter case control study, and ask you kind of the same questions
here.

JUDGE DAVIDSON: Got a docket number? I mean, exhibit number?

MR. KRAUSS: Yes, Your Honor. Yes. One aspect of it is G-1452, Exhibit 3
‑‑ Attachment 3.

JUDGE DAVIDSON: More? Others? Other aspects?

MR. KRAUSS: I believe it\'s also G-1488, and there\'s discussion of it
in the Kassenborg testimony.

JUDGE DAVIDSON: Okay. That\'s 1460?

MR. KRAUSS: Yes. And there\'s another aspect of it, Your Honor, that I
believe is Attachment 4 to G-1452, the Angulo testimony.

JUDGE DAVIDSON: Okay. Proceed.

MS. STEINBERG: Your Honor, if Mr. Krauss is going to ask Dr. Tollefson
about those specific documents, can he please provide them to her?

MR. KRAUSS: Well, I\'ve already provided 1452, Attachment 3, and that
should be sufficient, Your Honor, to handle the questions, I believe.

JUDGE DAVIDSON: Okay.

BY MR. KRAUSS:

Q Now, Dr. Tollefson, is it your understanding that the CDC
Campylobacter case control study was analyzed by, for different aspects,
by different CDC epidemiologists?

A Correct.

Q And, for example, Dr. Freedman ‑‑

MS. STEINBERG: Your Honor, this is beyond the scope of Dr. Tollefson\'s
testimony.

MR. KRAUSS: Your Honor, she testified that she reviewed the CDC
Campylobacter case control study as part of the decision for bringing
the NOOH, if I\'m not mistaken.

JUDGE DAVIDSON: All right. I\'ll let it go. But, you know, there are
going to be other witnesses in this proceeding besides Dr. Tollefson.

MR. KRAUSS: I understand that, Your Honor.

JUDGE DAVIDSON: And, you know, you keep referring to things that Dr.
Smith did and Dr. Angulo, and they\'re going to be here, too. Okay? Go
ahead. I\'m just reminding you ‑‑

MR. KRAUSS: Yes, Your Honor.

JUDGE DAVIDSON: ‑‑ of something you already know.

MR. KRAUSS: I\'ll speed it up, Your Honor.

JUDGE DAVIDSON: Okay.

BY MR. KRAUSS:

Q So Dr. Freedman, her part of the analysis was the risk factors of
getting a Campylobacteriosis infection; isn\'t that right?

A Yes, I believe that\'s right.

Q And Dr. Kassenborg, her part of the analysis was the risk factors of
getting a fluoroquinolone resistant Campylobacter infection; isn\'t that
right?

A Correct.

Q And there\'s a report by a Jennifer McClellan, also known as Jennifer
Nelson, right, and her part of the study was the differences between, or
the consequences of a resistant infection versus a non-resistant
infection, right?

A Right.

Q Now, with respect to the CDC Campylobacter case control study, and
those three analyses, did FDA audit those studies?

A No.

Q Did FDA review the protocols of those studies?

A I don\'t know.

Q Did FDA get the raw data from those studies?

A We got, yes, we got some of the raw data of those studies.

Q Okay. From any particular of the three studies or what do you recall?

A From the case control data set.

Q Did FDA audit the raw data that it did receive?

A No.

Q Did FDA do any assessment of the validity of those studies? And by
those studies, I mean Freedman, Kassenborg, Nelson/McClellan.

A No.

Q Dr. Tollefson, I\'m a little bit confused about one thing that you
said earlier today, and that is with respect to the most recent
publication from CDC MMWR with respect to Campylobacter incidence.

A Mm-hmm.

Q I believe you testified that, for through 2002, Campylobacter
incidence was up. Is that what you said?

A I thought it was, slightly, yes.

Q Slightly up?

A But I don\'t have a ‑‑

MR. KRAUSS: Let me hand to you ‑‑ and Your Honor, this is B-1924, and
it\'s attached to our motion. This just came out April 18, 2003, and
it\'s Attachment 3 to the motion. I\'m sorry. It may be Attachment 2. I
was given bad advice, Your Honor.

BY MR. KRAUSS:

Q Dr. Tollefson, we already established ‑‑ I believe, you have the
document G-1791 ‑‑ that for 2001, Campylobacter, overall incidence was
13.8; isn\'t that right?

A Right.

Q And B-1924, on Page 6 of 8, the table does not have a table number,
but would you agree with me that the Campylobacter incidence is 13.37
overall?

A Yes. Well, that\'s what the table says, but hold on, because I didn\'t
use the draft of this.

Yeah. If you look at Figure 1, it looks like it\'s going up slightly,
but I agree, that must not be right, because the number is slightly
down.

Q Right. So going into, from 2001 to 2002, Campylobacteriosis incidence
in the United States has gone down, correct?

A Yes.

MR. KRAUSS: Thank you. Your Honor, with that, I have no further
questions of this witness, at this time.

JUDGE DAVIDSON: Do you have redirect?

MS. STEINBERG: Yes, we do.

Your Honor, at the outset, we had talked about switching tables for
redirect.

MR. KRAUSS: Perhaps we should go off the record quickly, Your Honor?

JUDGE DAVIDSON: Off the record.

(A discussion was held off the record.)

REDIRECT EXAMINATION

BY MS. STEINBERG:

Q Dr. Tollefson, I only have a few questions for redirect. I would like
to clear up a couple of questions from the cross examination.

On cross examination, you were asked whether you agreed that
Campylobacteriosis is mainly a diarrheal disease or the main effect is
diarrhea, and I wanted to ask you whether there are other symptoms of
Campylobacteriosis?

A Yes. Diarrhea is only one of the symptoms. There\'s cramping, there
can be bloody diarrhea. It\'s ‑‑ it can be a very severe illness.

Q Are there common complications from Campylobacteriosis?

A Yes, there are complications that can range from minor to very severe,
like reactive arthritis and Guilliam-Barre, which is a paralysis.

Q I also wanted to ask you a question about G-410, which is the lead
document.

A Yes.

Q Do you need a copy of that?

A No.

Q How often does CDC produce a document like that, a comprehensive
survey?

A A comprehensive review of the Food Net, of the food data, food-borne
illness data, not very often, usually about every seven to 10 years.

Q Is Exhibit G-410, that lead article, the most comprehensive study to
date ‑‑

A Yes.

Q ‑‑ the most recent comprehensive study to date?

A Yes.

Q Do people still cite to it as the most recent comprehensive study?

A Yes, they do.

Q Does the fact that Campylobacteriosis is now reported as the second
most common bacterial diarrheal disease for enteric gastroenteritis,
does that play a part in the factor that\'s an important food-borne
disease?

A It\'s only slightly below Salmonellosis. It\'s still a very important
food-borne disease in humans in the U.S.

Q I have a couple of questions for you about G-1452, Attachment 3.

A Mm-hmm.

Q Do you still have a copy of that?

A Yes, I do.

Q Mr. Krauss asked you to agree that people who did not eat chicken at
home were more likely to be Campylobacter case than people who did eat
chicken at home.

What about people who do not ever eat chicken? Are people who eat
chicken at home more likely to be a Campylobacter case than people who,
for example, eat cheese sandwiches at home?

A You can\'t answer that from the data set, from the Attachment Number
3, G-1452, but it gets to the question of what is protective, really,
and it\'s unlikely that people would be ‑‑ who eat cheese sandwiches ‑‑
would be less likely than people who eat chicken at home to get
Campylobacteriosis.

Q In fact, in the list on Pages, beginning on Page 98 of Attachment 3,
G-1452, and going on, are there, in fact, situations where chicken is
considered a risk factor for acquiring Campylobacteriosis?

A Yes, there are.

Q Could you point out some of those to us, please?

A Yes. Chicken prepared ‑‑ just going down the list ‑‑ on an outdoor
grill at a large social gathering, that\'s statistically significant.

Chicken in a restaurant. Turkey prepared at a restaurant. Broiled
chicken prepared at a restaurant. Chicken wings prepared at a
restaurant. There are many.

Q And I notice that you mentioned turkey, which was going to be one of
my questions, so are there also situations where turkey presents as a
risk factor for acquiring Campylobacteriosis?

A Yes. It looks like ate turkey prepared at a restaurant and ate
oven-roasted turkey prepared at a restaurant are both, and there\'s also
contact with animals. It discussion say chickens or turkeys. Yes.

Q Turning attention to two other exhibits, G-285 and B-252, Mr. Krauss
asked you about those two exhibits, and asked whether it was true that
those two exhibits dealt with Salmonella rather than Campylobacter?

A Correct.

Q What did you cite those exhibits for?

A This was in my testimony under the heading of \"Background on
Anti-Microbial Resistance,\" and the purpose of it was to describe how
food-borne pathogens may be transmitted from animals to humans. It\'s
not meant to be specific to Campylobacter.

Q Would the transfer of resistant bacteria from animals to humans be
different if you\'re talking about Campylobacter as a bacteria rather
than Salmonella as a bacteria?

A No, no different.

Q Now, I want to turn to the issue of ‑‑ I guess the chart is gone ‑‑
the first chart that Mr. Krauss had drawn about Paula Cray\'s lab and
the various problems with speciation.

A Okay. Right. I have that in my testimony.

Q What is the net result of using nalidixic susceptibility and
resistance to cephalothin in speciation?

A The net result is that Paula Cray\'s lab received a biased data set in
that they were more likely to be susceptible to ciprofloxacin than
resistant to ciprofloxacin.

She, in other words, received a sub-sample, if you will, until 2001.

Q Thank you. Mr. Krauss also had a chart up there with a calculation of
the incidence rates, and various other things.

Did his chart take into account any changes in the population during the
years on the chart?

A No.

Q Does that matter for his calculation?

A Yes.

Q Can you explain why?

A What he was trying to ‑‑ well, I don\'t know what he was trying to
show. But he was indicating that since the incidence of Campylobacter
was decreasing, then proportion ‑‑ then the incidence of resistant
Campylobacter was also decreasing.

However, if the population is increasing over time, then the absolute
numbers may or may not be decreasing.

Q Do you still have G-589 with you, Dr. Smith\'s study?

A No, I don\'t.

Q Maybe a copy would help.

Dr. Tollefson, was Dr. Smith\'s study published?

A Yes.

Q In what journal?

A In the New England Journal of Medicine.

Q To your knowledge, is that a peer review journal?

A Yes.

Q I have one more question on the MMWR.

A Mm-hmm.

Q Do you have both of the exhibits ‑‑

A Yeah, I do ‑‑

Q ‑‑ G-748 and G-1791?

A Yes.

Q Mr. Krauss\'s last questions concerned whether or not Campylobacter
has gone up from 2001 to 2002.

I\'d like to start with Exhibit G-748 and ask you, on the first page,
under the heading \"2000 Surveillance,\" whether or not this indicates
the number of Campylobacteriosis cases for 2000?

A Yes.

Q Can you tell us what that was?

A It was 4,640.

Q And then turning to G-1791?

A Yes, there, 2001 is 4,740 Campylobacter ‑‑

Q So did the number of Campylobacteriosis cases go up from the year 2000
to 2001?

A Yes.

MS. STEINBERG: Thank you. May I have a moment?

JUDGE DAVIDSON: Certainly.

(Pause.)

MS. STEINBERG: I don\'t believe that the witness has a copy of this.
This was in the motion that Mr. Nicholas handed to us this afternoon. It
is marked as Exhibit B-1924, and I\'d like to bring it to the witness,
if that\'s okay with you, Your Honor.

JUDGE DAVIDSON: Go ahead. Go ahead.

BY MS. STEINBERG:

Q This is on Page 2 of B-1924, and under the title, \"2002
Surveillance,\" can you tell us what the number of Campylobacteriosis
cases is there?

A 5,006.

MS. STEINBERG: Thank you. At this time, Your Honor, I have no further
questions on redirect.

MR. KRAUSS: Your Honor, I have a brief recross.

JUDGE DAVIDSON: Go ahead. Go ahead.

MR. KRAUSS: I can do it from right here.

JUDGE DAVIDSON: Oh, you\'re so kind. That\'s all right. Would you like
to move?

MR. KRAUSS: No.

RECROSS EXAMINATION

BY MR. KRAUSS:

Q Dr. Tollefson, I\'ll work backwards. Ms. Steinberg just asked you
about the numbers of cases of Campylobacteriosis using these MMWR
reports, and it\'s G-1791, G-748, and B-1924.

Now, it\'s not your testimony here today, is it, that the overall
incidence of Campylobacteriosis from 2000 to 2001 to 2002 is increasing,
is it?

A No.

Q In fact, those numbers that Ms. Steinberg asked you about is the
laboratory culture confirmed cases, isn\'t it?

A Yes.

Q And that would depend on how many people go to a doctor, right?

A Correct.

Q And get a culture, right?

A Correct.

Q And then have that culture be confirmed, right?

A Correct.

Q Now, with respect to the analysis that you and I walked through on the
incidence rates ‑‑ you called it an incidence, or Ms. Steinberg called
it an incidence rate ‑‑ you didn\'t want to call it an incidence rate,
right?

A (Shakes head.)

Q On that analysis, your testimony, when Ms. Steinberg was asking you
about it, was that if the population changes, the numbers can change;
isn\'t that right?

A The absolute, the total numbers can change.

Q Right. Are you aware of any analysis that\'s looked at the population
changes in Food Net case control ‑‑ I\'m sorry ‑‑ Food Net areas for
which Campylobacter are sampled and performed a calculation to determine
a rate of fluoroquinolone resistant Campylobacteriosis in the United
States?

A No, that\'s not what I was referring to. I was referring ‑‑ if you\'re
going to go to a rate, which is a population-based number, then it would
be the population throughout the U.S., not in Food Net sites. Right?

Q Right. But what we walked through together it was incidence rates of
Campylobacteriosis in the United States per 100,000.

A Correct.

Q And you said, well, if the population changes, the numbers can change.

A No, no, total numbers.

Q Total numbers meaning?

A How many cases, not rates, cases.

Q Okay. Oh, so the rates are accurate?

A Yeah. Yes.

Q Okay. Thank you. Now, one last thing. You testified regarding the
symptoms of Campylobacteriosis and about the complications ‑‑

A Mm-hmm.

Q ‑‑ when Ms. Steinberg was questioning you, and I was kind of
surprised, because you referred to reactive arthritis as a common
complication. That\'s not true, is it?

A No.

Q Reactive arthritis is not a common complication, is it?

A No, but that\'s not what I said. I said some complications include.
Ms. Steinberg asked me the question as to common, but I did not say that
it was common.

Q Okay. And that would be true of Guilliam-Barre Syndrome, too, isn\'t
it?

A Correct.

Q Guilliam-Barre Syndrome is not a common complication?

A No, it is not.

MR. KRAUSS: Nothing further, Your Honor.

JUDGE DAVIDSON: Okay. I just have one little question, not ‑‑ it
doesn\'t have great import, but I wanted to find out, because I read
your ‑‑ do you have your testimony in front of you?

THE WITNESS: Mm-hmm.

JUDGE DAVIDSON: I was confused by Page 3, starting on Line 19, when you
say all three bacteria can cause severe food-borne illness in humans,
even though they are non-pathogenic in animals.

THE WITNESS: Correct.

JUDGE DAVIDSON: Now, even though the Commissioner of FDA, in years gone
by, has said that I have lot of expertise scientifically, I deny it. I
don\'t have any. Okay.

So then we go down to Line 46, where it seems to me you\'re saying that
E. Coli caused mortality. Now, if it\'s non-pathogenic, how could it
cause mortality?

THE WITNESS: It\'s a respiratory pathogen in that case, of chickens.

JUDGE DAVIDSON: Oh, so it is pathogenic, but not ‑‑

THE WITNESS: Right, it\'s not a food-borne, it\'s not an enteric
pathogen.

JUDGE DAVIDSON: Gotcha. Thank you very much.

THE WITNESS: Sure.

JUDGE DAVIDSON: You\'re excused.

(The witness was excused.)

MR. KRAUSS: Thank you, Your Honor.

JUDGE DAVIDSON: Now, any other housekeeping matters before we ‑‑

MS. STEINBERG: No, Your Honor.

JUDGE DAVIDSON: Okay. Now, do we have a problem tomorrow with meeting at
9:30 instead of 9 o\'clock? Anybody unhappy about that?

MR. KRAUSS: No.

MS. STEINBERG: No.

JUDGE DAVIDSON: Okay. We\'re adjourned until 9:30 a.m. tomorrow morning.

(Whereupon, the hearing was adjourned.)

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