Brief of U.S. v. Prigmore, 243 F.3d 1 (1st Cir. 2001)
Related lower court case - Criminal Prosecution for Misrepresentations to the FDA - United States v. Leichter, 160 F.3d 33 (1st Cir. 11-03-1998)
|||United States Court of Appeals For the First Circuit
|||No. 00-1158, No. 00-1229, No. 00-1230
|||March 16, 2001
|||UNITED STATES, APPELLEE,
DAVID W. PRIGMORE, DEFENDANT, APPELLANT,
UNITED STATES, APPELLEE,
LEE H. LEICHTER DEFENDANT, APPELLANT,
UNITED STATES, APPELLEE,
JOHN F. CVINAR, DEFENDANT, APPELLANT.
|||Richard G. Taranto, with whom Farr & Taranto, Andrew Good, Harvey
A. Silverglate, Silverglate & Good, William H. Kettlewell, Michael B.
Galvin, Dwyer & Collora, Llp, Robert D. Keefe, Daniel W. Halston, Jason
T. Sherwood, and Hale and Dorr Llp, were on brief, for appellants. David
S. Kris, Attorney, Department of Justice, with whom David S. Mackey, Acting
United States Attorney, Stephen A. Higginson, Special Assistant United States
Attorney, and Michael K. Loucks, Assistant United States Attorney, were
on brief, for appellee.
|||Before Selya, Circuit Judge, Coffin, Senior Circuit Judge, and Stahl,
|||The opinion of the court was delivered by: Stahl, Circuit Judge.
|||APPEALS FROM THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF MASSACHUSETTS
[Hon. Joseph L. Tauro, U.S. District Judge]
|||On August 24, 1995, after a twenty-seven day trial, a jury convicted defendants-appellants
Lee H. Leichter, John F. Cvinar, and David W. Prigmore of conspiring to
defraud and impair the functioning of the United States Food and Drug Administration
(FDA) in connection with its oversight and regulation of medical devices.
See 18 U.S.C. § 371. The jury simultaneously acquitted George Maloney and
Kenneth Thurston of the same charge. The district court thereafter sentenced
each convicted defendant to 18 months' imprisonment and two years of supervised
release, but stayed execution of the sentences pending appeals. In these
appeals, Leichter, Cvinar, and Prigmore ("defendants") raise a
host of arguments challenging the legality of their convictions. In addition,
Prigmore claims that insufficient evidence supports his conviction and that
his sentence is unlawful. We vacate the convictions and remand for further
|||Because we review the trial record primarily to ascertain whether an error
in the district court's jury instructions was harmless, see infra Section
II, we look at the evidence as a whole and not in the light most favorable
to the government, see Arrieta-Agressot v. United States, 3 F.3d 525, 528
(1st Cir. 1993). Thus, although we give a detailed account of the evidence
the government relies on to support its case theory and harmless-error argument,
we also provide an overview of relevant responsive evidence and arguments.
See id. at 528-29. We note too that this case has a complicated procedural
history which we describe only insofar as is relevant to these appeals.
Readers interested in additional procedural background should consult our
previous opinion in this matter. See United States v. Leichter, 160 F.3d
33, 34 (1st Cir. 1998).
|||A. Statutory and Regulatory Background
|||In 1976, Congress amended the Food, Drug, and Cosmetics Act (FDCA), 21
U.S.C. § 360 et seq., by passing what it denominated the Medical Device
Amendments (MDA), 21 U.S.C. § 360c et seq. The amendments made the FDA responsible
for ensuring the safety and effectiveness of medical devices distributed
to the American public. This prosecution proceeded on the theory that, in
testing and marketing medical devices known as "heart catheters,"
the defendants conspired to violate provisions of these statutes and regulations
|||A heart catheter is a tiny instrument consisting primarily of a thin metal
wire with a small inflatable balloon at or near one end. The device is used
in a surgical procedure called angioplasty, which seeks to treat heart disease
by opening clogged coronary arteries. During angioplasty, a physician inserts
a heart catheter into a patient's body, typically through an artery in the
leg or groin area. The physician then steers the device through the patient's
circulatory system to the site of the blockage and inflates the balloon
with fluid. As it is inflated, the balloon breaks the "plaque"
that is clogging the artery and pushes it against the artery wall. The physician
subsequently withdraws the liquid, deflates the balloon, and removes it
and the catheter, thereby allowing blood to flow freely through the artery.
|||Regulations promulgated pursuant to the FDCA and MDA designate heart catheters
as Class III medical devices. See generally 21 C.F.R. Part 870. Class III
medical devices are the most heavily regulated medical devices in the country.
See 21 U.S.C. § 360c(a). Before a manufacturer may market a new Class III
medical device, the manufacturer must apply for and receive "premarket
approval" (PMA) from the FDA. 21 U.S.C. § 360c(a)(C). In connection
with its PMA application, the manufacturer must submit information sufficient
to provide the FDA with "reasonable assurance" that, inter alia,
the device is both "safe" and "effective." 21 U.S.C.
|||Under the MDA,
|||[T]he safety and effectiveness of a [Class III] device are to be determined
|||(A) with respect to the persons for whose use the device is represented
|||(B) with respect to the conditions of use prescribed, recommended, or
suggested in the labeling of the device, and
|||(C) weighing any probable benefit to health from use of the device against
any probable risk of injury or illness from such use. 21 U.S.C. § 360c(a)(2).
|||Regulations promulgated pursuant to this statute (and others) elaborate:
|||In determining the safety and effectiveness of a device for purposes of
[deciding whether to grant] . . . premarket approval of class III devices,
the Commissioner . . . will consider the following, among other relevant
factors: (1) The persons for whose use the device is represented or intended;
(2) The conditions of use for the device, including conditions of use prescribed,
recommended, or suggested in the labeling or advertising of the device,
and other intended conditions of use; (3) The probable benefit to health
from the use of the device weighed against any probable injury or illness
from such use; and (4) The reliability of the device. 21 C.F.R. § 860.7(b).
|||There is reasonable assurance that a device is safe when it can be determined,
based upon valid scientific evidence, that the probable benefits to health
from use of the device for its intended uses and conditions of use, when
accompanied by adequate directions and warnings against unsafe use, outweigh
any probable risks. Id. § 860.7(d)(1).
|||There is reasonable assurance that a device is effective when it can be
determined, based upon valid scientific evidence, that in a significant
portion of the targeted population, the use of the device for its intended
uses and conditions of use, when accompanied by adequate directions for
use and warnings against unsafe use, will provide clinically significant
results. Id. § 860.7(e)(1).
|||Two additional sets of regulations governing Class III surgical devices
are of particular importance to this case, so we describe them in some detail.
The first requires, insofar as is relevant, that a manufacturer of a previously
approved Class III surgical device "submit a PMA supplement for review
and approval by FDA before making a change affecting the safety or effectiveness
of the device . . . ." 21 C.F.R. § 814.39(a). As with an application
for initial PMA, the so-called "PMA supplement" must contain scientific
information that provides a basis for approval of the modified device. See
id. § 814.39(c). The regulation lists eight "types of changes"
for which a PMA supplement must be filed "if [the changes] affect the
safety or effectiveness of the device," id. § 814.39(a), including
the following: "[n]ew indications for use of the device," id.
§ 814.39(a)(1); "[t]he use of a different facility or establishment
to manufacture, process, or package the device," id. § 814.39(a)(3);
and "[c]hanges in the performance or design specifications, circuits,
components, ingredients, principle of operation, or physical layout of the
device," id. § 814.39(a)(7). By operation of § 814.39(c) ("All
procedures and actions that apply to [a PMA] application under § 814.20
also apply to PMA supplements . . ."), the manufacturer also must "periodically
update [a] pending [PMA] application with new safety and effectiveness information
learned about the device from on-going or completed studies that may reasonably
affect an evaluation of the safety or effectiveness of the device . . .
." Id. § 814.20(e).
|||As implied by the regulations just quoted, a manufacturer need not submit
a PMA supplement "if the change does not affect the device's safety
and effectiveness . . ., e.g., an editorial change in labeling which does
not affect the safety or effectiveness of the device." Id. § 814.39(b).
But where the FDA has required periodic reports as a condition of approval
of the device, the manufacturer must report any changes to the FDA "in
[its] postapproval periodic reports . . . ." Id. The PMAs of the heart
catheters at issue in this case explicitly required postapproval reports
documenting any and all changes to the catheters.
|||The second set of regulations underlying this prosecution arise from the
background fact that, prior to submitting a PMA application or PMA supplement,
the manufacturer of a new or modified Class III medical device may desire
to test the device in humans. To do so lawfully, the manufacturer must apply
to the FDA for an "investigational device exemption" (IDE). An
IDE "permits a device that otherwise would be required . . . to have
premarket approval to be shipped lawfully for the purpose of conducting
investigations of that device." 21 C.F.R. § 812.1(a). An IDE thus permits
limited use of an unapproved device for the purpose of collecting human
test data. See id. But the testing regulations themselves specify a number
of situations in which an IDE is not a prerequisite to the investigational
use of unapproved Class III medical devices in humans. See id. § 812.2(a),
(c). Such "exempted investigations" include "consumer preference
testing" and the "testing of a modification" to an approved
Class III medical device, so long as "the testing is not for the purpose
of determining [the unapproved device's] safety or effectiveness and does
not put subjects at risk." Id. § 812.2(c)(4).
|||B. Relevant Factual Background
|||Defendants had leadership positions at United States Catheter and Instrument,
Inc. (USCI), a division of C.R. Bard, Inc. (Bard), for most or all of the
alleged conspiracy period, which ran from 1987 to 1990. Defendant Leichter
was USCI's head of regulatory affairs and quality assurance; defendant Cvinar
was USCI's president; and defendant Prigmore, who previously had been president
of USCI, was until September 1989 a vice president at Bard with authority
over USCI's operations. All three defendants had offices in Billerica, Massachusetts,
where USCI operated a manufacturing plant and maintained its corporate headquarters.
|||USCI's chief decision-making body was its Management Board. Cvinar presided
over the Board and Leichter was a member. Cvinar reported to Prigmore. Representatives
from middle management at USCI made up an organization known as the "Breakfast
Club." The Breakfast Club reported regularly to the Board and provided
the Board with the minutes of its meetings. The Breakfast Club had no authority
to make decisions without the Board's approval. Leichter was not a member
of the Breakfast Club, but he sometimes attended its meetings.
|||The conspiracy alleged in this case involved two lines of heart catheters
manufactured by USCI. In 1987, USCI introduced the first line, which we
shall call the "Probe Line," with a catheter known as "Probe
A." In 1988, USCI modified Probe A and renamed it "Probe B."
In early 1989, USCI began distributing Probe B commercially. Later in 1989,
USCI modified Probe B and renamed it "Probe C." At trial, the
government's conspiracy theory with respect to the Probe Line was that,
under defendants' leadership and with defendants' knowledge and approval,
USCI tested Probe B and Probe C in humans in violation of the Class III
medical device testing regulations; marketed Probe B and Probe C in violation
of the Class III medical device marketing regulations; and otherwise deceived
the FDA in order to avoid the agency's oversight.
|||In 1987, the second line of heart catheters, which we shall call the "Miniprofile
Line," featured a catheter called the "Simplus." In 1988,
the Simplus evolved into a catheter called the "Miniprofile,"
which, in 1989, evolved into a catheter called the "Solo." In
1989, USCI also filed a PMA supplement for a catheter called the "Solo
Sr.," but the company never manufactured the Solo Sr. and ultimately
withdrew the filing. With respect to the Miniprofile Line, the government's
conspiracy theory once again was that, under defendants' leadership and
with defendants' knowledge and approval, USCI committed a number of violations
of the Class III medical device testing and marketing regulations and otherwise
lied to the FDA to avoid the agency's oversight. The following is a summary
of the evidence supporting the government's conspiracy theories.
|||1. The Probe Line
|||In the early 1980s, when angioplasty first became available in this country,
USCI controlled 100% of the market for heart catheters. By the late 1980s,
however, USCI's market share had declined by about half and the market had
become very competitive. When USCI introduced the FDA-approved Probe A in
1987, the device initially sold very well. But the device had a significant
limitation. Although USCI marketed Probe A with a label warning that it
should not be rotated more than one full turn (360 degrees) in the same
direction, physicians performing angioplasties sometimes saw it as necessary
to rotate the device beyond its warned-against limitation. When this occurred,
the device's balloon had a tendency to wrap itself around the wire, which
prevented deflation. This, in turn, blocked blood flow through the artery
and complicated efforts to remove the device from the body.
|||USCI's solution to Probe A's wrapping problem was Probe B, a redesigned
version of the same catheter. In Probe A, the balloon attached at the end
of the wire, but in Probe B, the balloon attached to a polymer tube threaded
over the wire. The result was that Probe B could be rotated more than once
in the same direction without the balloon becoming entangled. Unfortunately,
however, the new design created different problems.
|||There was evidence that, in actual use in humans, Probe B's wire broke
25 times more frequently than Probe A's wire. There also was evidence that,
when compared to Probe A, these breaks were far more likely to occur when
the device was rotated more than once in the same direction. Moreover, the
consequences of a Probe B wire break tended to be more serious. In the relatively
unlikely event of a Probe A wire break, the catheter's metal tip typically
would not detach and could be removed with the wire and balloon. By contrast,
when Probe B broke, the broken tip frequently could not be removed with
the rest of the catheter. In such a situation, the physician either had
to leave the tip in the patient or remove it by invasive surgery. Evidence
of these problems poured into USCI in early 1989, but, contrary to the urgings
of certain USCI "Crisis Team" members appointed by Cvinar to handle
the situation, USCI, and then Bard, declined to order a voluntary recall
of Probe B.
|||The government contends that this disastrous state of affairs was a direct
result of USCI violating the regulations governing the testing and marketing
of Class III medical devices in connection with bringing Probe B to market.
We start with a synopsis of the evidence of unlawful testing in connection
with Probe B.
|||a. Misconduct Involving the Probe B
|||On November 11, 1988, one of Leichter's subordinates filed a PMA supplement
for Probe B asserting that it should be approved without being tested in
humans. Upon receipt of the supplement, the FDA questioned USCI's assertion
and asked for proof that clinical testing was unnecessary. In a December
13, 1988 letter and in a December 15, 1988 meeting, certain of Leichter's
subordinates explained to FDA representatives that Probe B's safety and
effectiveness had been established by laboratory "bench" testing
and that the FDA could rely on data submitted in connection with Probe A's
PMA application because the two devices were similar. The December 13 letter
also explained that clinical testing was not necessary because bench testing
had showed that Probe B "allows for more independent rotation of the
core wire and balloon" than Probe A. Leichter sent the Management Board
a copy of the December 13 letter and a memorandum summarizing the December
15 meeting. On these documents he handwrote "Excellent work."
On January 19, 1989, the FDA approved Probe B for commercial distribution
without requiring testing in humans.
|||In fact, however, notwithstanding its representations to the FDA and without
having applied for an IDE, in late October 1988, USCI began shipping Probe
B catheters for purposes of gathering feedback as to how they performed
in humans. Documentary evidence suggests that this feedback gathering, which
USCI called "disaster checking," was for purposes of ascertaining
Probe B's rotational capabilities, steerability, and "performance characteristics
. . . as compared to the [Probe A]." The government contends that testing
for such purposes was safety or effectiveness testing, and thus violated
a negative implication to be found in the Class III medical device testing
regulations: that an unapproved Class III medical device may not be tested
in humans for safety or effectiveness without an IDE. See generally 21 C.F.R.
Part 812. With the exception of Prigmore, who explicitly challenges the
sufficiency of the government's proof linking him with this evidence, defendants
do not dispute that they were aware of and approved of this course of conduct.
Rather, pointing to testimonial evidence supporting their case theory, they
(joined by Prigmore arguing in the alternative) take the position that this
"testing" was solely for purposes of establishing consumer preferences;
was not for purposes of determining safety or effectiveness as defendants
reasonably understood the regulations to define those terms; and did not
pose risks to humans beyond those associated with Probe A. Defendants thus
understood the testing to be exempted from Part 812's IDE requirements by
§ 812.2(c)(4). We shall have considerably more to say on the defendants'
understanding of Part 812 and the terms "safety" and "effectiveness"
later in this opinion.
|||The government also argues that, in bringing Probe B to market, USCI violated
the Class III medical device marketing violations in two ways. First, USCI
failed to report to the FDA that it was conducting clinical tests in humans
in several documents: the Probe B PMA supplement (which was filed after
clinical tests in humans began in October 1988); the December 13, 1988 letter
to the FDA; the December 15, 1988 meeting with FDA representatives; and
the subsequent updates required by the FDA when it approved Probe A. See
21 C.F.R. §§ 814.39(c), 814.20(e). Moreover, USCI failed to report that,
in Probe B's clinical tests, the device experienced breakage rates far beyond
those reported with respect to Probe A as marketed. See id. Here too, only
Prigmore disputes the sufficiency of the evidence that he was aware of Probe
B's test results and the subsequent failure to share those results with
the FDA; the other defendants take the position that, under their understanding
of the regulatory mandates and the typical circumstances of a Probe B tip
break, no reporting was required.
|||Second, USCI representatives were marketing Probe B with the claim that
it could be rotated more than once in the same direction even though Probe
B's PMA supplement represented that the device would retain Probe A's label
warning against more than a single revolution. There was evidence that,
despite the label warning, the device was presented to USCI sales staff
as the solution to Probe A's rotational limitations. Presentations to sales
staff at the company's annual national meeting held at Lake Tahoe, California,
from January 15-17, 1989, left at least one salesman with the impression
that "Probe B could be torqued more than once, and that was the whole
idea of freeing the wire [from the balloon]." Also, written promotional
materials for Probe B explained that "[t]his new device allows increased
torque delivery because of the new design" and that "with every
rotation, it's the wire you're steering and not the balloon." In addition,
a USCI videotape designed to instruct doctors on use of Probe B contained
remarks from a doctor suggesting that the device could be rotated two or
|||USCI's sales force, which had been instructed to warn physicians against
overrotation of Probe A, were not so instructed with respect to Probe B.
Indeed, USCI sales staff informed physicians that, although there would
be no labeling change, Probe B contained improvements "that should
prevent the twisting problem" that occurred with overrotation of Probe
A. One USCI representative told a doctor that he could rotate Probe B as
many as 10 times, and another told several doctors at a physicians' conference
that they could rotate the device up to 15 times (although the second representative
subsequently was admonished not to advocate such extreme use).
|||Defendants do not contest that USCI representatives in fact told physicians
that they could rotate Probe B more than once, and that USCI promotional
materials might have given the same impression. Defendants vigorously contest,
however, that they themselves knew of and condoned promotion of Probe B
contrary to its label warning. The evidence as to defendants' knowledge
and condonation was thin; Cvinar and Prigmore attended the January 1989
Lake Tahoe conference, but no witness placed them at the presentation in
question. All promotional materials relating to use of a Class III device
were approved by the regulatory affairs department (which Leichter headed),
but there was evidence that the doctor's remarks on the videotape were added
after regulatory affairs had approved it. In any event, no witness or document
ever directly tied defendants to the promotional materials in question.
Finally, there was evidence that Leichter insisted that label warnings be
followed when he learned that some USCI salespeople had been promoting Probe
B contrary to its label warnings.
|||b. Misconduct Involving the Probe C
|||The government asserts that USCI committed similar regulatory infractions
with respect to the testing and marketing of Probe C. In early 1989, at
the same time the Crisis Team was reacting to the problems with Probe B,
USCI was working urgently on modifications designed to rectify those problems.
The result was Probe C. USCI bench tested eight Probe C prototypes and,
without having secured an IDE from the FDA, shipped two or three of the
prototypes for use in humans to see whether the changes improved the strength
of the catheter's tip and thus reduced the chance of breakage. Some of the
prototypes used in humans did not perform as well as Probe B, but, by March
1989, USCI had settled on a final version. In this version, USCI increased
the diameter of the device's core wire by 30% and eliminated a solder joint
used to attach the wire to a spring. USCI also modified the device's assembly
|||USCI then marketed Probe C without filing a PMA supplement. In fact, the
company took steps that can be taken to evince an intent to conceal Probe
C's changes and thus to blur the differences between Probe C and its predecessor.
For example, USCI basically retained the Probe B label for the new device
but placed on the label an inconspicuous dot or small letter "C"
so that USCI, and USCI alone, would know the model's identity. In the government's
view, the unapproved testing and marketing of Probe C was unlawful because
the testing was for purposes of establishing the device's safety or effectiveness,
see 21 C.F.R. Part 812, and because the new product contained design changes
affecting its safety or effectiveness, see id. § 814.39(a), (b). Once more,
Prigmore contests the sufficiency of the evidence establishing his knowledge
and approval of USCI's conduct with respect to Probe C, and the other defendants
assert that their conduct was perfectly lawful under their understanding
of the applicable regulations.
|||c. Additional Deceptions
|||In the spring of 1989, the FDA learned that USCI had modified Probe B
so as to create Probe C without filing a PMA supplement. At the same time,
the FDA came into possession of information that caused it to become concerned
about Probe B tip breaks. On April 25, 1989, an FDA reviewer met with Leichter
and informed him that she was concerned whether Probe B was sufficiently
safe. Leichter denied that there were safety concerns and failed to reveal
the tip breaks that had occurred during the investigational use of Probe
B in humans. The next day, Prigmore sent Leichter a memo conveying a "personal
'job well done' with regard to your recent dealings on the Probe, and particularly
your meeting with the FDA."
|||The FDA later requested explanations for both Probe B's failure rates
and USCI's failure to file a PMA supplement with respect to Probe C. On
May 15, 1989, USCI responded to the FDA's concerns by letter. All three
defendants spent several hours reviewing the contents of the letter. The
letter explained that, following field observation and analysis of broken
catheters, it had become clear to USCI that Probe B's breakage problems
were attributable to "overtorque[ing] during clinical use while the
tip was restricted." In other words, the device was only breaking when
it was being used contrary to its label warning against more than a single
revolution in either direction. The letter also took the position that Probe
B was sufficiently safe because the device's actual breakage rate was statistically
identical to the breakage rate of Probe A observed in clinical testing and
reported to the FDA before the agency acted favorably on the Probe A PMA
application. But the letter did not reveal that the tip of Probe B had a
tendency to remain in the patient following a break. Nor did it acknowledge
that, in actual use, Probe B in fact broke 25 times more frequently than
did Probe A, and that, during what defendants call the "consumer preference
testing" of Probe B, the device broke many times more frequently than
did Probe A in actual use. Defendants contend that, under their understanding
of the regulations and the circumstances of Probe B tip breaks, none of
the foregoing representations or omissions was fraudulent.
|||The letter also explained that, although the design modifications in Probe
C "substantially reduced the risk of critical tip failure," these
modifications did not affect the device's safety or effectiveness. The asserted
basis for these seemingly contradictory assertions was a tripartite argument:
(1) the regulations only require the filing of a PMA supplement when a design
modification affects the safety or effectiveness of the device when it is
used in accordance with its labeling; (2) the modifications to Probe B inhering
in Probe C only affected (by improving) the safety and effectiveness of
the device when it was used in a manner contrary to its labeling (i.e.,
when, contrary to its label warning, the device was rotated more than a
single revolution in the same direction); and (3) the modified catheter
that became Probe C thus could be marketed without a PMA supplement. This
argument presaged defendants' trial position in the dispute about the meaning
of the regulations at the core of this case.
|||On June 9, 1989, the FDA ordered a recall of Probes B and C and directed
USCI to file a PMA supplement before marketing Probe C in the future. In
August 1989, USCI submitted such a supplement. In the supplement, USCI asserted
that the Probe C was in fact safe and effective and cited in support of
this claim the data gathered during its earlier investigational use of the
device in humans, along with additional follow-up data collected at the
direction of the FDA. The PMA supplement stated without limitation that
Probe C had been "distributed from March 1989 until August 1989"
in order "to determine the safety and efficacy of the device."
|||2. The Miniprofile Line
|||During the conspiracy period, the Miniprofile line was USCI's second most
profitable line of catheters, ranking just behind the Probe line in sales.
At trial, the government introduced evidence tending to show that, with
defendants' knowledge and approval, USCI engaged in four courses of conduct
with respect to the Miniprofile line that the government sees as fraudulent:
(1) in late 1987, USCI changed the manufacturing location for the Miniprofile
line and then marketed catheters manufactured at the new location without
obtaining the FDA's prior approval; (2) in 1988, USCI modified the design
of the Miniprofile, tested the modified catheter in humans without having
secured an IDE, marketed the modified version without having filed a PMA
supplement, and adopted complex inventory sorting and labeling methods designed
to conceal the change; (3) in 1989, in PMA supplements filed in connection
with several additional changes to the Miniprofile, USCI (a) represented
that clinical testing was not necessary to evaluate the safety or effectiveness
of the changes at the same time it allegedly was conducting such testing,
and (b) failed to reveal the 1988 design change; and (4) in August 1989,
USCI filed a PMA supplement crafted to "legitimize" the 1988 design
change. We elaborate briefly on each of these four blocs of evidence.
|||a. The Change in Manufacturing Location
|||As previously detailed, the first catheter in the Miniprofile line was
called the "Simplus." Until the end of 1987, USCI manufactured
the Simplus at a plant in Billerica, Massachusetts. In September 1987, USCI
acquired a factory building in Haverhill, Massachusetts, and began preparations
to move its Simplus manufacturing operations there. The move required approximately
six weeks of work from a 25-person crew, structural changes to the buildings,
and the installation of filters and purifiers to de-ionize the air and water.
The idea was essentially to "replicate" the Billerica Simplus
manufacturing operations, although only some Billerica machines and workers
were transferred to the new plant.
|||On December 15, 1987, USCI filed a PMA supplement requesting FDA approval
to manufacture the Simplus at its Haverhill facility. On March 3, 1988,
the FDA sent inspectors to the Haverhill plant. After a five-day inspection,
the inspectors identified a number of problems with various pieces of equipment
at the new plant. On March 23, 1988, Cvinar wrote to the FDA and promised
to correct the problems. On June 7, 1988, the FDA approved the PMA supplement
for the Haverhill facility, stating in a cover letter that "[y]ou may
begin marketing of the device manufactured at this facility upon receipt
of this letter." But by that time, USCI already had marketed several
thousand catheters manufactured at the Haverhill plant.
|||As noted above, the regulations for Class III medical devices require
the filing of a PMA supplement when an approved device is manufactured at
"a different facility and establishment" and the change in location
affects the device's safety or effectiveness. See 21 C.F.R. § 814.39(a)(3).
The government takes the position that the move from Billerica to Haverhill
was one that affected safety or effectiveness and thus required FDA approval
prior to the marketing of any catheters assembled in Haverhill. Defendants
respond that, because the Haverhill operations were designed to replicate
the Billerica operations, the move was "safety neutral" and the
PMA supplement USCI filed was in fact unnecessary. Defendants also contest
the sufficiency of the evidence linking them with the decision to market
Haverhill-manufactured catheters prior to FDA approval.
|||b. The 1988 Design Change
|||On May 24, 1988, the FDA approved the marketing of the Miniprofile catheter,
which evolved from the Simplus. As approved, the Miniprofile contained three
"lumens," which are the tiny tubes used to inflate and deflate
the balloon. Originally, USCI intended to manufacture the Miniprofile with
a "fast purge" system that facilitated quick elimination of air
from the lumens prior to filling them with the liquid that would inflate
the balloon. The fast purge system was patented, however, and USCI ultimately
could not use it in the Miniprofile.
|||Following its commercialization, the Miniprofile developed a reputation
for having a deflation problem. There was evidence that the problem was
largely traceable to end users not preparing and purging the catheter in
accordance with the instructions in its labeling. But there also was evidence
that the round shape of the Miniprofile's lumens may have been a contributing
factor. In any event, the perception that the Miniprofile had a deflation
problem affected sales, and USCI began investigating the possibility of
an ameliorative modification.
|||Eventually, USCI decided that a reduction in the number of lumens from
three to two would positively affect Miniprofile deflation issues. The company
created a two-lumen prototype and, after bench testing, shipped it for investigational
use in humans. USCI did not secure an IDE prior to its investigation of
the device, the objective of which (as stated in an internal USCI document)
was "[t]o evaluate the 2 Lumen Mini/Simplus catheter for improved inflation/deflation
times; and to verify that non-deflation of the balloon will not occur."
On November 3, 1988, a USCI employee sent the Management Board and Breakfast
Club a memorandum summarizing the results of the company's testing. On November
7, 1988, Cvinar informed Prigmore in writing that testing of the two-lumen
Miniprofile had been completed, that the testing revealed "significantly
better inflation/deflation times with latest 2 lumen version," and
that USCI would be changing to the two-lumen design "post haste."
On November 17, 1988, Cvinar sent the Management Board a memo explaining
that the changeover to a two-lumen Miniprofile was a "safety issue"
and linking the decision with the need to "remain competitive in key
|||USCI did not file a PMA supplement prior to marketing the two-lumen Miniprofile.
Moreover, the company took steps that tend to evince an intent to conceal
the change from the FDA. For example, Leichter would not permit USCI's vice
president of marketing to issue a brochure with a diagram of the modified
catheter because the diagram was "inconsistent with what had been submitted
to the FDA . . . ." Leichter also rejected a subordinate's suggestion
that the label of the modified device reflect the decreased number of lumens,
explaining that "[w]e don't want it to be evident to the FDA, so I
would rather have something different that would not be so obvious."
Instead, USCI adopted more complicated inventory-sorting and labeling methods.
The government takes the now-familiar position that the testing and marketing
of the two-lumen Miniprofile violated the Class III medical device regulations
because the testing was for purposes of determining the modified device's
safety or effectiveness yet was performed without an IDE, see 21 C.F.R.
Part 812, and because the change from three to two lumens affected the device's
safety or effectiveness yet was implemented without a PMA supplement, see
id. § 814.39(a). Here again, Prigmore asserts evidentiary insufficiency
and all defendants contend that, under their understanding of the regulations,
neither an IDE nor a PMA supplement was required in connection with the
testing and marketing of the two-lumen Miniprofile.
|||c. The 1989 PMA Supplements
|||Throughout 1989, USCI modified the Miniprofile by creating versions of
the device with (1) a silicone coating, (2) a balloon bond cured by ultraviolet
light, (3) longer and thicker balloons, and (4) a thinner shaft (the so-called
"Solo" model). USCI filed PMA supplements for these modifications,
asserting that clinical testing was not required to verify the continued
safety and effectiveness of the device. In fact, however, USCI investigated
how each of these models performed in humans without having secured an IDE
from the FDA. The plans for and results of these tests were documented in
various memoranda sent to Leichter and Cvinar. In addition, with the exception
of the Solo submission (which in one section mentioned that the device had
two lumens), the PMA supplements for these modifications did not reveal
that the Miniprofile was, by 1989, a two-lumen catheter. This apparently
was not an accident. There was evidence that Leichter directed that a draft
of the PMA supplement for the Miniprofile with the new balloon sizes be
altered to remove a passage describing the catheter as having two lumens
because "right now it wasn't a good time" to mention the change
in light of "what had happened with the Probe."
|||Defendants' response to the government's argument that this evidence suggests
a conspiracy to defraud is basically the same as that with respect to the
three-to-two lumen change. Prigmore asserts that there is insufficient evidence
that he knew or approved of these events. The other defendants do not disclaim
the necessary knowledge and approval. Rather, they assert that the "testing"
of these modifications without an IDE and the failure to reveal the three-to-two
lumen change were not unlawful given their understanding of the regulatory
|||d. The "Legitimizing" 1989 PMA Supplement
|||In August 1989, USCI allegedly conceived a plan to obtain post hoc FDA
approval of the two-lumen Miniprofile. The company decided to file a PMA
supplement for a new catheter in the Miniprofile line called the "Solo
Sr." The supplement would disclose and seek approval for the three-to-two
lumen change as if it were not already a done deed. As explained in a memorandum
summarizing an August 30, 1989 Regulatory Affairs Meeting attended by Leichter
and Prigmore, USCI would "'legitimize' the changes [it] ha[d] already
made (3 lumen to 2 . . .)" by submitting a PMA supplement "within
a month." Leichter told a subordinate that the Solo Sr. PMA supplement
was designed as a "cleanup" filing to secure FDA approval of a
product already being shipped. As noted previously, the PMA supplement submitted
for the Solo Sr. was eventually withdrawn.
|||During the late summer of 1989, Leichter walked into a Management Board
meeting carrying a group of files on the Miniprofile line and announced
that the files were problematic and "not clean." William Longfield,
the Chief Operating Officer of Bard, replied by asking whether the records
could be "purged." In response, Cvinar halted the meeting and
sent the participants out of the room. After a break, the meeting resumed
and the subject of purging the files did not arise again.
|||Despite his presence at the meeting where it was decided that USCI would
attempt to "legitimize" already-made changes to the Miniprofile,
Prigmore again argues that there is insufficient evidence to prove that
he knew of or condoned USCI's actions with respect to the Solo Sr. The other
defendants contend that the Solo Sr. was not in fact the then-extant Miniprofile,
pointing to evidence that the device was to have a blood-pressure monitoring
capability not then present in the Miniprofile. In other words, defendants
take the position that the Solo Sr. PMA supplement was not fraudulently
filed in an attempt to legitimize already made changes to the Miniprofile;
rather, it was filed "in order to seek approval of changes and features
other than the number of lumens." Defendants additionally contend that
the Solo Sr. PMA supplement was filed at the direction and under the supervision
of David Thomas, USCI's Vice President of Regulatory Affairs and an immunized
|||C. Relevant Procedural History
|||As indicated above, the primary defense theme at trial was that, under
defendants' understanding of the applicable statutory and regulatory requirements,
the testing and marketing efforts at the root of the charged conspiracy
were not fraudulent. This theme had two components pressed by defendants
in the alternative: (1) defendants' understanding of the legal requirements
was correct; or (2) defendants' understanding of the legal requirements,
even if incorrect, was objectively reasonable and therefore foreclosed a
fraud prosecution based on a stricter reading of the law. See, e.g., United
States v. Rowe, 144 F.3d 15, 21-23 (1st Cir. 1998) (applying the rule that,
in a fraud prosecution premised on an alleged violation of ambiguous positive
law, the defendant is entitled to have his culpability assessed against
the interpretation of the law that most tends to rebut the charge of intentional
deceit so long as the interpretation is objectively reasonable).
|||Although defendants took a number of different legal positions based on
the specific language of the pertinent regulations, the foundation supporting
their primary defense theme tracked USCI's earlier argument, set forth in
the May 15, 1989 letter to the FDA, that a Class III medical device manufacturer
is only required to file a PMA supplement when it modifies an approved device
and the modification affects the device's safety or effectiveness when the
device is used in accordance with its "intended conditions of use"
- i.e., the conditions of use prescribed in the labeling. Thus, the argument
ran, modifications affecting the device's safety or effectiveness only during
"unlabeled," and thus unintended, conditions of use, such as overrotation
with respect to the Probe line and improper preparation and purging with
respect to the Miniprofile line, did not affect the device's safety or effectiveness
within the meaning of the applicable regulations.
|||In support of their argument, defendants relied heavily upon 21 U.S.C.
§ 360c(a)(2) and 21 C.F.R. § 860.7, which by their terms define for the
FDA when a device is to be regarded as safe and effective. These provisions
combine to suggest that the safety and effectiveness of a device are to
be determined by, inter alia, weighing its benefits to health against the
probable risks from use of the device for its intended conditions of use.
See id. In a nutshell, defendants' position was that, if the FDA determines
a device's safety and effectiveness within the context of the device's intended
conditions of use, it was at least reasonable for them to assume that modifications
which affect a device's safety or effectiveness only during unintended conditions
of use do not affect "safety" or "effectiveness" within
the meaning the applicable law. *fn1
|||The government did not agree with defendants' asserted understanding of
the crucial statutory and regulatory provisions, or with defendants' alternative
argument that, even if not correct, defendants' understanding was objectively
reasonable and therefore the appropriate benchmark against which criminal
liability should be judged. Rather, the government took the position that
any modification known by the manufacturer to affect the safety or effectiveness
of an approved Class III device - even a modification only affecting safety
or effectiveness during unlabeled and warned-against conditions of use -triggers
the obligation to file a PMA supplement. The government supported this so-called
"plain" or "dictionary" meaning of the phrase "affecting
the safety or effectiveness of the device" in 21 C.F.R. § 814.39(a)
with the testimony of two FDA experts and a Bard executive, all of whom
shared with the jury their understandings of the crucial Class III medical
device regulations. Although the experts gave testimony that generally tended
to support the government's case, defendants were able to elicit on cross-examination
of the FDA witnesses that a manufacturer attempting to divine the meaning
of the phrase "affecting the safety or effectiveness of the device"
reasonably might cross-reference § 860.7, and that this regulation does
indeed circumscribe the concepts of "safety" and "effectiveness"
in terms of "intended . . . conditions of use."
|||Consistent with their position on the meaning of the phrase "affecting
the safety or effectiveness of the device," defendants requested that
the district court instruct the jury to construe the phrase in the light
cast by 21 C.F.R. § 860.7. Accordingly, defendants asked the court to quote
§ 860.7(d)(1) and (e)(1) verbatim and to instruct the jury to "seek
the definition[s] of 'safe' and 'effective'" in these provisions. Defendants
further asked that the court instruct the jury "to determine the safety
and effectiveness of a device or of a change to a device, not under any
conditions of use, but in light of the conditions of use, directions for
use, and warnings against unsafe use contained in the manufacturer's labeling
for that device." Finally, defendants asked the court to instruct the
jury that "the defendants' interpretation of the standard they were
to use in determining safety and effectiveness was reasonable."
|||The government, by contrast, opposed defendants' attempt to link 21 C.F.R.
§ 860.7 to the phrase "affecting the safety or effectiveness of the
device" in § 814.39(a). The government argued that § 860.7 is intended
only to guide the FDA as to whether a device is safe and/or effective; it
is not intended to advise the manufacturers of Class III medical devices
in connection with their PMA supplement filing obligations. Accordingly,
the government asked that, in instructing the jury, the district court (1)
simply quote the relevant portions of § 814.39 (but not § 860.7); (2) define
the terms "safety" and "effectiveness" according to
"their plain ordinary meaning," - i.e., "freedom from danger
or risks" and "having a definite or desired effect," respectively;
and (3) state that there is no exemption from the relevant filing requirements
"based upon a misuse of the device by users of the device," and
that "a PMA supplement must be filed . . . for a change that affects
safety and efficacy regardless of the reason for the change" - i.e.,
even if the change affects safety or effectiveness of the device only in
the event of unlabeled or warned-against conditions of use.
|||The district court did not adopt either approach. Instead, the court advised
counsel on the day before closing arguments that, although it would permit
defendants and the government to argue to the jury their respective interpretations
of the applicable Class III medical device statute and regulations, it would
only instruct on conspiracy to defraud. The court thus would not instruct
on either the meaning of the underlying statute and regulations or objectively
reasonable interpretations thereof.
|||Accordingly, counsel for Leichter and Cvinar stressed in their closing
arguments that, as the relevant statute and regulations were reasonably
understood by their clients, a modification to an approved Class III medical
device affected the device's safety or effectiveness (and triggered the
PMA supplement filing requirement) only when the modification impacted safety
or effectiveness during the device's intended conditions of use. Counsel
for Leichter and Cvinar also emphasized that the intended conditions of
use were to be found in the device's labeling instructions and warnings.
Counsel for Prigmore primarily focused on whether there was sufficient evidence
to tie his client to the conspiracy, but also joined in Leichter and Cvinar's
legal arguments to the district court. The government, for its part, prominently
argued that "safety" and "effectiveness" should be given
their plain or dictionary meanings, and that modifications affecting safety
or effectiveness during unlabeled or warned-against uses were subject to
the regulatory filing requirements. The government also suggested that 21
C.F.R. § 860.7 is intended only to guide the FDA in making its safety and
effectiveness assessments, and has no bearing on a manufacturer's obligation
to file a PMA supplement.
|||Subsequently, as promised, the district court declined to instruct the
jury on the meaning of the statute and regulations. Rather, the court instructed
on the elements of conspiracy to defraud, and specified that defendants
were accused of conspiring to defraud the FDA in three respects: (1) "knowingly
and willfully, and with an intent to defraud, failing to submit applications
for product approval and testing [to] the FDA, which allegedly they were
required to submit"; (2) "concealing or failing to report material
facts which allegedly they were required to report"; and (3) "making
false statements in documents that they submitted to the FDA."
|||The district court also gave detailed state-of-mind instructions, emphasizing
that the government was required to prove beyond a reasonable doubt that
defendants had knowledge of their legal duties (on this point, the court
simply provided the jury with copies of the applicable Class III medical
device statutory and regulatory provisions); that defendants specifically
intended to agree to violate these duties and thus defraud the FDA; and
that defendants "did not act in good faith or by mistake, accident,
or neglect." Defendants timely objected to the court's refusal to instruct
that the terms "safety" and "effectiveness" in the provisions
spelling out defendants' legal duties must be understood as described and
confined by 21 C.F.R. § 860.7 and, alternatively, to the court's refusal
to instruct that defendants' interpretation of the regulatory requirements
was at the very least reasonable. On the sixth day of its deliberations,
the jury convicted defendants. These appeals eventually ensued.
|||As we stated at the outset, defendants raise a number of issues. All three
defendants press various arguments that the underlying convictions should
be reversed and the conspiracy charge dismissed. All three defendants also
assert a number of alternative arguments that their convictions should be
vacated and the matter remanded for further proceedings. Prigmore additionally
contends, again in the alternative, that his sentence was unlawful.In the
end, we are not persuaded by defendants' arguments for reversal and dismissal.
Yet we are convinced that the convictions should be vacated and the case
remanded for further proceedings. To simplify our analysis, we shall begin
by explaining why vacatur is warranted and then proceed to explain why reversal
and dismissal is not. We do not reach the merits of any arguments for vacatur
beyond the one we regard as dispositive because, in any retrial, the issues
giving rise to these other arguments are either not likely to arise again
or likely to arise in materially different contexts. For the same reason,
we do not address the merits of Prigmore's sentencing challenge.
|||A. The Dispositive Issue
|||Defendants contend, inter alia, that the district court committed reversible
error in refusing to instruct the jury that defendants' asserted understanding
of when a change should be regarded as "affecting the safety or effectiveness"
of a Class III medical device, and thus trigger the PMA supplement filing
requirement, was at least reasonable and therefore the measure against which
defendants' criminal culpability should be assessed. In defendants' view,
the trial record and the logic of the rule we applied in Rowe, see 144 F.3d
at 21-23, entitled them to such an instruction as a matter of law. We do
not believe that the court was obliged to discuss the concept of reasonableness
in its instructions; an instruction that the jury should simply apply a
definition of the applicable phrase informed by the limitations of 21 C.F.R.
§ 860.7 and tailored to the evidence in this case would have covered the
point just as well. Nonetheless, on the facts of this case, we agree that
the court erred in not instructing the jury to determine defendants' guilt
against the backdrop of such a definition.
|||We begin by acknowledging that the district court has considerable discretion
in how it formulates, structures, and words its jury instructions. See,
e.g., United States v. Woodward, 149 F.3d 46, 68 n.14 (1st Cir. 1998). Moreover,
the court often acts within its discretion in refusing to elaborate the
meaning of even an important legal term or phrase that falls short of being
self-explanatory. Indeed, we have recognized that, in some instances, attempts
to clarify inherently nebulous concepts can do more harm than good. Cf.
United States v. Andujar, 49 F.3d 16, 23 (1st Cir. 1995) (explaining our
repeated warnings that district courts within this circuit should avoid
defining the phrase "reasonable doubt" in their jury instructions).
The applicable standard, informed in part by these principles, is that a
court's refusal to give a requested instruction is reversible error only
if the requested instruction was (1) substantively correct; (2) not substantially
covered elsewhere in the charge; and (3) concerned a sufficiently important
point that the failure to give it seriously impaired the defendant's ability
to present his or her defense. See, e.g., United States v. Rose, 104 F.3d
1408, 1416 (1st Cir. 1997). In our view, this is the relatively rare case
where all three of these requirements are met.
|||As an initial matter, defendants are plainly correct in asserting that,
under settled circuit law, they were entitled to have their intent assessed
in the light of the interpretation of the underlying filing requirements
that is most congenial to their case theory and yet also objectively reasonable.
See Rowe, 144 F.3d at 21-23 (bankruptcy fraud case) (applying this principle
to hold that an allegedly false statement was not fraudulent because it
was not in fact false under an objectively reasonable interpretation of
the underlying disclosure requirement); United States v. Migliaccio, 34
F.3d 1517, 1525 (10th Cir. 1994) (applying the rule in a mail fraud prosecution);
cf. United States v. Bradstreet, 135 F.3d 46, 52 (1st Cir. 1998) (securities
fraud case) (endorsing such a rule in dicta). This rule, rooted in the due
process-based "fair warning requirement," see United States v.
Lanier, 520 U.S. 259, 265-67 (1997), recognizes that, in a prosecution based
on the theory that a defendant has defrauded the government by making false
statements in information defendant was duty-bound to divulge to the government
(or by failing to divulge information defendant was duty-bound to divulge),
there has been no crime if the statements were not false (or if there was
no duty to divulge) under an objectively reasonable interpretation of the
law imposing the duty. See Rowe, 144 F.3d at 21. The government does not
take issue with this general principle; in fact, it makes no mention at
all of Rowe or Bradstreet despite defendants' significant reliance on them.
|||We also think it apparent that, if the evidence at trial gives rise to
a genuine and material dispute as to the reasonableness of a defendant's
asserted understanding of applicable law, the judge, and not the jury, must
resolve the dispute. See United States v. Cheek, 498 U.S. 192, 203 (1991)
(tax fraud case) (observing that the objective reasonableness of defendant's
view of the law is a legal question); Rowe, 144 F.3d at 21-23 (treating
the reasonableness question raised in that case as a matter of law). *fn2
On this general point, the government's agreement is explicit.
|||Indeed, despite its position at trial, the government no longer affirmatively
takes issue with the general proposition that it was reasonable for defendants
to have regarded the definition of the phrase "affecting the safety
or effectiveness of the device" in 21 C.F.R. § 814.39(a) as properly
informed by the context-providing qualifications set forth in § 860.7. Although
at oral argument the government declined to disavow the "plain meaning"
or "dictionary" definitions of the terms "safety" and
"effectiveness" that it pressed at trial and in its closing arguments,
the government makes no real effort to defend those definitions in its brief
to this court. Perhaps this is because the Supreme Court recently recognized
that "virtually every drug or device poses dangers under certain conditions,"
FDA v. Brown & Williamson Tobacco Corp., 120 S. Ct. 1291, 1305 (2000),
and repeatedly emphasized that a drug or device is safe within the meaning
of the FDCA when, in connection with its intended uses and conditions of
use, see generally id. at 1301-06, its "therapeutic benefits outweigh
the risk of harm," id. at 1305. Perhaps this is because, on cross-examination,
the FDA experts who testified concerning the meaning of the applicable regulations
conceded that it was reasonable to refer to the phrase "intended .
. . conditions of use" in § 860.7(d)(1) and (e)(1) in ascertaining
the meaning of the phrase "affecting the safety or effectiveness of
the device" in § 814.39(a). *fn3
Perhaps the government has simply changed its position because it now agrees
with defendants' argument that terms and phrases repeated throughout a given
law generally carry the same meaning. See, e.g., United States v. Nippon
Paper Indus. Co., Ltd., 109 F.3d 1, 4-5 (1st Cir. 1997). In any event, to
the extent that the government may have tacitly conceded the general point,
we regard the concession as proper. For the reasons just stated, and regardless
how the phrase "affecting the safety or effectiveness of the device"
in § 814.39(a) ultimately ought to be understood, it was objectively reasonable
for defendants to regard the phrase as definitionally circumscribed by the
"intended . . . conditions of use" qualification found in, among
other places, § 860.7(d)(1) and (e)(1).
|||That said, the government does not concede that the district court committed
reversible error in declining to give the instruction defendants requested.
Put in the language of the three-part test under which we review the court's
refusal to instruct, see Rose, 104 F.3d at 1416, the government's argument,
in essence, is that there has been no error because the instruction defendants
requested was neither substantively correct nor concerned a sufficiently
important point that the court's failure to give it seriously impaired defendants'
ability to present their defense, see id. *fn4
|||As to the first Rose factor, substantive correctness, the government points
out that defendants requested that the court instruct the jury not only
that it should link the phrase "affecting the safety or effectiveness
of the device" in 21 C.F.R. § 814.39(a) with the phrase "intended
. . . conditions of use" in § 860.7(d)(1) and (e)(1), but that it also
should understand "intended . . . conditions of use" in terms
of the device's labeling. Such a definition was too narrow, according to
the government, because there was evidence that, with respect to Probe B,
defendants knew of and acquiesced in USCI's on-the-side promotion of the
overrotation against which the device's label warned. As the government
sees it, all actual conditions of use that the manufacturer intends or even
knows of are relevant to the safety-or-effectiveness inquiry, and modifications
affecting a device's safety or effectiveness during such conditions of use
trigger the PMA supplement-filing requirements even if they are specifically
warned against on the label. In making this argument, the government points
out that § 860.7(b)(2) specifies that "[t]he conditions of use for
[a] device includ[e] conditions of use prescribed, recommended, or suggested
in the labeling or advertising of the device, and other intended conditions
of use." (emphasis supplied). *fn5
|||Given the explicit references to intention in 21 C.F.R. § 860.7(d)(1)
and (e)(1), and in the absence of some clarifying regulatory or judicial
gloss to support the government's position, see Lanier, 520 U.S. at 266
(recognizing that "uncertain" laws can be clarified by authoritative
construction), we are not persuaded that a criminal fraud prosecution can
be premised upon a failure to file a PMA supplement in connection with a
modification to an approved device that affects the device's safety or effectiveness
only with respect to a sincerely unintended and warned-against, albeit known,
condition of use. *fn6
Yet we think that the regulatory text does accommodate the government's
argument that a manufacturer must take into account unlabeled, though promoted
(and thus "intended"), conditions of use in determining whether
a modification affects safety or effectiveness. Moreover, given the evidence
of USCI's promotion of Probe B overrotation, such a jury instruction might
well be necessary at any retrial if there is sufficient evidence that defendants
knew of or acquiesced to such promotion.
|||But under the circumstances of this case, we do not think it appropriate
to hold that the defendants' reference to labeling in their requested instruction
effectively waived their right to an instruction that, for purposes of this
prosecution, the "intended . . . conditions of use" qualification
in 21 C.F.R. § 860.7(d)(1) and (e)(1) limits the meaning of the phrase "affecting
safety or effectiveness" in § 814.39(a). Although defendants' proposed
instruction did request that the jury be instructed in terms of labeling,
it more generally requested (over the government's objection) that the jury
be instructed in the specific language of § 860.7(d)(1) and (e)(1), both
of which state broadly, without specific reference to labeling, that "intended
. . . conditions of use" are relevant to safety and effectiveness determinations.
In other words, but for a proposed refinement suggesting that the label
instructions reveal the manufacturer's intended conditions of use (as in
most cases they would), defendants' request was sufficiently close to the
mark. Moreover, and more to the point, we think it evident that the government's
promotion at trial of an overly broad (at least for purposes of assessing
criminal liability) definition of the relevant statutory and regulatory
terms had as much, if not more, to do with this issue not emerging in sharp
relief as did any lapse on defendants' part. Defendants' requested instruction
was thus adequate to preserve the issue. Cf. United States v. Sanborn, 563
F.2d 488, 490-91 (1st Cir. 1977) (vacating a conviction on the basis of
a rule of law slightly different, and less defendant-friendly, than that
sought by the defendant in his requested instruction).
|||As to the third Rose factor, whether the requested instruction concerned
a sufficiently important point that the district court's failure to give
it seriously impaired defendants' ability to present their defense, the
government appears to make two arguments. First, the government makes a
halfhearted claim that the court's good-faith instructions "adequately
articulated" the no-mens-rea defense theory and thus rendered unimportant
the court's failure to define the disputed underlying regulatory requirements.
See Gov't Br. at 111. We disagree. While the court's good-faith instructions
were comprehensive, articulate, and beyond reproach insofar as they generally
described the concept of good faith, the jury's good-faith finding may well
have been affected by its view of what the underlying law required. The
trial evidence, closing arguments, and the jury instructions might well
have left the jury with an erroneous belief that manufacturers face criminal
liability for failing to file a PMA supplement when they make a modification
to an approved device that has an effect only during a sincerely unintended
and specifically warned-against condition of use. This erroneous belief,
in turn, might well have been the basis upon which the jury rejected the
good-faith defense. The good-faith instruction thus did not undo the harm
caused by the court's failure to give the requested instruction in and of
itself. See Migliaccio, 34 F.3d at 1525.
|||Second, the government in substance contends that, even if erroneous,
the district court's failure to define the underlying regulatory terms was
unimportant because it was harmless beyond a reasonable doubt within the
meaning of Neder v. United States, 527 U.S. 1, 16-20 (1999) (holding harmless
the trial court's erroneous failure to instruct the jury to determine whether
a failure to report taxable income was "material" where the failure
to report involved over $5 million, the evidence regarding the failure to
report was not controverted, and defendant did not argue to the jury that
his failure to report was immaterial). The government suggests that, as
in Neder, it is here "clear beyond a reasonable doubt that a rational
jury would have found" defendants guilty even if properly instructed.
Id. at 18 (emphasis supplied). *fn7
|||Indeed, in the government's view, "[t]his case . . . presents a stronger
candidate for a finding of harmlessness" than did Neder because the
legal error in Neder affected the jury's consideration with respect to all
of defendant's allegedly illegal acts. Gov't Br. at 80. In contrast to Neder,
the government asserts, the error in this case only affected the jury's
deliberations with respect to those acts pertaining to the failure to obtain
a PMA supplement; the error did not affect the jury's consideration of the
evidence of the testing violations, the evidence that defendants failed
to disclose the three-to-two lumen change in the 1989 Miniprofile PMA supplements,
the evidence regarding deceptive intentions with respect to the filing of
the Solo Sr. PMA supplement, the evidence of USCI's failure to report modifications
in mandatory follow-up reports, or the evidence of other assorted deceit
and trickery (e.g., promoting Probe B contrary to its label warnings and
adopting complicated inventory and labeling methods designed to conceal
device modifications from the FDA). And, the argument concludes, the evidence
with respect to these matters was "overwhelming." Id.
|||In our view, the evidence of guilt in this case is quite substantial;
certainly, it is more than sufficient to permit a retrial on a properly
formulated theory that defendants conspired to defraud the FDA with respect
to its oversight and regulation of medical devices. We do not believe, however,
that the evidence is so one-sided as to render harmless the underlying instructional
error we have identified. Unlike the government, we do not see this as a
case, like Neder, where it is far-fetched to conclude that a properly instructed
jury might have returned different verdicts than those returned. In explaining,
we follow the government's lead and focus upon the nature and weight of
the evidence asserted to have been unaffected by the instructional defect.
|||The government first asserts that the trial evidence showed conclusively
that defendants tested their device modifications for the purpose of determining
safety and effectiveness with respect to intended conditions of use and
in such a way as to put patients at prohibited risks. In responding to this
argument, we limit ourselves to the factual nature of the evidence presented
and put to the side defendants' legal argument that, because an IDE is an
exemption permitting the clinical testing of unapproved devices that otherwise
could not lawfully be shipped without premarket approval, the lawfulness
of most of the testing at issue in this case turns in the first place on
whether the modification at issue was subject to the PMA supplement requirement.
See supra note 1.
|||As to the nature of the testing evidence, we think that, while the factual
inference the government would have us draw surely would be permissible
on the present record, see, e.g., supra at 13, 20, 23-24 (summarizing documentary
evidence suggesting that the testing was for purposes of evaluating safety
and/or efficacy during intended conditions of use), it is not the only rational
inference. Unlike Neder, the government's evidence as to the purpose of
the testing was contested by defendants; as we have stated, defendants introduced
testimonial evidence that the purposes of this testing were to determine
whether the modifications were ameliorating safety concerns during unintended
conditions of use and/or to establish consumer preferences within the meaning
of 21 C.F.R. § 812(c)(4). See supra at 13-14. Given Neder's repeated emphasis
on the "uncontested" nature of the evidence of materiality in
that case, see 527 U.S. at 15, 17, 17 n.2, & 19, the contested nature
of the testing evidence in this case might well suffice to distinguish it
from Neder in and of itself.
|||In any event, while the government's evidence of the purpose behind the
testing was strong, the competing evidence was not inherently incredible.
That effectively ends the matter. As an appellate court, we are not equipped
to make the credibility determinations that must be made in choosing between
these clashing blocs of evidence, each of which is sufficient to render
rational a finding in favor of its proponent. See Neder, 527 U.S. at 19.
We also are mindful that, in denying defendants' motions for judgments of
acquittal, the trial court thought it a very "close" call whether
the motions should be granted, and that, in overruling defendants' objections
to its failure to give the requested safety-and-efficacy instruction, the
court opined that instructing the jury as the defendants requested would
be tantamount to directing a verdict for them. In sum, we do not regard
the government's evidence of the purpose of the testing, alone or combination
with the other evidence discussed below, to be of such a nature as to render
the court's instructional error harmless.
|||Our analysis with respect to the other evidence mentioned by the government
in support of its harmless-error argument follows a similar path. As we
have observed, defendants explained the failure to file a PMA supplement
with respect to the three-to-two lumen change in the Miniprofile with evidence
and argument that a filing was unnecessary because the change was designed
to ameliorate safety issues caused by unintended preparation and purging
techniques by end users. See supra at 23. The evidence on this point was
not inherently incredible. If a correctly instructed jury were to have accepted
this evidence and line of defense (as it might have), we think it might
well also have regarded the subsequent failure to report the three-to-two
lumen change in the 1989 Miniprofile PMA supplements as inconsequential.
So too with the Solo Sr.; we think it possible that the jury might have
accepted defendants' supported and argued contention that USCI filed the
Solo Sr. PMA supplement in order to seek approval of changes other than
those pertaining to lumen number and/or at the direction and under the supervision
of David Thomas, and not defendants.
|||Finally, with respect to the evidence of failure to submit follow-up reports
and the evidence of other assorted deceptions and trickery, it suffices
to note that such evidence was either largely tangential to the primary
trial themes or not particularly probative of any of the principal fraud
theories as to which the jury was instructed. See supra at 34. As we have
explained, instructional error and the absence of one-sided and overwhelming
evidence of guilt combine to prevent us from affirming defendants' convictions
on the basis of the primary criminal liability theories advanced at trial:
fraudulent marketing and fraudulent testing. Moreover, the experienced trial
judge who presided over the case stated on the record that he was not sure
he was correct in even sending the case to the jury. Given this state of
affairs, it would be improper to affirm defendants' convictions on the basis
of evidence that, on the whole, played a supporting rather than a starring
role at trial.
|||B. Other Issues
|||As noted, defendants press various arguments for reversal and dismissal
of the conspiracy charge. These arguments do not merit extended discussion.
|||First, all three defendants argued in their initial briefs that the regulations
under which they were prosecuted did not give fair warning of the "dictionary"
or "plain language" interpretation that the government relied
upon in pressing this prosecution. Then, when defendants perceived in the
government's brief a shift in position towards (if not all the way to) the
interpretation of the regulations they have advanced all along (and we herein
confirm as objectively reasonable), all three defendants suggested in their
reply briefs that the conspiracy charge should be dismissed outright because
the government's "switch . . . confirms the . . . unconstitutionality
of this prosecution." Defendants do not, however, place this argument
within the context of a recognized legal theory; nor do they cite authority
which supports the drastic remedy they seek. We therefore reject the argument
as insufficiently elaborated. See Zannino, 895 F.2d at 17.
|||Second, defendants Cvinar and Prigmore contend that they are entitled
to dismissal of the conspiracy charge because the FDA did not provide them
with notice and an opportunity to present to the FDA their "views"
as to the events underlying this case prior to reporting their alleged violations
of the FDCA to a United States Attorney for prosecution. 21 U.S.C. § 335.
But even assuming that Cvinar and Prigmore were entitled to such notice
and opportunity, the Supreme Court has made it clear that they are not entitled
to dismissal of the prosecution. See United States v. Dotterweich, 320 U.S.
277, 279 (1943).
|||Third, and finally, Prigmore asserts that there was insufficient evidence
to link him to the conspiracy charged and thus to sustain his conviction.
Frankly, in reviewing those portions of the record the government points
to in response to Prigmore's sufficiency argument, we are not particularly
impressed by the strength of the case against him. Nonetheless, mindful
that "in a criminal conspiracy, culpability may be constant even though
responsibilities are divided," United States v. Sepulveda, 15 F.3d
1161, 1173 (1st Cir. 1993), and that a successful sufficiency claim requires
a showing that "no rational jury could have found [defendant] guilty
beyond a reasonable doubt," United States v. Scharon, 187 F.3d 17,
21 (1st Cir. 1999) (emphasis supplied), we are persuaded that there was
sufficient evidence to tie Prigmore to the conspiracy.
|||As we have noted, there was evidence that, on November 7, 1988, Cvinar
informed Prigmore that testing of the modified two-lumen Miniprofile had
been completed, that the testing revealed "significantly better inflation/deflation
times" in the new model, and that USCI would be adopting the two-lumen
design "post haste." See supra at 23-24. There thus was evidence
to ground a conclusion that Prigmore knew that the three-to-two lumen change
was a change affecting the safety and/or the effectiveness of the Miniprofile
- at least with respect to its unintended conditions of use.
|||Further, there was evidence that Prigmore reviewed for several hours the
May 15, 1989 letter in which USCI took the position that the modifications
to Probe B that became Probe C did not require a PMA supplement because
they did not affect the safety or effectiveness of the catheter during its
intended uses and conditions of use. See supra at 18-20. There thus was
evidence to ground a conclusion that, by May 1989, Prigmore knew that USCI
was under a regulatory obligation to file a PMA supplement with respect
to all changes affecting the safety or effectiveness of its approved heart
catheters during their intended uses and conditions of use prior to marketing
the altered product.
|||Moreover, there was evidence that, on August 30, 1989, Prigmore participated
in the meeting where it was decided that USCI, according to a memorandum
memorializing the meeting, would file a PMA supplement for the Solo Sr.
designed to "'legitimize' the changes [it] already ha[d] made (3 lumen
to 2 . . .)" to the Miniprofile by submitting to the FDA a cleanup
PMA supplement. See supra at 26. There is no indication that Prigmore, who
then was a Bard vice president with authority over USCI operations, dissented
from the proposed course of conduct, which eventually was implemented. In
our view, the memorandum describing the August 30 meeting suggests that
Prigmore acquiesced in an unlawful plan to conceal from the FDA a dubious
course of conduct, particularly in light of Prigmore's authority, his knowledge
of the three-to-two lumen change, and his awareness of the relevant regulatory
requirements. This evidence is sufficient to implicate Prigmore in the conspiracy
of which he was convicted.
|||As we have stated, there was substantial evidence that defendants in fact
committed the serious crime of which the jury convicted them. But there
is too great a possibility that the jury's verdicts were affected by an
erroneous failure to define crucial and disputed regulatory terms for us
to affirm the convictions under the harmless-error doctrine. We thus vacate
defendants' convictions and remand for further proceedings consistent with
|||Vacated and remanded.
|||*fn1 As to the claim
that the clinical testing described above violated 21 C.F.R. Part 812 because
it was done without an IDE "to determine [the] safety and effectiveness"
of the various device modifications, § 812.2(a), defendants in part relied
on a derivative of their argument responding to the government's claims
of illegal marketing. With respect to modifications for which, in defendants'
view, no PMA supplement was required, defendants reasonably understood that
an IDE also was not required because an IDE is nothing more than an "exemption
permit[ting] a device that otherwise would be required . . . to have premarket
approval to be shipped lawfully," id. § 812.1(a). With respect to the
preapproval testing conducted on modified devices for which a PMA supplement
admittedly was required (e.g., Probe B), defendants asserted that they regarded
the testing to be consumer preference testing exempted from the IDE requirements
by § 812.2(c)(4). In their submissions to this court, defendants also hint
at an all-encompassing argument that they reasonably did not regard any
of the allegedly unlawful clinical "testing" charged by the government
to violate Part 812. According to this argument, as we understand it, defendants
reasonably read Part 812 as merely prescribing the protocols for the gathering
of the "valid scientific evidence" upon which the FDA will assess
the safety and effectiveness of new and modified devices pursuant to § 860.7(d)(1)
and (e)(1). The testing at issue in this case was not for purposes of gathering
this type of "valid scientific evidence"; it was more in the way
of informal feedback gathered on the front lines by USCI sales representatives
and passed back to corporate headquarters. Thus, the argument concludes,
while the prior shipment of the catheters in question might have violated
§ 814.39(a), their actual use in humans did not independently violate Part
812. Whatever merits this alternative argument might have, we disregard
it for present purposes because defendants did not sufficiently develop
and preserve it as a defense theory in the district court. See United States
v. Zannino, 895 F.2d 1, 17 (1st Cir. 1990).
|||*fn2 To be sure, a
reasonableness determination sometimes requires preliminary resolution of
underlying factual disputes, and the court almost certainly acts within
its rights in asking the jury to resolve these disputes. Cf. Bradstreet,
135 F.3d at 50-52 (suggesting in dicta that, had there been a genuine dispute
as to which of several "revenue recognition policies" defendant
had been "booking" revenue under, and had an allegedly fraudulent
booking of revenue been appropriate under an objectively reasonable interpretation
of one such policy, then the court would have been obliged to instruct the
jury to assess culpability in the light of that reasonable interpretation
so long as it first found defendant to have been using that policy in booking
the revenue in question); St. Hilaire v. City of Laconia, 71 F.3d 20, 24
n.1 (1st Cir. 1995) (civil rights damages action) (observing in a discussion
of the qualified immunity defense and its "objective reasonableness"
criterion that it is an open question whether the judge may decide underlying
factual disputes bearing on reasonableness or must ask the jury to resolve
such disputes). But as a legal question, the reasonableness of defendants'
understanding is ultimately a question for the judge. See Nieves-Villanueva
v. Soto-Rivera, 133 F.3d 92, 99 (1st Cir. 1997) (noting that, in our legal
system, purely legal questions are exclusively within the domain of the
|||*fn3 In referring to
the experts' testimony regarding the meaning of the applicable laws, we
do not wish to be understood as more generally endorsing the use of expert
testimony on legal meaning. Neither side contests the appropriateness of
the expert testimony that took place in this case, so we do not address
its admissibility. We feel it important to note, however, that expert testimony
proffered solely to establish the meaning of a law is presumptively improper.
See Nieves-Villanueva v. Soto-Rivera, 133 F.3d at 99-101; see also Benjamin
J. Vernia, Annotation, Admissibility of Expert Testimony Regarding Questions
of Domestic Law, 66 A.L.R. 5th 135 (1999) (detailing how, despite the inroads
courts have made into the rule against expert testimony on questions of
law, such testimony is still usually excluded).
|||*fn4 It is undisputed
that the instruction defendants requested was not substantially covered
elsewhere in the charge. See Rose, 104 F.3d at 1416. Thus, we address only
the first and third prongs of the Rose standard.
|||*fn5 The government
also draws support for this argument from 21 C.F.R. § 801.4, which was neither
the subject of trial argument nor given to the jury. In relevant part, §
801.4 states: The words "intended uses" or words of similar import
in [three regulations not relevant to this case] refer to the objective
intent of the persons legally responsible for the labeling of devices. The
intent is determined by such persons' expressions or may be shown by the
circumstances surrounding the distribution of the article. The objective
intent may, for example, be shown by labeling claims, advertising matter,
or oral or written statements by such persons or their representatives.
It may be shown by the circumstances that the article is, with the knowledge
of such persons or their representatives, offered and used for a purpose
for which it is neither labeled nor advertised
|||*fn6 We of course recognize
that, if a modification makes an approved device more dangerous in the event
of a condition of use that sometimes occurs despite the manufacturer's best
efforts to prevent it, there may be sound policy reasons for requiring the
manufacturer to file a PMA supplement. But we are concerned here not with
the most socially useful interpretation of the relevant regulations; we
are concerned with whether those regulations gave fair warning that a failure
to file a PMA supplement in such a circumstance is a felony under federal
law. See Lanier, 520 U.S. at 265-67. Because the most relevant regulation
defines device safety in terms of "intended . . . conditions of use,"
§ 860(d)(1) (emphasis supplied), and because there has been no authoritative
judicial or regulatory pronouncement clarifying that a sincerely warned-against
but known condition of use should be regarded as "intended," see
Lanier, 520 U.S. at 266, we reject the government's argument on this narrow
|||*fn7 In arguing that
any error here was harmless "beyond a reasonable doubt," the government
appears to take the position that instructional error of the type we have
identified is constitutional in dimension. See Chapman v. California, 386
U.S. 18, 24 (1967) (holding that, "before a federal constitutional
error can be held harmless, the court must be able to declare a belief that
it was harmless beyond a reasonable doubt"). One member of the panel,
however, believes that the error likely was not constitutional, and that
the applicable harmless-error standard therefore comes from Kotteakos v.
United States, 328 U.S. 750, 776 (1946) (interpreting the predecessor to
the federal harmless-error statute, 28 U.S.C. § 2111, to require reversal
only when the error "had substantial and injurious effect or influence
in determining the jury's verdict"). See Brecht v. Abrahamson, 507
U.S. 619, 630-32 (1993) (noting that the Chapman standard applies to direct
review of constitutional errors and that the Kotteakos standard applies
to direct review of non-constitutional errors). Because the panel unanimously
agrees that the error we discern cannot be said to be harmless under either
test, we do not decide which test applies or, concomitantly, whether the
error deprived defendants of a constitutional right.
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