Filed: Mar. 16, 2001
Latest Update: Feb. 21, 2020
Summary: 6, 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.
United States Court of Appeals
For the First Circuit
No. 00-1158
UNITED STATES,
Appellee,
v.
DAVID W. PRIGMORE,
Defendant, Appellant,
No. 00-1229
UNITED STATES,
Appellee,
v.
LEE H. LEICHTER
Defendant, Appellant,
No. 00-1230
UNITED STATES,
Appellee,
v.
JOHN F. CVINAR,
Defendant, Appellant.
APPEALS FROM THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF MASSACHUSETTS
[Hon. Joseph L. Tauro, U.S. District Judge]
Before
Selya, Circuit Judge,
Coffin, Senior Circuit Judge,
and Stahl, Circuit Judge.
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.
March 16, 2001
STAHL, Circuit 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 proceedings.
I.
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
-3-
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 promulgated
thereunder.
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
-4-
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. § 360e(d)(2).
Under the MDA,
[T]he safety and effectiveness of a [Class
III] device are to be determined –
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(A) with respect to the
persons for whose use the
device is represented or
intended,
(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
-6-
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.
-7-
§ 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
-8-
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).
-9-
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
-10-
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
-11-
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
-12-
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
-13-
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.
-14-
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
-15-
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
-16-
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
three times.
USCI's sales force, which had been instructed to warn
physicians against overrotation of Probe A, were not so
-17-
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
-18-
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 process.
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
-19-
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
-20-
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
-21-
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.
-22-
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
-23-
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
-24-
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
-25-
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
-26-
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
-27-
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 market areas."
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
-28-
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
-29-
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
requirements.
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
-30-
. . .)" 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
-31-
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 government witness.
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
-32-
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
-33-
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.1
1
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
-34-
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
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).
-35-
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
-36-
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.
-37-
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"
-38-
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
-39-
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.
-40-
II.
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
-41-
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
-42-
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
-43-
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)
-44-
(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). 2 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
2 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 judge).
-45-
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).3 Perhaps
3
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
-46-
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,
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).
-47-
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.4 We disagree.
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
4
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.
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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).5
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
5The 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 . . . .
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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. 6 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.
6
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 point.
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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
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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
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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).7
7
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
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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
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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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
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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
-56-
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
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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.
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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
-59-
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
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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
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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,
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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.
III.
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 this opinion.
Vacated and remanded.
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