Court Opinion

ID: 199311
Source: CourtListenerOpinion
Date Created: 2011-02-07 04:28:16+00
Date Added: 2024-06-11T09:43:00.929803
License: Public Domain

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 –

                                        -5-
                     (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.

                                                -48-
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 . . . .

                                           -49-
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.

                                            -50-
            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

                                   -51-
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

                                        -52-
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

                                        -53-
          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.

                                   -54-
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

                                          -55-
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

                                        -57-
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.

                                           -58-
           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

                                         -60-
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

                                    -61-
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,

                                      -62-
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.

                                      -63-