How to Stay Out of Jail if You Work In Regulatory Affairs; my capstone paper for my MSRA in 2015.
Hi Everybody! I've decided to post my capstone project paper from my MSRA in 2015 at Cal Sate San Diego. Better to get it out there, and maybe it can be of some use, or serve as a "morality play". Note that the below document is a converted word doc from a PDF, then downloaded in its entirety, so the formatting may be a bit funky, but so be it! Enjoy!
How to Stay Out of Jail if You Work in Regulatory Affairs Peter Lindwall
San
Diego State University
Abstract
This paper will discuss behaviors that are expected to be inherent to the Regulatory Affairs profession, such as integrity, honesty, courage and a respect for the law, which in this case is the 1938 Food, Drug and Cosmetic Act (“the Act”) and all of its subsequent amendments. It will also illustrate what can happen if there are breaches of the aforementioned, using the Synthes Norian off-label marketing case as a backdrop. In the Synthes Norian case, four high-ranking medical device executives received hitherto unprecedented jail sentences under the Park Doctrine. Specifically, the paper will use the fate of John J. Walsh, who was Vice President of Regulatory Affairs at Synthes, and how his behavior and decisions resulted in a $100,000 fine, five months in jail, and a three-year probation prohibiting him from working in the medical device industry.
How to Stay Out of Jail if You Work in Regulatory Affairs Introduction
The Regulatory Affairs profession for medical devices is relatively new, dating from the
1976 Medical Device Amendments, which amended the 1938 Food, Drug and Cosmetic
Act (FD&C Act). Before the
introduction of the Medical Device Amendments (MDA), few if any medical device
filings were made to the Food and Drug Administration (FDA), since before the
MDA, devices were regulated as pseudo-drugs, and only encompassed a few devices
such as re- absorbable sutures. However, the MDA introduced such concepts
as the 510(k) filing (which is a section of the FD&C
Act proper) and the Pre-Market Approval (PMA) filings. Consequently, a new profession started to
emerge: a Regulatory Affairs Professional who would specialize in medical
devices, as opposed to those professionals involved in drugs or biologics.
Today, this profession is well established, and most Regulatory Affairs Professionals choose either
to specialize in medical devices,
drugs or biologics, due to the highly complex, technical and specialized nature
of the profession. Furthermore, the
Regulatory Affairs profession is often a second career; many individuals gravitate
from other specialties such as quality,
laboratory work, or internal audits to Regulatory Affairs.
Consequently, speaking
from my own experience, Regulatory Affairs Professionals tend to be well seasoned with decades of
experience, and are often looked upon as being the final arbiters of what is an
appropriate action to take. Also, it
is a general understanding that the Regulatory Affairs profession carries much
responsibility and that a relatively “thick skin” is needed, in order to not
get ruffled when faced with disappointed and frustrated coworkers, who are not
sympathetic to the need for regulatory filings and the amount of time it takes
to get a
regulatory filing
approved. It is with
“tongue-in-cheek” that many Regulatory Affairs departments are known as “the
department of “NO!”” Nevertheless,
most of us in Regulatory Affairs believe that we “have arrived” and that no future career
changes are needed.
Why move to another
department when one has reached the pinnacle, both in terms of responsibility
and salary?
This paper concerns the Synthes Norian off-label marketing case, wherein
four high- ranking medical device company executives received jail sentences,
ranging from five to nine months (Kimes,
M. 2012). The case is unprecedented, not because the FDA and the US
government chose to use the Park Doctrine
to prosecute the four executives: but because the Park
Doctrine had not previously been used to impart jail sentences. This paper will discuss the perils of
off-label marketing, why informed consent is essential to clinical trials, the
history of the Park Doctrine, and what behaviors led to the hitherto unprecedented jail sentences. Also, this paper will discuss what
Regulatory Affairs professionals in the medical device industry can and must do
in order to protect patients and also protect the companies for which they
work.
This
paper will focus on one of the four individuals, namely John J. Walsh, who was
Director of Regulatory Affairs at the time that the off-label marketing
activities at Synthes took place. Even though Mr. Walsh was a relative newcomer
to Synthes (he started at Synthes Norian in 2003; see the background
section below), there is, in my opinion (and that of the court), that, when it
comes to regulated industries, there is a higher expectation of Regulatory
Affairs professionals than from other individuals. To bolster the above argument, here is what the sentencing
judge, the Honorable Legrome D. Davis, had this to say about Mr. Walsh’s involvement:
“You are in
regulation [Regulatory Affairs]. And
we expect and require that you speak the truth as you understand it and know
it… I think that we [the public and the U.S. Government] have a right to expect
and require regulation [Regulatory Affairs] to tell these people
[presumably the other
Synthes defendants] who are so inclined that the law
means something, that the law has to be respected and honored [bold added]. And so, that’s part of the reason that…
I’m sending you to jail.”
Subsequently,
Mr. Walsh was sentenced to five months in jail, in addition to paying a fine of
$100,000. Furthermore, the Health and
Human Services barred Mr. Walsh from “participating in Medicare, Medicaid, and
all federal health care programs for a minimum of three years.” (John J. Walsh v. The Inspector General). This debarment effectively ended Mr. Walsh’s medical device career (he is
presently an adjunct professor of mathematics).1
Therefore,
this paper will build a “morality play”, which I will use for educating my
fellow Regulatory Affairs professionals at Edwards Lifesciences (my current
employer) and maybe that of others (such as members of the Orange County
Regulatory Affairs Discussion Group, or OCRA). My aim is to write the paper, and from the paper also develop a PowerPoint
presentation, to be used for the aforementioned purpose.
Key Terms
Vertebral Compression Fracture
(VCF): A painful
fracture in the vertebra, often
as a result of the onset of osteoporosis; consequently, the patients
are often elderly.
See Figure 1 below:
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1 https://www.linkedin.com/pub/john‐walsh/39/307/859
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Kyphoplasty: A variation of vertebroplasty, in which a
balloon is inserted in the fractured vertebra, in order to create a cavity. After the cavity is created, bone cement
mixed with contrast is injected into the cavity.
The main aim in the kyphoplasty procedure
is to restore the vertebra to its original shape and height (United
States of America v. Norian Corporation, Synthes, Inc.). See Figure 3 below:
Figure 3: Kyphoplasty
http://gsmedicalcenter.org/wp-content/uploads/2014/01/kyphoplasty_how.jpg
Key Players
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Figure 3: Kyphoplasty http://gsmedicalcenter.org/wp-content/uploads/2014/01/kyphoplasty_how.jpg |
Richard (Rick) Earl Bohner. Government records indicate that Mr.
Bohner was born on May 26, 19542.
According to his LinkedIn profile, he attended Purdue University between
1972 and 1977. Court records
indicate that he started working
for Synthes in June of 1997, and from 1999 through 2005 he served as
Synthes’ Vice President of Operations.
Thomas (Tom) B. Higgins. Government records indicate that Mr.
Higgins was born on October 26, 19563. According to his LinkedIn profile, he attended Dickinson College
between 1974 and 1978,
where he earned
a BA in Philosophy and Economics. Later, he attended
Harvard
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2
https://exclusions.oig.hhs.gov/Verify.aspx
3
https://exclusions.oig.hhs.gov/Verify.aspx
Business School
between 1978 and 1980, where he earned a Masters Degree in Business
Administration (MBA). Court records indicate
that he was the President
of Synthes Spine,
1997 through 2004; later to become the President of Synthes
Biomaterials, 2005 through 2010.
Michael Dennis Huggins. Government records indicate that Mr. Huggins
was born on November 26, 19574. According to his LinkedIn profile, he
attended Villanova University between 1975 and 1979, where he earned a Bachelor
of Science in Accounting and Finance.
Later he attended the University of Pennsylvania – The Wharton
School, between 1983 and 1984 where he earned his MBA, with a
focus on Strategic Planning. Court
records indicate that Mr.
Huggins was hired
by Synthes at the end of 1994. From 1999 through January
2004, he served as President of Synthes
North America, Inc., a subsidiary of Synthes, Inc. From February
2004 through January 7, 2007, he held the position of President of
Global Synthes Spine Division, reporting directly to the Chief Executive
Officer of Synthes, Hansjorg Wyss.
John Joseph Walsh. Government records indicate that Mr. Walsh was born April
18, 1963. According to court records
and his LinkedIn profile, he attended Wilkes University between 1983 and 1989,
where he earned a Bachelor’s in Economics. Later
he attended the University of Miami, School of Law, between 1989 and 1994,
earning a Juris Doctorate. He started working
full-time at Synthes
Norian in August of 2003 as Director
of Regulatory Affairs, eventually becoming Vice
President of Regulatory and Clinical Affairs.
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4 https://exclusions.oig.hhs.gov/Verify.aspx
Background
Synthes Norian
The Synthes
Norian story centers around Vertebral Compression Fractures (VCFs), which are
fractures in the vertebra, often
stemming from the onset of osteoporosis. During
the 1980s, some orthopedic surgeons had started to
use Poly-Methyl Methacrylate (or PMMA, which was originally used in intra-ocular lenses) off-label, i.e. for a use that is not supported by the labeling, to fill cracks in the vertebra. Nevertheless, PMMA is not ideal as a bone
filler, due to its hardness in the cured state, and also the fact that PMMA
heats up during its curing stage, which can cause thermal necrosis in the
surrounding tissue. Furthermore, PMMA
has also been linked to embolic events, due to hypotension, or an abnormally
low blood pressure (hypotension also played a central role in the Synthes
Norian case).5
Synthes, a multi-billion dollar orthopedic implant company, bought
Norian, a Cupertino medical device start-up, in the summer of 1999. During the 1990s, Norian had developed the
Norian Skeletal Repair System (Norian SRS), a calcium phosphate bone cement, to
be used to fill cracks in the long bone in the arm (FDA PMA P970010). Norian SRS has a unique feature; when injected
in the bone structure, it is slowly
replaced by the re-growth of natural bone,
which makes it ideal as a bone filler, as opposed to PMMA.
Synthes was well aware
of the lucrative VCF market,
and had presumably bought Norian in order to enter this market, even
though Norian SRS was not indicated to be used during VCF surgeries. Nevertheless, instead of filing
for an IDE with the FDA, Synthes
Norian embarked on conducting “market evaluations”, or
off-label marketing, i.e. for a use other than that approved on the existing
labeling, of Norian SRS during VCF surgeries.
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5 https://en.wikipedia.org/wiki/Poly(methyl_methacrylate)
During the fall of 2001, Synthes
Norian filed a 510(k) for Norian SRS Bone Void Filler, with the
following indication: “Norian SRS Bone Void Filler is intended only for bony
voids or defects that are not intrinsic to the stability of the bony structure. Norian SRS Bone Void Filler is intended to
be placed or injected into bony voids or gaps in the skeletal system (i.e. the
extremities, spine or pelvis)” (U.S. Department of Health and Human Services,
Food and Drug Administration, 510(k) Summary, Norian SRS Bone Void Filler,
2001). Also, the label warned “Do not
mix…with any other substance” (United States of America v. Michael D. Huggins).
The 510(k) was cleared
on December 20, 2001.
The
first series of “market evaluations” (illegal off-label clinical trials), were
started in the summer of 2002, in which Norian SRS was “back-table mixed” with
barium sulfate (contra to the label
indication), in order to increase the radio-opacity of the Norian SRS. In January of 2003, 70-year old Mrs. Lois Eskind
died while being
injected with the back-table mixed
Norian SRS during a VCF surgery (United States of America v. Norian
Corporation, Synthes, Inc.).
Since Synthes
had not filed an IDE, Mrs. Eskind
did not have any opportunity for informed consent.
In the fall of
2002, Synthes Norian filed another 510(k), that for Norian XR, essentially
Norian SRS pre-mixed with barium sulfate. This
510(k) was cleared on December 19, 2002. The
indication for Norian XR was the following:
“Norian XR Calcium Phosphate Bone Void Filler is intended only for bony
voids or defects that are not intrinsic to the stability of the bony structure.
Norian XR Calcium Phosphate Bone Void Filler is intended to be placed or
injected into bony voids or gaps of the skeletal system (i.e., the extremities,
spine and pelvis). These defects may
be surgically created osseous defects or osseous defects created from traumatic
injury to the bone. The product provides
a bone void filler that resorbs over a period of years and
is replaced
with bone during the healing process.” A
warning was also added to the labeling: “not
intended for treatment of vertebral compression fractures [bold added].”
(U.S. Department of Health and Human Services, Food and Drug Administration, 510(k)
Summary, Norian XR, 2002).
Nevertheless,
in the summer of 2003, Synthes Norian embarked on yet another “market
evaluation” in which
Norian XR was used in the treatment
of VCFs. This market evaluation lead to two other deaths, that of 83-year old Ryoichi Kikuchi
on September 19, 2003 and 83-year old Barbara Marcelino on January 22, 2004. Again, since there was no IDE, there was
no informed consent.
On May 11 through June 18, the FDA conducted an inspection of Synthes,
Inc. During this inspection, the government alleged
that Mr. Walsh, Huggins and Bohner deliberately tried to mislead the
FDA investigator. After the
inspection, a number of 483 investigation observations6 were given
to Synthes, which subsequently responded to the observations. Synthes’ responses were not adequate,
which lead the FDA to issue a Warning Letter on November 5, 2004 to Synthes,
alleging that Synthes was “Marketing the Norian XR for New Intended Uses
Without Approval or Clearance.” Furthermore,
the Warning Letter stated that during the inspection, documents presented by
Synthes showed that:
Synthes Spine
personnel made presentations to surgeons during training forums for potential participants… These presentations included
discussions of the use of Norian
XR for vertebroplasty and kyphoplasty in association with the treatment of
vertebral compression fractures.
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6 Note that a “483” refers to FDA Form 483, which
is used to list investigation observations. In industry, the term “483” has
come to mean any individual observation resulting from an FDA establishment
inspection.
Guest surgeons made presentations during
training forums sponsored
by your firm…discussed the use
of the Norian XR for off-label indications, including vertebroplasty.
Synthes Spine provided packets
of information and compact discs (CDs) to surgeons who attended the training sessions. These materials included abstracts of
papers describing uses of bone void fillers in vertebroplasty and kyphoplasty
procedures, which would be considered off-label uses for Norian XR.
[b]ecause the…was
a study conducted to determine the safety and effectiveness of using
the Norian XR in a manner not cleared by FDA, you were required to have an FDA-
approved Investigational Device Exemption (IDE) before you could legally
conduct the Test Market…
Your promotion of
the Norian XR and introduction of this device into interstate commerce for new
intended uses is a violation of the law. Specifically,
this device is adulterated under section…of the Act because you do not have an
approved application for premarket approval
(PMA)…or an approved
application for an IDE… This device is also misbranded… (U.S. Department of
Health and Human Services, Food and Drug Administration, Center For Devices and
Radiological Health, Synthes Warning Letter, 2004).
Consequently, in 2004 the FDA started
to build its case against
Synthes Norian and the
four executives. In March of 2006,
Synthes received a grand jury subpoena to present information on Norian XR; in
June of 2009, the U.S. Department of Justice presented an indictment against
Synthes, Norian, and the four executives Mr. Huggins, Mr. Higgins, Mr.
Bohner and Mr. Walsh. Shortly thereafter in July of 2009, all four of the executives entered misdemeanor guilty pleas. Also see Appendix 1,
Synthes Norian Timeline.
Off-Label
Marketing
To a certain
extent, the 1938 Food, Drug and Cosmetic Act was a response to off-label
marketing. Patent medicines, which
were often concoctions of alcohol, morphine, opium, cannabis and cocaine, had
become popular in the late 18th century, only to become a major
industry in the US by the middle of the 19th century. Much of the advertising of patent
medicines was done through the press, which became dependent on the advertising
dollars from the patent medicine
manufacturers. The Proprietary Association, a trade
association formed by a
group of medicine producers, was founded in 1881, and became a major player in
the food and drug legislative battles that were fought in the early 20th
century (Hagley Museum and Library). For an example of patent medicine
advertising, see Figure 4 below:
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Figure 4: Patent Medicine Example: Mrs. Winslow’s Soothing Syrup, available from
about 1850 through 1930. The
formula consisted of morphine sulphate (an opiate related to heroin), sodium
carbonate, spirits foeniculi (most probably alcohol), and aqua
ammonia (a cleaning agent). The concoction was also known as “the baby killer.” |
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By the 1930s, consumers and others had started to realize that the 1906 Food and Drugs
Act had many deficiencies. Since the
1906 Act focused on truthful package labeling of foods
and drugs,
members of the Bureau of Chemistry (which would later become the Food and Drug
Administration in 1930) were concerned that the 1906 Act did not extend to
exaggerated or fraudulent statements made in advertising of foods and drugs,
especially the so called “Patent Medicines.”
The 1906 act only prohibited false advertising if such advertising was attached to or
packaged with the product. If the
advertising were done through a magazine or newspaper, the 1906 Act offered no
protection of the unsuspecting or gullible public.
The battle for the new and improved Food and Drugs Act started in earnest
in 1933, with a bill introduced by Senator Copeland of New York; the bill
become known as S. 1944. One of the
skirmishes regarding the new Act was fought over who should have the authority
to oversee and regulate advertising, the FDA or the Federal Trade Commission
(FTC). Many in industry favored the
FDA, since they had the scientific expertise, but the Proprietary Association
and the Institute for Medicine Manufacturers argued that the jurisdiction
should rest with the FTC, since these industry groups
felt less threatened by the FTC. In the end, the jurisdiction over food, drug and cosmetics advertising was given
to the FTC (Hoffman, S. & Taylor, M, R., 2005).
In 1991, the Office of the
Inspector General (OIG) conducted a study to evaluate the truthfulness and
educational value of pharmaceutical advertising. Among the OIG’s findings from the study was that most drug
advertising potentially violated the FD&C Act and FDA regulations. Furthermore, if the advertising was relied on, the outcome
would lead to physician’s
prescribing the drugs inappropriately. The
findings confirmed the suspicions of the FDA; consequently, the FDA stepped up
their oversight over prescription drug advertising (Abood, R, R. 2011).
About
the same time, a congressional investigation had raised concerns regarding
educational programs sponsored
by the pharmaceutical industry, and the inducements that some
drug manufacturers were offering the attending health care professionals. It appeared that some
educational programs were simply promotional in nature, and offered little
educational value.
As a
result, on November 27, 1992, the FDA published a “Draft Policy Statement on Industry- Supported Scientific and Educational Activities.” In this policy statement, the FDA maintained their position that
educational and scientific activities performed or sponsored by the drug
industry are subject to the FD&C Act.
Five
years later, the Final Guidance on
Industry-Supported Scientific and Educational Activities was published by
the FDA on December 3, 1997. The
guidance is encompassing of FDA-regulated therapeutic products; human and
animal drugs, biological products, and medical devices. This guidance makes mention of “constraints on advertising and
labeling,” and provisions that “require
the company to ensure that the content
[of the educational program] does not
promote unapproved uses…” Furthermore,
the guidance indicates that:
In particular, discussions of unapproved uses, which can be an important component
of scientific and educational activities, are not permissible in
programs that are or can be (because the provider [of the educational program]
is not functionally independent), subject to substantive influence by companies
that market products related to the discussion. (U.S. Department of Health and Human Services, Food and Drug
Administration, Center For Devices and Radiological Health, Final Guidance on
Industry-Supported Scientific and Educational Activities, 1997).
Shortly after its publication, the legality of the guidance was
challenged in 1998 on First Amendment grounds in Washington Legal v. Friedman, arguing that the guidance was
unconstitutional. The district court
found that the guidance was overly restrictive, and enjoined the FDA from the prohibition of discussions around off-label uses, as long as the unapproved use
was disclosed as such. Nevertheless, in 1999 the FDA appealed
and prevailed, having
convinced the court that the guidance
provided a “safe
harbor,” informing manufacturers of conduct that the
FDA would not challenge, and the court reversed the district court’s decision. The 1997 guidance is still available on
the FDA website, and has not been replaced by an updated guidance; therefore, the guidance is still in effect.
Furthermore, in 1998, the FDA published
the guidance “”Off-Label” and Investigational
Use Of Marketed Drugs, Biologics, and Medical Devices – Information Sheet”. This guidance states the following:
If physicians
use a product for an indication not in the approved labeling, they have the
responsibility to be well informed about the product, to base its use on firm
scientific rationale and on sound medical
evidence, and to maintain records
of the product's use and effects. Use of a marketed product in this manner when the intent is the "practice of medicine" does not
require the submission of an…Investigational Device Exemption (IDE) or review
by an Institutional Review Board (IRB).
However, the guidance states
further:
The
investigational use of approved, marketed products differs from the situation
described above. "Investigational
use" suggests the use of an approved product in the context of a clinical
study protocol [see 21 CFR 312.3(b)]. When
the principal intent of the investigational use of a test article
is to develop information about the product's
safety or efficacy, submission of an IND or IDE may be required. For additional information on whether or not an IND or IDE is required
in a specific situation, contact:
[the FDA] (U.S. Department of Health and Human
Services, Food and Drug Administration, Center
For Devices
and Radiological Health,
“Off-Label” and Investigational Use of Marketed Drugs, Biologics, and Medical
Devices – Information Sheet, 1998).
Therefore, by the year 2000, when Synthes bought
Norian, the FDA had made it quite clear that any off-label use could
not be promoted by a manufacturer, and in the case of investigational off-label
use, an IDE would at least need to be discussed with the FDA. Informed Consent; Part 50 Regulation; and
the Investigational Device Exemption
One
of the central themes regarding clinical trials, be it for drugs, biologics or
medical devices, is the issue of informed consent. Having its origin from the post-World War II Nuremberg trials
(1947), in which
German Nazi concentration camp doctors were found to have
been involved in performing cruel
and inhuman experimentation on prisoners ( often tantamount to torture and murder),
the Nuremberg Code was the first internationally recognized code for the
conduct of clinical trials. The Code
states the following:
1: The voluntary consent of the human subject
is absolutely essential. This means that the person involved should have legal capacity to give consent;
should be so situated as to be able to exercise free power of
choice, without the intervention of any element of force, fraud, deceit,
duress, over-reaching, or other ulterior form of constraint or coercion; and
should have sufficient knowledge and comprehension of the elements of the subject
matter involved, as to enable him to make an understanding and enlightened
decision (U.S. Department of Health and Human Services, The Nuremberg Code).
The element
of informed consent
is carried through
in the United States Code of Federal Regulations, Part 50, Protection of Human Subjects, which was
first codified in 1981. This
regulation identifies the requirements that any sponsor and/or investigator
that is involved in
performing clinical
trials need to fulfil in order to ensure that study subjects
are informed and protected. These are some of the pertinent sections from the Part 50
regulation:
Section
50.1: Scope. (a) This part applies to all clinical investigations regulated
by the FDA…that support applications for research or marketing permits
for products regulated by the FDA, including…medical
devices for human use… Compliance with these parts is intended to
protect the rights and safety of subjects involved investigations [bold
added]…
Section
50.20: General requirements for informed consent [bold added]. …no investigator may involve a human being
as a subject in research covered by these regulations unless the investigator has obtained the legally effective
informed consent of the
subject [bold added]…
Section 50.25: Elements
of informed consent [bold added]. (a) Basic elements of informed consent.
(1) A statement that the study involves
research, an explanation of the purposes of
the research… (2) A description of any reasonably
foreseeable risks or discomforts to the subject. (8) A statement that
participation is voluntary…
Section 50.27: Documentation
of informed consent [bold added]. (a) …informed consent shall be documented by the use of a written consent
form approved by the IRB and signed and dated by the subject…
As
can be seen from the above excerpts, the central theme of the Nuremberg Code
that informed consent is essential, is indeed carried through the regulation. Furthermore, the informed consent theme is
also carried thorough the regulation for the performance of clinical trials for
medical devices, 21 CFR 812 Investigational
Device Exemptions (the IDE regulation). This regulation, which was codified in 1980, spells
out the requirements which must be fulfilled
in order
to legally conduct
a clinical trial
for a new or improved
medical device. Below are some of the most pertinent sections of the
IDE regulation:
Section 812.2:
Applicability. (a) General.
This part applies
to all clinical investigations
of devices to determine safety and effectiveness…
Section 812.5: Labeling of investigational devices. (a) Contents. An investigational device or its immediate package
shall bear a label with the following
information…and the following statement: “CAUTION—Investigational device. Limited
by Federal (or United States) law to investigational
use.”
Section
812.25: Investigational plan. (b) Protocol. A written protocol describing the
methodology to be used and an analysis of the protocol demonstrating that the
investigation is scientifically sound. (e) Monitoring procedures. The sponsor’s written procedures for monitoring the investigation… (g) Consent materials. Copies of all forms and informational materials to be provided
to subjects to obtain informed consent [bold added].
Section 812.42:
FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both
approved the application…relating to the investigation…
Section 812.43:
Selecting investigators and monitors. (c) Obtaining agreements. (4) A statement of the
investigator’s commitment to: (iii) Ensure that the requirements for informed
consent are met [bold added].
Section 812.140:
Records. (3) Records
of each subject’s case history and exposure to the device. Case histories include the case report forms and supporting data
including…signed and dated consent forms
[bold added]… (i) Documents
evidencing informed consent
[bold added]… The case history
for each individual shall document that
informed consent was obtained prior to participation in the study [bold
added].
Section 812.150: Reports.
(a) Investigator reports. An investigator shall prepare and submit the following complete,
accurate, and timely reports: (5) Informed
consent [bold added]. (b) Sponsor
reports. A sponsor shall prepare and
submit the following complete, accurate, and timely reports: (8) Informed
consent [bold added].
As
noted above in the Background, Synthes enlisted surgeons to perform “test
market” off-label studies, in order to gather information regarding the safety
of Norian SRS, which were performed without any IDE approval. As such, these studies did not consider
the safety of the patient, nor were the patients informed about the
investigational aspect of these studies, and no informed consent was sought. Consequently, the apparent lack of any
consideration for the patients that were involved in the Synthes Norian “test
marketing” is quite possibly the most damning of the transgressions that were
perpetrated by the convicted Synthes executives. The need for an IDE in order to legally carry out these studies
had been identified by several of Synthes’ regulatory affairs
staff, but was rejected by top management. As early as August 2000, Michael Sharp, PhD, group manager
of regulatory and clinical affairs at Synthes7, had warned Mr.
Huggins that:
“As everyone
is well aware,
I hope, we do not have a spine indication for Norian SRS at
this time…We cannot promote the use of SRS for unapproved indications, and this
is especially true for use in the spine, where FDA has previously made it clear
to Norian
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7 https://www.linkedin.com/pub/stewart‐michael‐sharp/8/270/2ab
that any intra-spinal use would require
additional approval…” (United
States of America v. Norian Corporation, Synthes,
Inc., Superseding Information.)
Instead, Synthes chose to carry out a company-sponsored off-label campaign, in order
to compile information which could later be used as inducements for
further off-label promotions. Park
Doctrine, Origins and Implementation
All four of the Synthes executives were convicted under the Park
Doctrine. The Park Doctrine, or “the
responsible corporate officer” doctrine, stems
from a 1975 United States Supreme Court decision in United States v. Park. The
Park Doctrine enables the U.S. government to seek misdemeanor convictions
against executives at companies regulated by the FD&C Act, whether the
executive(s) instigated the wrongdoing (as the government asserted in the
Synthes case), the executive(s) knew about the wrongdoing but did nothing, or
had no knowledge of any illegal activities, as long as the executive(s) had authority to prevent or correct
the violation, but took no action. Under
the Park Doctrine, the misdemeanor case carries a maximum of one year in prison
and/or a maximum of $100,000 fine.
The history of the Park Doctrine
has its origin in the 1943 case United States
v.
Dotterweich, which was the first
significant decision under the relatively new 1938 FD&C Act (Grant, T, W., 1992).
In the Dotterweich case, Buffalo
Pharmacal Company, Inc., a re-packer
of drugs, and its general manager Joseph H. Dotterweich were accused of
adulteration and misbranding of digitalis and cascara tablets (National
Institute of Health, U.S. National Library of
Medicine). There was no evidence
that Mr. Dotterweich knew
about any wrongdoing, or that he himself participated in any of the violative
acts. Nevertheless, Mr. Dotterweich
was convicted, and the U.S. Supreme Court upheld the conviction. In the Dotterweich case, the Supreme Court
noted that the Food, Drug and Cosmetic Act “dispenses with the conventional
requirement for criminal conduct
– awareness of some wrongdoing.” In the eyes of the Supreme
Court, this was the outcome of the design of the FD&C Act, which was
intended to offer the protection of the health and lives of the United States
public “which, in the circumstances of modern industrialism, are largely beyond
self-protection.” (Grant, T, W., 1992).
Later
in the early 1970s, John Park was the President and CEO of Acme Markets, Inc.,
a large national chain of food markets, with some 36,000 employees and over 870
retail outlets and 16 warehouses. In 1970, the FDA had found unsanitary
conditions, such as a rodent infestation, in Acme’s Philadelphia warehouse. Furthermore, in 1971 and 1972, the FDA had
found similar unsanitary conditions in Acme’s Baltimore warehouse. Consequently, the government asserted that
Park knew about the conditions, but had delegated his responsibility to
correcting the violations to his subordinates.
The jury in the case found Mr. Park guilty on five counts of a
misdemeanor; Park appealed the decision and the Court of Appeals reversed the
charge. The case then went to the Supreme Court,
which upheld the conviction. Chief Justice C.
J. Burger, who delivered the
opinion of the court, wrote:
[T]he Act imposes not only a positive duty to seek out and remedy
violations when they occur but also, and primarily, a duty to implement
measures that will insure that violations do not occur. The requirements of foresight and vigilance imposed on
responsible corporate agents are beyond question demanding, and perhaps
onerous, but they are no more stringent than the public has a right to expect
of those who voluntarily assume positions of authority in business enterprises
whose services and products affect the health and well-being of the public
that supports them (Keller and Heckman, 2013).
The Park Doctrine
was frequently used during the 1970s, but it appears
that the Doctrine went dormant from about 1985
until 2007, when the Purdue Frederick Company, Inc., a drug
manufacturer
based in Stamford, Connecticut, pleaded guilty to felony charges regarding
misbranding. In this case, the Purdue
Company was charged with “misbranding the pain-killer OxyContin with the intent
to defraud or mislead” (Fleder, J. R., 2009).
Purdue had instructed its sales force to inform health
care professionals that OxyContin was less addictive, that OxyContin users
could stop use without withdrawals, and that OxyContin would not cause any
sensations of euphoria. Nevertheless,
none of the aforementioned statements were supported by the labeling, which
simply stated that OxyContin had a reduced dosing schedule as compared to other
similar pain killers (Holland & Knight, 2012). Furthermore, in the Purdue case, three top executives pleaded
guilty to misdemeanor charges under the Park Doctrine; Chief Executive Officer Michael Friedman, Chief Medical Officer
Paul Goldenheim and General Council Howard Udel. In the Purdue Fredrick Company case, the company was fined $600
million, and each of the aforementioned defendants received
three years’ probation, 400 hours of community service,
and had to pay collective penalties (disgorgement) of $34 million
(Holland & Knight, 2012).
Method
This
paper has been derived in whole from internet searches; no time was spent in
law libraries, or in the basements of courthouses. With the availability of the internet,
all information is readily
available, assuming that the curious person has computer access. Consequently, the focus has been on
identifying the most appropriate search words, which would lead to the
pertinent information. The following
is a list of such search words: Synthes
Norian; John J. Walsh; John Joseph Walsh; Park Doctrine; Synthes Norian Warning
Letter; Synthes Norian 510(k) Submission. Note
that the list is not exhaustive; at times, “surfing” the internet leads to
unexpected treasures. Nevertheless,
all of the pertinent documents are listed in the Reference section of this
paper.
The
fact that all of the background information for this paper can be readily
accessed through the internet should serve as a caution for all of us involved
in Regulatory Affairs. It is
difficult to keep a secret,
and any and all breaches
of integrity can be dredged
up from the murky bottoms of
bad behavior. Therefore, it is much
better to “keep one’s nose clean.”
Results
John J. Walsh Background
 |
According
to government records, John Joseph Walsh was born in Wilkes-Barre,
Pennsylvania, on April
18, 19638. According
to his “Defendant’s Sentencing Memorandum, his mother left when he was 13 years of age; subsequently, he
had to work while attending high school and college.
During
his senior year at Wilkes University, Walsh was encouraged by the late
Honorable Max Rosen to attend
law school (Rosen
served on the Board of Trustees for Wilkes
|
8 https://exclusions.oig.hhs.gov/Verify.aspx (John Joseph Walsh)
University);
and Mr. Walsh went to law school. However,
he did not take the bar; instead, he started working for Beckman-Coulter in
January of 1994 as a Senior Regulatory Affairs Specialist. He was promoted to Regulatory Affairs
Manager in 1998, and stayed at Beckman- Coulter until December 20009. In 2001, he moved to Centerpulse
Orthopedics, Inc., where he started as Director
of Regulatory Affairs
and Quality systems.
He was later promoted to Global
Vice President of Regulatory Affairs (United States of America v. John J.
Walsh. Defendant’s Sentencing
Memorandum, 2011).
In February
of 2003, Walsh
left Centerpulse, to start his own consulting service (United
States of America v. John J. Walsh. Defendant’s
Sentencing Memorandum, 2011). Shortly
thereafter, in June of 2003,
he started working
for Synthes Norian,
first as a consultant, then by
August 20, 2003, as a full-time employee. From
August 2003 to January 2004 he served as Director of Regulatory and Clinical
Affairs, then eventually becoming Vice President of Regulatory and Clinical
Affairs (John J. Walsh v. The Inspector General, 2014).
Mr.
Walsh’s involvement in the Norian XR off-label marketing activities started
almost immediately after he joined Synthes.
In the middle of August, 2003, Mr. Walsh was sent minutes of an August
14, 2003 strategic planning meeting. According
to court records and the meeting minutes, the participants discussed the Norian
XR indications, the test market, and the recommendation that a formal
FDA study should
be conducted to gain approval
for using Norian XR in vertebroplasties (United
States of America v. Michael D. Huggins, Thomas B. Higgins, Richard E. Bohner,
John J. Walsh, 2010).
Furthermore, court records
show that on October 16, 2003, Mr. Walsh received
a copy of a January 2003 e-mail exchange between Synthes and the FDA. According to the e-mail
|
9 https://www.linkedin.com/pub/john‐walsh/39/307/859
exchange, “[t]he
FDA position is that “[u]se in treating compression
fractures of the spine is not a cleared
use for any of the bone void fillers (MQV product code).
This indication is considered
a new intended use and requires a PMA and clinical data. Even with proper fixation, the bone void filler in this
situation (VCFs) would not be used in a way that is “non-intrinsic to the
stability of the bony structure” which is what the indication for MQV bone void
fillers require.” Later, toward the end of October 2013, Mr. Walsh, Huggins and
Higgins attended a company meeting where the death of Dr. Nottingham’s patient
and some additional findings from the University of Washington studies were
discussed (United States of America v. Michael D. Huggins, Thomas B. Higgins,
Richard E. Bohner, John J. Walsh, 2010).
After the FDA establishment inspection, which took place in the spring
of 2004, the FDA
issued a number of 483 inspection observations. Court records show that in June of 2004, Huggins, Higgins,
Bohner and Walsh met to discuss their response to the 483s. The government claims that the outcome of
this meeting was documented misrepresentations from Synthes, such as “(i) the
Norian XR “test market” was for cleared indications, instead of the treatment
of VCFs; (ii) the Norian XR “test
market” was not designed to obtain safety and efficacy information from
surgeons about use of Norian XR to treat VCFs; and (iii) the two “test market”
surgeon training meetings
and the surgeon
forum had not trained surgeons
how to use Norian XR to treat VCFs.” This information was later used
to build the case against Synthes, Walsh and the others (United States
of America v. Michael D. Huggins, Thomas B. Higgins, Richard E. Bohner, John J. Walsh, 2010).
After a lengthy investigation, Synthes
was indicted, along with Walsh and the others, on June 16, 2009. Shortly thereafter, Walsh entered his misdemeanor guilty plea.
Discussion
The
duties of Regulatory Affairs Professionals in the medical device industry are
varied, ranging from relatively simple and routine regulatory filings such as
5-day Investigational Device
Exemption (IDE) notices and 30-day manufacturing change notices (both driven by
the FDA), Notices of Change (for the European Union notified bodies), to more
complex filings such as design
changes (Real-Time and 180-day FDA filings), 510(k) filings for new products,
and culminating in Pre-Market Application/Approval (PMA) filings, which are the
most time- consuming and complex
of all medical device filings.
Also, Regulatory Affairs
Professionals are expected to
review and approve routine documentation and labeling changes. Furthermore, we are expected to review proposed changes
and give our professional opinion
as to whether or not a
regulatory filing is needed, and if so, which filing is appropriate, and how
long it will take to get approval. We
rely on varied tools for our
decision-making, ranging from the various FDA regulations, such as 21 CFR Part
801 Labeling; 21 CFR Part 803 Medical Device Reporting; 21 CFR Part 807,
Establishment Registration and Medical Device Listing; 21 CFR Part 812
Investigational Device Exemption (IDE); 21 CFR Part 814 Premarket Approval; 21
CFR 820 Quality System Regulation/Good Manufacturing Practices (this is our
“bible”); and 21 CFR 830 Universal Device Identification. We also rely on FDA Guidance Documents,
Notified Body guidance documents, and also our internal Standard Operating
Procedures (SOPs).
There
is a universal expectation that Regulatory Affairs professionals act as agents
of their employers, that they fully
understand the legal
requirements, and that they have the courage to say no, if they believe that
suggested company actions are unlawful, regardless of pressure.
This is also
identified by the RAPS Code of Ethics, which states that a Regulatory Affairs
professional should “Have
the courage to make difficult decisions. As a regulatory professional,
I will present
all relevant information to my organization to promote wise decisions. I must be able to withstand challenges to
my views, while at the same time being accountable for my mistakes.10” This above statement
is the key to the Synthes Norian case; no one had the courage to stop these “test case” market trials until three people had died. The adverse
impact to patients was indeed identified by the
government. In the United States
Consolidated Response to Defendants’ Objections to the Presentence Reports, the
U.S. Attorneys Memeger, Crawley and Sullivan asserted that “If Synthes had
decided to conduct its clinical research legally, it would have had to obtain
FDA approval prior [original italics]
to the commencement of the research.
The FDA would
have reviewed the Investigational Plan, which would have included the
following: “...(4) all forms and informational materials to be used to gain informed consent
of the subjects;” Furthermore,
the U.S. Attorneys stated that:
The fact that
NONE of these important patient safeguards were employed is shocking, and was unethical as well as illegal. Perhaps
the most shocking
omission, however, is the
complete lack of regard for the patients who at the very least should be given
the choice about whether they want to participate in a clinical investigation. This choice should be an informed choice,
where the foreseeable risks are described and the alternative treatments are
disclosed. In addition, the subjects
should be given an explanation of who to contact for answers to pertinent
questions about their rights as research subjects, including who to contact if
there is a research-related injury (United States of America v. Michael D.
Huggins, Thomas B. Higgins, Richard E. Bohner, John J. Walsh, United States
Consolidated Response to Defendants’ Objections to the Presentence Reports).
|
10 http://www.raps.org/code‐of‐ethics.aspx
During
the sentencing hearing, Judge Davis found that “patients were directly and
proximately harmed by the conduct of the Defendants and others at Synthes.” He also asserted that Synthes
employees “disregarded the safety of all members
of society (John
J. Walsh v. The
Inspector General). Therefore, it is
evident that the government found the lack of informed consent to be egregious,
indeed “shocking…unethical as well as illegal.”
Consequently,
the fact that Judge Davis elected to impose jail sentences for the defendants should
not be surprising, since informed
consent is such a big part of clinical trials,
as evident from the above discussion.
Had the three patients that died received information regarding the
experimental nature of the “test cases” been informed of the risks, and
subsequently asked for their informed consent, they may not have elected to
have the surgeries. Instead, no such information was given, and the informed consent
was never obtained, to the detriment of the patients and the Synthes
defendants.
Lastly,
there is also a belief that if we, as Regulatory Affairs professionals, conduct
ourselves with both the patient
and the law in mind, we will not get into trouble.
Nevertheless, as the case of Mr. Walsh illustrates, Regulatory Professionals do indeed go to jail, which could indeed end our careers. In order to ensure that we do not end up
in Mr. Walsh’s predicament, here are some recommendations, for staying out of
jail:
Do Not
Sign Off on Documents That Instruct Doctors to Perform Off-Label Use
Government
records indicate that Mr. Walsh approved the final Norian XR “Technique Guide,”
in December of 2003. This Technique
Guide did not mention the label warning “not intended for the treatment of
vertebral compression fractures.” In
fact, Judge Legrome Davis concluded that the omission of the warning
was “more likely
than not” intentional. Government records also assert that “Remarkably, the guide includes spinal x-rays of the first patient
to die
during surgery [original italics] for
vertebral compression fractures using Norian SRS [back- table] mixed
with barium sulphate.” When Mr. Walsh
was later confronted about this issue,
he claimed that his signature was protected by the First Amendment, an
assertion that was later rejected by Judge Davis (John J. Walsh v. The
Inspector General).
Do Not Water Down the Message
in a “Dear Surgeon” Letter
After Three Patients
Have Died
Government records indicate that by the end of January 2004, after three
patients had died while being
injected with Norian SRS and XR during vertebroplasty surgeries, Mr. Walsh
revised a “Dear Surgeon” letter,
presumably to protect
the interests of Synthes. It appears that a
first draft of the letter was circulated, which in the eyes of Judge Davis
“gave fair notice,” but Mr. Walsh re-drafted the letter “to a degree that made
it less clear what the issue was,” and omitting the dangers of using Norian SR to treat vertebroplasties (John
J. Walsh v. The Inspector General).
Do Not Lie to an FDA Investigator During an Establishment Inspection
Court records show that the government believed that Mr. Walsh and his
co-defendants Huggins and Bohner repeatedly tried to mislead the FDA
investigator, by the telling the investigator that “they were not aware of the
test market for SRS in the spine…that the Norian XR test market was for
approved indications, not VCFs,…and
argued that vertebroplasty could be used for treating conditions other than
VCFs, when they knew such other uses were de minimis at best and that…Synthes
had sought to capture the VCF market.” (United
States of America v. Michael
D. Huggins, Thomas
B. Higgins, Richard
E. Bohner, John J. Walsh, 2010).
Do not
present an internal white paper as fact
Government records indicate that John Walsh and his staff apparently
generated an internal memorandum declaring the “use of void bone fillers in the
augmentation of pedicle screws…is not intrinsic to the stability of the bony structure” and is therefore
permissible” (John J. Walsh v.
The Inspector General).
Do Not Lie to the FDA in a 483 Response
Court records show that the FDA believed that John Walsh and the other
defendants met in June 2004 to draft a response to the 483 inspection
observations. In this response, the
government claimed that John Walsh and the others claimed that “(a) the Norian
XR “test market” was for cleared indications, rather than the treatment of VCFs; (b) the “test market” was not designed to obtain safety and efficacy information from surgeons about use of Norian XR to treat
VCFs [which, in the case of safety and efficacy, would have entailed seeking an
IDE], and
(c) the two
“test market” surgeon training meetings and the surgeon forum had not trained
surgeons to use Norian XR to treat
VCFs.” (United States
of America v. Norian Corporation, Synthes, Inc., 2010).
Aftermath
On August 9, 2009, the New England Journal of Medicine published a study
called A Randomized Trial of
Vertebroplasty for Osteoporotic Spinal Fractures. In this trial, from June
2004 through August of 2008, 131 patients received either a complete
vertebroplasty (68 patients) or a sham (placebo) vertebroplasty procedure (63
patients). In this trial, PMMA was
used. The outcome of the trial was
that “[p]atients with osteoporotic vertebral fractures who were randomly
assigned to undergo either a full vertebroplasty or a control intervention
consisting of a simulated vertebroplasty without infusion of PMMA did not [bold added]
differ
significantly at one month
after the procedure on measures of back-pain intensity, functional disability, and quality of life.” Consequently, in this study there was an
indication that vertebroplasty is not effective (Kallmes, D. F., Comstock, B.
A., et al, 2009).
Nevertheless, about a year later on September 25, 2010, the Lancet
published the article Vertebroplasty
versus conservative treatment in acute osteoporotic vertebral compression
fractures (Vertos II): an open-label
randomized trial. In this study,
101 patients were treated using Vertebroplasty between October 2003 and June
2008. The interpretation of the study
was the following: “In a subgroup
of patients with acute osteoporotic vertebral compression fractures and persistent pain,
percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for
at least a year, and is significantly greater than that achieved with
conservative treatment, at an acceptable cost.” The study was founded in part by COOK Medical, a manufacturer of
PMMA (Klazen, C. A. H., Lohle, P. N. M., et al, 2010).
Vertebroplasty is continuously being investigated in clinical trials. A search of www.clinicaltrials.gov, using the search word “vertebroplasty” returned a list of 38 active and
closed clinical
trials, starting around 2003. Much of
the work is done in Europe, but it is not always clear who the real sponsor
is. So, in many respects,
the vertebroplasty saga continues;
see Appendix 2.
In
June 2009, the American Association of Orthopedic Surgeons (AAOS) published a
Position Statement, titled
Off-Label Use of Medical
Devices. In this position statement, AAOS states the following:
The American
Academy of Orthopaedic Surgeons
(AAOS) believes that surgeons may prescribe or administer any legally
marketed product for an off-label use within the authorized practice
of medicine in the exercise
of appropriate medical
judgment for the
best interest
of the patient. If surgeons
use a product for an indication not in the approved
or cleared labeling, they have the
responsibility to be well informed about the product, to base its
use on firm scientific rationale and on sound medical evidence, and to maintain
awareness of the product’s use and effects. Surgeons should appropriately counsel patients about the benefits and
risks of the proposed treatment, and alternative treatments that might be
available [bold added]… (American
Association of Orthopaedic Surgeons, 2009).
It
is unclear if any of the three patients that died while being injected with
Norian ever received any counseling regarding the off-label
use of Norian. Nevertheless, it is clear
that the AAOS certainly
believe that its members should do so, if indeed they are going to perform a
surgery involving off-label use of any medical product.
On October 10, 2010,
Synthes pleaded guilty
to the charges, and agreed
to pay a
$22,500,000 fine.
In June of 2011,
Johnson & Johnson
purchased Synthes, headquartered in West Chester, PA for $20 billion.
Richard (Rick) E. Bohner
Mr.
Bohner was ordered to pay a $100,000 fine and sentenced to eight months in
prison in December of 2011. On or around March 2012, it is believed
that he was also mentioned as a defendant in a civil law suit filed in the Superior Court of California on behalf of the Kikuchi
and Marcelino families (OrthoSpineNews, 2012). On September 28, 2012, the Inspector General of the Department
of Health and Human Services informed Mr. Bohner that he would be excluded from
the program (Medicare, Medicaid, etc.) for a minimum of four years (Richard E.
Bohner v.
The Inspector
General, 2014). He was excluded on
October 18, 201211. He
subsequently appealed the decision
from the Inspector General, to no avail. The Appellate Division
upheld the decision on May
26, 2015 (Department of Health and Human Services, Departmental Appeals Board,
2015). His LinkedIn profile has not
been updated; as of October 11, 2015, he is still listed as “VP, US Operations
at Synthes USA”12.
Thomas (Tom) B. Higgins
Mr.
Higgins was sentenced to nine months in prison on November 21, 2011. On December 19, 2011, he reported to the
Canaan federal prison; he was put in the minimum- security portion (Sell, D.,
2012). On or around March 2012, it is
believed that he was also mentioned as a defendant in a civil law suit filed in the Superior
Court of California on behalf of the
Kikuchi and Marcelino
families (OrthoSpineNews, 2012).
He was excluded (from Medicare and Medicaid) on October 18,
201213 According to his
LinkedIn website, he is now an “Independent Medical Devices Professional.”14
Michael D. Huggins
Mr. Huggins was sentenced to nine months in prison on November 22, 2011. On or around March 2012, it is believed
that he was also mentioned
as a defendant in a civil law suit
filed in the Superior Court of California on behalf of the Kikuchi and
Marcelino families ((OrthoSpineNews, 2012). He
was excluded (from Medicare and Medicaid) on October 18, 2012. According to his LinkedIn profile, after
leaving Synthes in 2007, he held a variety of
|
11
https://exclusions.oig.hhs.gov/Verify.aspx
12
https://www.linkedin.com/profile/view?id=ADEAAAE3OpsBcIpCnma89SNlK1goKh6Gqm‐ qWS0&authType=NAME_SEARCH&authToken=0Ifp&locale=en_US&srchid=233553971444590839906&srchindex= 1&srchtotal=10&trk=vsrp_people_res_name&trkInfo=VSRPsearchId%3A233553971444590839906%2CVSRPtargetI
d%3A20396699%2CVSRPcmpt%3Aprimary%2CVSRPnm%3Atrue%2CauthType%3ANAME_SEARCH
13 https://exclusions.oig.hhs.gov/Verify.aspx
14 https://www.linkedin.com/pub/tom‐higgins/24/9a5/aa4
positions both as
an executive and as an adjunct professor. Around
2010, he got involved in yoga, and now lists himself as the “Founder of the
Transformation Yoga Project,” which is a “Non-profit
organization whose mission is to expand the practice of Hatha Yoga and
Mindfulness Meditation to prisons, rehabilitation facilities and veterans,
and to provide training for
Yoga instructors interested in teaching to at-risk populations in prisons,
residential rehabilitation facilities, VA hospitals and community programs.”15
John J. Walsh
Mr.
Walsh was sentenced to five months in prison on November 22, 2011. On or around March 2012, it is believed
that he was also mentioned as a defendant in a civil law suit filed in the
Superior Court of California on behalf of the Kikuchi and Marcelino families
(OrthoSpineNews, 2012). He was excluded
from working for any company
that was involved
in Medicare or Medicaid
on October 18, 2012. According
to his LinkedIn website, he went back to
school at West Chester University of Pennsylvania in 2012, earning a masters’
degree in mathematics. He is
currently an assistant professor of mathematics at the same institution.
|
15
https://www.linkedin.com/profile/view?id=AAEAAAvLNLwBDVmpopNhRpZ0Jr6ZDB50vLxf6yw&authType=name&a uthToken=x6lz&trk=prof‐sb‐browse_map‐name
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Adulteration and misbranding of digitalis tablets…
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November 14, 2011). Defendant’s
Sentencing Memorandum. Retrieved on
09/14/2015 from http://media.philly.com/documents/PreSentMemo-Walsh-11-15-11-main.pdf
United
States of America v. Michael D. Huggins, Criminal no. 09-403-3. Memorandum from the Honorable Legrome D. Davis. (U.S. District Court,
Eastern District of Pennsylvania,
December 13, 2011). Retrieved on
09/14/2015 from https://www.paed.uscourts.gov/documents/opinions/11D1348P.pdf
United States of America v.
Michael D. Huggins, Thomas B.
Higgins, Richard E. Bohner, John
J. Walsh, Criminal No. 09-403-03-06. Governments
Amended Presentence Memorandum. (U.S. District
Court, Eastern District
of Pennsylvania, March 30, 2010). Retrieved on 09/14/2015 from http://www.circare.org/lex/synthes/09cr00403_94_20100330.pdf
United States of America v.
Michael D. Huggins, Thomas B.
Higgins, Richard E. Bohner, John
J. Walsh,
Criminal No. 09-403-03-06. United
States Consolidated Response to Defendants’ Objections to the Presentence Reports. (U.S. District
Court, Eastern District of Pennsylvania, March 22,
2011). Retrieved on 10/03/2015 from http://www.circare.org/lex/synthes/09cr00403_138_20110422.pdf
United States of America
v. Norian Corporation, Synthes, Inc., Criminal No. 09-403.
Superseding Information. (U.S. District Court, Eastern District
of Pennsylvania, October 2010). Retrieved on 09/14/2015 from http://www.justice.gov/sites/default/files/usao-
edpa/legacy/2011/05/05/synthes_supersedinginformation.pdf
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U.S. Department of Health and Human Services, Food and Drug Administration. (2001).
510(k) Summary, Norian
SRS Bone Void Filler. File K011897. Retrieved on 10/22/2015
from http://www.accessdata.fda.gov/cdrh_docs/pdf/k011897.pdf
U.S. Department of Health and Human Services, Food and Drug Administration. (2002).
510(k) Summary, Norian XR. File K023862. Retrieved on 10/22/2015 from http://www.accessdata.fda.gov/cdrh_docs/pdf2/k023862.pdf
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(1997). Final Guidance on Industry-Supported
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(2004). Warning Letter,
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Retrived on 10/22/2015 from http://www.circare.org/fdawls2/synthes_20041105.pdf
Figures
Figure 1: Vertebra compression fracture, curtesy of Huston Methodist
(http://www.houstonmethodist.org/orthopedics/where-does-it-hurt/upper-back/spinal-
compression-fractures/
Figure 2: Vertebroplasty
https://www.preferredpaincenter.com/vertebroplasty-kyphoplasty.html
Figure 3: Kyphoplasty
http://gsmedicalcenter.org/wp-content/uploads/2014/01/kyphoplasty_how.jpg
Figure 4: Patent Medicine Example
Figure 5: Picture of John J. Walsh, believed
to have been taken in 2011.
http://www3.nd.edu/~rroeder/ame50571/slides/fortunesynthes.pdf
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