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RECEIVED
April 16 2007
at 8:30________________m
William T. Walsh, Clerk |
CHRISTOPHER J. CHRISTIE
United States Attorney
By: PETER W. GAETA
Assistant United States Attorney
970 Broad Street, Suite 700
Newark, New Jersey 07102
(973) 645-2927
UNITED STATES OF AMERICA, Plaintiff,
v.
Undetermined quantities of boxes
of articles of device, labeled
in part:
(box) "*** Shelhigh No-React® VascuPatch* **
Shelhigh, Inc. ***,"
undetermined quantities of boxes of
articles of device, each box containing
one jar, which contains the device
labeled in part:
(box) "t*** Shelhigh Pulmonic Valve Conduit
No-React® Treated *** Model NR-4000 ***
Shelhigh, Inc. ***,"
(jar)
"*** Shelhigh No-React® Pulmonic Valve
Conduit *** Shelhigh, Tnc. ***," and
all other quantities of all articles of
device, with any lot number and in any
size or type container that are labeled or
unlabeled, including finished
products, in-process materials, and raw
materials used in the manufacture of
such finished products, that are located
anywhere on the premises of
Shelhigh, Inc., 650 Liberty Avenue,
Union, New Jersey,
and
all other quantities of all articles of
device that are labeled as manufactured
by Shelhigh, Inc. that are located
anywhere on the premises of: Future Medical
Diagnostics
Manufacturers Inc.,
141 South Avenue, Suite 200-205,
Fanwood, New Jersey,
Defendants in-rem.
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UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
Hon.
Civil Action No.
07 CV 1769 WJM
VERIFIED COMPLAINT
FOR FORFEITURE
IN REM |
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Plaintiff, United States of America, by and through its attorney,
Christopher J. Christie, United States Attorney for the District
of New Jersey (By: Peter W. Gaeta, Assistant United States Attorney),
respectfully brings this complaint and alleges as follows in accordance
with Supplemental Rule G(2) of the Federal Rules of Civil Procedure:
NATURE OF THE ACTION
- That this complaint is filed by the United States of America,
and requests seizure and condemnation of articles of device, as
described in the caption, for violations of the Federal Food,
Drug, and Cosmetic Act (Act), 21 U.S.C. 301, et seq..
- That there are at Union, New Jersey, in the possession of Shelhigh,
Inc. ("Shelhigh or "the firm"), 650 Liberty Avenue,
and at Fanwood, New Jersey, in the possession of Future Medical
Diagnostics Manufacturers Inc., 141 South Avenue, Suite 200-205,
or elsewhere within the jurisdiction of this Court, articles of
device, as described in the caption.
JURISDICTION AND VENUE
- That plaintiff brings this action in rem in its own right to
condemn and forfeit the defendant property. This Court has jurisdiction
over an action commenced by the United States under 28 U.S.C.
1345 and 21 U.S.C. 334, which provides the Court with jurisdiction
over seizures brought under the Act.
- That this Court has in rem jurisdiction over the defendant property
because the defendant property is located in the District of New
Jersey. Upon filing of this complaint, the plaintiff requests
that the Court issue an arrest warrant in rem pursuant to Supplemental
Rule G(3)(b), which the plaintiff will execute upon the property
pursuant to Supplemental Rule G(3).
- That venue is proper in this district pursuant to 28 U.S.C.
1395(b) and 21 U.S.C. 334(a)(1) because the defendant property
is located at Shelhigh, Inc., 650 Liberty Avenue, Union, New Jersey,
and at Future Medical Diagnostics Manufacturers tnc., 141 South
Avenue, Suite 200-205, Fanwood, New Jersey.
BASIS FOR FORFEITURE
- That the defendant articles of device are adulterated under
21 U.S.C. 351(h) because the methods used in, and the facilities
and controls used for, their manufacture, packing, storage, and
installation are not in conformity with current good manufacturing
practice (CGMP) requirements for devices as set forth in the QS
regulation, 21 CFR Part 820.
- That by reason of the foregoing, the defendant property is held
illegally within the jurisdiction of this Court and is liable
to seizure and condemnation pursuant to 21 U.S.C. 334.
FACTS
- That the articles of device manufactured by Shelhigh are cardiovascular,
neurological, and general surgery sterile implantable medical
devices, including pulmonic and aortic heart valves and pericardial
patches that are surgically implanted, often in compromised patients
and infants. All of the devices that the firm manufactures undergo
a No-React® rinse that occurs after sterilization. The purpose
of this final rinse process is to stabilize the sterilant to prevent
it from leaching off the device and causing an allergic reaction
in patients. This No-React® process is performed in the firm's
purported class 100 aseptic manufacturing room (class 100 room),
the purpose of which is to prevent contamination of the sterile
devices.
- That the Food and Drug Administration (FDA) issued Warning Letters
to the firm on April 26, 2000, and December 14, 2005. The December
14, 2005 Warning Letter advised Shelhigh that it was, among other
things, violating the Quality System (QS) regulation. In addition,
in a regulatory meeting held on June 16,2006, the firm was again
warned by FDA that continuation of the violative conduct could
result in seizure, injunction, and/or civil money penalties. The
deficiencies identified during the recent inspection of Shelhigh
demonstrate that the firm continues to violate the QS regulation
in many significant respects and that the firm has not established
and maintained a quality system that is appropriate for the medical
devices it designs and manufacturers. 21 C.F.R. 820.5.
- That FDA inspected Shelhigh on October 11-December 20, 2006.
The inspection revealed that the methods used in, and the facilities
and controls used for, the manufacture, design, packing, storage,
and installation of the above-captioned articles of device do
not comply with the QS regulation, 21 CFR Part 820, which was
promulgated pursuant to 21 U.S.C.3 60j(f) to assure that the devices
will be safe and effective and otherwise in compliance with the
Act.
These QS deviations include, but are not limited to, the following:
- Procedures for the acceptance or rejection of finished device
production runs, lots, or batches were not complete and adequate
[21 CFR 820.80(d)]. For example:
- The firm does not have a procedure describing how samples
used to test for sterility are processed and controlled
prior to sterilization to ensure that they are representative
of finished devices. Specifically, the firm's sterility
samples are selected from products that fail initial leak
testing early in the manufacturing process and are commingled,
and thus are not representative of the finished product
lot and do not permit lot traceablility. Accordingly,
those samples are not subject to the additional manual
manipulation of the manufacturing process that occurs
prior to the No-React® rinse process and are not representative
of the lot that is released;
- The firm allowed at least four lots of devices that
failed sterility testing to be released for distribution
in the last two years. FDA reviewed all 89 initial sterility
tests performed for Shelhigh by its independent testing
contractor (contract laboratory) during 2005 and the first
10 months of 2006. This review showed that 7.4% of samples
tested in 2005 failed sterility and that 5.7% failed sterility
testing in 2006. Although retesting failed to find non-sterile
product, such retesting was not justified (and should
not have been conducted) under accepted industry standards
because the firm had not first shown that the initial
positive test results were due to errors committed by
its contract laboratory. (In fact, in the one instance
in which Shelhigh asked its contract laboratory to evaluate
its positive result for laboratory error, no such error
was found.) In addition, because of the inherent limitations
of sterility testing (e.g., contamination is random and
sampling amounts are very low) and in the absence of a
showing of meaningful laboratory error, a retest result
of apparent sterility does not establish sterility; and
- The firm failed to identify device lots that did not
meet specifications during endotoxin testing. Specifically,
the firm released two lots of devices that failed initial
endotoxin testing, even though initial tests and retests
were performed on an inadequate sample size (one sample
unit from each lot), which could lead to a false negative
result. See also 21 C.F.R. 820.250 (b) (manufactures must
establish and maintain procedures to ensure that sampling
methods are adequate for their intended use; sampling
plans must be based on a valid statistical rationale).
Endotoxins can cause fever, shock, coagulation of blood,
and a rapid fall in blood pressure when introduced into
blood or tissues of the body.
- manufacturer's final acceptance activities are the last chance
to assure that finished devices meet specified requirements. Failure
to verify that appropriate acceptance criteria have been met can
result in the distribution of defective finished devices.
- Adequate procedures to control product that does not conform
to specified requirements were not established and maintained
[21 CFR 820.90(a)]. For example:
- The firm does not investigate initial sterility failures
for devices that it manufactures. As set forth above, the
firm does not investigate to determine whether laboratory
error or the manufacturing process caused a non-sterile result
before permitting a retest for sterility; nor does the firm
investigate its manufacturing process to identify the source
of contamination; and
- The firm failed to identify non-conforming results during
the pulmonic valve pressure leak testing (a test conducted
to ensure that the device will not leak after it is implanted
in patients) and subsequently released non-conforming products
for distribution, despite the firm's procedure which required
that such devices be rejected.
Proper control of non-conforming product is critical to ensure
that finished devices and products that do not conform to
specifications are not used or distributed. The investigation
of non- conformances is an essential part of ensuring ongoing
control of a manufacturing process, to determine the cause
and effect of a non-conformance and to prevent its recurrence.
- Adequate quality requirements that must be met by suppliers
were not established, and procedures to ensure that all purchased
or otherwise received services conform to specified requirements
were not complete [21 CFR 820.50(a)]. For example:
- Appropriate quality requirements have not been established
for the firm's contract laboratory, which supplies bioburden
testing, environmental monitoring, Limulus Amebocyte Lysate
(LAL) testing, and sterility testing; the firm did not require
the sterility test used for its products to be validated by
its contract laboratory. The firm's sterility test method
only includes the use of one culture medium, Soybean Casein
Digest Broth (SCDB), which does not support the growth of
anaerobic microorganisms. Accordingly, the test will not detect
such organisms, which may be present and contaminate the devices
and infect patients. In addition, the SCDB was incubated at
an improper temperature, which may reduce the recovery of
certain microbiological contaminants.
Failure to establish and maintain procedures to assure appropriate
services to test a finished device can result in failure of
the device to meet its specifications and distribution of
nonconforming product.
- Production processes were not adequately developed, conducted,
controlled, and monitored to ensure that devices conform to their
specifications [21 CFR 820.70(a)]. For example:
- The firm's procedure for testing quality of water used to
process products does not include analysis for the presence
of endotoxins, even though its device specifications require
that the level of bacterial endotoxins in finished devices
not exceed a specific limit. This water is used to prepare
various solutions that come in direct contact with raw materials,
components, and finished devices. Minimizing the presence
of endotoxins in process components is important because the
firm has no process to remove them in subsequent processing
steps.
Production and process controls are necessary to ensure that
each manufacturer produces devices that conform to their specifications.
Where any deviations from specifications could occur during
manufacturing, process control procedures must be established
to ensure conformance to specifications.
- A critical process whose results cannot be fully verified by
subsequent inspection and test has not been adequately validated,
and procedures were not established to monitor and control process
parameters for validated processes [21 CFR 820.75(a),(b)]. For
example:
- The firm has not adequately validated the No-React®
detoxification process, a final rinse process used on all
devices after sterilization and performed in the class 100
room, to demonstrate with a high degree of assurance that
the process will not adversely affect the sterility of all
devices manufactured at its facility, Although the firm stated
that it had submitted validation data to FDA, the firm submitted
only a procedure and general data that were not generated
by the procedure. Also, the procedure submitted for the No-React®
process is different than that actually performed by the firm.
Because the firm's devices are implanted into patients, ensuring
continued sterility is critical. The microbiological control
of the Shelhigh No-React® process cannot be fully verified
by subsequent inspection and testing because the firm cannot
perform sterility testing on every finished device without
destroying the devices. Thus, the firm is required to validate
the process with a high degree of assurance and thereafter
follow the precise process that was validated. Process validation
means confirmation by objective evidence that a process consistently
produces a result or product meeting its predetermined specifications.
21 CFR 820.3(z). Examples of factors that must be considered
when validating an aseptic manufacturing process include the
absence of microbiological, and the level of particulate,
contamination contributed by the air, surfaces, and employee
practices, among others.
- Adequate procedures to prevent contamination of equipment or
product by substances that could reasonably be expected to have
an adverse effect on product quality were not established and
maintained [21 CFR 820.70(e)]. For example:
- The firm's class 100 room has no separate gowning room for
employees to dress in sterile garments before entering the
room;
- Employees do not wear sterile shoe covers before entering or
when inside the class 100 room. In the class 100 room, the
entire body should be covered by sterile garments. Sterile
shoe covers are necessary to cover shoes, which are recognized
vectors for transporting high levels of microorganisms throughout
a facility;
- Employees use a broom to sweep the floor of the class 100 room.
Such sweeping causes dust, bacteria, and mold spores to spread
throughout the ambient air of the room onto table tops, walls,
shelves, and other surfaces that later may be touched by personnel
who process product. Although this sweeping is done prior
to disinfection, the firm's standard operating procedures
provide for inadequate disinfection of surfaces, and the firm's
disinfectant does not kill microbiological spores;
- A non-sterile stainless steel cart is transported into the class
100 room during product processing;
- Pieces of raw and painted wood were observed in the firm's class
100 and class 1,000 rooms. Wood is porous, difficult to disinfect,
can allow for the growth of bacteria and mold and contamination
of the environment, and is inappropriate in a class 100 and
class 1,000 environment; and
- The following conditions were also observed in the firm's controlled
manufacturing areas immediately adjacent to the class 100
room, where fresh porcine and bovine tissue products are processed:
ceiling panels stained with unknown substances; dislodged
ceiling panels; portions of ceiling panels missing; and air
diffusers with corrosion and dirt accumulation. Each manufacturer
is required to establish and maintain procedures to prevent
contamination of components, manufacturing materials, in-process
devices, finished devices, equipment, and returned devices
by substances that could adversely affect device safety or
effectiveness.
- Adequate procedures to control environmental conditions that
could reasonably be expected to have an adverse effect on product
quality were not established and maintained [21 CFR 820.70(c)].
For example:
- The firm's procedure for determining whether surfaces in
the class 100 room are contaminated requires the use of Isopropyl
Alcohol to wipe down only one small area prior to sampling
for contamination. In addition, because Isopropyl Alcohol
may prevent growth of microorganisms and Shelhigh does not
add a neutralizing agent to its surface monitoring media,
this process kills many surface microorganisms prior to monitoring,
masking the true count and types of potential microbes on
work surfaces that are used during device manufacturing in
the class 100 room. Accordingly, even the limited surface
sampling performed by Shelhigh (see (ii) below) is not reliable.
Lack of accurate sampling results fundamentally undermines
the ability of a firm to detect when hazards are present during
processing that can result in device non-sterility;
- Monitoring for air and surface contamination in the class
100 room is rarely performed and, when performed, not done
adequately. Shelhigh conducts surface monitoring only once
every three months; the firm's surface monitoring is performed
only on one spot in the class 100 room. Air monitoring is
done with only one exposure plate after each manufacturing
shift under static conditions and therefore does not reflect
actual processing conditions.
- The class 100 room is not properly constructed to perform
sterile operations and control contamination. For example,
there are gaps at the bottom of the walls and at the top of
each corner of the room, which are twenty feet from a door
to an environmentally uncontrolled warehouse area that may
be opened during product processing; the entryway to the room
consists of a series of plastic strips, which are located
approximately two feet from the work bench on which devices
are finally processed; and the high efficiency particulate
air (HEPA) filters, which are used to bathe the room in filtered
air, are periodically turned off thereby allowing unfiltered
and ambient air to enter the class 100 room. (See also 21
CFR 820.70(f)).
Manufacturers are required to establish and maintain adequate
procedures to carefully monitor and control environmental
conditions that could reasonably be expected to have an adverse
effect on product quality. As a part of the requirement, manufacturers
are required to frequently monitor and periodically inspect
environmental control systems to verify that the systems,
including necessaw equipment, are adequate and functioning
properly. In addition, these monitoring activities must be
documented and reviewed. To determine whether appropriate
environment and process controls are being maintained, manufacturers
who aseptically process products sample air and surfaces every
day and typically during each shift, using an appropriate
number and location of environmental monitoring plates.
- Adequate requirements for the health, cleanliness, personal
practices, and clothing of personnel were not established and
maintained [21 CFR 820.70(d)]. For example:
- Employees who handle porcine and bovine materials, finished
devices, sutures, surgical instruments, and solutions used
during the manufacture of the devices were observed leaving
the controlled manufacturing environment in their gowned attire
entering the restroom, and re-entering the controlled manufacturing
areas without changing their gowned attire, in violation of
the firm's procedure. These employees were working in a critical
device processing area that is in close proximity to the class
100 room.
- Manufacturers are required to establish and maintain
adequate procedures for the health, cleanliness, personal
practices, and clothing of their personnel who are working
in areas where contact between personnel and product or the
environment could adversely affect the product. Requirements
for sterile devices and environmentally-controlled room operations
necessitate a high level of control in order to minimize the
bioburden and particulate contamination of the devices and
the contamination of the environment.
- Procedures were not followed to confirm that the design changes
made to the Pulmonic Valve Conduit, a device used to replace a
diseased, damaged, or absent pulmonic artery in infants and children,
were controlled to include the identification, documentation,
validation or, where appropriate, verification, review, and approval
of the changes prior to their implementation [21 CFR 820.30(i)].
For example:
- The Pulmonic Valve Conduit design was changed from a straight
inflow conduit to a curved inflow conduit. This design change
was not adequately evaluated for the potential impact on the
functional, physical, or mechanical property features of the
device as a whole.
Manufacturers are required to have procedures to ensure that
after design requirements are established and approved, changes
to the design requirements are also documented, reviewed,
validated, and approved. The records of the design changes
create a history of the evolution of the design. Such records
are integral to failure investigations and preventing the
repetition of errors and the development of unsafe or ineffective
designs.
- Adequate design validation requirements to ensure that devices
conform to defined user needs and intended uses were not established
and maintained [21 CFR 820.30(g)]. For example:
- Although documentation submitted by the firm to FDA supported
only a three year product shelf-life, the firm's labeling
claims a four year shelf-life for all devices. The shelf-life
testing used to support the firm's claimed four-year expiration
date was inadequate because it did not evaluate device performance
for the extended period and did not include all devices.
- The firm has no test data to support multiple resterilizations
of its devices, which the firm believes may extend the shelf-life
of these devices to 12 years.
Because the firm produces tissue-based devices, it is critical to
conduct design validation studies to ensure that any processing
and reprocessing of these devices does not compromise performance
and adversely affect the safety and effectiveness of devices, e.g.,
by degrading the products.
- Adequate procedures for ensuring that all personnel are trained
to adequately perform their assigned responsibilities and for
identifying training needs were not established, maintained, and
documented [21 CFR 820.25(b)].
- In addition to the many clear deviations set forth above,
the lack of adequate training is also evident from the fact
that an employee of the firm fabricated shrink temperature
test results on retained samples and presented the data to
an FDA investigator because she could find no record of the
original test results;
- The firm has not adequately documented the training of its
employees. There are no current records documenting CGMP,
Quality System, or microbiological training for Shelhigh's
Chief Scientific Officer (CSO), who is responsible for training
quality assurance auditors, or the firm's General Manager,
who acts in the CSO's absence.
In order for a manufacturer's quality system to reliably function,
all personnel must be properly trained. At a minimum, such
training must include the consequences of improper performance
so that personnel will be aware of the effects that their
actions can have on the safety and effectiveness of the device
and know what process and product defects can occur as a result
of deficient practices, procedures, or conditions.
WHEREFORE, the plaintiff requests that the
Court issue a warrant and summons for the arrest and seizure
of the defendant property; that notice of this action be given
to all persons who reasonably appear to be potential claimants
of the defendant property; that the defendant property be
condemned and forfeited to the United States; that the defendant
property be disposed of as this Court may direct pursuant
to the provisions of the Act; and that plaintiff be awarded
its costs and disbursements in this action, and for such other
and further relief as this Court deems proper and just.
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CHRISTOPHER J. CHRISTE
United States Attorney
[Handwritten Signature]
By: PETER W. GAETA
Assistant U.S. Attorney
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STATE OF NEW JERSEY
COUNTY OF |
SS VERIFICATION
RECEIVED
-APR 11 6 2007
AT 8:30 M
WILLIAM T. WALSH. CLERK |
ROBERT MAFFEI, of full age, being duly sworn according to law, upon
his oath deposes and says:
- I am a Compliance officer, New Jersey District Office, United
States Food and Drug Administration, and as such am presently
assigned to the above-captioned matter.
- I have reviewed the attached Complaint and the allegations it
contains are true to the best of my knowledge, information, and
belief.
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[Handwritten Signature]
ROBERT MAFFEI |
Sworn and subscribed to
before me this 16th day
of April, 2007, at
Newark, New Jersey
[Handwritten Signature]
PETER W. GAETA
Attorney-at-Law
State of New Jersey |
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