EXHIBIT 10.38
[FDA letterhead]
Xxxxxx X. Xxxxxxxx
President and CEO
CryoLife, Inc.
0000 Xxxxxxx Xxxx., XX
Xxxxxxxx, XX 00000
Dear Xx. Xxxxxxxx:
This letter sets forth the entire agreement between CryoLife, Inc. (CryoLife),
and the Food and Drug Administration (FDA) pertaining to the disposition of
certain human allograft tissues, which are subject to the August 13, 2002, FDA
Order for Retention, Recall, and/or Destruction. FDA and CryoLife agree that for
the next 45 working days the tissues specified below may be distributed for
medically urgent use when all alternative treatments have been exhausted or are
unavailable and the conditions specified below have been fulfilled. FDA and
CryoLife agree that only the following human allograft tissues will be
distributed for the specified medically urgent uses when alternative therapies
are exhausted or unavailable:
o Non-valved cardiac conduits and patches procured from the ascending
aorta and pulmonary trunk and branch for use in neonates and pediatric
patients.
o Saphenous veins used for peripheral vascular bypass when no
alternative materials are available.
o Femoral veins and arteries used for dialysis access when synthetic
access device becomes infected and when external bridging is not
possible.
o Aorto-iliac artery for infected abdominal grafts:
o femoral veins and arteries for iliac extension.
o Saphenous veins used for cardiac bypass when no suitable autologous
tissue is available, including internal mammary, saphenous and other
sites.
CryoLife and FDA agree that the specified tissues will be released for
distribution only after CryoLife completes the following steps:
1. CryoLife will obtain a prescription from the surgeon for the tissue
requested, including its specific use. The prescription will include the
surgeon's tissue requirements for the patient. CryoLife will obtain from
the surgeon a written certification that all other alternatives have been
exhausted or are unavailable and that there is an urgent medical need for
the tissue requested. For non-valved cardiac conduits and patches, CryoLife
will obtain from each pediatric surgical center, in addition to the
information described above, a request for the number of tissues that the
center estimates it may use during the 45 day period for which this
agreement is in effect.
2. CryoLife will inform surgeons that patients should be notified that the
tissue is subject to an FDA recall, that there is a risk of infection
associated with these tissue implants, and that alternative approaches,
including non-surgical, should be exhausted or unavailable before using
this tissue. CryoLife will obtain from the surgeon either a written
acknowledgement that he has or will inform the patient of the above factors
or, if this is contained in the informed consent, a copy of that document.
CryoLife will also request immediate feedback from surgeons of any
suspected infections after use of the tissue.
3. CryoLife will contact Tissue and Organ Procurement Organizations (TOPOs or
OPOs) or other facilities that procured the tissues described above to
ascertain if microbial cultures were performed during or after procurement;
if cultures were performed, CryoLife will obtain documentation of the
results of that testing. Any tissues shown by these tests to have been
obtained from a donor whose tissue has cultured positive for microorganisms
that have been associated with infection, or could be indicative of other
microorganisms that have been associated with infections, including but not
limited to, Clostridium, Candida and Escherichia coli (hereafter referred
to as indicator organisms), will not be released. If there are no microbial
records available from the procurement site, CryoLife will include
additional labeling as described in paragraph number 6 below.
4. CryoLife will perform a retrospective review of its own pre-packaging
microbiological testing records for all associated donor tissue. If
indicator microorganisms were isolated, the tissue will not be released.
5. CryoLife will perform a search of its complaint files to ascertain if there
are any complaints regarding infections for all associated donor tissue. If
there are any such complaints with regard to any associated donor tissue,
no tissue from the same donor will be released.
6. CryoLife will provide the following information in addition to its routine
labeling for tissue for distribution: in bold, red caps, in at least
12-point, " BIOHAZARD: THIS TISSUE IS SUBJECT TO AN FDA ORDER FOR RECALL
AND RETENTION BASED ON FDA CONCERNS OVER THE VALIDATION OF THE METHODS USED
TO PREVENT INFECTIOUS DISEASE CONTAMINATION AND CROSS-CONTAMINATION. IT IS
BEING RELEASED DUE TO URGENT MEDICAL NEED AND IS ONLY FOR USE FOR THE
INTENDED RECIPIENT."
For tissue not tested at procurement, CryoLife will further label the
tissue as, "PROCUREMENT CULTURES WERE NOT PERFORMED PRIOR TO RECEIPT AND
PROCESSING BY CRYOLIFE."
7. CryoLife will document and maintain records of its actions under this
agreement, and make such records available for FDA review. For non-valved
cardiac conduits and patches, CryoLife will also track and document all
tissue that is released pursuant to this agreement.
In addition, CryoLife agrees to implement the following interim procedures to
help prevent infectious disease contamination or cross-contamination of tissue
during processing:
1. CryoLife will perform pre-processing cultures on all incoming tissues prior
to antibiotics, disinfectants, or sterilizing agents that would include
either 100% swabbing or 10% destructive testing. All testing of
pre-processing samples will be performed by a contract laboratory with
validated methods, until such time as CryoLife's test methods are
adequately validated. Tissues contaminated with indicator microorganisms
that cannot be reliably cleared by CryoLife's processing system will be
discarded.
2. CryoLife will perform pre-packaging cultures on all tissue made available
for distribution, using either 100% swabbing or 10% destructive sterility
testing. All testing of pre-packaging samples will be performed by a
contract laboratory with validated methods, until such time as CryoLife's
test methods are adequately validated. All tissue from a donor will be
discarded if indicator microorganisms are found in any tissue from that
donor. In lieu of 100% swabbing or 10% destructive sterility testing,
CryoLife will demonstrate that the current practice of processing companion
tissue for the purpose of pre-packaging cultures adequately represents the
tissue being processed through validation of this process.
3. CryoLife will establish a corrective action plan within 30 days that will
include steps to validate its processing procedures to prevent infectious
disease contamination and cross-contamination of tissue during processing,
including any procedures to ensure that tissue distributed by CryoLife is
free, or reasonably free, from microbial contamination. This corrective
action plan will include specific and prompt timeframes for completion of
each step. CryoLife agrees to engage a consultant/third party reviewer to
assist CryoLife in this validation.
4. CryoLife agrees to replace tissue subject to the FDA Order and specified in
this agreement with tissue that has been processed using the interim
procedures above as soon as such tissue is available. As such newly
processed tissue becomes available, CryoLife agrees not to release tissue
subject to the Order and this agreement pending further arrangements for
ensuring the proper disposition of such tissues. Any further arrangements
must be agreed upon in writing between CryoLife and an authorized official
of the FDA.
This agreement will remain in effect for forty-five (45) working days from the
date of signature by all parties. FDA will review records and other relevant
information related to CryoLife's release of tissue under this agreement, as
well as the status of CryoLife's corrective action plan, before determining
whether this agreement should be renewed or modified to provide for any further
release of tissue subject to the Order of Retention, Recall, and/or Destruction.
FDA has encouraged CryoLife, and CryoLife has agreed, to implement adequate
corrective actions as rapidly as possible and to replace tissue subject to the
Order with tissue processed subsequently under the interim procedures. This
agreement supplements the August 13, 2002, FDA Order for Retention, Recall,
and/or Destruction and, except to the limited extent provided herein, does not
in any way supercede, limit, or modify that Order.
/s/ Xxxxxxx X. Xxxx 9/5/02
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Xxxxxxx X. Xxxx Date
Acting Director
Atlanta District Office
/s/ Xxxxxx X. Xxxxxxxx 9/5/02
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Xxxxxx X. Xxxxxxxx Date
President and CEO CryoLife, Inc.
0000000x0
