Patient Safety and Recall Update for Health Care Professionals

Regeneration Technologies, Inc. (RTI) would like to take this opportunity to provideinformation about the stepswe take to ensure patient safety. When implanting biologics, ultimately, the level of risk any patient faces depends on the method of processing.

Attention Health Care Professionals:
In conjunction with the FDA, following is a list of tissue ID numbers for which we are still seeking information for final disposition. Please check to see if your organization had received any of these tissues. If your hospital or organization has received any tissue on this list, please contact Regeneration Technologies' Customer Service at (800) 624-7238 as soon as possible. The following list includes only tissue for which RTI is still seeking final disposition confirmation from health care providers. This list represents all remaining tissue that was subject to the October 14, 2005, recall - all other tissues have been accounted for.
- Sports Medicine Allografts
- General Orthopedic Allografts
- Spine Allografts

About Tissue Transplants
Updated:March 20, 2006 Released:February 2006

What is a bone or tissue allograft?
The bones or tissues that transplanted from the body of one person to another person are
called allografts. Tissue allografts can include: bones, heart valves, blood vessels, skin and
tendons.

Where do allograft bones and tissues come from?
Most allograft bones and tissues are obtained from deceased donors. Family members give
consent to donate the tissues of their loved ones.

What laws and regulations govern the recovery, processing and distribution of tissues in
the United States?
Human tissues intended for transplantation have been regulated by Food and Drug
Administration (FDA) since 1993. In May of 2005, three new, comprehensive regulations
went into effect that address manufacturing activities associated with human cells, tissues and
cellular and tissue- based products (HCT/Ps). The first requires that companies that produce
and distribute HCT/Ps register with the FDA. The second provides criteria that must be met
for donors to be eligible to donate tissues and is referred to as the Donor Eligibility rule.
The third rule governs the processing and distribution of the tissues and is often referred to as
the Current Good Tissue Practices rule. Together they are designed to ensure that sound,
high quality practices are followed to reduce the risk of tissue contamination and of
communicable disease transmission to recipients. These rules are available at:
www.fda.gov/cber/tissue/docs.htm.

How common is the use of bone and tissue allografts?
According to data from the American Association of Tissue Banks (AATB), a voluntary
accreditation organization that sets standards for tissue banking, approximately 1.5 million
bone and tissue allografts are distributed each year by AATB-accredited tissue banks in the
United States.

What are allografts used for?
Bone and tissue allografts are used for a variety of reasons. For example, they are used to
replace damaged heart valves and skin. They are also frequently used in orthopedic surgery to
replace tendons or bones damaged by trauma, tumors or other conditions. Bone and tissue
allografts are used in a variety of procedures that can save lives, repair limbs, relieve pain or
enhance a patient�s quality of life.

Why would an allograft be used instead of a person�s own tissue or a synthetic material?
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Sometimes, there is not enough of the person�s own tissue to use in an operation. Synthetic
materials have different properties from human tissue and may not be suitable for some
patients or purposes.

Can allograft tissues transmit infections?
There have been rare instances where allograft tissues have transmitted infections to
recipients. In most instances the infection was present in the donor at the time of death but
was not detected. In some cases, tissues have been contaminated during removal, transport,
processing, or storage. It is important to note that many of these instances have been
investigated carefully and resulted in improvements to methods for screening and testing
donors for infections, for processing to prevent contamination, and for removing or
inactivating organisms that may be present in allografts. The Donor Eligibility rule requires
up-to-date and appropriate donor screening and testing. The Current Good Tissue Practices
rule requires methods be put in place to reduce risks during the production of the tissues.

What measures are in place to ensure that donors of allograft tissues do not have
infections that could be transmitted to recipients?
Potential donors of allograft tissues are screened for possible infections in a variety of ways.
First, detailed information regarding the potential donor�s medical history is reviewed for
evidence of diseases that might be transmissible to a tissue recipient. In addition, someone
who knew the donor completes a detailed questionnaire to review a number of potential risks
for and any symptoms of infections that might have been present when the donor died. The
Food and Drug Administration (FDA) has set forth a number of criteria that include risk
factors, clinical evidence, and other findings that might be an indication of a transmissible
disease in the donor. Presence of these factors or symptoms would make a donor ineligible to
donate tissues. These factors are very similar to those examined for blood donors.
If there are no risk factors, symptoms, or other findings of infection in the donor, the next step
is to test the donor for infectious diseases. Blood samples from all potential tissue donors are
tested for HIV, Hepatitis B, Hepatitis C, and syphilis. If any of these tests are positive, the
potential donor is ineligible to donate tissues.

Who removes tissues from donors?
Tissues are removed by personnel working for tissue recovery agencies. Under federal law,
these agencies must be registered with the Food and Drug Administration and must adhere to
applicable FDA regulations that govern tissue recovery. These regulations are found in the
Current Good Tissue Practices rule.

Where are tissues sent once they are removed (recovered)?
Tissues are sent to tissue banks for processing and distribution. Tissue banks are
establishments that are regulated by the Food and Drug Administration (FDA). By law, any
company that wishes to receive, process, or distribute tissues must register with FDA and
must adhere to all FDA regulations governing tissue banking. These establishments are
subject to regular inspection by the FDA.

What is done with tissues from eligible donors once they are removed?
After they are removed, tissues are subjected to one or more disinfection processes that are
designed to kill or remove any bacteria, fungi or viruses that might be present. Different
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companies use different methods to accomplish this goal, including rinsing with antimicrobial
chemicals, sometimes under pressure, as well as irradiation. In some instances, multiple
methods might be used. Various methods have different levels of effectiveness in killing or
removing infectious organisms.

What testing is done on the tissues themselves?
Individual tissues from eligible donors are tested for the presence of bacteria, mold and fungi
when they are removed from the donor. This testing is repeated after the tissues have been
subjected to the procedures designed to remove organisms.

What should I do if I am worried that I may have contracted an infection from a bone or
tissue allograft?
You should discuss your concerns with your healthcare provider. Cases of suspected
transmission of infections by bone and tissue allografts should be reported to MedWatch,
FDA's voluntary reporting program at http://www.fda.gov/Medwatch/report.htm; by
telephone, 1-800-FDA-1088; by fax, 1-800-FDA-0178; or by mail, MedWatch, Food and
Drug Administration, 5600 Fishers Lane, Rockville, MD 20852-9787. These cases should
also be reported to the tissue bank who distributed the tissues.
On October 26, 2005, Centers for Disease Control and Prevention and Food and Drug
Administration recommended that recipients of tissues recovered by Biomedical Tissue
Services (BTS) be tested for evidence of infection with HIV, hepatitis B virus (HBV),
hepatitis C virus (HCV), and syphilis. What tests should be performed and how often?
There are no set guidelines on how this testing should be done for tissue recipients. CDC thus
recommends that clinicians follow the post-exposure follow-up testing recommendations that
are used for occupational exposures to HIV, HBV or HCV, as described in the �Guidelines for
the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations
for Postexposure Prophylaxis� (available at:
www.cdc.gov/ncidod/dhqp/gl_occupational.html). The recommendations below can be
used for all recipients who have normal immune systems. For those who have very weakened
immune systems because of immune system suppressing medications, other tests might be
indicated.
Patients who had tissue implanted more than six months ago should be offered the
following tests: HIV antibody, antibody to hepatitis B core antigen, antibody to hepatitis C
virus, a non-treponemal syphilis test (e.g. RPR or VDRL), and a treponemal syphilis test (TPPA
or any ELISA test). If all of these tests are negative it is very unlikely that the recipient
will contract any of these diseases from an implanted tissue that was potentially contaminated
and no further follow-up testing is necessary.
Patients who had tissue implanted less than six months ago can be offered the same series
of tests as above immediately, but should also be re-tested six months after the tissue was
implanted. Again, if all of these tests are negative six months after the tissue was implanted, it
is very unlikely that the recipient will contract any of these diseases from an implanted tissue
that was potentially contaminated and no further follow up testing is necessary.

What if one of the screening tests is positive?
Patients who had tissue implanted less than six months ago can be offered the same series of
tests as above immediately, but should also be re-tested six months after the tissue was
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implanted. Again, if all of these tests are negative six months after the tissue was implanted, it
is very unlikely that the recipient will contract any of these diseases from an implanted tissue
that was potentially contaminated and no further follow up testing is necessary.

What if one of the screening tests is positive?
It is important to remember that these initial tests are screening tests and hence positive
results do not always mean that the patient has been infected. Patients who have a positive
result for any of these tests should undergo confirmatory or supplemental testing. Clinicians
who have questions about confirmatory or supplemental testing should contact a clinician
with expertise in infectious diseases.

Should nucleic acid tests (direct virus tests) for HIV, HBV, and HCV be used as initial,
screening tests for recipients of BTS tissues?
No. Most nucleic acid tests (e.g. PCR assays) that are used by clinical laboratories are not
intended to screen patients for disease, but are FDA-approved to confirm the results of
screening tests or to monitor virus activity in patients who are known to have the disease.
These tests should not be used in place of the antibody tests recommended here.
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Date last modified: March 20, 2006
Content source: Division of Healthcare Quality Promotion (DHQP)
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