Quick Summary

Transmissible Spongiform Encephalopathies Advisory Committee Meeting

June 26 & 27, 2002

Topic #1

**Validation of Procedures to Prevent Contamination and
Cross-Contamination with TSE Agents of Human Tissue Intended for
Transplantation**

FDA asked the TSEAC to advise them on appropriate measures to prevent
contamination and cross-contamination by TSE agents of human cells and
tissues intended for transplantation. Since FDA is in the process of
finalizing its proposed tissue regulations, and of issuing draft
guidance, the agency thought that this was an appropriate time to
discuss this issue. Speakers presented information on the three
approaches that could be taken to reduce the risk of TSE
transmission---careful screening of the donor for TSE and risk factors
for TSE, control of the recovery and processing of cells and tissues to
prevent contamination and cross-contamination, and the use of steps
during manufacturing of cells and tissues to remove or inactivate any
TSE agents that may be present. The committee heard talks about possible
additional screening measures, risk assessment models, the potential
value of post-mortem brain autopsy or biopsy, previous transmissions of
CJD by dura mater, cornea and human pituitary-derived growth hormone,
effects of batch size on risk of infectious agent contamination,
experiments on transmission of CJD through various tissues and body
fluids, single donor aseptic recovery and processing of ocular and bone
tissue, equipment and instrument disinfection methods, process
validation, and TSE agent clearance studies in experimental models.

# Committee Discussion and Votes on Questions 

1.  Which of the following measures and controls is (are) appropriate to
    prevent TSE agent transmission to the recipient of human cells and
    tissues?

> **A. Recommend additional donor eligibility/exclusion criteria**

-   **Upper age limit**

> YES-0; NO-14; ABSTAIN-0; INDUSTRY REP-No

-   **Head trauma exclusion**

> YES-0; NO-14; ABSTAIN-0; INDUSTRY REP-No

-   **Negative brain autopsy or biopsy for all donors**

> YES-0; NO-14; ABSTAIN-0; INDUSTRY REP-NO

-   **Negative brain autopsy or biopsy [only]{.underline} for dura
    mater**

> YES-14; NO-0; ABSTAIN-0; INDUSTRY REP-Yes

B.  **Recommend specified methods for HCT/P recovery and/or processing
    to prevent contamination and cross-contamination by TSE agents:**

    -   **Decontamination of instruments and surfaces**

    -   **Methods for removal and/or inactivation of TSE agents during
        manufacturing**

The committee members did not vote on the questions as stated. The
Chairman posed a revised question, as follows:

"Do the Committee members recommend that FDA should define validated
inactivation procedures for TSE decontamination of instruments and
surfaces, and propose methods for removal and/or inactivation of TSE
agents from HCT/Ps that may be contaminated by TSEs, differentiating
high risk from low risk tissues?"

The vote on this recommendation was:

YES-14; NO-0; ABSTAIN-0; INDUSTRY REP-Yes

-   **Single-donor aseptic processing or permit pooled processing under
    certain circumstances with adequate controls**

Recommended that FDA should consider single-donor aseptic processing as
the gold standard, [and]{.underline} that FDA should permit pooled
processing under certain circumstances with adequate controls.

The vote on this recommendation was:

YES-14; NO-0; ABSTAIN-0; INDUSTRY REP-Yes

**C. Other**

2.  **Please comment on the design of a satisfactory TSE agent clearance
    study for HCT/Ps, in terms of the following criteria:**

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A.  **Suitable TSE agent strain and animal model**

B.  **Accept measurement of abnormal forms of prion protein alone, or
    require infectivity assays**

C.  **Accept substantial reduction (how much?) or require complete
    elimination of detectable prion protein and/or infectivity**

D.  **Accept a single validated method or require that more than one
    validated method for eliminating TSE agents be included in the
    study**

E.  **Other**

Recommended that the TSE strain and animal model used could vary,
depending upon the study.

Recommended to require infectivity assays, and commented that in order
to show validity and reproducibility, measurement of abnormal prion
protein would also be needed.

The committee did not comment on the amount of log reduction that would
be acceptable, or on the need for more than one validated method.

**Topic \# 2**

**FDA Draft Guidance on Preventive Measures to Reduce the Possible Risk
of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant
Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular
and Tissue-Based Products (HCT/Ps)**

FDA published draft guidance, entitled "Preventive Measures to Reduce
the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and
Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and
Cellular and Tissue-Based Products (HCT/Ps)" in June 2002. This draft
guidance was based upon recommendations made by the TSEAC in the January
2001 meeting. At that meeting the TSEAC members unanimously agreed that
there is a significant risk of transmission of vCJD through
transplantation of HCT/Ps, compared to the risk of transmission of vCJD
by blood transfusion. The recommendations for tissue donor deferral in
this draft guidance were similar to the recommendations for blood donor
deferral recently published in January 2002. The contents of the draft
guidance (specifically detailing the deferral criteria and highlighting
the differences between the tissue draft guidance and the blood
guidance) were presented. Potential strategies for assessing the impact
of this guidance on the tissue supply in the United States were
discussed.

FDA asked the TSEAC to comment on the recommendations made in the draft
guidance, and to consider how information can be obtained about the
effect of implementing these tissue donor deferral criteria on the
tissue supply in the United States.

The committee discussed the difficulty of obtaining reliable information
from the person being interviewed, rather than the donor himself. The
committee could not recommend what to do with an "I don't know" answer
and suggested that the eye bank community and/or EBAA conduct a pilot
study to assess the potential impact that these draft recommendations
could have on the tissue supply and/or how frequently family members
would answer "I don't know." The committee distinguished between those
tissues that have transmitted classic CJD (dura mater and cornea) from
other types of tissues.

The committee felt that survey questionnaires may not be an effective
way to assess the impact of these criteria on the tissue supply because
of differences in between blood and tissue donors, since tissue donors
are largely a cadaveric population. The committee is interested in being
updated on information obtained about the effect of these deferral
criteria on the tissue supply.

**June 27, 2002**

**Committee Updates**

The committee was presented with a review of FDA's revised guidance on
blood donor deferrals for risk of CJD and vCJD. The committee then heard
a presentation from the Department of Health and Human Services on its
new tracking procedure to monitor the blood supply. The committee also
listened to presentations from blood centers and related organizations
on the effect of implementing geographic donor deferrals for risk of
vCJD. The current decrease in blood supplies was felt to be due to
several factors, including initiation of new donor deferrals, typical
summertime decrease in donations, and donor disenchantment since 9-11.
Blood organizations have anticipated and responded to the new deferrals
with increased donor recruitment efforts, and development of blood
supply monitoring systems.

The committee expressed concerns about the diminishing blood inventories
and the effect that the annual decrease in blood donations in the summer
months could have on the country's blood supply. They asked that this
situation continue to be monitored, and suggested that if needed, FDA
should review their guidance on donor requirements as they relate to CJD
issues, and should continue to address other strategies to augment the
blood supply.

This quick summary is written as an overview of the committee discussion
until transcripts are available. Please refer to the committee
transcripts for a detailed account of the meeting.