Manufacture of blood and blood components (3/20/91)

DATE    :   March 20, 1991

TO      :   All Registered Blood Establishments

SUBJECT:    Deficiencies Relating to the Manufacture of Blood
            and Blood Components

FROM :      Acting Director
            Center for Biologics Evaluation & Research

INTRODUCTION:

The Food & Drug Administration (FDA) has reviewed and evaluated
inspectional findings, error and accident reports, blood product
recalls, and enforcement actions for the past year. This
evaluation indicates continued deficiencies relating to the
release of unsuitable blood and blood components.

Areas where significant deficiencies from current good
manufacturing practices (21 CFR 606, et. seq.) have occurred
include, but are not limited to, donor deferral, viral marker
testing, computer systems, and procedures relating to product
release and control operations. We believe that providing a brief
listing of the more significant errors reported to the FDA and
those found during inspections will be beneficial to blood
establishments and provide information that may be useful in
performing self audits.

DONOR DEFERRAL:

Significant deficiencies in donor deferral systems included, but
were not limited to:

-    Deferral records were incomplete, not current, or did not
     provide for accurate identification of the donor (See 21
     CFR 606.160);

-    Donors were no: recognized as having multiple reasons for
     deferral (See 21 CFR 606.160);

-    Computer systems contributed to the loss of donor records
     or did not recognize all deferrals (See 21 CFR 606.160 and
     606.60).

TESTING FOR VIRAL MARKERS AND REVIEW OF TESTING RECORDS:

Significant deficiencies in viral marker testing and review of
testing records included, but were not limited to:

-    Test samples were of poor quality, sample identification
     was inadequate, and back-up samples were not properly
     stored or identified (See 21 CFR 606.140);

-    Test kit manufacturer's directions for use were not
     followed for proper storage and preparation of reagents and
     for proper dilution of samples and/or controls (See 21 CFR
     606.65);

-    Equipment was not properly maintained or calibrated, and
     investigations were inadequate to correct recurrent
     performance problems (See 21 CFR 606.60);

-    Samples were tested multiple times without proper
     invalidation of tests, and investigations were not adequate
     to clarify technologist error or malfunction of the test
     kit or equipment. As a result, test interpretations were
     incorrect (See 21 CFR 606.65 and 606.140).

COMPUTER SYSTEMS:

Significant deficiencies found relating to the use and operation
of computer systems in manufacturing included, but were not
limited to:

-    Written procedures were not available describing proper use
     of the system in daily operations; no provisions for manual
     back-up or for controlling changes to the hardware and
     software (See 21 CFR 606.100);

-    Records did not include documentation concerning initial
     installation and validation procedures or for changes to
     the hardware and software that were components of the
     current system in use (See 21 CFR 606.160 and 606.60);

-    Personnel were not properly trained in the use of the
     system(s) concerning capabilities and limitations of the
     system when used in critical steps in manufacturing such as
     donor suitability, testing, labeling, and product release
     (See 21 CFR 606.20).

STANDARD OPERATING PROCEDURES (SOP's) AND CONTROL OPERATIONS:

Significant deficiencies found relating to SOP's and general
control operations included, but were not limited to:

-    SOP's did not comply with FDA guidance concerning re-entry
     of donors who previously tested reactive for hepatitis B
     surface antigen (HBsAg) or antibody to human
     immunodeficiency virus (anti-HIV); SOP's were either not
     followed, not sufficiently detailed, or did not reflect 
     current manufacturing operations (See 21 CFR 606.100 and
     640.3);

-    The wrong unit was quarantined and retested, or the wrong
     test was repeated (See 21 CFR 606.100 and 606.140).

-    Components from untested autologous units were released for
     further manufacturing use (See 21 CFR 606.100, 610.40, and
     610.45).

SUMMARY:

The Food & Drug Administration requests that blood bank directors
and appropriate personnel review current standard operating
procedures and manufacturing operations with regard to the
potential for errors in the areas described in this memorandum
and for consistency with applicable regulations contained in
Title 21, Code of Federal Regulations, Parts 600, 606, 610, and
640.


                         Gerald V. Quinnan, Jr., M.D.