Errors & accidents in manufacturing (3/20/91)

DATE   :  March 20, 1991

TO     :  All Registered Blood Establishments

SUBJECT:  Responsibilities of Blood Establishments Related to
          Errors & Accidents in the Manufacture of Blood &
          Blood Components

FROM:     Acting Director
          Center for Biologics Evaluation & Research

During the past two years, there has been a significant increase
in the number of product recalls initiated by blood
establishments. A large percentage of these recalls were directly
attributed to errors or accidents in manufacturing resulting in
the release of unsuitable blood and blood components. Many of
these errors or accidents were not reported to the Center for
Biologics Evaluation and Research (CBER), and frequently reports
were not submitted in a timely manner. For these reasons, we are
reminding licensed blood establishments of the reporting
requirement of 21 CFR 600.14 that CBER shall be notified promptly
of errors or accidents in the manufacture of products
that may affect the safety, purity, or potency of the biological
product.

This memorandum also requests that unlicensed, registered blood
establishments and transfusion services voluntarily report to
CBER those errors or accidents in the manufacture of blood and
blood components that may affect the quality of blood and blood
components, i.e., units that are not suitable for transfusion or
for further manufacturing use. In addition, this memorandum
reminds blood collection and transfusion facilities of
requirements in 21 CFR, Part 606 relating to investigations and
recordkeeping associated with errors and accidents.

Examples of reportable errors or accidents in manufacturing which
may affect product quality include, but are not limited to, the
release of: (1) units repeatably reactive to viral marker
testing; (2) units from donors for whom test results were
improperly interpreted due to testing errors related to improper
use of equipment or failure to strictly follow the reagent
manufacturer's directions for use; (3) units from donors who are
(or should have been) either temporarily or permanently deferred
due to medical history or a history of repeatably reactive
results to viral marker tests; 4) units prior to completion of
all tests; (5) incorrectly labeled blood components [e.g., ABO,
expiration date]; and (6) microbially contaminated blood
components when the contamination is attributed to an error in
manufacturing.

Blood collection or transfusion facilities may receive complaints
and/or adverse reaction reports that include information relating
to cases of hepatitis or evidence of HIV infection associated
with transfusion of blood or a blood component. Records of such
reports must be maintained and investigations conducted as
required by 21 CFR 606.160 and 606.170(a), and notification to
CBER is required under 21 CFR 600.14 if the investigation reveals
that the release of the implicated unit(s) was the result of an
error or accident in manufacturing.

We request that all directors and appropriate personnel of blood
collection and transfusion facilities promptly review procedures
to determine that written standard operating procedures include
provisions for recording errors and accidents as required by 21
CFR 606.160(b)(7)(iii). These standard operating procedures
should supplement procedures which have been established to
comply with the requirement of 21 CFR 606.100(c) that: (1)
manufacturing (including testing) records must be reviewed before
release or distribution of final products, (2) any unexplained
discrepancy or failure to meet any product specifications shall
be thoroughly investigated, and (3) follow-up actions and
conclusions shall be recorded. The Food & Drug Administration
(FDA) will continue to review and evaluate these procedures and
related records during scheduled inspections.

Notification to CBER under 21 CFR 600.14 is necessary when the
error or accident is associated with making a finished unit
available for distribution whether or not actual shipment has
occurred. If an error is detected during product manufacturing or
processing and prior to the finished unit being made available
for release, notification is not necessary. However, a thorough
investigation and documentation of corrective action is required
by 21 CFR 606.100(c) and 606.160. The notification requirement
under 21 CFR 600.14 is separate from the requirement of 21 CFR
606.170(b) for reporting to CBER fatalities associated with blood
collection or transfusion.

Product quality and labeling errors discovered in transfusion
facilities and relating to blood and blood components received
from outside sources should be referred to the manufacturer. The
manufacturer of the unit should then notify CBER concerning these
types of errors. However, errors in manufacture which occur in
transfusion facilities, such as incorrect identification of
samples used in compatibility testing, errors in compatibility
testing which result in the wrong unit being released for
transfusion, or issuing the wrong unit for transfusion, should be
reported to CBER directly by the transfusion facility.

The release and distribution of unsuitable blood and blood
components requires prompt action to identify all affected
components and to advise all consignees as to the appropriate
action for correction or disposition of the distributed product.
Each situation relating to the distribution of unsuitable blood
and blood components should be evaluated within the context of
Title 21, Code of Federal Regulations, Part 7.40 - Recalls
(Including Product Corrections) - Guidelines on Policy,
Procedures, and Industry Responsibilities. In the event that a
field correction or product recall is initiated by a blood
establishment, CBER and the local FDA district office should be
advised.

Notification of errors or accidents pursuant to 21 CFR 600.14
should be forwarded to:

           Food & Drug Administration
           Center for Biologics Evaluation & Research
           Division of Inspections & Surveillance (HFB-120)
           8800 Rockville Pike
           Bethesda, Maryland 20892

In order to facilitate the Food & Drug Administration's review
and evaluation, the attached outline may be used as a guide for
the type of information that should be reported.

Telephone contact with the CBER/Division of Inspections &
Surveillance can be made at: (301) 295-8191.

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