CONSENT DECREE NOTIFICATION

Marsha Johnson Evans
President and Chief Executive Officer
American National Red Cross
430 17^th Street, N.W.
Washington, D.C.   20006

Re:  United States v. American National Red Cross, Civil Action No. 93 0949 (JGP)

Dear Ms. Evans:

A team of Food and Drug Administration (FDA) investigators inspected the American National Red Cross (ARC), Biomedical Headquarters (BHQ), located at 1616 Fort Myer Drive, Arlington, Virginia, from April 2002 through December 2002.  During that inspection, the FDA investigators observed numerous deviations from FDA law, regulations, and the Consent Decree of Permanent Injunction (Decree) entered May 12, 1993.  Pursuant to Paragraph VI.A. of the Decree, FDA is notifying ARC of its determination that ARC has violated the law.  Corrective action by ARC is necessary.  This is the thirteenth letter issued by FDA to ARC, pursuant to Paragraph VI.A. of the Decree.  Numerous violative conditions cited in this letter have also been cited in other such letters issued by FDA to ARC.

At the conclusion of the inspection, the investigators issued a Form FDA 483, Inspectional Observations (FDA 483).  The observations include, but are not limited to, the following:

HOTLINE RECORDS:

1. ARC failed to thoroughly investigate employee allegations of serious deviations from the law and to correct and prevent recurrences of such deviations.  For example employees reported:
   1. that records were created to document work that was not actually performed;
   2. blood components were labeled with results of a test that was not actually performed;
   3. supervisors instructed records to be falsified;
   4. training records were falsified;
   5. Blood Donation Records (BDR) were altered to allow acceptance of an unsuitable donor;
   6. employees were reprimanded for deferring too many donors; and
   7. inappropriate handling of donor adverse reactions, such as failure to discontinue phlebotomy of two donors who had “passed out.”

   In August 2000, ARC informed FDA that it had implemented an employee hotline program to “reinforce the ARC policy which requires all staff to report any potential violative activities, and to further ensure all staff understands their role in ensuring patient and donor safety and the need to follow legal requirements and ARC standards.”  ARC promised to thoroughly investigate each hotline report.  However, ARC established no written procedures for correcting confirmed deviations from the law and ARC’s procedures. The quality assurance /quality control unit was not informed of all reported problems to determine whether they bear on product quality and donor safety.  ARC also failed to maintain an adequate record of each hotline report and the conclusion and follow up for each investigation.

   [21 CFR 211.22, 21 CFR 211.198, Decree Paragraph III.B.1.; FDA 483 observations 1, 2, 3, 4, 5, 89, 90, 93, 94]

   INADEQUATE INVESTIGATION OF SUSPECTED POST TRANSFUSION HEPATITIS CASES:

2. ARC failed to thoroughly investigate suspected transfusion transmitted disease cases, including one fatality.  Additionally, ARC’s procedures are inadequate in that they do not require a thorough investigation of reports of suspected transfusion transmitted diseases.  For example,   
   1. In November 2001, a post transfusion fatality was reported to an ARC Blood Service Region (region). Viral marker test records and associated quality control records were not reviewed.  Donors of the transfused blood products were not contacted for additional testing and health history verification.  Additionally, ARC failed to determine the disposition of other blood components manufactured from the two suspected donations and failed to determine whether other recipients experienced post transfusion infections.
   2. ARC’s procedure for investigating suspected post-transfusion hepatitis (SPTHEP) cases limits investigation of such reports to only those cases involving transfusion of components from 10 or fewer donors, unless ARC is contacted by a local government health department or becomes involved in litigation and receives approval by BHQ to perform the investigation. FDA investigators found that, during the period January 1, 2000 through June 30, 2002, 134 SPTHEP cases were reported to, but not investigated, by ARC.

   [21 CFR 606.170(a), Decree Paragraph III.B.14; FDA 483 observations 6, 7, 8, 9]

   INVENTORY MANAGEMENT:

3. ARC failed to establish procedures that include a system by which the distribution of each unit of blood or blood component can be readily determined to facilitate recall, if necessary, and to investigate and correct continuing inventory management deviations.  For example,
   1. During the period April 1, 2000 through August 12, 2002, ARC could not determine the final disposition of (lost)1062 blood products, including at least six products with positive viral marker tests.
   2. ARC procedures fail to require regions to investigate and prevent recurrence of lost blood products unless their individual monthly rate of loss is equal to or greater than the upper control limit, established by ARC, or unless a region has a three consecutive month upward trend for rate of loss.
   3. In November 1998, ARC was first notified by a region of the inability to fully track the disposition of plasma products.  As recently as September 2, 2002, another region reported that 52 units of plasma could not be located for recall or market withdrawal.  As of September 23, 2002, ARC had not fully corrected this problem.
   4. ARC failed to investigate and correct continuing deviations that involve shipment of blood products physically, but not electronically.  When ARC ships blood products physically, but not electronically, there is no record of distribution to facilitate recall, if necessary.  During the period, July 1, 2001 through June 30, 2002, 233 such deviations were reported to BHQ by regions. 
   5. ARC failed to ensure that inventory management procedures are adequate and are being followed in each region.  BHQ did not assess deviations associated with inventory reconciliation of quarantine locations until this inspection.
   6. ARC failed to establish an adequate procedure to control storage of frozen red blood cells.  For example, results of an April 2001 BHQ audit of a region revealed problems with controlling storage and quarantine of frozen red blood cells.  ARC has not implemented a system to maintain control of inventory of its rare frozen red blood cells.   

   [21 CFR 606.165, 21 CFR 211.22, Decree Paragraphs III.B.1., III.B.12., III.B.13.; FDA 483 observations 10, 13, 14, 15, 17, 19, 25, 26, 27, 28, 30]

4. ARC failed to establish an adequate procedure to prevent reissue of unsuitable blood products that have been returned, recalled, or market withdrawn.  FDA observed that between November 2000 and April 2002, ARC reissued 16 unsuitable products. 

   [21 CFR 606.100(b), 21 CFR 606.100(b)(12), 21 CFR 211.204, 21 CFR 211.22, Decree Paragraphs III.B.1., X.; FDA observation 20]

5. ARC failed to correct and prevent deviations that resulted in release and/or distribution of unsuitable blood products. For example,
   1. Between January 2001 and June 2002, ARC identified 1850 blood products that were unsuitable due to blood collection quality control errors.
   2. In January 2002, ARC documented a systemic problem related to release and/or distribution of blood products that had been identified by ARC as unsuitable during review of quality control records, during review of BDRs, during review by regional Material Review Boards, or through post donation information received from donors.  ARC records state that its corrective action for this systemic problem would be considered effective if, based on data collected six months post-implementation, release of unsuitable blood products was decreased by only 50%.
   3. Biological Product Deviation Reports for the period December 20, 2001 through June 1, 2002 show continuing deviations involving distribution of unsuitable blood products collected from donors who were not eligible to donate.  For example,
   1. Blood products collected from approximately 58 donors were collected and distributed, although the donors reported to ARC’s health historians that they had traveled in malarial areas.
   2. Blood products from 16 donors were collected and distributed, although the donors reported to ARC’s health historians that they were taking medication that caused them to be ineligible to donate blood for transfusion.
   3. Blood products from 48 donors were collected and distributed, although the donors reported to ARC’s health historians information that caused them to be ineligible to donate blood for transfusion, such as a history of hepatitis and residence in certain European countries.

   [21 CFR 211.22, 21 CFR 211.100(b), 21 CFR 640.3(a), Decree Paragraphs III.B.1., X.; FDA 483 observations 21, 22, 23, 24]

   FDA first notified ARC of similar deviations pertaining to inventory management in the October 20, 1999 VI.A. letter issued following the inspection of ARC’s Southern Region.  Additionally, FDA investigators observed these same types of inventory management deviations during the February-April 2000 inspection of BHQ.  More recently, inventory management deviations were brought to ARC’s attention in the October 19, 2001 VI.A. letter FDA issued following the inspection of ARC’s Salt Lake City facility and in the July 31, 2002 VI.A. letter FDA issued following the inspection of the ARC’s Greater Chesapeake and Potomac Region.

   LABELING:

6. ARC failed to establish and implement procedures to ensure that blood products are labeled correctly.  ARC also failed to investigate and correct deviations involving mislabeled blood products.  For example,
   1. Between April and July 2001, regions reported 29 deviations relating to release of blood products labeled with incorrect CMV test results.  BHQ did not assess those deviations and implemented no corrective action.
   2. On June 12, 2002, a region incorrectly labeled and subsequently distributed three blood products as CMV negative.
   3. On July 9, 2002, another region incorrectly labeled and subsequently distributed one blood product as CMV negative.    

   [21 CFR 211.22, 21 CFR 211.130, 21 CFR 606.122(h), Decree Paragraphs III.B.1.,X.; FDA observations 31, 32, 37, 38]

7. ARC failed to establish and implement adequate labeling procedures, including safeguards to prevent labeling mix-ups and to correct deviations, such as discrepant blood types caused by test tube mix-ups, different BDRs associated with the same whole blood number, and different whole blood numbers on primary and satellite bags.

   [21 CFR 211.22, 21 CFR 606.100(b)(16), 21 CFR 606.120(b)(3), 21 CFR 606.160(c), Consent Decree Paragraph III.B.1; FDA 483 observations 95, 96, 101, 102]

   FDA investigators observed similar deficiencies, involving CMV labeling and labeling mix-ups, during the February-April 2000 inspection of BHQ.

   NATIONAL DONOR DEFERRAL REGISTRY and DONOR FILE CHECK:

8. ARC failed to establish and implement an adequate procedure to ensure maintenance of a record from which unsuitable donors may be identified so that products from such donors will not be distributed.  For example,
   1. Two National Biomedical Computer System (NBCS) queries run in May 2000 found more than 3,000 unsuitable donors who were not included in the National Donor Deferral Registry (NDDR).  A query run in March 2001 found 39 donors who had not been screened against the NDDR.
   2. On February 27, 2001, BHQ failed to enter three deferred donors into the March 2001 Donor Deferral Registry (DDR) cycle, resulting in those donors not appearing in the NDDR until April 2001.   
   3. On May 3, 2001, BHQ failed to compare the NDDR and each regional copy of the NDDR, in accordance with ARC’s procedures, resulting in 30 discrepant records in the March 2001 DDR cycle.
   4. ARC’s procedure failed to describe the complete donor file check process that must be performed by regions in order to identify any donations accepted from donors who should have been deferred, but whose names had not been properly placed in the NDDR.
   5. ARC procedures fail to include a time frame for completion of donor file check processes, resulting in delay of recall of unsuitable blood products.  BHQ allowed the regions up to one year to complete donor file check for two lists of donors.  The results of that donor file check included three donors who were not properly placed in the NDDR and who had donated after having been determined to be unsuitable.
   6. Effective March 28, 2002, ARC procedures state that certain categories of donors may be omitted from the monthly donor file check process.  Those categories include donors who are at high risk for HIV, hepatitis, and CJD.

   [21 CFR 606.100(b), 21 CFR 606.160(e), 21 CFR 211.22, Decree Paragraphs III.B.1., III.B.12., III.B.13.e.; FDA 483 observations 40, 42, 43, 44, 48, 49, 50, 51, 53]

   FDA investigators also noted similar deficiencies relating to the NDDR and donor file check process during the February-April 2000 inspection of BHQ.

   AUTOASSERTION [REDACTED] SYPHILIS & OTHER COMPUTER SOFTWARE DEFICIENCIES:

9. ARC failed to maintain a record of unsuitable donors so that products from such individuals will not be distributed.  For example,
   1. On January 31, 2002, a NBCS query determined that 11 donations did not have the correct [REDACTED] deferral code for syphilis.
   2. NBCS queries run on July 26, 2001 and in February 2002 determined that approximately 1,500 donor records with positive test results for HIV did not have the appropriate defer ral code.
   3. An undated NBCS query identified 796 records without a deferral code for unacceptable health history.

   [21 CFR 606.160(e), Decree Paragraphs III.B.1, III.B.12., III.B.13.e.; FDA 483 observations 58, 106, 107, 119]

10. ARC failed to maintain or review records of investigations of software problems.  For example,
    1. Records do not identify the individual who reviewed the results of a query run on NBCS records on July 26, 2001 to identify donor records without the appropriate deferral code for HIV positive test results.