Biological Product Deviation Reports

Annual Summary for Fiscal Year 2005

Printable version of this document

Table of Contents

  1. Executive Summary
  2. FY05: BPD Reports Submitted by Blood and Plasma Establishments
    1. Most Frequent BPD Reports Submitted by Licensed Blood Establishments
    2. Most Frequent BPD Reports Submitted by Unlicensed Blood Establishments
    3. Most Frequent BPD Reports Submitted by Transfusion Services
    4. Most Frequent BPD Reports Submitted by Plasma Centers
    5. Timeliness of BPD Reports
  3. FY05: BPD Reports Submitted by Manufacturers of Biological Products Other than Blood and Blood Components
  4. Attachments
    1. Number of BPD Reports by Type of Blood Establishment
    2. List of BPD Codes for Blood and Plasma
    3. Number of BPD Reports by Type of Non-Blood Manufacturer
    4. List of BPD Codes for Non-Blood

  1. Executive Summary:

    2. Biological Product Deviations (BPD) Reports must be submitted to the Center for Biologics Evaluation and Research (CBER) by licensed manufacturers of blood and blood components, including Source Plasma; unlicensed registered blood establishments; transfusion services who had control over the product when the deviation occurred (21 CFR 606.171), and by the non-blood manufacturer who holds the biological product license for and had control over the product when the deviation occurred (21 CFR 600.14). Detailed information concerning BPD reporting is available at www.fda.gov/cber/biodev/biodev.htm.

    From October 1, 2004 through September 30, 2005 (Fiscal Year 2005 or FY05), CBER's Office of Compliance and Biologics Quality/Division of Inspections and Surveillance entered 38,756 BPD reports into the BPD database:

    • We received more than 38,756 reports, but reports that did not meet the reporting threshold were not captured. The reporter was notified that a report was not required.
    • 38,372 reports were submitted by blood and plasma establishments, an increase of 1.4% above FY04 (37,830) {Table #2}.
    • 384 reports were submitted by non-blood manufacturers of biological products (allergenic, in-vitro diagnostic, derivative, or vaccine), an increase of 16% above FY04 (332) {Table #2}.
    • The number of reporting establishments decreased by 5% (1,479 establishments in FY04 and 1,409 establishments in FY05) {Table #2).
      • Unregistered transfusion services typically report few BPDs (67% of those reporting in FY04 and FY05 submitted 1 or 2 reports) and may file no reports (180 transfusion services that reported in FY04 did not report in FY03; 199 that reported in FY05 did not in FY04). Only 18% of the transfusion services submitted more than 5 reports during FY05.
      • The number of source plasma centers (individual registered locations) reporting in FY05 (286) decreased by 20% below FY04 (357). There was a corresponding 6% decrease in the number of reports submitted by plasma centers, from 5,115 in FY04 to 4,805 in FY05.
    • There was an increase of 3 percentage points in the number of establishments reporting electronically. (FY04 - 66% {970/1,479}; FY05 - 69% {974/1,409}). We continue to encourage electronic reporting.
    • Reports of post-donation information (PDI) continue to represent the largest subset of BPD reports submitted by blood and plasma establishments (72%) {Table #7}. Most often (90%), the blood collector is made aware during a subsequent donation interview {Table 9}. In 88% of the PDI reports the donor was aware of the information, but the donor screening process failed to elicit the information {Table #10}. It is unclear why information not elicited during the first donor screening is successfully elicited during a subsequent interview. It is clear that the most common PDI relates to travel (54%). Eliciting proper information regarding a donor candidate's travel history is apparently the most problematic part of the donor qualification process.
    • 2,271 (6%) of the reports received by CBER were sent to FDA District Offices for follow-up/evaluation as potential recall situations {Table #1}.
      • Of the 2,238 reports submitted by blood and plasma establishments, deviations and unexpected events that occur during the donor screening process continue to be leading cause of potential recall situations (43%) {Table #8}.
    • There was a 36% increase in the number of reports submitted by blood and plasma establishments in which a unit was distributed that was collected from a donor who subsequently tested confirmed positive for HCV (FY03 - 154, FY04 - 244, FY05 - 333). Based the number of questions we received regarding the requirement to report this event, we believe the increase was most likely due to under reporting of this type of event in the previous year, rather than an increase in the number of donors who subsequently tested confirmed positive for any viral marker.
    • The number of reports submitted by blood and plasma establishments involving donor screening decreased by 19% (FY04 - 2,007, FY05 - 1,628) {Table #3}.
      • The number of reports involving records which were incomplete, incorrect, or not reviewed related to donor history questions decreased by 32% (FY04 - 478, FY05 - 324).
      • The number of reports in which a donor provided disqualifying information regarding travel to a malarial endemic area and was inappropriately accepted decreased by 15% (FY04 - 461, FY05 - 391).

    BPD reports must be submitted within 45 calendar days of the date of discovery of the reportable event. In FY05, 87% of the blood BPD reports and 75% of the non-blood BPD reports were submitted within 45 days {Tables #26 and #30}. The number of reports submitted by non-blood manufacturers within 45 days increased by 6% (226/330 {69%} in FY04). FDA investigators review reporting practices during establishment inspections and we continue to publicize reporting requirements through professional meetings and publications.

    FDA published two draft guidance documents in FY01 to assist industry in determining what events are reportable1,2. We are evaluating the comments received concerning these drafts and anticipate publication of final guidance in the near future.

    Questions concerning this summary may be submitted to:
    FDA/Center for Biologics Evaluation and Research
    Office of Compliance and Biologics Quality
    Division of Inspections and Surveillance (HFM-650)
    1401 Rockville Pike, Suite 200 North
    Rockville , Maryland 20852-1448

    You may also contact us by email at bp_deviations@fda.hhs.gov, sharon.ocallaghan@fda.hhs.gov (Sharon O'Callaghan), or susan.cannon@fda.hhs.gov (Sue Cannon) or by phone at 301-827-6220.

    Attachments

    1. Number of BPD Reports by Type of Blood Establishment
    2. List of BPD Codes for Blood and Plasma
    3. Number of BPD Reports by Type of Non-Blood Manufacturer
    4. List of BPD Codes for Non-Blood

    Footnotes

    1Guidance for Industry - Biological Product Deviation Reporting for Blood and Plasma Establishments 8/11/2001
    2Guidance for Industry - Biological Product Deviation Reporting for Licensed Manufacturers of Biological Products Other than Blood and Blood Components 8/11/2001

    Total BPD Reports
    FY05

    Table 1

      Number Of Reporting Establishments Total Reports Received Potential Recalls
    Blood/Plasma Manufacturers        
    Licensed Blood Establishments 230(115*) 28,153 1,925 6.8%
    Unlicensed Blood Establishments 1 392 3,897 44 1.1%
    Transfusion Services 2 457 1,517 0 0%
    Plasma Centers 286(53*) 4,805 269 5.6%
    Sub-Total 1,365 38,372 2,238 5.8%
    Non-Blood Manufacturers        
    Allergenic 8 200 13 6.5%
    Blood Derivative 14 47 2 4.2%
    In-Vitro Diagnostic 11 100 18 18.0%
    Vaccine 11 37 0 0%
    Sub-Total 44 384 33 8.6%
    Total 1,409 38,756 2,271 5.9%

    1Unlicensed Blood Establishments - unlicensed blood establishments performing manufacturing of blood and blood components that require registration with FDA
    2 Transfusion Service - blood banks that perform limited blood and blood component manufacturing (e.g. pooling, thawing, compatibility testing), may or may not be registered with FDA.
    *Number of license holders; one or more establishments operate under one biologics license.

    Total BPD Reports
    FY02 - FY04

    Table 2

      Number Of Reporting Establishments Total Reports Received Potential Recalls
    Blood/Plasma Manufacturers FY03 FY04 FY05 FY03 FY05 FY05 FY03 FY04 FY05
    Licensed Blood Establishments 236(125*) 237(117*) 230(115*) 28,361 27,621 28,153 1,598 2,170 1,925
    Unlicensed Blood Establishments 374 371 392 3,022 3,502 3,897 53 58 44
    Transfusion Services 499 468 457 1,502 1,592 1,517 0 0 0
    Plasma Centers 378(59*) 357(55*) 286(53*) 7,611 5,115 4,805 635 377 269
    Sub-Total 1,487 1,433 1,365 40,496 37,830 38,372 2,286 2,605 2,238
    Non-Blood Manufacturers                  
    Allergenic 9 9 8 165 158 200 3 5 13
    Blood Derivative 19 17 14 56 44 47 5 4 2
    In-Vitro Diagnostic 7 10 11 44 86 100 4 8 18
    Vaccine 12 9 11 56 42 37 5 1 1
    Sub-Total 56 46 44 339 332 384 19 18 33
    Total 1,543 1,479 1,409 40,835 38,162 38,756 2,305 2,623 2,271

    * Number of license holders; one or more establishments operate under one biologics license.

    Blood & Plasma BPD Reports By Manufacturing System
    FY03 - FY05

    Table 3

    MANUFACTURING SYSTEM FY03 FY04 FY05
    DONOR SUITABILITY 32,443 80.1% 28,952 76.5% 29,148 76.0%
        POST DONATION INFORMATION 30,321 74.9% 26,854 71.0% 27,452 71.5%
        DONOR SCREENING 2,030 5.0% 2,007 5.3% 1,628 4.2%
        DONOR DEFERRAL 92 0.2% 91 0.2% 68 0.2%
    QC & DISTRIBUTION 2,705 6.7% 3,740 9.9% 3,934 10.3%
    LABELING 2,430 6.0% 2,415 6.4% 2,405 6.3%
    LABORATORY TESTING 1,126 2.8% 1,122 3.0% 981 2.6%
        ROUTINE TESTING 1,037 2.6% 1,027 2.7% 912 2.4%
        VIRAL TESTING 89 0.2% 95 0.3% 69 0.2%
    COLLECTION 1,133 2.8% 851 2.2% 972 2.5%
    COMPONENT PREPARATION 371 0.9% 368 1.0% 407 1.1%
    MISCELLANEOUS 288 0.7% 382 1.0% 525 1.4%
    TOTAL 40,496 100% 37,830 100% 38,372 100%

    Non-Blood BPD Reports By Manufacturing System
    FY03 - FY05

    Table 4

    Manufacturing System Allergenic Derivative In-Vitro Diagnostic
      FY03 FY04 FY05 FY03 FY04 FY05 FY03 FY04 FY05
    Incoming Material 1 2 0 1 9 9 2 5 4
    Process Controls 0 2 1 6 9 5 9 20 18
    Testing 0 0 0 8 0 3 7 14 17
    Labeling 5 8 22 1 3 15 10 16 24
    Product Specifications 158 146 177 31 15 11 10 23 30
    Quality Control & Distribution 1 0 0 7 7 4 5 6 7
    Miscellaneous 0 0 0 0 1 0 1 2 0
    TOTAL 165 158 200 56 44 47 44 86 100

     

    Manufacturing System Vaccine Total
      FY03 FY04 FY05 FY03 FY04 FY05
    Incoming Material 4 1 1 11 17 14
    Process Controls 1 7 4 16 38 28
    Testing 12 4 1 27 18 21
    Labeling 15 10 12 31 37 73
    Product Specifications 21 17 17 210 201 235
    Quality Control & Distribution 2 1 2 15 14 13
    Miscellaneous 1 2 0 2 5 0
    TOTAL 56 42 37 321 330 384

    The on-line electronic BPD report form was implemented on June 18, 2001. The percentage of reports submitted electronically in FY05 increased by 5.4 percentage points from FY04 (from 56.5% to 61.9%). We continue to encourage all reporters to use the electronic reporting format.

    BPD Reports Submitted Electronically

    Table 5

      Total Reports # of eBPDR % eBPDR
    BLOOD/PLASMA MANUFACTURERS      
    LICENSED BLOOD ESTABLISHMENTS 28,153 16,501 58.6%
    UNLICENSED BLOOD ESTABLISHMENTS 3,897 3,537 90.8%
    TRANSFUSION SERVICES 1,517 1,212 79.9%
    PLASMA CENTERS 4,805 2,482 51.7%
    SUB-TOTAL 38,372 23,732 61.8%
    NON-BLOOD MANUFACTURERS      
    ALLERGENIC 200 187 93.5%
    DERIVATIVE 47 14 29.8%
    IN-VITRO DIAGNOSTIC 100 53 53.0%
    VACCINE 37 2 5.4%
      SUB-TOTAL 384 256 66.5%
    TOTAL 38,756 23,988 61.9%

    Percent of Electronic BPD Reports

    Table 6

      FY03 FY04 FY05
    BLOOD/PLASMA MANUFACTURERS      
    LICENSED BLOOD ESTABLISHMENTS 41.8% 52.1% 58.6%
    UNLICENSED BLOOD ESTABLISHMENTS 84.2% 88.9% 90.8%
    TRANSFUSION SERVICES 75.5% 81.9% 79.9%
    PLASMA CENTERS 28.3% 49.6% 51.7%
    SUB-TOTAL 43.7% 56.4% 61.8%
    NON-BLOOD MANUFACTURERS      
    ALLERGENIC 60.0% 81.6% 93.5%
    DERIVATIVE 19.3% 50.0% 29.8%
    IN-VITRO DIAGNOSTIC 72.7% 65.1% 53.0%
    VACCINE 8.9% 14.3% 5.4%
    SUB-TOTAL 45.9% 64.2% 66.5%
    TOTAL 43.7% 56.5% 61.9%

    II. FY05: BPD Reports Submitted By Blood And Plasma Establishments:

    Total BPDs By Manufacturing System

    Table 7

    Manufacturing System Licensed Establishments Unlicensed Establishments Transfusion Services Plasma Centers Total
    DS-Post Donation Information 22,498 530 NA 4,424 27,452 71.5%
    QC & Distribution 1,486 1,618 727 103 3,934 10.3%
    Labeling 854 1,052 492 7 2,405 6.3%
    DS-Donor Screening 1,272 169 NA 187 1,628 4.2%
    Blood Collection 931 39 NA 2 972 2.5%
    LT-Routine Testing 228 391 292 1 912 2.4%
    Miscellaneous 455 6 0 64 525 1.4%
    Component Preparation 320 81 6 0 407 1.1%
    LT-Viral Testing 60 8 NA 1 69 0.2%
    DS-Donor Deferral 49 3 NA 16 68 0.2%
    TOTAL 28,153 3,897 1,517 4,805 38,372 100%

    DS - Donor Suitability
    LT - Laboratory Testing
    NA - Not applicable: manufacturing not performed in transfusion service

    Potential Recalls By Manufacturing System

    Table 8

    Manufacturing System Licensed Establishments Unlicensed Establishments Transfusion Services Plasma Centers Total
    DS-Donor Screening 786 24 NA 148 958 42.8%
    QC & Distribution 579 6 0 91 676 30.2%
    Component Preparation 172 7 NA 0 179 8.0%
    Blood Collection 174 1 NA 1 176 7.9%
    Labeling 74 3 0 0 77 3.4%
    DS-Post Donation Information 44 1 NA 18 63 2.8%
    DS-Donor Deferral 36 2 NA 11 49 2.2%
    LT-Viral Testing 33 0 NA 0 33 1.5%
    LT-Routine Testing 26 0 0 0 26 1.2%
    Miscellaneous 1 0 0 0 1 0.0%
    TOTAL 1,925 44 0 269 2,238 100%

    DS - Donor Suitability
    LT - Laboratory Testing
    NA - Not applicable: manufacturing not performed in transfusion service

    Post donation information (PDI) continues to be the most frequently reported event associated with the manufacturing of blood and plasma products. The most common PDI involved donors providing information concerning travel to malarial endemic areas and travel to an area at potential risk for vCJD. It is unclear why information not elicited during the first donor interview is successfully elicited during a subsequent interview. Eliciting proper information regarding a donor candidate's travel history is apparently the most problematic part of the donor qualification process.

    FY05 Reports of Post Donation Information (PDI)

    Table 9

    PDI OBTAINED THROUGH: LICENSED ESTABLISHMENTS UNLICENSED ESTABLISHMENTS PLASMA CENTERS TOTAL
    Subsequent Donation 20,450 468 3,729 24,648 89.8%
    Telephone Call from Donor 1,429 56 30 1,515 5.5%
    Third Party (e.g., doctor, family) 393 6 665 1,064 3.9%
    Telerecruitment 226 0 0 226 0.8%
    TOTAL 22,498 530 4,424 27,452 100%

    Table 10

    THE PDI WAS: LICENSED ESTABLISHMENTS UNLICENSED ESTABLISHMENTS PLASMA CENTERS TOTAL
    Known, but not Provided at Time of Donation* 20,132 435 3630 24,197 88.1%
    Not Known at Time of Donation** 2,366 95 794 3,255 11.9%
    TOTAL 22,498 530 4,424 27,452 100%

      *Known, e.g., travel outside of U.S., tattoo or body piercing, history of cancer
    **Not known, e.g., post donation illness, cancer diagnosed post donation, sex partner participated in high risk behavior or tested positive

    REPORTING ISSUES

    In response to request for providing more useful information in the annual summary reports, this section addresses non-reportable events and problems in reporting.

    Non-Reportable Events

    Most of the non-reportable reports were submitted by blood establishments. The reports were determined to not meet the reporting threshold. The events were either not associated with manufacturing, did not affect the safety, purity or potency of the product, or involved products that were not distributed. Examples of events that were considered not reportable include:

    • Donor traveled to malarial endemic area and non-transfusable plasma product was the only product distributed.
    • Testing was not complete, but the unit was released using emergency release protocol.
    • No products were distributed.
    • The event occurred outside the control of the manufacturer, for example on the nursing floor.
    • Donor reported post donation cold or flu symptoms.
    • Allogeneic unit was issued when an autologous or directed unit was available.
    • Recipient had Transfusion Related Acute Lung Injury (TRALI).

    Coding Issues

    In some cases the incorrect deviation code was selected to capture the event. The most common errors in coding were:

    • Donor screening events were coded as post donation information. The event should only be coded as post donation information if the disqualifying information was not known by the blood center at the time of donation. If the disqualifying information is known and the donor is not appropriately deferred, the event should be coded as a donor screening deviation.
    • Events in which testing was not performed were coded as Routine Testing (incorrectly performed or interpreted) deviations instead of Quality Control & Distribution. For example, if a patient had a history of an antibody and the unit was not screened for the corresponding antigen, the deviation code should be QC9311 (Required testing not performed or documented for: antigen screen), not RT6106 (Testing performed, interpreted, or documented incorrectly for: antigen typing)
    • Blood Collection events in which a unit was distributed that was clotted (BC4305) were coded as QC & Distribution - associated product contained clots (QC9409). If the product that was clotted was distributed, the Blood Collection deviation code should be used. If the product (e.g., FFP) associated with a component that was clotted (e.g., RBC) was distributed, the QC & Distribution code should be used.
    • A number of reports involving units distributed in which bacterial detection testing was positive, not performed, incomplete or performed incorrectly were coded incorrectly. All events associated with bacterial detection testing should be coded as QC & Distribution; Distribution of product that did not meet specifications; Product with unacceptable (e.g., positive), undocumented, or incomplete product QC (QC9404).

    Product Information

    The incorrect number of units was listed on a number of reports. When identifying the number of units and components, the number of units should equal the number of donations. For example if the event involved 2 donations and each donation was manufactured into red blood cells, platelets and plasma, the number of units would be 2 and the number of components would be 6. Some reports listed the number of units as 6 and the number of components as 6.

    II. A. Most Frequent BPD Reports Submitted by Licensed Blood Establishments

    Of the 28,153 reports submitted by licensed blood establishments, 22,498 (79.9%) reports involved post donation information.

    • In FY05, the number of these reports increased by 3% (FY04 - 21,840).
    • The number of reports in which a donor subsequently provided information regarding travel to a CJD risk area decreased by 7% (FY04 - 6,053).
    • The number of reports in which a donor reported a subsequent diagnosis of cancer decreased by 24% (FY04 - 728).

    Most Frequent BPD Reports - Post Donation Information
    From Licensed Blood Establishments

    Table 11

    POST DONATION INFORMATION (PD)                       22,498 # Reports % of Total PD
    Behavior/History 20,168 89.64%
    Travel to malaria endemic area/history of malaria 6,562 29.17%
    Risk factors associated with Creutzfeldt-Jakob Disease (CJD) - travel 5,659 25.15%
    History of cancer 1,159 5.15%
    Donor received tattoo within 12 months of donation 817 3.63%
    Male donor had sex with another man 618 2.75%
    Received Proscar, Tegison or Accutane 603 2.68%
    History of disease 486 2.16%
    IV drug use 421 1.87%
    Donor received bone graft or transplant 418 1.86%
    Sex partner lived in or immigrated from an HIV Group O risk area 243 1.08%
    Illness 1,906 8.47%
    Post donation illness (not hepatitis, HIV, HTLV-I, STD, or cold/flu related) 1,261 5.60%
    Reaction at phlebotomy site 66 0.29%
    Babesiosis 28 0.12%
    Non-specific symptoms - possible West Nile Virus 27 0.12%
    West Nile Virus 7 0.03%
    Post donation diagnosis of cancer 551 2.45%
    Testing * 299 1.33%
    Tested reactive for Hepatitis C post donation 56 0.25%
    Tested reactive for HIV post donation 50 0.22%
    Tested reactive for Hepatitis B post donation 44 0.20%
    Tested reactive for HIV prior to donation 33 0.15%
    Tested reactive for hepatitis not specified, prior to donation 29 0.13%
    Not specifically related to high risk behavior 125 0.56%
    Donated to be tested or called back for test results 71 0.32%
    Donor does not want their blood used 53 0.24%

    *Includes: tested positive for viral marker either prior to or post donation

    Of the 28,153 reports submitted by licensed blood establishments, 1,486 (5.3%) reports involved quality control and distribution deviations and unexpected events.

    • In FY05, the number of these reports was similar to reports received in the previous fiscal year (FY04 - 1,452).
    • The number of reports involving the release of a product with unacceptable, undocumented, or incomplete product QC, specifically related to bacterial detection testing used as a quality control test, increased 58% (FY04 - 243).

    Most Frequent BPD Reports - Quality Control & Distribution
    From Licensed Blood Establishments

    Table 12

    QC & DISTRIBUTION (QC)                       1,486 # Reports % of Total (QC)
    Distribution of product that did not meet specifications 1,031 69.4%
    Product with unacceptable, undocumented, or incomplete product QC 553 37.2%
    Bacterial Detection Testing 385 25.9%
    Platelet count 66 4.4%
    White Blood Cell count 31 2.1%
    Product in which instrument QC or validation was unacceptable or not documented 104 7.0%
    Product released prior to resolution of discrepancy 88 5.9%
    Product identified as unsuitable due to a donor screening deviation or unexpected event 74 5.0%
    Product associated with product that contained clots or hemolysis 65 4.4%
    Shipping and storage 212 14.3%
    Product not packaged in accordance with specifications 61 4.1%
    No documentation that product was shipped or stored at appropriate temperature 38 2.6%
    Shipped at incorrect temperature 34 2.3%
    Distribution procedures not performed in accordance with blood bank transfusion service's specifications 116 7.8%
    Product not documented as issued in computer 31 2.1%
    Product not irradiated as required 20 1.4%
    Improper product selected for patient 16 1.1%
    Required testing incorrect, incomplete, or positive 50 3.4%
    Failure to quarantine unit due to medical history: 46 3.1%
    Post donation illness 16 1.1%
    Required testing not performed or documented 29 2.0%

    Of the 28,153 reports submitted by licensed blood establishments, 1,272 (4.5%) reports involved donor screening deviations and unexpected events.

    • In FY05, the number of these reports decreased by 21% (FY04 - 1,617). Specific areas in which there was a decrease in the number of report were as follows:
      • 51% decrease in reports in which the incorrect donor identification was used to check the deferral file or the deferral file was not checked, i.e., deferral screening not done (FY04 - 327, FY05 - 160)
      • 32% decrease in reports involving donor records which were incomplete, incorrect or not reviewed, specifically related to the donor history questions (FY04 - 399). Of the 268 reports related to donor history questions incomplete, incorrect or not reviewed, there were 22 reports related to the use of an abbreviated donor history questionnaire when a full-length questionnaire should have been used compared to 60 reports in FY04.

    Most Frequent BPD Reports - Donor Screening
    From Licensed Blood Establishments

    Table 13

    DONOR SCREENING (DS)                1,272 # Reports % of Total DS
    Donor gave history which warranted deferral and was not deferred 705 55.4%
    Travel to malaria endemic area/history of malaria 362 28.5%
    Risk factors associated with Creutzfeldt-Jakob Disease (vCJD) - travel 110 8.6%
    Received medication or antibiotics 52 4.1%
    History of cancer 47 3.7%
    History of disease 24 1.9%
    Donor record incomplete or incorrect 337 26.5%
    Donor history questions 268 21.1%
    Donor identification 27 2.1%
    Arm inspection 14 1.1%
    Incorrect ID used during deferral search 145 11.4%
    Donor not previously deferred 122 9.6%
    Donor previously deferred due to history 12 0.9%
    Donor previously deferred due to testing 11 0.9%
    Donor did not meet acceptance criteria 65 5.1%
    Hemoglobin or Hematocrit unacceptable or not documented 32 2.5%
    Temperature unacceptable or not documented 26 2.0%
    Deferral screening not done 15 1.2%
    Donor previously deferred due to history 9 0.7%
    Donor previously deferred due to testing 5 0.4%
    Donor not previously deferred 1 0.1%

    Of the 28,153 reports submitted by licensed blood establishments, 931 (3.3%) reports involved blood collection deviations and unexpected events.

    • In FY05, the number of these reports increased by 17% (FY04 -798).
    • The number of reports in which a clotted product was discovered after distribution increased by 27% (FY04-511).

    Most Frequent BPD Reports - Blood Collection
    From Licensed Blood Establishments

    Table 14

    BLOOD COLLECTION (BC)                     931 # Reports % of Total BC
    Collection Process 762 81.8%
    Product contained clots, not discovered prior to distribution 647 69.5%
    Product hemolyzed, not discovered prior to distribution 51 5.5%
    Sterility compromised 96 10.3%
    Bacterial contamination 46 4.9%
    Air contamination 25 2.7%
    Arm prep not performed or performed inappropriately 24 2.6%
    Collection Bag 39 4.2%
    Apheresis collection device 25 2.7%

    Of the 28,153 reports submitted by licensed blood establishments, 854 (3.0%) reports involved labeling deviations and unexpected events.

    • In FY05, the number and distribution of these reports were similar to the reports received in the previous fiscal year (FY04 - 868).

    Most Frequent BPD Reports - Labeling
    From Licensed Blood Establishments

    Table 15

    LABELING (LA) 854 #Reports % of Total LA
    Blood unit labels 443 51.9%
    Extended expiration date or time 86 10.1%
    Volume incorrect or missing 66 7.7%
    ABO and/or Rh incorrect 50 5.9%
    Donor number or lot number incorrect or missing 43 5.0%
    Crossmatch tag or tie tag labels incorrect or missing information 375 43.9%
    Recipient identification missing or incorrect 245 28.7%
    Autologous unit 99 11.6%
    Crossmatch tag switched, both units intended for the same patient 20 2.3%
    Antigen incorrect or missing 18 2.1%
    Transfusion record (crossmatch slip) incorrect or missing information 35 4.1%
    Recipient identification missing or incorrect 15 1.8%

    II. B. Most Frequent BPD Reports Submitted by Unlicensed Blood Establishments

    Of the 3,897 reports submitted by unlicensed blood establishments, 1,618 (41.5%) involved quality control and distribution deviations and unexpected events.

    • In FY05, the number of these reports increased by 17% (FY04 - 1,381). This increase was associated with an increase by 83% in the number of reports in which a product was not documented as issued in the computer (FY04 - 237). This type of event is reportable if the computer system is used as the only documentation of the final checks of the issue process.
    • The number of reports involving the release of a product with unacceptable, undocumented or incomplete product QC, specifically associated with the implementation of bacterial detection testing used as a quality control test, increased from 46 reports in FY04 to 115 reports (86 reports involved bacterial detection testing) in FY05.

    Most Frequent BPD Reports - Quality Control & Distribution
    From Unlicensed Blood Establishments

    Table 16

    QC & Distribution (QC)                   1,618 # Reports % of Total QC
    Distribution procedures not performed in accordance with blood bank transfusion service's specifications 1,199 74.1%
    Product not documented as issued in the computer 434 26.8%
    Product not irradiated as required 173 10.7%
    Procedure for issuing not performed or documented in accordance with specifications 97 6.0%
    Improper product selected for patient 97 6.0%
    Improper ABO or Rh type selected for patient 92 5.7%
    Unit issued from the blood bank to wrong patient 62 3.8%
    Unit released prior to obtaining current sample for ABO, Rh, antibody screen and/or crossmatch testing 50 3.1%
    Required testing not performed or documented for: 181 11.2%
    Antigen screen 50 3.1%
    Antibody screen or identification 46 2.8%
    Compatibility 36 2.2%
    Distribution of product that did not meet specifications:: 180 11.1%
    Product with unacceptable, undocumented, or incomplete product QC 115 7.1%
    Bacterial Detection Testing 86 5.3%
    Outdated product 32 2.0%
    Product in which i nstrument QC or validation unacceptable or not documented 16 1.0%
    Required testing incomplete or positive: 33 2.0%
    Antibody screen or identification 16 1.0%
    Compatibility 5 0.3%
    Shipping and storage 22 1.4%
    Product not packaged in accordance with specifications 6 0.4%
    Stored at incorrect temperature 5 0.3%

    Of the 3,897 reports submitted by unlicensed blood establishments, 1,052 (27%) involved labeling deviations and unexpected events.

    • In FY05, the number of these reports was similar to the previous fiscal year (FY04 - 1,062).

    Most Frequent BPD Reports - Labeling
    From Unlicensed Blood Establishments

    Table 17

    LABELING (LA)                     1,052 # Reports % of Total LA
    Crossmatch tag or tie tag labels incorrect or missing information467 44.4%
    Recipient identification incorrect or missing 199 18.9%
    Crossmatch tag switched, both units intended for the same patient 87 8.3%
    Unit or pool number incorrect or missing 49 4.7%
    Crossmatch tag incorrect or missing 27 2.6%
    Expiration date or time extended or missing 22 2.1%
    Unit ABO and/or Rh incorrect or missing 21 2.0%
    Blood unit labels 276 26.2%
    Extended expiration date or time 120 11.4%
    Donor number or lot number incorrect or missing 43 4.1%
    ABO and/or Rh incorrect 36 3.4%
    Product type incorrect 20 1.9%
    Transfusion record (crossmatch slip) incorrect or missing information 309 29.4%
    Recipient identification incorrect or missing 70 6.7%
    Transfusion record switched, both units intended for the same patient 57 5.4%
    Unit or pool number incorrect or missing 53 5.0%
    Product type incorrect or missing 26 2.5%
    Expiration date or time extended or missing 26 2.5%

    Of the 3,897 reports submitted by unlicensed blood establishments, 530 (13.6%) reports involved post donation information.

    • In FY05, the number of these reports increased by 28% (FY04 - 413).
    • The number of reports of involving donor traveling to a malarial endemic area increased by 71% (FY04 - 100).

    Most Frequent BPD Reports - Post Donation Information
    From Unlicensed Blood Establishments

    Table 18

    POST DONATION INFORMATION (PD)                       530 # Reports % of Total PD
    Behavior/History 444 83.8%
    Travel to malaria endemic area/history of malaria 171 32.3%
    Risk factors associated with Creutzfeldt-Jakob Disease (CJD) - travel 98 18.5%
    History of cancer 25 4.7%
    Illness 70 13.2%
    Post donation illness (not hepatitis, HIV, HTLV-I, STD, or cold/flu related) 44 8.3%
    Post donation diagnosis of cancer 24 4.5%
    Testing* 16 3.0%

    * Includes: tested positive for viral marker either prior to or post donation


    Of the 3,897 reports submitted by unlicensed blood establishments, 391 (10%) reports involved routine testing deviations and unexpected events.

    • In FY05, the number and distribution of these reports were similar to the reports received in the previous fiscal years (FY02 - 407, FY03 - 404, FY03 - 386).

    Most Frequent BPD Reports - Routine Testing
    From Unlicensed Blood Establishments

    Table 19

    ROUTINE TESTING (RT)                     391 # Reports % of Total RT
    Incorrectly tested for: 269 68.8%
    Compatibility 85 21.7%
    Antibody screening or identification 83 21.2%
    Antigen typing 29 7.4%
    Rh 28 7.2%
    ABO 22 5.6%
    Sample (used for testing) identification 83 21.2%
    Sample used for testing was incorrectly or incompletely labeled 63 16.1%
    Unsuitable sample used for testing (e.g., too old) 10 2.6%
    Incorrect sample tested 9 2.3%
    Reagent QC unacceptable or expired reagents used 39 10.0%
    Antibody screening or identification 16 4.1%
    Antigen typing 7 1.8%
    ABO 6 1.5%

    II. C. Most Frequent BPD Reports Submitted by Transfusion Services

    Of the 1,517 reports submitted by transfusion services, 727 (47.9%) reports involved quality control and distribution deviations and unexpected events.

    • In FY05, the number of these reports was similar to the reports received in the previous fiscal year (FY04 - 743).

    Most Frequent BPD Reports - Quality Control & Distribution
    From Transfusion Services

    Table 20

    QC & Distribution (QC)                         727 # Reports % of Total QC
    Distribution procedures not performed in accordance with blood bank transfusion service's specifications 533 73.3%
    Product not documented as issued in the computer 256 35.2%
    Product not irradiated as required 63 8.7%
    Procedure for issuing not performed or documented in accordance with specifications 34 4.7%
    Improper ABO or Rh type selected for patient 33 4.5%
    Improper product selected for patient 36 5.0%
    Product released prior to obtaining current sample for ABO, Rh, antibody screen or compatibility testing 26 3.6%
    Unit issued from the blood bank to the wrong patient 23 3.2%
    Required testing not performed or documented for: 94 12.9%
    Antibody screen or identification 24 3.3%
    Antigen screen 25 3.4%
    ABO and Rh 19 2.6%
    Distribution of product that did not meet specifications: 56 7.7%
    Outdated product 21 2.9%
    Product with unacceptable, undocumented or incomplete product QC - pH for bacterial detection testing 25 3.4%
    Shipping and storage 26 3.6%
    Stored at incorrect temperature 11 1.5%
    Temperature not recorded or unacceptable upon receipt, unit redistributed 5 0.7%
    No documentation that product was shipped or stored at appropriate temperature 5 0.7%
    Product not packaged in accordance with specifications 3 0.4%
    Required testing incomplete or positive: 17 2.3%
    Antibody screen or identification 9 1.2%

    Of the 1,517 reports submitted by transfusion services, 492 (32.4%) reports involved labeling deviations and unexpected events.

    • In FY05, the number and distribution of these reports was similar to the reports received in the previous fiscal year (FY04 - 470).

    Most Frequent BPD Reports - Labeling
    From Transfusion Services

    Table 21

    LABELING (LA) 492 # Reports % of Total LA
    Crossmatch tag or tie tag labels incorrect or missing information 273 55.5%
    Recipient identification incorrect or missing 99 20.1%
    Crossmatch tag switched, both units intended for the same patient 41 8.3%
    Unit or pool number incorrect or missing 40 8.1%
    Crossmatch tag incorrect or missing 23 4.7%
    Unit ABO and/or Rh incorrect or missing 14 2.8%
    Expiration date or time extended or missing 11 2.2%
    Transfusion record (crossmatch slip) incorrect or missing information 156 31.7%
    Recipient identification incorrect or missing 45 9.1%
    Unit or pool number incorrect or missing 23 4.7%
    Transfusion record switched, both units intended for the same patient 22 4.5%
    Expiration date or time extended or missing 16 3.3%
    Blood unit labels 63 12.8%
    Expiration date or time extended or missing 29 5.9%
    ABO and/or Rh incorrect 13 2.6%
    Donor number or lot number incorrect or missing 6 1.2%

    Of the 1,517 reports submitted by transfusion services, 292 (19.2%) reports involved routine testing deviations and unexpected events.

    • In FY05, the number of these reports decreased by 21% (FY04 - 369).
    • The number of reports involving testing decreased by 14% (FY04 - 204).
    • The number of reports involving samples used for testing that were incorrectly or incompletely labeled decreased by 38% (FY04 - 128).

    Most Frequent BPD Reports - Routine Testing
    From Transfusion Services

    Table 22

    ROUTINE TESTING (RT)                     292 # Reports % of Total RT
    Incorrectly tested for: 175 59.9%
    Antibody screening or identification 61 20.9%
    Compatibility 52 17.8%
    Antigen typing 20 6.8%
    Rh typing 15 5.1%
    Sample (used for testing) identification 83 28.4%
    Sample used for testing was incorrectly or incompletely labeled 60 20.5%
    Incorrect sample tested 14 4.8%
    Unsuitable sample used for testing 9 3.1%
    Reagent QC unacceptable or expired reagents used 34 11.6%
    Antigen typing 8 2.7%
    Antibody screening or identification 6 2.1%
    Rh typing 6 2.1%
    ABO & Rh 6 2.1%
    Multiple testing 5 1.7%

    II. D. Most Frequent BPD Reports Submitted by Plasma Centers

    Of the 4,805 reports submitted by Source Plasma centers, 4,424 (92.1%) involved post donation information.

    • In FY05, the number of these reports decreased by 4% (FY04 - 4,601).
    • In FY04, 460 reports were submitted by 80 plasma centers that did not submit reports in FY05 due to closure of center.
    • The number of post donation information reports in which the donor was previously incarcerated decreased by 33% (FY04 - 494).

    Most Frequent BPD Reports - Post Donation Information
    From Plasma Centers

    Table 23

    POST DONATION INFORMATION (PD)                     4,424 # Reports % of Total PD
    Behavior/History 3,998 90.4%
    Donor received tattoo within 12 months of donation 1,579 35.7%
    Donor received body piercing within 12 months of donation 630 14.2%
    Incarcerated 330 7.5%
    Risk factors associated with Creutzfeldt-Jakob Disease (CJD) - travel 244 5.5%
    Donor received ear piercing within 12 months of donation 158 3.6%
    Sex partner tested reactive for HCV 129 2.9%
    Donor received tattoo and piercing within 12 months of donation 116 2.6%
    IV drug use 98 2.2%
    Testing * 294 6.6%
    Tested reactive for HCV post donation 91 2.1%
    Tested reactive at another center, specific testing unknown 78 1.8%
    Tested reactive for HIV post donation 76 1.7%
    Tested reactive for Hepatitis B post donation 35 0.8%

    * Includes testing positive for viral marker prior to or post donation

    Of the 4,805 reports submitted by Source Plasma centers, 187 (3.9%) reports involved donor screening deviations and unexpected events.

    • In FY05, the number of these reports decreased by 34% (FY04 - 285).
    • The number of reports in which the donor provided disqualifying information and was not deferred decreased by 71% (FY04 - 134).
    • The number of reports in which the donor record was incomplete, incorrect or not reviewed decreased by 40% (FY04 - 104).

    Most Frequent BPD Reports - Donor Screening
    From Plasma Centers

    Table 24

    DONOR SCREENING (DS)                         187 # Reports % of Total DS
    Donor record incomplete or incorrect 62 33.2%
    Donor history questions 42 22.5%
    Arm inspection 8 4.3%
    Donor identification 7 3.7%
    Donor signature missing 5 2.7%
    Donor gave history which warranted deferral and was not deferred 39 20.9%
    Donor received tattoo within 12 months of donation 11 5.9%
    Donor received body piercing within 12 months of donation 7 3.7%
    Risk factors associated with Creutzfeldt-Jakob Disease (vCJD) - travel 4 2.1%
    Donor received vaccine or immune globulin 2 1.1%
    Donor did not meet acceptance criteria 29 15.5%
    Temperature unacceptable or not documented 17 9.1%
    Medical review or physical not performed or inadequate 9 4.8%
    Deferral screening not done 48 25.7%
    Donor previously deferred due to history 29 15.5%
    IV drug user 6 3.2%
    Deferred by another center 3 1.6%
    Incarcerated 3 1.6%
    Donor previously deferred due to testing: 18 9.6%
    Elevated for ALT 7 3.7%
    Other-unknown 6 3.2%
    Incorrect ID used during deferral search 9

    4.8%
    Donor not previously deferred 4 2.1%
    Donor previously deferred due to history 3 1.6%
    Donor previously deferred due to testing 2 1.1%

    II. E. Timeliness of BPD Reports

    BLOOD AND PLASMA ESTABLISHMENTS
    Timeliness Of BPD Reports
    Number of Days From Date Discovered To Date FDA Received

    Table 25

    CUMULATIVE % OF REPORTS Licensed BB (Days) Unlicensed BB (Days) Transfusion Service (Days) Plasma Centers(Days) Total (Days)
    10% 11 3 1 14 9
    25% 20 10 6 24 19
    50% 30 24 18 34 30
    75% 39 41 39 40 40
    90% 47 58 54 44 47
    # REPORTS 28,153 3,897 1,517 4,805 38,372
    RANGE 0-2738 0-950 0-893 1-1504 0-2738
    AVERAGE 34 36 29 37 34
    # Reports lacking date discovered 1 1 1 0 0

    Adherence To 45 Day Required Timeframe For Reporting
    (Reporting Time = Date of FDA receipt - Date of discovery of BPD)

    Table 26

    Reporting Time (days) Licensed Establishments Unlicensed Establishments Transfusion Services Plasma Centers Total
    < or = 45 24565 87% 3203 82% 1281 85% 4363 91% 33412 87%
    > 45 and <=90 2951 11% 501 13% 168 11% 325 7% 3945 10%
    > 90 636 2% 192 5% 67 4% 117 2% 1012 3%
    Total 28,152 100% 3,896 100% 1,516 100% 4,805 100% 38,369 100%
    *Reporting time=0 18   78   59   0   155  

    *Reporting time = 0 - reports were submitted electronically on the day discovered.

    Graph showing BPDR reporing times from the day of discovery to FDA receipt for blood and plasma establishments in 2005

    Graph showing total BPDR reports from blood and plasma establishments and the reporting times range from less than 45 days to more than 90 days

    Graph showing BPDR reporting time and potential recalls ranging from less than 45 days to more than 90 and the percentage of reports

    III. FY05: BPD Reports Submitted by Manufacturers of Biological Products Other Than Blood and Blood Components (Non-Blood)

    The number of reports submitted by non-blood manufacturers was approximately the same as the previous fiscal year.

    • The number of reports submitted by in-vitro diagnostic, derivative and vaccine manufacturers, were similar to the number of reports submitted the previous year (FY04 - in-vitro diagnostic - 86, derivative - 44, vaccine - 42).
    • There was a slight increase in the number of reports submitted by Allergenic manufacturers (FY04 - 158).
      • 166 of 177 (94%) of product specification reports were related to precipitate discovered in allergenic extracts.

    Total BPD Reports By Manufacturing System

    Table 27

    MANUFACTURING SYSTEM Allergenic Derivative In-Vitro Diagnostic Vaccine TOTAL
    Incoming Material 0 9 4 1 14 3.6%
    Process Controls 1 5 18 4 28 7.3%
    Testing 0 3 17 1 21 5.5%
    Labeling 22 15 24 12 73 19.0%
    Product Specifications 177 11 30 17 235 61.2%
    Quality Control & Distribution 0 4 7 2 13 3.4%
    Miscellaneous 0 0 0 0 0 0.0%
    Total 200 47 100 37 384 100%

    Potential Recalls By Manufacturing System

    Table 28

    MANUFACTURING SYSTEM Allergenic Derivative In-Vitro Diagnostic TOTAL
    Incoming Material 0 1 1 2 6.1%
    Process Controls 0 1 1 2 6.1%
    Testing 0 0 0 0 0.0%
    Labeling 9 0 2 11 33.3%
    Product Specifications 4 0 12 16 48.5%
    Quality Control & Distribution 0 0 2 2 6.1%
    Miscellaneous 0 0 0 0 0.0%
    Total 13 2 18 33 100%

    NON-BLOOD MANUFACTURES
    Timeliness of BPD Reports
    Number Of Days From Date Discovered To FDA Received

    Table 29

    CUMULATIVE % OF REPORTS Allergenic (Days) Derivative (Days) In-Vitro Diagnostic (Days) Vaccine (Days) TOTAL (Days)
    10% 6 27 28 21 9
    25% 13 35 37 36 20
    50% 22 44 43 42 35
    75% 35 82 57 55 44
    90% 43 418 141 369 82
    # REPORTS 200 47 100 37 385
    RANGE 0-196 6-737 12-722 11-761 0-761
    AVERAGE 27 123 72 105 58
    # Reports lacking date discovered 0 0 1 0 1

    Adherence To 45 Day Required Time For Reporting
    (Reporting Time = Date of FDA receipt - Date of discovery of BPD)

    Table 30

    Reporting Time (days) Allergenics Derivatives In-Vitro Diagnostics Vaccines Total
    < or = 45 185 92% 24 51% 59 60% 21 57% 289 75%
    > 45 and <=90 11 6% 13 28% 22 22% 11 30% 57 15%
    > 90 4 2% 10 21% 18 18% 5 13% 37 10%
    Total 200 100% 47 100% 99 100% 37 100% 383 100%
    *Reporting time=0 1   0   0   0   1  

    *Reporting time = 0 - reports were submitted electronically on the day discovered.

    graph showing BPDR reporting time for non blood manufacturers ranging from 10 days to more than 500

    graph showing reporting time of the total reports received for non blood manufacturers

    graph showing reporting time of potential recalls by non blood manufacturers

    Attachments

    1. Number of BPD Reports by Type of Blood Establishments
    2. List of BPD Codes for Blood and Plasma Establishments
    3. Table-Number of BPDs by Type of Non-Blood Manufacturer
    4. List of BPD Codes for Non-Blood Manufacturers
 
Updated: May 22, 2006