I. Executive Summary

Licensed manufacturers of blood and blood components, including Source Plasma; unlicensed registered blood establishments; and transfusion services who had control over the product when the deviation occurred must submit Biological Product Deviation (BPD) reports to the Center for Biologics Evaluation and Research (CBER) (21 CFR 606.171). Manufacturers of licensed biological products other than blood and blood components (non-blood) who hold the biological product license for and had control over the product when the deviation occurred are also required to submit BPD reports (21 CFR 600.14). In addition, manufacturers of nonreproductive Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/P) regulated under section 361 of the Public Health Service Act are required to submit deviation reports (21 CFR Part 1271.350(b)). Detailed information concerning deviation reporting is available at http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/BiologicalProductDeviations/default.htm.

The purpose of the annual summary report is to provide detailed information regarding the number and types of reports received during the fiscal year. We compare the number and types of reports received to previous fiscal years and highlight changes in reporting from the previous year.

From October 1, 2007 through September 30, 2008 (FY08), CBER’s Office of Compliance and Biologics Quality/Division of Inspections and Surveillance entered 44,740 deviation reports into the BPD database:

• We received more than 44,740 reports, but did not capture data for reports that did not meet the reporting threshold. We notified the reporter when a report was not required.
• There was a 3% increase in the number of reports received in FY08 compared to FY07 {Table 2}
  • We received 3% more reports from blood and plasma establishments in FY08 compared to FY07 {Table 2}

• • We received 8% more reports from traditional non-blood product manufacturers in FY08 compared to FY07 {Table 2}
  • We received 46% more reports from HCT/P manufacturers in FY08 compared to FY07 {Table 2}
• The number of reporting establishments increased by 6% compared to FY07 {Table 2}
  • Unregistered transfusion services typically report few BPDs (67% of those reporting in FY08 submitted 1 or 2 reports) and may file no reports in a given year. Only 14% of the transfusion services submitted more than five reports during FY08.
  • The percentage of establishments reporting electronically remained the same as the previous year {Table 6}. We continue to encourage electronic reporting.
• The percentage of reports submitted electronically remained the same as the previous year {Table 7}. There was an increase in the percentage of reports submitted electronically from blood derivative manufactures (FY07-56%, FY08-80%) and in-vitro diagnostic manufacturers (FY07-77%, FY08-80%).
• Reports of post-donation information (PDI) continue to represent the largest subset of BPD reports submitted by blood and plasma establishments (68%) {Table 8}. Most often (86%), the collection facility becomes aware of disqualifying information during a subsequent donation interview {Table 10}. In 93% of the PDI reports, the donor was aware of the information, but the donor screening process failed to elicit the information {Table 11}. It is unclear why blood establishments are unable to elicit information during the first donor interview, but successfully elicit the information during a subsequent interview. It is clear that the most common PDI relates to travel (38%). Eliciting proper information regarding a donor candidate’s travel history is apparently the most problematic part of the donor qualification process. We encourage blood establishments to review their donor screening processes to reduce the frequency of PDI reports. We also encourage those who implement successful strategies to share their information so that others may also fashion promising strategies to reduce PDI in their system.
  • Blood establishments submitted 3,718 fewer reports in FY08 involving post donation information. A policy change implemented in October 2007 may have attributed to the decrease in post donation information reports. Following review by our Blood Safety Team CBER determined that BPD reports are not required for distributed products collected from a donor who either had a history of cancer or was diagnosed with cancer after donating. We found no evidence that the safety, purity or potency of these products may be affected. In addition, blood establishments submitted 677 fewer reports involving travel to malarial endemic areas or Variant Creutzfeldt-Jakob Disease (vCJD) risk areas.
  • Source plasma centers submitted 3,450 more reports in FY08 compared to FY07. Most of these reports involved donors who had a history of tattoo and/or piercing, history of non-sexual exposure to Hepatitis C, or tested positive at another center for an unspecified viral marker.
  • Table A illustrates the major differences in post donation information reports from FY07 to FY08. It does not include all post donation information reports.

Table A

• We sent 2,399 (5.4%) reports to FDA District Offices for follow-up/evaluation as potential recalls {Table 1}. The number of reports identified as potential recall situations increased by 6% compared to FY07 {Table 2}. However, the percentage of the total reports that we identified as potential recall situations remained approximately the same.
  • Of the 2,399 reports blood and plasma establishments submitted, deviations and unexpected events that occur during the donor screening process continue to be the leading cause of potential recall situations (49%) {Table 9}
  • From the previous year, there was an 10% increase in the number of reports licensed blood establishments submitted and 59% increase in the number of reports licensed plasma centers submitted involving donor screening that were potential recall situations in FY08. Table B illustrates the most common potential-recall reports. It does not include all donor screening reports.

Table B

• The number of reports blood and plasma establishments submitted in which they distributed a unit collected from a donor who subsequently tested confirmed positive for a viral marker (on a later donation) increased by 38% from the previous year. The number of these reports submitted by blood establishments increased by 18% (FY07-721, FY08-852) and the number of these reports submitted by plasma establishments increased by 60% (FY07-646, FY08-1,038). The majority of this increase in reports involved donors who subsequently tested confirmed positive for Hepatitis B or Hepatitis C. CBER’s Blood Safety Team (BST) evaluated the notable increase in the number of BPDRs received in FY07 regarding donors who subsequently tested confirmed positive for a viral marker (specifically markers for HIV, HBV and HCV). The sub-committee requested seroconversion data for each of the markers from a few Source Plasma manufacturers, and a representative blood establishment. The data indicated that the shift was primarily due to increased donor activity and a shift in reporting patterns following release of our guidance in October 2006 (Ref. 1). It is not surprising that the trend has continued into FY08 because the reporting change began part the way through FY07. The BST will continue to evaluate. We encourage individual firms to evaluate seroconversion rates among their donor population. Table C illustrates the number of reports related to units collected from donors who subsequently tested confirmed positive for a viral maker. The table does not include all reports.

Table C

Reports Submitted by Blood Establishments

Reports Submitted by Plasma Establishments

• Allergenic manufacturers submitted five fewer reports in FY08 than in FY07 {Table 4}. Most of these reports involved product specifications not met, specifically, product contained precipitate.
• Blood Derivative manufacturers submitted 10 fewer reports in FY08 than in FY07 {Table 4}. Most of these reports involved product specifications not met, specifically, stability testing failures.
• Vaccine manufacturers submitted 37 more reports in FY08 than in FY07 {Table 4}. Most of these reports involved product specifications not met for appearance and stability testing failures.
• Cellular HCT/P manufacturers submitted 33 more reports in FY08 than in FY07 {Table 5}. Most of these reports involved processing and process controls, specifically related to contamination or potential contamination.
• Non-cellular HCT/P (tissue) manufacturers submitted 37 fewer reports in FY08 than in FY07 {Table 5}. Most of these reports involved donor eligibility.
• Manufacturers must submit deviation reports within 45 calendar days of the date of discovery of the reportable event. In FY08, manufacturers submitted 90% of the blood and plasma BPD reports, 82% of the non-blood BPD reports, and 73% of the HCT/P deviation reports within 45 days {Tables 27, 30, and 33}. FDA investigators review reporting practices during establishment inspections, and we continue to publicize reporting requirements through professional meetings.

You may submit questions concerning this summary 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 ,  hctp_deviations@fda.hhs.gov , or  sharon.ocallaghan@fda.hhs.gov (Sharon O’Callaghan) or by phone at 301-827-6220.

FY08

Table 1

 ¹ Unlicensed Blood Establishments – unlicensed blood establishments performing manufacturing of blood and blood components that require registration with FDA

 ² Transfusion Services – blood banks that perform limited blood and blood component manufacturing (e.g. pooling, thawing, compatibility testing), may or may not register with FDA.

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

Total Deviation Reports

FY06 - FY08

Table 2

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

Blood & Plasma BPD Reports By Manufacturing System

FY06 - FY08

Table 3

Non-Blood Deviation Reports By Manufacturing System

FY06 - FY08

Licensed Biological Products Other Than Blood and Blood Components

Table 4

Table 4 (continued)

361 HCT/Ps

Table 5

Non-Blood Deviation Reports By Manufacturing System

FY06 - FY08

Licensed Biological Products Other Than Blood and Blood Components

Table 4

Table 4 (continued)

361 HCT/Ps

Table 5

We implemented the on-line electronic deviation report form on June 18, 2001. In FY08, 80% of all the facilities filing reports filed at least some reports electronically. The portion of all reports submitted electronically in FY08 was the same as the previous year (FY07 - 90.6%). We continue to encourage all reporters to use the electronic reporting format.

Deviation Reports Submitted Electronically

Table 6

Percent of Electronic Deviation Reports

Table 7

† Reports of events involving products manufactured on or after 5/25/05 {implementation of 21 CFR 1271.350(b)}