Biological Product Deviation Reports

Annual Summary for Fiscal Year 2004

Table of Contents

1. Executive Summary
2. FY04: 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. FY04: 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 Manufacturers

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1. Executive Summary

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, 2003 through September 30, 2004 (Fiscal Year 2004 or FY04), CBER's Office of Compliance and Biologics Quality/Division of Inspections and Surveillance entered 38,162 BPD reports into the BPD database:

• We received more than 38,162 reports, but reports that did not meet the threshold for reporting were not captured in the database and the reporting establishment was notified that a report was not required.
• 37,830 reports were submitted by blood and plasma establishments, which was a decrease of 7% below FY03 (40,496).
• 332 reports were submitted by non-blood manufacturers of biological products (allergenic, in-vitro diagnostic, therapeutic, derivative, or vaccine), which was similar to the number of reports submitted in FY03 (339).
• The number of reporting establishments decreased by 4.1% (1,543 establishments in FY03 and 1,479 establishments in FY04).
• The number of transfusion services reporting in FY04 (468) decreased by 6% below FY03 (499). 208 transfusion services reported in FY03, but did not report in FY04 and 180 reported in FY04, but not in FY03. 68% of the transfusion services reporting in FY03 and FY04 only submitted 1 or 2 reports. Only 11% of the transfusion services submitted more than 5 reports during this reporting period.
• The number of plasma centers (individual registered locations) reporting in FY04 (357) decreased by 6% below FY03 (378), which resulted in a 33% decrease in the number of reports submitted by plasma centers, from 7,611 in FY03 to 5115 in FY04.
• The number of therapeutic biological manufacturers reporting decreased from 9 in FY03 to 1 in FY04 due to the transfer of regulatory responsibility for therapeutic biological products to CDER on June 30, 2003.
• There was an increase of 16% in the number of establishments reporting electronically. In FY04, 66% (970/1479) of the reporting establishments submitted reports electronically. In FY03, 53% (819/1543) of the reporting establishments submitted electronically. We continue to encourage electronic reporting.
• Reports of post-donation information (PDI) continue to represent the largest percentage of reports submitted by blood and plasma establishments (71%). In 88% of the PDI reports the donor was aware of the information at the time they were interviewed, but failed to provide the information during the interview. Most often (91%), the blood collector is made aware during a subsequent donation interview.
• The number of reports submitted by licensed blood establishments involving donor records which were incomplete, incorrect, or not reviewed increased by 71%. Of the 399 reports received in FY04, 60 reports related to use of the abbreviated donor history questionnaire when the full-length questionnaire should have been used.
• There was a 4-fold increase in the number of reports submitted by blood establishments involving the release of a product with unacceptable, undocumented, or incomplete product QC. There were 105 reports submitted in FY03 and 527 reports submitted in FY04. Of the reports submitted in FY04, 280 reports were related to the implementation of bacterial detection testing used as a quality control test.
• 2,623 (7%) of the reports received by CBER were sent to FDA District Offices for follow-up/evaluation as potential recall situations.
• Deviations and unexpected events that occur during the donor screening process continue to be leading cause of potential recall situations (48%).

BPD reports must be submitted within 45 calendar days of the date of discovery of the reportable event. In FY04, 89% of the blood BPD reports and 69% of the non-blood BPD reports were submitted within 45 days. 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 reportable. ^{1, 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@cber.fda.gov, ocallaghan@cber.fda.gov (Sharon O'Callaghan), or cannon@cber.fda.gov (Sue Cannon) or by phone at 301-827-6220.

Attachments:

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

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References

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

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FY04
Total BPD Reports

	Number of Reporting Establishments	Total Reports Received	Potential Recalls
Blood / Plasma Manufacturers
Licensed Blood Establishments	237 (117*)	27,621	2,170	7.9%
Unlicensed Blood Establishments 1	371	3,502	58	1.7%
Transfusion Services 2	468	1,592	0	0%
Plasma Centers	357 (55*)	5,115	377	7.4%
Sub-Total	1,433	37,830	2,605	6.9%
Non-Blood Manufacturers
Allergenic	9	158	5	3.2%
Blood Derivative	17	44	4	9.1%
In-Vitro Diagnostic	10	86	8	9.3%
Therapeutic	1	2	0	0%
Vaccine	9	42	1	2.4%
Sub-Total	46	332	18	5.4%
Total	1,479	38,162	2,623	6.9%

¹ Unlicensed 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.

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Total BPD Reports
FY02 - FY04

	Number of Reporting Establishments			Total Reports Received			Potential Recalls
Blood / Plasma Manufacturers	FY02	FY03	FY04	FY02	FY03	FY04	FY02	FY03	FY04
Licensed Blood Establishments	224 (169*)	236 (125*)	237 (117*)	21,852	28,361	27,621	1,481	1,598	2,170
Unlicensed Blood Establishments	383	374	371	5,142	3,022	3,502	157	53	58
Transfusion Services	472	499	468	1,304	1,502	1,592	2	0	0
Plasma Centers	361 (62*)	378 (59*)	357 (55*)	5,168	7,611	5,115	533	635	377
Sub-Total	1,440	1,487	1,433	33,466	40,496	37,830	2,173	2,286	2,605
Non-Blood Manufacturers
Allergenic	8	9	9	273	165	158	14	3	5
Blood Derivative	17	19	17	45	56	44	5	5	4
In-Vitro Diagnostic	11	7	10	93	44	86	13	4	8
Therapeutic	13	9	1	23	18	2	4	2	0
Vaccine	10	12	9	42	56	42	4	5	1
Sub-Total	59	56	46	476	339	332	40	19	18
Total	1,499	1,543	1,479	33,942	40,835	38,162	2,213	2,305	2,623

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

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Blood & Plasma BPD Reports By Manufacturing System
FY02 - FY04

Manufacturing System	FY02		FY03		FY04
Donor Suitability	25,312	75.6%	32,443	80.1%	28,952	76.5%
Post Donation Information	23,162	69.2%	30,321	74.9%	26,854	71.0%
Donor Screening	2,032	6.1%	2,030	5.0%	2,007	5.3%
Donor Deferral	118	0.4%	92	0.2%	91	0.2%
QC & Distribution	3,875	11.6%	2,705	6.7%	3,740	9.9%
Labeling	2,367	7.1%	2,430	6.0%	2,415	6.4%
Laboratory Testing	1,120	3.3%	1,126	2.8%	1,122	3.0%
Routine Testing	1,039	3.1%	1,037	2.6%	1,027	2.7%
Viral Testing	81	0.2%	89	0.2%	95	0.3%
Collection	207	0.6%	1,133	2.8%	851	2.2%
Component Preparation	424	1.3%	371	0.9%	368	1.0%
Miscellaneous	161	0.5%	288	0.7%	382	1.0%
Total	33,466	100%	40,496	100%	37,830	100%

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Non-Blood BPD Reports By Manufacturing System
FY02 - FY04

Manufacturing System	Allergenic			Derivative			In-Vitro Diagnostic
	FY02	FY03	FY04	FY02	FY03	FY04	FY02	FY03	FY04
Incoming Material	1	1	2	3	3	9	2	3	5
Process Controls	0	0	2	7	6	9	30	9	20
Testing	2	0	0	4	8	0	11	7	14
Labeling	29	5	8	4	1	3	11	10	16
Product Specifications	225	158	146	20	31	15	29	9	23
Quality Control & Distribution	15	1	0	7	7	7	7	5	6
Miscellaneous	1	0	0	0	0	1	3	1	2
Total	273	165	158	45	56	44	93	44	86

 

Manufacturing System	Therapeutic			Vaccine			Total
	FY02	FY03	FY04	FY02	FY03	FY04	FY02	FY03	FY04
Incoming Material	2	4	0	0	4	1	8	15	17
Process Controls	7	5	1	10	1	7	54	21	39
Testing	4	3	0	10	12	4	31	30	18
Labeling	1	4	0	3	15	10	48	35	37
Product Specifications	6	1	0	17	21	17	297	220	201
Quality Control & Distribution	3	1	1	2	2	1	34	16	15
Miscellaneous	0	0	0	0	1	2	4	2	5
Total	23	18	2	42	56	42	476	339	332

 

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The on-line electronic BPD report form was implemented on June 18, 2001. The percentage of reports submitted electronically in FY04 increased by 12.8 percentage points from FY03 (from 43.7% to 56.5%). We continue to encourage all reporters to use the electronic reporting format.

BPD Reports Submitted Electronically

	Total Reports	# of eBPDR	% eBPDR
Blood / Plasma Manufacturers
Licensed Blood Establishments	27,621	14,391	52.1%
Unlicensed Blood Establishments	3,502	3,114	88.9%
Transfusion Services	1,592	1,304	81.9%
Plasma Centers	5,115	2,537	49.6%
Sub-Total	37,830	21,346	56.4%
Non-Blood Manufacturers
Allergenic	158	129	81.6%
Derivative	44	22	50.0%
In-Vitro Diagnostic	86	56	65.1%
Therapeutic	2	0	0.0%
Vaccine	42	6	14.3%
Sub-Total	332	213	64.2%
Total	38,162	21,559	56.5%

Percent of Electronic BPD Reports

	FY02	FY03	FY04
Blood / Plasma Manufacturers
Licensed Blood Establishments	33.0%	41.8%	52.1%
Unlicensed Blood Establishments	39.2%	84.2%	88.9%
Transfusion Services	64.4%	75.5%	81.9%
Plasma Centers	17.8%	28.3%	49.6%
Sub-Total	32.8%	43.7%	56.4%
Non-Blood Manufacturers
Allergenic	49.5%	60.0%	81.6%
Derivative	6.7%	19.3%	50.0%
In-Vitro Diagnostic	31.2%	72.7%	65.1%
Therapeutic	21.7%	50.0%	0.0%
Vaccine	7.1%	8.9%	14.3%
Sub-Total	36.8%	45.9%	64.2%
Total	32.9%	43.7%	56.5%

Table of Contents

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2. FY04: BPD Reports Submitted By Blood And Plasma Establishments

Total BPD Reports By Manufacturing System

Manufacturing System	Licensed Establishments	Unlicensed Establishments	Transfusion Services	Plasma Centers	Total
DS - Post Donation Information	21,840	413	NA	4,601	26,854	71.0%
QC & Distribution	1,452	1,381	743	164	3,740	9.9%
Labeling	868	1,062	470	15	2,415	6.4%
DS - Donor Screening	1,617	105	NA	285	2,007	5.3%
LT - Routine Testing	272	386	369	0	1,027	2.7%
Blood Collection	798	47	NA	6	851	2.2%
Miscellaneous	370	2	0	10	382	1.0%
Component Preparation	277	81	10	0	368	1.0%
LT - Viral Testing	74	9	NA	12	95	0.3%
DS - Donor Deferral	53	16	NA	22	91	0.2%
Total	27,621	3,502	1,592	5,115	37,830	100%

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

Potential Recalls By Manufacturing System

Manufacturing System	Licensed Establishments	Unlicensed Establishments	Transfusion Services	Plasma Centers	Total
DS - Donor Screening	1,006	30	NA	221	1,257	48.3%
QC & Distribution	619	8	0	113	740	28.4%
Blood Collection	149	1	NA	6	156	6.0%
Component Preparation	150	2	NA	0	152	5.8%
Labeling	93	8	0	2	103	4.0%
DS - Post Donation Information	53	0	NA	11	64	2.5%
DS - Donor Deferral	37	5	NA	16	58	2.2%
LT - Viral Testing	42	3	NA	8	53	2.0%
LT - Routine Testing	20	1	0	0	21	0.8%
Miscellaneous	1	0	0	0	1	0.0%
Total	2,170	58	0	377	2,605	100%

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

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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.

FY04 Reports of Post Donation Information (PDI)

PDI Obtained Through:	Licensed Establishments	Unlicensed Establishments	Plasma Centers	Total
Subsequent Donation	19,850	355	4,145	24,350	90.7%
Telephone Call From Donor	1,523	46	13	1,582	5.9%
Third Party (e.g., doctor, family)	467	12	443	922	3.4%
Total	21,840	413	4,601	26,854	100%

 

The PDI Was:	Licensed Establishments	Unlicensed Establishments	Plasma Centers	Total
Known, but not Provided at Time of Donation *	19,160	311	4,086	23,557	87.7%
Not Known at Time of Donation **	2,680	102	515	3,294	12.3%
Total	21,840	413	4,601	26,854	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

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1. Most Frequent BPD Reports Submitted by Licensed Blood Establishments

Of the 27,621 reports submitted by licensed blood establishments, 21,840 (79.1%) reports involved post donation information.

• In FY04, the number of these reports decreased by 5.9% (FY03 - 23,211).
• The number of reports in which a donor subsequently provided information regarding travel to a CJD risk area decreased by 22% (FY03 - 7,794).
• The number of reports in which a donor reported a subsequent diagnosis of cancer increased by 38% (FY03 - 527).

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

Post Donation Information       21,840	# Reports	% of Total
Behavior / History	19,174	87.8%
Risk factors associated with Creutzfeldt-Jakob Disease (CJD) - travel	6,053	27.7%
Travel to malaria endemic area / history of malaria	5,303	24.3%
History of cancer	1,187	5.4%
Donor received tattoo within 12 months of donation	773	3.5%
History of disease	661	3.0%
Received Proscar, Tegison or Accutane	536	2.5%
Male donor had sex with another man	432	2.0%
IV drug use	418	1.9%
Donor received bone graft or transplant	353	1.6%
History of Jaundice	302	1.4%
Illness	2,175	10.0%
Post donation illness (not hepatitis, HIV, HTLV-I, STD, or cold/flu related)	1,266	5.8%
Post donation diagnosis of cancer	728	3.3%
Testing *	349	1.6%
Tested positive for hepatitis not specified, prior to donation	60	0.3%
Not specifically related to high risk behavior	142	0.7%
Donated to be tested or called back for test results	75	0.3%
Donor does not want their blood used	62	0.3%

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

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Of the 27,621 reports submitted by licensed blood establishments, 1,617 (5.9%) reports involved donor screening deviations and unexpected events.

• In FY04, the number of these reports increased by 25% (FY03 - 1,290).
• The number of reports involving donor records which were incomplete, incorrect or not reviewed, specifically related to the donor history questions increased from 233 in FY03 to 399 in FY04.
• There were 60 reports related to the use of an abbreviated donor history questionnaire when a full-length questionnaire should have been used.

Most Frequent BPD Reports - Donor Screening
From Licensed Blood Establishments

Donor Screening       1,617	# Reports	% of Total
Donor gave history which warranted deferral and was not deferred	775	48.9%
Travel to malaria endemic area / history of malaria	431	26.7%
Risk factors associated with Creutzfeldt-Jakob Disease (vCJD) - travel	89	5.5%
Received medication or antibiotics	58	3.6%
History of cancer	44	2.7%
History of disease	40	2.5%
Donor record incomplete, incorrect, or not reviewed	475	29.4%
Donor history questions	399	24.7%
Donor identification	37	2.3%
Donor signature	10	0.6%
Arm inspection	10	0.6%
Incorrect ID used during deferral search	278	17.2%
Donor not previously deferred	216	13.4%
Donor previously deferred due to history	33	2.0%
Donor previously deferred due to testing	29	1.8%
Donor did not meet acceptance criteria	39	2.4%
Hemoglobin or Hematocrit unacceptable or not documented	20	1.2%
Temperature unacceptable or not documented	10	0.6%
Deferral screening not done	49	3.0%
Donor previously deferred due to history	23	1.1%
Donor previously deferred due to testing	24	1.5%
Donor not previously deferred	2	0.1%

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Of the 27,621 reports submitted by licensed blood establishments, 1,452 (5.3%) reports involved quality control and distribution deviations and unexpected events.

• In FY04, the number of these reports increased by 69.2% (FY03 - 858).
• The number of reports involving the release of a product with unacceptable, undocumented, or incomplete product QC increased more than 3-fold (FY03 - 97). This was primarily due to the implementation of bacterial detection testing used as a quality control test.

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

QC & Distribution       1,452	# Reports	% of Total
Inappropriate release of:	966	66.5%
Product with unacceptable, undocumented or incomplete product QC	471	32.4%
Bacterial Detection Testing	243	16.7%
Platelet count	56	3.9%
White Blood Cell count	42	2.9%
Product in which instrument QC or validation was unacceptable or not documented	129	8.9%
Product released prior to resolution of discrepancy	96	6.6%
Product associated with product that contained clots or hemolysis	81	5.6%
Shipping and storage	219	15.1%
Product not packaged in accordance with specifications	56	3.9%
No documentation that product was shipped or stored at appropriate temperature	50	3.4%
Shipped at incorrect temperature	49	3.4%
Improper blood bank practices	127	8.8%
Failure to quarantine unit due to incorrect, incomplete, or positive testing	51	3.5%
Failure to quarantine unit due to medical history:	50	3.4%
Post donation illness	28	1.9%
Failure to quarantine unit due to testing not performed or documented	39	2.7%

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Of the 27,621 reports submitted by licensed blood establishments, 868 (3.1%) reports involved labeling deviations and unexpected events.

• In FY04, the number and distribution of these reports were similar to the reports received in the previous two fiscal years (FY02 - 948 ; FY03 - 949).

Most Frequent BPD Reports - Labeling
From Licensed Blood Establishments

Labeling       868	# Reports	% of Total
Blood unit labels	504	58.1%
Volume incorrect or missing	99	11.4%
Extended expiration date or time	93	10.7%
ABO and / or Rh incorrect	62	7.1%
Donor number incorrect or missing	59	6.8%
Crossmatch tag or tie tag labels incorrect or missing information	409	47.1%
Recipient identification missing or incorrect	231	26.6%
Autologous unit	105	12.1%
nit ABO and / or Rh incorrect or missing	12	1.4%
Crossmatch tag switched, both units intended for the same patient	12	1.4%
Unit or pool number incorrect or missing	11	1.3%
Transfusion record (crossmatch slip) incorrect or missing information	25	2.9%
Recipient identification missing or incorrect	10	1.2%

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Of the 27,621 reports submitted by licensed blood establishments, 798 (2.9%) reports involved blood collection deviations and unexpected events.

• In FY04, the number of these reports decreased by 25% (FY03 -1,067).
• The number of reports in which a clotted product was discovered after distribution decreased from 672 in FY03 to 511 in FY04.

Most Frequent BPD Reports - Blood Collection
From Licensed Blood Establishments

Blood Collection       798	# Reports	% of Total
Collection Process	641	80.3%
Product contained clots, not discovered prior to distribution	511	64.0%
Product hemolyzed, not discovered prior to distribution	79	9.9%
Sterility compromised	103	12.9%
Bacterial contamination	55	6.9%
Arm prep not performed or performed inappropriately	24	3.0%
Collection Bag	28	3.5%
Apheresis collection device	15	1.9%

Table of Contents

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2. Most Frequent BPD Reports Submitted by Unlicensed Blood Establishments

Of the 3,502 reports submitted by unlicensed blood establishments, 1,381 (39%) involved quality control and distribution deviations and unexpected events.

• In FY04, the number of these reports increased by 35% (FY03 - 1,022). This increase was due to an increase in the number of reports in which a product was not documented as issued in the computer. 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 8 reports in FY03 to 46 reports (27 reports involved bacterial detection testing) in FY04.

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

QC & Distribution       1,381	# Reports	% of Total
Improper blood bank practices	997	96.9%
Product not documented as issued in the computer	237	23.0%
Product not irradiated as required	184	17.9%
Procedure for issuing not performed or documented in accordance with specifications	101	9.8%
Improper product selected for patient	86	8.4%
Improper ABO or Rh type selected for patient	69	6.7%
Product not leukoreduced as required	61	5.9%
Unit issued from the blood bank to wrong patient	55	5.3%
Unit released prior to obtaining current sample for ABO, Rh, antibody screen and / or crossmatch testing	52	5.1%
Failure to quarantine unit due to testing not performed or documented for:	184	17.9%
Antigen screen	50	4.9%
Antibody screen or identification	34	3.3%
ABO and Rh	28	2.7%
Inappropriate release of:	122	11.9%
Product with unacceptable, undocumented, or incomplete product QC	46	4.5%
Product in which instrument QC or validation unacceptable or not documented	22	2.1%
Outdated product	19	1.9%
Failure to quarantine due to incorrect, incomplete, or positive testing:	44	4.3%
Compatibility	16	1.6%
Antibody screen or identification	12	1.2%
Shipping and storage	40	3.9%
Stored at incorrect temperature	12	1.2%
Product not packaged in accordance with specifications	8	0.8%

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Of the 3,502 reports submitted by unlicensed blood establishments, 1,062 (30%) involved labeling deviations and unexpected events.

• In FY04, the number of these reports increased by 8% (FY03 - 974).
• There was an increase in the number of reports in which the recipient identification was incorrect or missing on the crossmatch tag and/or transfusion record, from 211 reports in FY03 to 246 reports in FY04.
• There was an increase in the number of reports in which the crossmatch tag and/or the transfusion record were switched, but both units were intended for the same patient, from 101 reports in FY03 to 139 reports in FY04.

Most Frequent BPD Reports - Labeling
From Unlicensed Blood Establishments

Labeling       1,062	# Reports	% of Total
Crossmatch tag or tie tag labels incorrect or missing information	517	48.7%
Recipient identification incorrect or missing	196	18.5%
Crossmatch tag switched, both units intended for the same patient	90	8.5%
Unit or pool number incorrect or missing	52	4.9%
Expiration date or time extended or missing	27	2.5%
Crossmatch tag incorrect or missing	24	2.3%
Unit ABO and / or Rh incorrect or missing	24	2.3%
Blood unit labels	279	26.3%
Extended expiration date or time	139	13.1%
Donor number incorrect or missing	37	3.5%
ABO and / or Rh incorrect	33	3.1%
Product type incorrect	20	1.9%
Transfusion record (crossmatch slip) incorrect or missing information	265	25.0%
Recipient identification incorrect or missing	50	4.7%
Transfusion record switched, both units intended for the same patient	49	4.6%
Unit or pool number incorrect or missing	43	4.1%

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Of the 3,502 reports submitted by unlicensed blood establishments, 413 (12%) reports involved post donation information.

• In FY04, the number of these reports increased by 11% (FY03 - 373).
• The number of reports of post donation illness increased from 28 in FY03 to 71 in FY04.

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

Post Donation Information       413	# Reports	% of Total
Behavior / History	324	78.5%
Travel to malaria endemic area / history of malaria	100	24.2%
Risk factors associated with Creutzfeldt-Jakob Disease (CJD) - travel	99	24.0%
History of cancer	15	3.6%
Illness	71	17.2%
Post donation illness (not hepatitis, HIV, HTLV-I, STD, or cold/flu related)	43	10.4%
Post donation diagnosis of cancer	24	5.8%
Testing *	15	3.6%

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

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Of the 3,502 reports submitted by unlicensed blood establishments, 386 (11.0%) reports involved routine testing deviations and unexpected events.

• In FY04, the number and distribution of these reports were similar to the reports received in the previous fiscal years (FY02 - 407, FY04 - 404).

Most Frequent BPD Reports - Routine Testing
From Unlicensed Blood Establishments

Routine Testing       386	# Reports	% of Total
Incorrectly tested for:	227	58.8%
Compatibility	88	22.8%
Antibody screening or identification	63	16.3%
Antigen typing	20	5.2%
ABO	12	3.1%
Sample (used for testing) identification	117	30.3%
Sample used for testing was incorrectly or incompletely labeled	86	22.3%
Unsuitable sample used for testing (e.g., too old)	17	4.4%
Incorrect sample tested	14	3.6%
Reagent QC unacceptable or expired reagents used	41	10.6%
Multiple testing	12	3.1%
Antibody screening or identification	10	2.6%
Antigen typing	8	2.1%
ABO	5	1.3%

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3. Most Frequent BPD Reports Submitted by Transfusion Services

Of the 1,592 reports submitted by transfusion services, 743 (47%) reports involved quality control and distribution deviations and unexpected events.

• In FY04, the number of these report was similar to the reports received in the previous fiscal year (FY03 - 681).
• There was an increase in the number of reports in which a product was not documented as issued in the computer. There were 77 reports submitted in FY03 and 208 reports submitted in FY04. This type of event is reportable if the computer system is used as the only documentation of the final checks of the issue process.

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

QC & Distribution       743	# Reports	% of Total
Distribution procedures not performed in accordance with blood bank transfusion service's specifications	538	72.4%
Product not documented as issued in the computer	208	28.0%
Product not irradiated as required	74	10.0%
Procedure for issuing not performed or documented in accordance with specifications	54	7.3%
Improper ABO or Rh type selected for patient	44	5.9%
Improper product selected for patient	27	3.6%
Unit issued from the blood bank to the wrong patient	24	3.2%
Product not leukoreduced as required	23	3.1%
Failure to quarantine unit due to testing not performed or documented for:	105	14.1%
Antibody screen or identification	28	3.8%
Antigen screen	44	5.9%
Crossmatch	16	2.2%
Inappropriate release of:	37	5.0%
Outdated product	15	2.0%
Product with unacceptable, undocumented or incomplete product QC - pH for bacterial detection testing	10	1.4%
Shipping and storage	31	4.2%
Temperature not recorded or unacceptable upon receipt, unit redistributed	9	1.2%
Stored at incorrect temperature	8	1.1%
No documentation that product was shipped or stored at appropriate temperature	5	0.7%
Product not packaged in accordance with specifications	5	0.7%
Failure to quarantine due to incorrect, incomplete, or positive testing:	32	4.3%
Antibody screen or identification	11	1.5%

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Of the 1,592 reports submitted by transfusion services, 470 (30%) reports involved labeling deviations and unexpected events.

• In FY04, the number and distribution of these reports was similar to the reports received in the previous fiscal year (FY03 - 500).

Most Frequent BPD Reports - Labeling
From Transfusion Services

Labeling       470	# Reports	% of Total
Crossmatch tag or tie tag labels incorrect or missing information	264	56.2%
Recipient identification incorrect or missing	94	20.0%
Crossmatch tag switched, both units intended for the same patient	48	10.2%
Unit or pool number incorrect or missing	50	10.6%
Crossmatch tag incorrect or missing	18	3.8%
Expiration date or time extended or missing	13	2.8%
Unit ABO and / or Rh incorrect or missing	13	2.8%
Transfusion record (crossmatch slip) incorrect or missing information	123	26.2%
Recipient identification incorrect or missing	43	9.2%
Unit or pool number incorrect or missing	16	3.4%
Transfusion record switched, both units intended for the same patient	13	2.8%
Expiration date or time extended or missing	12	2.6%
Blood unit labels	77	16.4%
Expiration date or time extended or missing	45	9.6%
ABO and / or Rh incorrect	10	2.1%
Donor number incorrect or missing	10	2.1%

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Of the 1,592 reports submitted by transfusion services, 369 (23%) reports involved routine testing deviations and unexpected events.

• In FY04, the number of these reports increased 16% (FY03 - 317).
• There was an increase in the number of reports involving testing, specifically antibody screening and compatibility testing performed or documented incorrectly, 117 reports in FY03 and 204 reports in FY04.

Most Frequent BPD Reports - Routine Testing
From Transfusion Services

Routine Testing       369	# Reports	% of Total
Incorrectly tested for:	204	55.3%
Antibody screening or identification	76	20.6%
Compatibility	58	15.7%
Antigen typing	21	5.7%
Rh typing	20	5.4%
Sample (used for testing) identification	128	34.7%
Sample used for testing was incorrectly or incompletely labeled	97	26.3%
Unsuitable sample used for testing	15	4.2%
Incorrect sample tested	14	3.8%
Reagent QC unacceptable or expired reagents used	37	10.0%
Antibody screening or identification	10	2.7%
Multiple testing	8	2.2%
Antigen typing	6	1.6%
Rh typing	6	1.6%

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4. Most Frequent BPD Reports Submitted by Plasma Centers

Of the 5,115 reports submitted by Source Plasma centers, 4,601 (90%) involved post donation information.

• In FY04, the number of these reports decreased by 32% (FY03 - 6,737).
• In FY03, 452 reports were submitted by plasma centers that did not submit reports in FY04 due to closure of center.
• There was an increase in the number of reports in which a donor tested positive for Hepatitis B, Hepatitis C, or HIV, post donation. In FY03 there were 32 reports and in FY04 there were 169 reports.

Most Frequent BPD Reports - Post Donation Information
From Plasma Centers

Post Donation Information       4,601	# Reports	% of Total
Behavior / History	4,304	93.5%
Donor received tattoo within 12 months of donation	1,593	34.6%
Donor received body piercing within 12 months of donation	667	14.5%
Incarcerated	494	10.7%
Risk factors associated with Creutzfeldt-Jakob Disease (CJD) - travel	268	5.8%
Donor received ear piercing within 12 months of donation	245	5.3%
Sex partner tested positive for HCV	178	3.9%
Donor received tattoo and piercing within 12 months of donation	93	2.0%
IV drug use	93	2.0%
Testing *	265	5.8%
Tested positive for HCV post donation	88	1.9%
Tested positive at another center, specific testing unknown	71	1.5%

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

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Of the 5,115 reports submitted by Source Plasma centers, 285 (5.6%) reports involved donor screening deviations and unexpected events.

• In FY04, the number of these reports decreased by 56% (FY03 - 642).
• In FY03, 69 reports were submitted by plasma centers that did not report in FY04 due to closure of the center.

Most Frequent BPD Reports - Donor Screening
From Plasma Centers

Donor Screening       285	# Reports	% of Total
Donor record incomplete, incorrect, or not reviewed	104	36.5%
Donor history questions	52	18.3%
Arm inspection	30	10.5%
Donor signature missing	15	5.3%
Donor identification	4	1.4%
Donor gave history which warranted deferral and was not deferred	134	47.0%
Risk factors associated with Creutzfeldt-Jakob Disease (vCJD) - travel	30	10.5%
Donor received tattoo within 12 months of donation	29	10.2%
Donor received vaccine or immune globulin	13	4.6%
Donor received body piercing within 12 months of donation	12	4.2%
History of disease or surgery	11	3.9%
Donor did not meet acceptance criteria	60	21.1%
Medical review or physical not performed or inadequate	32	11.2%
Temperature unacceptable or not documented	17	6.0%
Unexplained weight loss	4	1.4%
Deferral screening not done	40	14.0%
Donor previously deferred due to history	22	7.7%
Deferred by another center	7	2.5%
Other-unknown	3	1.1%
Other-Donor unreliable	2	0.7%
Donor previously deferred due to testing:	18	6.3%
Elevated for ALT	10	3.5%
Incorrect ID used during deferral search	19	6.7%
Donor not previously deferred	10	3.5%
Donor previously deferred due to history	7	2.5%
Donor previously deferred due to testing	2	0.7%

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5. Timeliness of BPD Reports

BLOOD AND PLASMA ESTABLISHMENTS

Timeliness Of BPD Reports
Number of Days From Date Discovered To Date FDA Received

Cumulative % of Reports	Licensed BB (Days)	Unlicensed BB (Days)	Transfusion Service (Days)	Plasma Centers (Days)	Total (Days)
10%	12	4	1	14	10
25%	20	10	7	26	19
50%	27	23	20	36	27
75%	33	41	39	44	36
90%	44	66	51	54	47
# Reports	27,621	3,502	1,592	5,115	37,830
Range	0-1325	0-711	0-433	1-1232	0-1325
Average	31	37	27	42	33
# Reports lacking date discovered	0	0	0	0	0

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

Reporting Time (days)	Licensed Establishments		Unlicensed Establishments		Transfusion Services		Plasma Centers		Total
< or = 45	25,234	91.36%	2,834	80.93%	1,377	86.49%	4,077	79.71%	35,522	88.61%
Between 45 and 90	1,885	6.82%	427	12.19%	164	10.30%	841	16.44%	3,320	8.78%
> 90	502	1.82%	241	6.88%	48	3.02%	197	3.85%	988	2.61%
Total	27,621	100%	3,502	100%	1,592	100%	5,115	100%	37,830	100%
* Reporting time=0	49		60		57		0		166

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

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3. FY04: 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.

• There was a decrease in the number of reports submitted by therapeutic manufactures, 18 in FY03 and 2 in FY04 due to the transfer of the oversight of these products to CDER on June 30, 2003.
• The number of reports submitted by in-vitro diagnostic manufacturers increased (FY03 - 44), however were similar to the reports submitted in FY02 (93).
• The number of reports submitted by derivative manufactures decreased from the previous fiscal year (FY03 - 56 for both types of manufacturers), however were approximately the same number of reports submitted in FY02 (45 and 42 respectively).
• There was a slight decrease in the number of reports submitted by Allergenic manufacturers (FY03 - 165, FY04 - 158).
• The majority of these reports continue to be related to precipitate discovered in allergenic extracts.

Total BPD Reports By Manufacturing System

Manufacturing System	Allergenic	Derivative	In-Vitro Diagnostic	Therapeutic	Vaccine	Total
Incoming Material	2	9	5	0	1	17	5.1%
Process Controls	2	9	20	1	7	39	11.7%
Testing	0	0	14	0	4	18	5.4%
Labeling	8	3	16	0	10	37	11.1%
Product Specifications	146	15	23	0	17	201	60.5%
Quality Control & Distribution	0	7	6	1	1	15	4.5%
Miscellaneous	0	1	2		2	5	1.5%
Total	158	44	86	2	42	332	100%

Potential Recalls By Manufacturing System

Manufacturing System	Allergenic	Derivative	In-Vitro Diagnostic	Therapeutic	Vaccine	Total
Incoming Material	0	2	0	0	0	2	11.1%
Process Controls	2	0	1	0	1	4	22.2%
Testing	0	0	0	0	0	0	0.0%
Labeling	3	0	2	0	0	5	27.8%
Product Specifications	0	1	5	0	0	6	33.3%
Quality Control & Distribution	0	0	0	0	0	0	0.0%
Miscellaneous	0	1	0	0	0	1	5.6%
Total	5	4	8	0	1	18	100%

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NON-BLOOD MANUFACTURERS

Timeliness Of BPD Reports
Number of Days From Date Discovered To Date FDA Received

Cumulative % of Reports	Allergenic (Days)	Derivative (Days)	In-Vitro Diagnostic (Days)	Therapeutic (Days)	Vaccine (Days)	Total (Days)
10%	15	16	26	0	18	18
25%	22	30	36	0	26	26
50%	28	46	43	40	43	40
75%	41	91	55	40	52	48
90%	61	222	112	40	91	117
# Reports	158	44	86	2	42	332
Range	0-603	9-710	14-2533	40-48	8-249	0-2533
Average	41	48	85	44	68	53
# Reports lacking date discovered	0	0	0	0	2	2

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

Reporting Time (days)	Allergenics		Derivatives		In-Vitro Diagnostics		Therapeutics		Vaccines		Total
< or = 45	127	80.4%	20	45.5%	55	64.0%	1	50.0%	23	57.5%	226	68.5%
> 45 and ≤ 90	18	11.4%	12	27.3%	17	19.8%	1	50.0%	12	30.0%	60	18.2%
> 90	13	8.2%	12	27.3%	14	16.3%	0	0.0%	5	12.5%	44	13.3%
Total	158	100%	44	100%	86	100%	2	100%	40	100%	330	100%

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Attachments

Attachment 1 - Number of BPD Reports by Type of Blood Establishment (PDF)

Attachment 2 - List of BPD Codes for Blood and Plasma (PDF)

Attachment 3 - Number of BPD Reports by Type of Non-Blood Manufacturer (PDF)

Attachment 4 - List of BPD Codes for Non-Blood Manufacturers (PDF)

Table of Contents

CBER Information

Useful Government Sites