Guidance for Industry 

Biological Product Deviation 

Reporting for Blood and Plasma 

Establishments 

Additional copies of this guidance document are available from the Office of Communication, 

Training and Manufacturers Assistance, (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, 

MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at 

http://www.fda.gov/cber/guidelines.htm. 

For questions on the content of this guidance, contact (CBER) Office of Compliance and 

Biologics Quality at 301-827-6220 or by email at bp_deviations@fda.hhs.gov. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Biologics Evaluation and Research 

October 2006
Contains Nonbinding Recommendations 

Table of Contents 

I. INTRODUCTION............................................................................................................. 1

II. BACKGROUND ............................................................................................................... 1

III. GUIDANCE....................................................................................................................... 3

A. Who Must Report? (21 CFR 606.171(a))............................................................ 3

Examples of who must report: ................................................................................ 4 

B. What Do I Report? (21 CFR 606.171(b))............................................................ 7

Biological Product Deviation Reporting Flow Chart for Blood and Plasma 

Establishments........................................................................................................ 8 

C. When Do I Report? (21 CFR 606.171(c)).......................................................... 15

D. How and Where Do I Report? (21 CFR 606.171(d) and (e)) .......................... 15

IV. EXAMPLES OF REPORTABLE AND NON-REPORTABLE EVENTS BY 

MANUFACTURING SYSTEM .................................................................................... 16

A. Donor Suitability................................................................................................. 16

1. Post Donation Information............................................................................... 17 

2. Donor Screening and Deferral ......................................................................... 19 

B. Collection ............................................................................................................. 21

C. Component Preparation..................................................................................... 22

D. Testing.................................................................................................................. 23

E. Labeling ............................................................................................................... 24

F. Quality Control and Distribution...................................................................... 25

G. Miscellaneous....................................................................................................... 29

V. REFERENCES................................................................................................................ 30
Contains Nonbinding Recommendations 

Guidance for Industry

Biological Product Deviation Reporting for Blood and Plasma 

Establishments 

This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this 

topic. It does not create or confer any rights for or on any person and does not operate to bind 

FDA or the public. You can use an alternative approach if the approach satisfies the 

requirements of the applicable statutes and regulations. If you want to discuss an alternative 

approach, contact the appropriate FDA staff. If you cannot identify the appropriate FDA staff, 

call the appropriate number listed on the title page of this guidance.

I. INTRODUCTION 

This guidance document provides you, a blood or plasma establishment, with the FDA’s current 

thinking related to the biological product deviation (BPD) reporting requirements. For the 

purposes of this document, “blood and plasma establishment” includes licensed manufacturers of 

blood and blood components, including Source Plasma, unlicensed registered blood 

establishments, and transfusion services. This guidance document finalizes the draft guidance of 

the same title dated August 2001. 

FDA’s guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should 

be viewed only as recommendations, unless specific regulatory or statutory requirements are 

cited. The use of the word should in Agency guidances means that something is suggested or 

recommended, but not required. 

II. BACKGROUND 

Previously, FDA regulations required licensed blood and plasma establishments to report 

promptly to FDA errors and accidents in manufacturing that may affect the safety, purity, or 

potency of a product (Title 21 Code of Federal Regulations (21 CFR) 600.14(a) (1999)). On 

March 20, 1991, we, FDA, issued a memorandum entitled, “Responsibilities of Blood 

Establishments Related to Errors & Accidents in the Manufacture of Blood & Blood 

Components” requesting voluntary reporting from unlicensed registered blood establishments 

and transfusion services. 

In the Federal Register of November 7, 2000 (65 FR 66621), we issued a final rule amending the 

CGMP (current good manufacturing practice) regulations for blood and blood components. The 

new rule required all establishments involved in the manufacture of blood and blood 

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Contains Nonbinding Recommendations 

components, including licensed manufacturers, unlicensed registered establishments and 

transfusion services, to report product deviations in manufacturing (21 CFR 606.171).1

 

The new regulation at 21 CFR 606.171, effective May 7, 2001: 

• Expands the reporting requirement to include all unlicensed blood establishments, 

including transfusion services and registered blood banks; 

• Replaces the term “error and accident” with “biological product deviation”; 

• More clearly describes the types of events that you must report to us; 

• Limits reporting to those events that may affect the safety, purity, or potency of 

distributed products; 

• Establishes a reporting time frame of 45 days from the date the event was discovered. 

Under 21 CFR 606.171, you are required to report certain events associated with the 

manufacturing, to include testing, processing, packing, labeling, or storage, or with the holding 

or distribution of blood or a blood component, which may affect the safety, purity, or potency of 

a distributed product. Safety, purity, and potency are defined in 21 CFR 600.3(p), (r), and (s). 

Under 21 CFR 606.171(c), you should submit reports as soon as possible, but you are required to 

submit reports at a date not to exceed 45 calendar days from the date of discovery of information 

reasonably suggesting a reportable event has occurred. To facilitate reporting, we have 

developed a standardized reporting format that you may submit electronically or in paper form, 

by mail. 

The new regulation at 21 CFR 606.171 does not change any of the requirements in 21 CFR Part 

606, or Part 211 for conducting investigations of an unexplained discrepancy or the failure of a 

lot or unit to meet any of its specifications. Those regulations require you to evaluate and 

investigate, as appropriate, unexplained discrepancies and failures to meet specifications, and to 

maintain complaint records, including records of investigations and follow-up (21 CFR 606.100, 

211.192 and 211.198). We recommend that your procedures for the investigation of any 

unexplained discrepancy or the failure of a lot or unit to meet any of its specifications include 

provisions for: 

-

-

-

-

-

 

a timely investigation; 

an appropriate corrective action plan to prevent recurrence; 

procedures to gain control of unsuitable products in a timely manner; 

appropriate disposition of all affected products (in-date and expired); 

for deviations and discrepancies associated with donor suitability, an assessment of 

the donor’s suitability to serve as a donor in the future. 

1 Under 21 CFR 600.14, manufacturers of licensed biological products other than blood and blood components, 

including vaccines, allergenic products, therapeutics, plasma derivatives, and in vitro diagnostics (IVD), are required 

to submit reports in a manner similar to the requirements in 21 CFR 606.171. We have issued a separate guidance 

for reporting of product deviations by licensed manufacturers of biological products other than blood and blood 

components (Guidance for Industry: Biological Product Deviation Reporting for Licensed Manufacturers of 

Biological Products Other than Blood and Blood Components, October 2006). This guidance document is available 

through the Internet at http://www.fda.gov/cber/guidelines.htm or through CBER’s Office of Communication, 

Training, and Manufacturers Assistance.

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Contains Nonbinding Recommendations 

For additional information on investigations of any unexplained discrepancy or failure of a lot or 

unit to meet any of its specifications, you may refer to the “Guideline for Quality Assurance in 

Blood Establishments,” July 11, 1995, which may be found at 

http://www.fda.gov/cber/guidelines.htm. 

III. GUIDANCE 

A. Who Must Report? (21 CFR 606.171(a)) 

Under 21 CFR 606.171, the manufacturer that had control over the product when the 

deviation from current good manufacturing practice, applicable regulations, applicable 

standards, or established specifications or an unexpected or unforeseeable event that may 

affect the safety, purity, or potency (such a deviation or unexpected, unforeseen event is 

referred to hereafter as an, “event”) occurred must submit a report. This reporting 

requirement applies to: 

• licensed manufacturers of blood and blood components, including Source 

Plasma; 

• unlicensed registered blood establishments; and 

• transfusion services. 

We define “control” in 21 CFR 606.3(l) as having responsibility for maintaining the 

continued safety, purity and potency of the product and for compliance with applicable 

product and establishment standards, and for compliance with current good 

manufacturing practice (CGMP). 

If you are a plasma fractionator or IVD manufacturer that collects Source Plasma or other 

blood components to be used as your source material for further manufacture into a 

finished product, you are subject to reporting as specified in 21 CFR 600.14(a)(2)(iii). 

You are required to report, under 21 CFR 606.171(a), events that occur during the 

manufacture of such source material. If you manufacture that source material into a 

finished product, you are required to report, under 21 CFR 600.14(a)(2)(iii), events that 

occur during the manufacture of the licensed finished product (e.g., Immune Globulin 

Intravenous (Human), Reagent Red Blood Cells). 

Occasionally, a blood establishment establishes a contract with another entity to perform 

some or all of the manufacture of a product. Some common manufacturing steps 

performed under contract include testing (e.g., viral marker or compatibility), irradiation, 

blood collection, storage and distribution. If you contract out any manufacturing step, for 

the purposes of 21 CFR 606.171(a), that step is performed under your control. Under 21 

CFR 606.171(a), you must establish, maintain, and follow a procedure for receiving 

information from that contract manufacturing facility on all deviations, complaints, and 

adverse events that may affect your products. 

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Contains Nonbinding Recommendations 

For the purpose of 21 CFR 606.171(a), we do not consider contract manufacturing to 

include the supply of blood products to a transfusion service from a blood establishment 

or the supply of plasma to a fractionator from a Source Plasma collection establishment. 

For the purposes of 21 CFR 606.171(a), we also do not consider a blood establishment to 

be performing contract manufacturing for an entity that does not perform manufacturing. 

A hospital would not perform manufacturing if the blood establishment performs the 

compatibility testing for a hospital, makes the final determination regarding the suitability 

of a product for a specific patient, and distributes the product to the hospital for 

transfusion. In this case the blood establishment acts as a transfusion service for the 

hospital and maintains the patient transfusion record and blood unit disposition history 

for a hospital. The blood establishment would be responsible for submitting reports 

related to the transfusion service events. 

If you are a contract manufacturer (i.e., under contract, you perform a step in 

manufacturing for another establishment), you must conduct such manufacturing in 

accordance with CGMP (21 USC 351(a)(2)(B)), but you are not required to report BPDs 

to us. 

Examples of who must report:

1. EVENT 

You are a blood establishment that contracts with a test laboratory to have 

the laboratory perform viral marker testing, including nucleic acid testing 

(NAT). The test laboratory did not perform the testing in accordance with 

the test kit manufacturer’s instructions or its own procedures. The test 

laboratory used the incorrect incubation time. Failure to follow the test kit 

instructions or validated procedures may affect the safety, purity, or 

potency of the product. 

REPORTING 

Under 21 CFR 606.100(c), 211.192, and 211.198, the test laboratory must 

perform an investigation. The test laboratory is NOT required to report to 

us. The test laboratory would provide the blood establishment with details 

of the deviation in viral marker testing. 

Under 21 CFR 606.171(a), you must establish, maintain, and follow a 

procedure for receiving information from the test laboratory about 

deviations concerning the viral testing. Under 21 CFR 606.171(b), you 

must submit a report to us if you distributed the improperly tested product. 

We recommend that you assure that the test laboratory performed an 

adequate investigation. 

2. EVENT 

You are a blood establishment that contracted with another blood 

establishment (referred to as an irradiator) to perform irradiation of blood 

4 
Contains Nonbinding Recommendations 

products. You sent a product to the irradiator. After irradiation, the 

product was returned to you. The irradiator notified you that the incorrect 

dosage was used (i.e., established specifications were not met), which may 

affect the safety, purity, or potency of the product. 

REPORTING 

Under 21 CFR 606.100(c), 211.192, and 211.198, the irradiator must 

perform an investigation. The irradiator is NOT required to report to us. 

The irradiator would provide you with details of the deviation in the 

irradiation process. 

Under 21 CFR 606.171(a), you must establish, maintain, and follow a 

procedure for receiving information from the irradiator about deviations 

concerning the irradiation process. Under 21 CFR 606.171(b), you must 

submit a report to us if you distributed the improperly irradiated product. 

We recommend that you assure that the irradiator performed an 

appropriate investigation. 

3. EVENT 

You are a blood establishment that distributed a blood product to another 

blood establishment (referred to as an irradiator), which subsequently 

irradiated it. The irradiator used the incorrect dosage during irradiation 

(i.e., established specifications were not met), which may affect the safety, 

purity, or potency of the product. 

REPORTING 

Under 21 CFR 606.100(c), 211.192, and 211.198, the irradiator must 

perform an investigation. Under 606.171(b), the irradiator must submit a 

report to us if it distributed the improperly irradiated product. You are 

NOT required to report to us or perform an investigation because the 

product was not in your control at the time the event occurred, i.e., it was 

not irradiated under a contract manufacturing agreement. 

4. EVENT 

You are a transfusion service that received a unit of Platelets from a blood 

establishment. When you received the product, you discovered that the 

product was labeled with an expiration date of more than the required 5 

days (i.e., improperly extended), which may affect the safety, purity, or 

potency of the product. You notified the blood establishment. 

REPORTING 

Under 21 CFR 606.100(c), 211.192, and 211.198, the blood establishment 

must perform an investigation of the deviation in labeling. Under 21 CFR 

606.171(b), the blood establishment must submit a report to us. 

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Contains Nonbinding Recommendations 

You are NOT required to report to us unless contrary to CGMP, applicable 

regulations, applicable standards, or established specifications, you further 

distributed the unit without correcting the label. 

5. EVENT 

You are a transfusion service that received 10 units of Platelets and 

subsequently pooled them into one unit. You improperly labeled the 

pooled unit with an incorrectly extended expiration date, which may affect 

the safety, purity, or potency of the product. 

REPORTING 

Under 21 CFR 606.100(c), 211.192, and 211.198, you must perform an 

investigation of the deviation in labeling. Under 21 CFR 606.171(b), you 

must submit a report to us if you distributed (i.e., issued for transfusion) 

the mislabeled product. 

6. EVENT 

You are a transfusion service that received a unit of Red Blood Cells from 

a blood establishment. The expiration date on the unit was incorrectly 

extended. According to your Standard Operating Procedures (SOPs), you 

should have recognized that the expiration was extended beyond any date 

appropriate for Red Blood Cells. You crossmatched the unit for a patient 

and distributed it to the surgical floor for transfusion. The surgical floor 

questioned the expiration date of the unit. You discovered that the unit 

was labeled with an extended expiration date, which may affect the safety, 

purity, or potency of the product. 

REPORTING 

Under 21 CFR 606.100(c), 211.192, and 211.198, you must perform an 

investigation of the inappropriate release of a product with an incorrectly 

extended expiration date because you failed to recognize the extended 

expiration date at the time of receipt or compatibility testing. Under 21 

CFR 606.171(b), you must submit a report to us because your failure to 

follow your own SOPs, which would have detected the improper 

expiration date, was an event that may effect the safety, purity, and 

potency of the product. We recommend that you notify the blood 

establishment of the incorrect labeling. 

Under 21 CFR 606.100(c), 211.192, and 211.198, the blood establishment 

must perform an investigation of the deviation in labeling. Under 21 CFR 

606.171(b), the blood establishment must also submit a report to us, since 

the use of an improperly extended expiration date was an event that may 

affect the safety, purity, and potency of the product. 

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Contains Nonbinding Recommendations 

7. EVENT 

You are a Source Plasma establishment that collected and tested a unit of 

Source Plasma, and shipped it to a fractionator, a licensed manufacturer. 

You discovered that the viral marker testing was incorrectly performed 

and subsequently retested a reserve sample of the unit. The unit retested as 

positive for a viral marker. The safety, purity, or potency of the Source 

Plasma may be affected. 

REPORTING 

Under 21 CFR 606.100(c), you must perform an investigation of the 

improper testing and distribution of the unit. Under 21 CFR 606.171(b), 

you must submit a report to us. We recommend that you evaluate the need 

for product retrieval or notification to the fractionator. Note: If your 

contract-testing laboratory performed the testing, you would be the 

reporting establishment. 

The fractionator would submit a report under 21 CFR 600.14, if it used the 

improperly tested plasma in the manufacture of a licensed biological 

product and distributed the final product. The use of the improperly tested 

plasma would represent an unexpected or unforeseeable event that may 

affect the safety, purity, or potency of the final product. (See footnote 1) 

B. What Do I Report? (21 CFR 606.171(b)) 

Under 21 CFR 606.171(b), you must report any event and any information relevant to the 

event associated with the manufacturing, to include testing, processing, packing, labeling, 

or storage, or with the holding or distribution, of both licensed and unlicensed blood or 

blood components, including Source Plasma, if that event meets all the following criteria: 

(1) Either 

(i) Represents a deviation from current good manufacturing practice, 

applicable regulations, applicable standards, or established 

specifications that may affect the safety, purity, or potency of that 

product; or 

(ii) Represents an unexpected or unforeseeable event that may affect 

the safety, purity, or potency of that product; and 

(2) Occurs in your facility or a facility under contract with you; and 

(3) Involves a distributed blood or blood component. 

An adequate procedure for deviation reporting (21 CFR 606.100(b)) would include steps 

for determining whether or not an event is one for which a report must be submitted. The 

decision to report should be based on whether the event had the potential to affect the 

safety, purity, or potency of a product. The terms safety, purity, and potency are defined 

in 21 CFR 600.3(p), (r), and (s), respectively. 

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Contains Nonbinding Recommendations 

Retrieval, Consignee Notification and Lookback

You are not required to submit a BPD report simply because you failed to follow your 

own internal procedures for retrieval, notification or lookback (e.g., you do not have to 

submit a report if you did not notify consignees within the time frame prescribed in your 

procedures). The failure to follow retrieval, notification, or lookback procedures does 

not, by itself, affect the safety, purity, or potency of the product. However, under 21 CFR 

606.171(b), you must submit a report if the underlying reason for the retrieval, 

notification, or lookback meets the reporting criteria found in Section III.B. In that case, 

the report must describe the event that may have affected the safety, purity, or potency of 

the distributed product and describe the failure to follow procedures. For example, you 

distributed a product collected from a donor with a history of high risk behavior, which 

may affect the safety, purity, or potency of the product. Your SOP requires that you 

notify consignees of the product within 5 days and you notified the consignee 8 days after 

discovering the event. You are required to report the improper release of the product. 

We recommend that you also include in the report that consignee notification was not in 

accordance with your SOP. 

You are not required to submit a report: 

1. When you did not distribute potentially affected products, regardless of the 

event. 

2. When you determined, prior to distributing the product, that the event did not 

actually affect the safety, purity, or potency of the product. 

3. When you detected the event and prior to distribution, made the appropriate 

corrections. 

4. When the event was related to donor safety only and did not have the potential 

to affect the safety, purity, or potency of the product. 

5. If your report would simply state that you were late in reporting the event to 

us. 

While the above examples would not be reportable under 21 CFR 606.171, the events 

may constitute deviations from the regulations, which we would assess during inspection. 

Biological Product Deviation Reporting Flow Chart for Blood and Plasma Establishments

You may use the following flow chart to help you determine if you are required to report 

an event to us. 

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Contains Nonbinding Recommendations 

(1) Was the event 

associated with 

“manufacturing” or with 

holding/distribution?

No Action under 

21 CFR 606.171

(2a) Was there a deviation 

that may affect the safety, 

purity, or potency of a 

product?

(2b) Was there an 

unexpected event that may 

affect the safety, purity, or 

potency of a product?

Record per 21 CFR

606.160(b)(7)(iii)

(3) Did it occur 

in your facility?

(3) Did it occur in 

a facility under 

contract with you?

You may notify 

responsible party

(4) Did you have control 

over the product when the 

event occurred?

You may notify the 

manufacturer with 

control over the product

(5) Was the product 

distributed?

Record per 21 CFR 

606.160(b)(7)(iii) & investigate 

per 21 CFR 606.100(c), 

211.192, 211.198

We recommend that you evaluate 

the need for product retrieval or 

consignee notification per 

21 CFR, Part 7

Submit report to CBER 

per 21 CFR 606.171

NO

NO NO

NO

NO

NO

YES

YES

YES

YES

YES

NO

Biological Product Deviation Flow Chart for Blood and Plasma Establishments

Investigate per 21 CFR 

606.100(c),

211.192, 211.198

Record per 21 CFR

606.160(b)(7)(iii)

Investigate per 21 CFR

606.100(c), 211.192, 

211.198

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Contains Nonbinding Recommendations 

The following questions correspond to the flow chart: 

(1) Was the event associated with “manufacturing” or holding or distribution 

as they are described in the regulation? 

As described in 21 CFR 606.171(b), manufacturing includes testing, processing, 

packing, labeling, or storage. In addition, you must report events associated with 

the holding or distribution of both licensed and unlicensed blood or blood 

components, including Source Plasma. 

 

Under 21 CFR 606.171, you are not required to report events that occur after you 

distribute the product, including those related to the administration of blood or 

blood components. 

Examples 

1. A Transfusion Service is NOT required to report to us if the event 

occurs during transfusion or administration procedures, after the blood 

product has left the control of the transfusion service. For example, a 

report is not required: 

• If the transfusion service issued a product from the laboratory to 

the nursing floor, operating room, emergency room, etc., for 

transfusion and the product was not held at the appropriate 

temperature outside of the transfusion service prior to transfusion. 

However, the transfusion service is required to report if the product 

was returned and the transfusion service determined it to be 

unsuitable, but contrary to CGMP, applicable regulations, 

applicable standards, or established specifications, reissued the 

product. 

• If the hospital staff, outside of the blood bank, transfused the 

wrong patient or transfused a patient with the wrong unit, provided 

the unit was labeled appropriately and the transfusion service 

conducted compatibility testing properly. If a complication of a 

transfusion was confirmed to be fatal, the facility that performed 

the compatibility testing must submit a fatality report to us in 

accordance with 21 CFR 606.170(b). 

• If the transfusion service issued a filter with the product and the 

hospital staff did not use the filter at the bedside. 

• If the patient has a transfusion reaction that is not related to an 

event in manufacturing. Fatalities due to Transfusion Related 

Acute Lung Injury (TRALI) or other transfusion complications 

must be reported to CBER in accordance with 21 CFR 606.170(b). 

We also accept voluntary reports of non-fatal TRALI as a serious 

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Contains Nonbinding Recommendations 

adverse reaction to transfusions. Such voluntary reports can be 

submitted via MedWatch by phone at 1-800-FDA-1088, by fax at 

1-800-FDA-0178, by US mail at MedWatch, HF-2, 5600 Fishers 

Lane, Rockville, MD 20852, or by email at 

http://www.fda.gov/medwatch. For additional information, see the 

“Dear Colleague” letter published October 19, 2001 at 

http://www.fda.gov/cber/ltr/trali101901.htm. 

2. A Blood Establishment is NOT required to report if the event is not 

associated with its manufacturing process and did not occur while the 

product was under the control of the blood establishment. For example 

the blood establishment is not required to report to us: 

• If the blood establishment shipped a product to a transfusion 

service and the transfusion service stored the product at the 

incorrect temperature. Under 21 CFR 606.171(b), if the 

transfusion service further distributed the product, the transfusion 

service must report to us.

• If the blood establishment received an unacceptable product (for 

example, a hemolyzed unit) from another blood establishment, 

identified the discrepancy and returned or discarded the product. 

Under 21 CFR 606.171(b), the blood establishment that distributed 

the unacceptable product, but not the establishment that received 

and returned or discarded it, must report to us.

(2a) Was there a deviation that may affect the safety, purity, or potency of a 

product? 

A deviation that may affect the safety, purity, or potency of a product could 

include any change in the manufacturing process that could prevent a product 

from meeting all CGMP requirements, applicable standards, and established 

specifications. The CGMP and applicable regulations for blood and blood 

components are currently found in 21 CFR Parts 210, 211, 600, 606, 610, 630, 

and 640. Standards refer to specifications and procedures applicable to the 

manufacture or release of products, which are established to help ensure the 

continued safety, purity, and potency of such products. Specifications refer to 

quality standards (i.e., tests, analytical procedures, and acceptance criteria) that 

confirm the quality of products and other materials used in the production of a 

product, e.g., the hematocrit level, or the temperature range for thawing a frozen 

component. 

 

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(2b) Was there an unexpected or unforeseeable event that may affect the 

safety, purity, or potency of a product? 

An unexpected or unforeseeable event is one in which, despite the fact that you 

followed all required procedures, something occurred that may affect the safety, 

purity, or potency of a product. This may be due to information that you did not 

have at the time of manufacturing. Examples of unexpected or unforeseeable 

events in which the safety, purity, or potency may be affected include the 

following: 

• Post Donation Information – A donor donated blood on one 

occasion. You followed all donor screening and deferral 

procedures, and determined that the donor was suitable. At a 

second donation, the donor disclosed additional information that 

would have resulted in deferral had the donor disclosed it at the 

earlier donation, such as information that the donor used 

intravenous drugs prior to the first donation. 

• After you distributed a product, you discovered that you performed 

compatibility testing using a patient sample that was collected 

from the wrong patient or labeled with incorrect patient 

information. 

• After you distributed a product, your materials vendor informed 

you that materials used in the collection or processing of blood and 

blood components, such as reagents, soft goods, software, or 

collection device, did not meet all requirements or specifications, 

and you could not have detected the deviation during your routine 

incoming material qualification procedures. 

If an event occurred, but could not have affected the safety, purity or potency of a 

product, 21 CFR 606.160(b)(7)(iii), 606.100(c), 211.192 and 211.198 require that 

you record and investigate it, but you do not need to report to us. 

Under 21 CFR 606.171(b), if you discover an event after you distributed a 

product and the safety, purity, or potency of the product may have been affected 

because of the event, you must report the event, regardless of whether consignee 

notification or product retrieval is necessary. You must report the event even if 

you ultimately determined, through investigation after distribution, that the safety, 

purity or potency of the product was not affected.

For example, if you distributed a product that was not tested for all viral markers, 

under 21 CFR 606.171(b), you must submit a report to us, even if you 

subsequently tested the product and found it to be negative. 

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Contains Nonbinding Recommendations 

If you discover an event prior to distribution of a product and determined that the 

event did not affect the safety, purity, or potency of the products, you are not 

required to report under 21 CFR 606.171. 

For example, if you discovered a deviation in testing prior to the distribution of a 

product and you appropriately retested the product and found it to be negative, 

you are not required to report to us under 21 CFR 606.171. 

(3) Did it occur in your facility or in a facility under contract with you? 

You are required to submit a report if the event occurred within your facility or a 

facility under contract with you, such as a testing laboratory. Under 21 CFR 

606.171(a) and (b), you must report events that occur at the contractor and you 

must establish, maintain, and follow a procedure for receiving information from 

the contract facility on all deviations, complaints, and adverse events concerning 

your potentially affected products. 

If you are a contract manufacturer, such as a testing laboratory, and an event 

occurs within your facility, you would notify the manufacturer with control over 

the product, if its products may be affected. You are not responsible for reporting 

the event to us. 

If you detect an event that occurred in another facility not under contract with 

you, we recommend that you contact that facility, which would be responsible for 

reporting to us, if appropriate. For example, if you receive a unit of Red Blood 

Cells shipped without ice we recommend that you notify the supplier. You are 

not required to report to us unless, contrary to CGMP, applicable regulations, 

applicable standards, or established specifications, you further distributed the 

unacceptable unit. 

(4) Did you have control over the product when the event occurred? 

You have control over the product if you have overall responsibility for: 

• maintaining the continued safety, purity, and potency of the product, 

• compliance with applicable product and establishment standards, and 

• compliance with current good manufacturing practice. 

You are responsible for reporting if you had control over the product when the 

event occurred and you distributed the affected product. 

You have control over the product if you contract with another entity to perform 

all or some of the manufacture of a product. Under 21 CFR 606.171(a), you must 

establish a procedure for receiving information from the contract manufacturing 

facility on all deviations, complaints and adverse events. The contract 

manufacturer is responsible for documenting the event in accordance with 21 

CFR 606.160(b)(7)(iii) and investigating in accordance with 21 CFR 606.100(c), 

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Contains Nonbinding Recommendations 

211.192 and 211.198. The contract manufacturer is not responsible for reporting 

to us. 

(5) Was the product distributed? 

We define ”distributed” in 21 CFR 606.3(k) as: 

(1) the blood or blood component has left the control of the licensed 

manufacturer, unlicensed registered blood establishment, or transfusion 

service; or 

(2) the licensed manufacturer has provided Source Plasma or any other blood 

component for use in the manufacture of a licensed biological product. 

If you are a licensed blood establishment, a product is considered distributed 

when you shipped the product to another facility or broker that is not part of your 

license or issued the product to staff outside the blood establishment for 

transfusion. A product is not considered distributed if it was shipped from one 

location to another and both locations are under the same license. 

If you are an unlicensed blood establishment, including a transfusion service, a 

product is considered distributed when you issued the product to staff outside of 

the blood establishment for transfusion or you shipped it to another facility or 

broker. 

If you are a Source Plasma establishment, the product is considered distributed 

when you released or shipped the product for further processing. Distribution 

includes shipment to a plasma broker. Distribution does not include shipment to 

an off-site storage facility if the product is still under your control. 

Examples: 

• If a blood establishment labeled a product with an incorrectly extended 

expiration date and shipped it to a hospital, under 21 CFR 606.171(b) 

the blood establishment must report to us. 

• If a hospital blood bank received 10 units of platelets from a blood 

establishment, pooled the platelets, mislabeled the final pooled product 

with an incorrectly extended expiration date, and issued the product to 

the nursing staff for transfusion, under 21 CFR 606.171(b) the hospital 

blood bank must report to us. However, if the blood bank detected and 

corrected the expiration date before distributing the product, under 21 

CFR 606.160(b)(7)(iii), 606.100(c), 211.192, and 211.198, the blood 

bank must document and investigate the deviation but is not required 

to report to us. 

14 
Contains Nonbinding Recommendations 

If you distributed the product, we recommend that you also assess the need for 

product retrieval or consignee notification in accordance with 21 CFR Part 7. 

You must document the event in accordance with 21 CFR 606.160(b)(7)(iii) and 

investigate in accordance with 21 CFR 606.100(c), 211.192 and 211.198, 

regardless of whether you distributed the product. 

C. When Do I Report? (21 CFR 606.171(c)) 

Under 21 CFR 606.171(c), you should report a biological product deviation as soon as 

possible, but you must report at a date not to exceed 45 calendar days from the date that 

you, your agent, or another person who performs a manufacturing, holding, or 

distribution step under your control, acquire information reasonably suggesting that a 

reportable event has occurred. You acquire such information when any employee of your 

facility, not just those involved in quality assurance or quality control activities, learns 

about the event. As soon as you acquire information, you should make an assessment of 

whether the event had the potential to affect the safety, purity, and potency of products 

and determine the status of the products (i.e., whether they have been distributed or need 

to be quarantined). 

If you contract with a facility to perform a manufacturing step and an event occurs at the 

contractor, the time period for reporting starts when your contractor learns about the 

event. 

D. How and Where Do I Report? (21 CFR 606.171(d) and (e)) 

Under 21 CFR 606.171(d), you must use Form FDA-3486 to report BPDs. You must 

submit the completed report either electronically through CBER’s web site at 

http://www.fda.gov/cber/biodev/biodev.htm or by mail to: 

Director, Office of Compliance and Biologics Quality (HFM-600) 

Center for Biologics Evaluation and Research 

1401 Rockville Pike, Suite 200N 

Rockville, Maryland 20852-1448 

If the event occurred at your contract manufacturer, we recommend that you include in 

the report the details reported to you by the contract manufacturer regarding the event. 

Complete a separate report for each event. If an event involves more than one product, 

you only need to complete one report listing all distributed products affected. 

The Form FDA-3486 and instructions for completing both formats are located at 

http://www.fda.gov/cber/biodev/biodev.htm 

15 
Contains Nonbinding Recommendations 

IV. EXAMPLES OF REPORTABLE AND NON-REPORTABLE EVENTS BY 

MANUFACTURING SYSTEM 

We categorize BPD reports according to the manufacturing system where the event occurred. 

Following the bulleted list below, each system is explained further and we provide examples of 

both reportable and non-reportable events. An event may be the result of a failure within a 

variety of systems. It is important for you to know both where the event occurred and why your 

product was allowed to continue through the manufacturing process and distributed, so that you 

can implement the appropriate corrective action to prevent recurrence. 

•

•

•

•

•

•

A donor suitability event occurs in the donor suitability process (for example, donor 

screening, donor deferral procedures and receipt of post donation information) (See 

Section IV. A). 

A collection event occurs during the collection process (See Section IV. B). 

A component preparation event occurs during the component preparation process (See 

Section IV. C). 

A testing event occurs during the testing process and includes sample deviations and 

unexpected events (See Section IV. D). 

A labeling event occurs during the labeling process, which includes identifying the 

information to include on the label, printing the label, and applying the label to the 

product (See Section IV. E). 

A quality control and distribution event involves a failure in either the quality control 

(QC) or distribution systems. This category includes the distribution of a product that did 

not meet specifications (See Section IV. F). 

The following examples of events are not all-inclusive and do not represent all variations that 

may occur. The examples include deviations from CGMP, applicable regulations, applicable 

standards, and established specifications, in addition to unexpected or unforeseeable events. Not 

all of these examples will necessarily apply to you or to all products you manufacture. Whether 

or not the examples apply to you depends on your manufacturing operations and procedures. 

Under 21 CFR 606.100(c), 211.192, and 211.198, all events must be investigated. 

A. Donor Suitability 

Over the past several years, donor suitability issues have represented the largest 

percentage of reports. This category includes issues related to post donation information, 

donor screening, and donor deferral. 

16 
Contains Nonbinding Recommendations 

1. Post Donation Information

The majority of reports related to donor suitability involved post donation 

information. We issued a Memorandum to All Blood Establishments entitled, 

“Guidance Regarding Post Donation Information Reports,” on December 10, 

1993, which described the process for handling post donation information. This 

guidance does not supersede the memorandum, but provides additional 

information regarding the reporting of post donation information. 

Post donation information includes information that a donor or other reliable 

source provides to you subsequent to a donation. Post donation information is 

most often reported at a subsequent donation. Report post donation information if 

you would have deferred the donor had you known the information at the time of 

donation and the safety, purity, or potency of the product could be affected. It is 

also reportable if the medical evaluation reasonably suggests that the safety, 

purity, or potency of the product could be affected, such as when a donor reports a 

post donation illness, or the information is insufficient to conclude that the safety, 

purity, or potency of the product is not affected, such as when a donor 

subsequently instructs an establishment not to use the donor’s blood without 

providing a reason. 

In some cases blood establishments cannot control post donation information, but 

they are responsible for the safety, purity, and potency of the product and for 

compliance with applicable standards and CGMP requirements. For example, a 

donor may call after donating to report a post donation illness, or information 

obtained post donation about exposure to a disease or a sex partner at high risk. 

In other cases, the donor has knowledge of a behavior or risk factor prior to 

donation that would cause the donor to be unsuitable, but the donor fails to report 

this at the time of donation. At some point after donation, the donor provides 

information that results in deferral. 

Submit a report when you receive post donation information that may affect the 

safety, purity or potency of a product you distributed. Examples of reportable 

events associated with post donation information may include: 

• Subsequent to the donation, a donor (or third party) provides disqualifying 

information that would have resulted in donor deferral at the time of 

donation. The relevant questions were asked at the donation, but the 

donor did not provide the information. Examples include the following: 

- Donor had a history of high risk behavior for hepatitis or HIV 

(Human Immunodeficiency Virus), such as intravenous (IV) drug 

use, male to male sex, received an accidental needlestick, or 

transfusion within the time frame for deferral according to your 

SOP, and did not report this at the time of donation. 

- Donor traveled to an area considered endemic for malaria within 

the time frame for deferral according to your SOP (e.g., less than 1 

17 
Contains Nonbinding Recommendations 

year prior to donation) and did not report this at the time of 

donation. 

- Donor traveled to an area at risk for vCJD (Variant CreutzfeldtJakob Disease) within the time frame for deferral according to your 

SOP and did not report this at the time of donation. 

♦ When reporting this type of post donation information, you 

should include in the BPD report all distributed products 

collected after the implementation of questions used to elicit 

this information even if you did not conduct notification or 

retrieval for those products (for example, the report would 

include Platelets, even if you did not conduct notification or 

retrieval because the Platelets were expired by the time you 

received the post donation information). 

•

•

•

•

•

•

Donor or third party provides information of a post donation illness, 

including, fever (with or without other symptoms), diarrhea, or diagnosis 

of a specific disease (e.g., mononucleosis, measles, Lyme disease, chicken 

pox, shingles). Post donation cold or flu symptoms are excluded from 

reporting. 

Donor later tells the blood establishment that his/her blood should not be 

used. 

Donor later tells the blood establishment that he/she donated to be tested 

for a disease or infectious agent (such as HIV). 

Donor provides information of probable or confirmed West Nile Virus 

infection. 

DO NOT REPORT: 

Donor provides disqualifying information as a result of newly 

implemented donor history questions and previously collected products 

were distributed. The donor would have been previously acceptable 

according to all procedures in place at the time and would not have been 

deferred even if the donor provided the newly disqualifying information. 

Examples include: 

- Implementation of new deferral criteria related to travel to a vCJD risk 

area; 

- Changes in areas identified by CDC (Center for Disease Control) as 

malarial endemic. 

Donor provides information of cold or flu symptoms to include any of the 

following symptoms: general malaise, cough, headache, fatigue, 

congestion, nausea, vomiting, chills, or runny nose that developed after the 

donation. The safety, purity, or potency is generally not affected by post 

donation cold or flu symptoms provided the donor screening process is 

adequate to detect and defer a donor who presents with any of these 

symptoms at the time of donation. 

18 
Contains Nonbinding Recommendations 

• Donor provides information that she was pregnant at the time of donation. 

This is a donor safety issue and not one that affects the quality of the 

product. 

2. Donor Screening and Deferral

Donor screening and deferral events include those relating to determining donor 

eligibility, which you did not discover until after you distributed the product. 

This category includes events concerning the interview or medical evaluation 

process, blood donor record documentation, and deferral procedures and records. 

a. Interview process 

Under 21 CFR 606.171(b), you must submit a report when there is an 

event (a deviation or unexpected or unforeseeable event) during the 

interview process that may affect the safety, purity, or potency of a 

product you distributed. Examples of reportable events associated with 

the interview process may include: 

•

•

•

•

•

Donor provided information that warranted deferral, but the donor 

was accepted. 

Donor provided partial information that was not resolved by 

follow-up questioning, and the donor was accepted. 

b. Medical evaluation 

Under 21 CFR 606.171(b), you must submit a report when there is an 

event (a deviation or unexpected or unforeseeable event) during the 

medical evaluation that may affect the safety, purity, or potency of a 

product you distributed. Examples of reportable events associated with 

medical evaluation process may include: 

Donor’s hemoglobin or hematocrit was unacceptable. 

Donor’s temperature was unacceptable. 

Plateletpheresis donor had an unacceptable platelet count and there 

was no documented platelet count for the product. 

• Medical review or physical was not performed or was inadequate. 

c. Donor record documentation 

Under 21 CFR 606.171(b), you must submit a report when there is an 

event (a deviation or unexpected or unforeseeable event) during donor 

record documentation that may affect the safety, purity, or potency of a 

product you distributed. Examples of reportable events associated with 

donor record documentation may include: 

19 
Contains Nonbinding Recommendations 

•

•

•

• -

-

•

•

•

•

•

•

•

No documentation of donor’s hemoglobin, hematocrit, 

temperature, arm inspection. 

Answers to the donor history questions, including high risk 

questions, were missing or incomplete, except those only affecting 

donor safety (e.g., history of pregnancy or heart disease). 

Donor’s signature was missing. 

Donor record was incomplete or incorrect, for example:

Both confidential unit exclusion stickers were applied to donor 

record;

Confidential unit exclusion stickers were applied by person 

other than donor.

d. Deferral procedures 

Under 21 CFR 606.171(b), you must submit a report when there is an 

event (a deviation or unexpected or unforeseeable event) during the 

deferral process that may affect the safety, purity, or potency of a product 

you distributed. Examples of reportable events associated with the 

deferral process may include: 

Donor was incorrectly omitted from the deferral list, and donor 

subsequently donated. 

Deferral list contained inaccurate information, such as temporary 

deferral instead of permanent deferral, and the donor subsequently 

donated. 

The donor tested positive for a viral marker, an appropriate reentry 

algorithm was not followed and the donor was subsequently 

allowed to donate. 

The incorrect donor identification information was used to check 

the deferral list (regardless of whether the donor was previously 

deferred). You would report even if the donor provided discrepant 

identification information, such as different names on two 

donations – J. Michael Smith and James M. Smith. 

The deferral list was not checked (regardless of whether the donor 

was previously deferred). 

DO NOT REPORT: 

Autologous donor did not meet the suitability criteria and the medical 

director authorized acceptance of the donor, provided the product was 

labeled appropriately and not crossed over for allogeneic use. 

Donor did not meet suitability criteria related to donor safety only, such as 

donor’s weight, age, donating within 56 days of last donation, or more 

20 
Contains Nonbinding Recommendations 

than 24 pheresis donations within 12 months. These criteria do not affect 

product quality. 

•

•

•

•

•

•

•

•

•

•

•

•

•

•

Plateletpheresis donor had an unacceptable platelet count, but the platelet 

count for the product was acceptable. 

A recordkeeping deviation that would not affect the safety, purity, or 

potency of the product, such as the second or supervisory review of the 

blood donor record, was not performed or documented, but the initial 

review was acceptable. 

The deferral list was not checked at the time prescribed in your 

procedures, or incorrect information was used to check deferral list and 

you determined prior to distribution of products from that donation that 

the donor was not previously deferred. 

Donor was accepted on the basis of incomplete information and you 

obtained additional information from the donor, prior to distribution of 

any products, demonstrating that the donor was acceptable. 

Donor was deferred and products were handled appropriately, donor was 

not placed on the deferral list, but the donor did not have subsequent 

donations, therefore there were no products affected. 

B. Collection 

Collection events include those that occur during the collection process, which you did 

not discover until after you distributed the product. 

Under 21 CFR 606.171(b), you must submit a report when there is an event (a deviation 

or unexpected or unforeseeable event) during the collection process that may affect the 

safety, purity, or potency of a product you distributed. Examples of reportable events 

associated with the collection process may include: 

Product was contaminated or potentially contaminated with bacteria or air. 

(The manufacturer that had control of the product during collection would be 

responsible for reporting this.) 

Arm preparation was not performed or was performed incorrectly. 

Outdated bag or collection set was used in collection. 

Outdated or incorrect anticoagulant was used in collection. 

Defective device or collection bag was used for collection. 

Donor was over bled and the product was distributed as Whole Blood. 

(Product may be affected if there was an inadequate volume of anticoagulant 

in the collection bag). 

Source Plasma for further manufacture into injectable products from two 

different donors was pooled into one pooling bottle. 

*Product was discovered to be clotted. 

**Product was discovered to be hemolyzed. 

21 
Contains Nonbinding Recommendations 

•

•

•

•

•

•

Collection specifications were not met, for example: 

- Collection time was extended; 

- Collection time was discrepant; 

- Collection time was not documented; 

- Collection status (e.g., satisfactory) was not documented. 

*The manufacturer who had control of the product during collection should 

report clotted products that were distributed. 

**The manufacturer who had control of the product during collection, component 

preparation and storage should report hemolyzed products that were distributed 

and were not accepted into the consignee’s inventory. A transfusion service 

would be responsible for reporting hemolyzed products if the product was 

inspected upon receipt from the collection facility and found acceptable (no 

hemolysis) and then later found to be hemolyzed while in the control of the 

transfusion service and subsequently distributed (reported under QC & 

Distribution system). 

DO NOT REPORT: 

A recordkeeping deviation that would not affect the safety, purity, or potency 

of the product, such as the phlebotomist’s signature was missing from the 

donor record. 

Donor has a reaction during the collection procedure. If the donor has a fatal 

reaction as a result of a complication of blood collection, a BPD report is not 

required, but the collection facility must report to CBER in accordance with 

the requirements for reporting fatalities (21 CFR 606.170(b)). 

C. Component Preparation 

Component preparation events include those that occur during the preparation or 

processing of a product, which you did not discover until after you have distributed a 

product. 

Under 21 CFR 606.171(b), you must submit a report when there is an event (a deviation 

or unexpected or unforeseeable event) during the component preparation process that 

may affect the safety, purity, or potency of a product you distributed. Examples of 

reportable events associated with the component preparation process may include: 

Component, such as Platelets or Fresh Frozen Plasma, was not prepared 

within the appropriate time frame after collection. 

Product was contaminated with bacteria, air or other contaminants during 

component preparation or processing, such as pooling. (The manufacturer that 

had control of the product during the component preparation process would be 

responsible for reporting this.) 

Component was not manufactured according to established procedures, which 

may affect the safety, purity, or potency for that particular product, such as: 

22 
Contains Nonbinding Recommendations 

- Platelets were prepared from a product collected from a donor who took 

aspirin or other drugs that affects platelets; 

- Fresh Frozen Plasma or Cryoprecipitated AHF did not meet freezing time 

requirements; 

- Platelets did not meet resting time requirements; 

- Component manufactured from a Whole Blood unit that did not meet 

spec c ifi ations, such as; 

♦ Overweight or underweight Whole Blood unit, 

♦ Whole Blood unit was collected or stored at unacceptable 

temperature, 

♦ Extended or undocumented collection time of a Whole Blood unit 

or collection was difficult or slow; 

- Incorrect filter was used for leukoreduction; 

- Product was not leukoreduced within the appropriate time frame; 

- Product was not washed/deglycerolized properly. 

DO NO

•

duct, such as the signature of the person preparing the product was 

missing.

D. Testing 

d to 

n unsuitable or inappropriate sample 

ay also be a testing deviation or unexpected event. 

or 

ou distributed. Examples of reportable events associated with 

testing may include: 

• rmed in accordance with test manufacturer’s 

-

- Incorrect dosage was used for irradiation; 

T REPORT: 

A recordkeeping deviation that would not affect the safety, purity, or potency

of the pro

Testing events include those that occur during the testing process, which you did not 

discover until after you have distributed the product. Testing includes all tests use

assure the safety, purity, and potency of a product, whether required by specific 

regulations or by your SOP. Product release testing may include testing performed under 

IND (investigational new drug application). Use of a

m

Under 21 CFR 606.171(b), you must submit a report when there is an event (a deviation 

or unexpected or unforeseeable event) during testing that may affect the safety, purity, 

potency of a product y

Testing was not perfo

instructions, such as 

- Incorrect incubation time or temperature was used; 

- Incorrect reagent was used/licensable components from two different test 

kit lots were used; 

Incorrect addition of reagents (incorrect sequence, volume or 

concentration). 

23 
Contains Nonbinding Recommendations 

•

anufacturer’s instructions. 

• testing until you obtained 

• idated. 

• m

•

ude QC on ABO/Rh typing 

 the day before and the day 

For tran

•

de of 

•

ibuted. 

 crossmatch performed when a patient’s history or testing 

DO NO

• y 

sting appropriately. 

riately invalidated an assay, and you retested samples and they 

ive before product was distributed. 

discove n istributed the product. Labeling events include incorrect, 

missing r y labeling pertaining to the product, including: 

•

• the labeling accompanying the product that identifies the patient for whom it 

has been crossmatched (transfusion record). 

Initial reactive was not repeated in duplicate (viral marker testing), when

required by test m

Sample was tested into compliance (repeated

negative result). 

Test assay was inappropriately inval

Sa ple that did not meet specifications for testing was used, such as 

- Sample was improperly stored; 

- Sample was diluted (e.g., saline dilution of samples collected after an 

apheresis procedure); 

- Sample was not identified appropriately to relate back to donor or patient

being tested. 

Testing was performed using a reagent or test kit in which QC was 

unacceptable or not documented. This may incl

reagents not documented one day, even if the QC

after was acceptable. 

• Testing was performed using expired reagents. 

sfusion services, reportable events may also include: 

Patient samples were mislabeled or collected from the wrong patient, if you 

used the sample to crossmatch a product that you distributed. This includes 

samples collected by transfusion service personnel and personnel outsi

the blood establishment. 

Mistyped or misinterpreted patient samples if the sample was used in 

crossmatching a product that you distr

• Immediate spin

requires an indirect antiglobulin test. 

T REPORT: 

A recordkeeping deviation that would not affect the safety, purity, or potenc

of the product such as a failure to make one testing record if there are other 

testing records to indicate that you performed te

• You approp

tested negat

E. Labeling 

Labeling events include those that occur during the labeling process, which you did not 

r u til after you have d

 o misleading information on an

• the product label; 

• tie tags; 

the circular of information; 

24 
Contains Nonbinding Recommendations 

 you distributed. Examples of reportable events associated with 

labeling may include: 

• O or Rh type, antigen type, antibody, 

• or Rh, expiration date, volume, weight, platelet 

• d. 

• showed testing information that is not 

• tion date, even if the product 

• mation, 

• as 

•

• rect donor or unit number or donor or unit number 

- crossmatched for the same patient, but unit identification is 

- rs of split or aliquot products labeled with an incorrect part 

• roduct name or product name is missing, for 

- not leukoreduced. 

DO NO

•

•

llection date (provided 

on. 

a license number. 

Events in q

Under 21 CFR 606.171(b), you must submit a report when there is an event (a deviation 

or unexpected or unforeseeable event) during labeling that may affect the safety, purity, 

or potency of a product

Labeling indicated an incorrect AB

anticoagulant, volume or weight. 

Information is missing – ABO

count (for platelet products). 

Labeling indicated testing was performed, but the product was not teste

Product was tested but labeling 

consistent with the test results. 

Labeling indicated an incorrectly extended expira

was transfused within the correct dating period. 

Autologous labeling is missing or showed incorrect identifying infor

such as the patient’s name, social security number, or date of birth. 

Labeling indicated product as crossmatch compatible when the product w

either not crossmatched or found incompatible. 

Labeling indicated incorrect recipient name or identification number. 

Labeling indicated an incor

is missing. This includes: 

Two units 

switched; 

Unit numbe

identifier. 

Labeling indicated an incorrect p

example: 

- Plasma labeled as Platelets; 

- Irradiated Red Blood Cells labeled as Red Blood Cells; 

Red Blood Cells labeled as Red Blood Cells Leukocytes Reduced, but 

product was

T REPORT: 

Labeling indicated a shortened expiration date. 

Any of the following information missing from or incorrectly stated on the 

label (provided the product is otherwise acceptable): co

the expiration date is correct), or facility identificati

• Unlicensed product labeled with 

F. Quality Control and Distribution 

uality control and distribution are those in which: 

25 
Contains Nonbinding Recommendations 

•

• iled to meet release criteria or was found 

-

as 

ct; or 

tion 

distributed. Examples of reportable events associated with quality control/assurance or 

distribution

• o t have been distributed due to: 

medical history; 

e 

- e 

hanges to an 

Approved Application: Biological Products: Human Blood and Blood 

ly 

ttp://www.fda.gov/cber/gdlns/bldchanges.pdf) 

For transfu

product in 

tion of product, when required by 

 to the patient’s 

• Shipping or storage events: 

- Product was shipped or stored at incorrect temperature; 

Quality control procedures were not followed or not performed. 

Distribution of product that fa

unacceptable. For example: 

Product was identified as not meeting specifications due to a deviation or 

unexpected event in donor suitability, collection, component preparation, 

testing, or labeling and product was distributed; 

- Product was distributed prior to determining whether the product w

suitable for distribution; 

- Events associated with the physical distribution of the produ

- Additional information reveals product to be unacceptable. 

Under 21 CFR 606.171(b), you must submit a report when there is an event (a devia

or unexpected or unforeseeable event) in quality control/quality assurance or in the 

distribution process that may affect the safety, purity, or potency of a product you 

 process may include: 

Pr duct was distributed that should no

- Unsuitable donor 

- Incorrect or incomplete testing; 

- Positive testing; 

- Testing not performed or not documented; 

- Outdated product; 

- Overweight or underweight unit/component; 

- Component prepared from the same Whole Blood unit in which one of th

products was determined to be clotted or hemolyzed; 

Licensed establishments: You made a change from what is in your 

approved biologics license application and you did not comply with th

requirements of 21 CFR 601.12 (e.g., distributed products prior to 

approval of a supplement), if the change may affect the safety, purity or 

potency of the product. (See, “Guidance for Industry: C

Components Intended for Transfusion or for Further Manufacture,” Ju

2001. (h

sion services, reportable events may also include the distribution of a 

which: 

- Antibody screen or identification testing was not performed or was 

incomplete on recipient prior to distribu

your SOP; 

- Product was not tested for an antigen, which corresponds

antibody, when required by your SOP. 

26 
Contains Nonbinding Recommendations 

- No documentation that product was shipped or stored at appropriate 

temperature; 

- Temperature of a shipment was not recorded upon

was redistributed; 

 receipt, and product 

ated container. 

•

• d not meet all specifications for distribution. 

•

•

o 

• uted in which quality control or product specifications 

ple: 

; 

-

ulture or positive screen using a 

For tra

produc

potency

•

d 

, 

• ient. 

•

- Shipment exceeded time allowed for shipping; 

- Product was shipped in an unvalid

Autologous product distributed as an allogeneic product, but the product did

not meet all allogeneic requirements. 

Product was distributed that di

Product was distributed that was processed using an instrument or reagent in 

which QC was unacceptable. 

Product was distributed that was processed using an instrument or reagent in 

which QC was not documented or not performed. Examples of reportable 

events include: 

- No documentation that weekly QC was performed, even if daily QC tasks 

were performed; 

- No documentation of QC trip scales, unless product was weighed prior t

distribution and was acceptable. 

Product was distrib

were not met, incompletely documented or not documented. For exam

- pH (monthly QC of platelets)

- Platelet count; 

White blood cell count (for leukoreduced product); 

- Red Blood Cell recovery; or 

- Bacterial Detection (when positive c

system approved for QC or pre-release testing of blood products). 

• Product distributed prior to resolution of a discrepancy in manufacturing, such 

as testing, labeling or donor suitability. 

nsfusion services, reportable events may also include the distribution of 

ts in which specifications were not met, which may affect the safety, purity, or 

 of a product, such as: 

Incorrect product or unit issued for a specific patient (unless the transfusion 

service notified the hospital staff that the product ordered was unavailable an

that the transfusion service was providing a substitute): 

- Special processing or testing requested, such as leukoreduced, irradiated

CMV (cytomegalovirus) negative, but product didn’t meet specification 

- Unit issued that was designated for different patient 

- Incorrect product type issued, such as Platelets instead of Fresh Frozen 

Plasma

Product with the improper ABO or Rh type was selected for a pat

Wrong filter was issued for use in transfusion or a filter was not issued when 

required.

27 
Contains Nonbinding Recommendations 

•

•

Product was accepted as suitable from a blood establishment, and the product 

, however it was discovered to be hemolyzed after distribution 

on service. 

DO NOT REPORT: 

•

• ual 

•

st, and the 

 Cells Irradiated was filled with a unit of Red 

• d 

•

t, was issued through emergency release procedures 

• uct bag (e.g., Fresh Frozen Plasma) broke during thawing and the 

•

•

•

not 

ge does 

the legal 

). 

•

lots or hemolysis and found acceptable. 

•

•

ple: 

-

Visual check of product was not performed prior to distribution. 

Product was distributed based on testing that was not performed on a current 

sample. 

•

was distributed

by the transfusi

Product was shipped to the incorrect facility. 

Product is properly labeled but the shipping invoice differs from the act

shipment. 

Blood establishment shipped an order to another blood establishment for a 

specific type of product, but did not fulfill the specific reque

product was properly labeled and not labeled for a specific patient. For 

example, an order for Red Blood

Blood Cells that were properly labeled as Red Blood Cells. 

Donor provides information regarding post donation cold or flu symptoms an

products were not quarantined. 

Otherwise unsuitable product, such as an expired HLA (human leukocyte 

antigen) matched platele

and documented appropriately. 

Frozen prod

product was discarded. 

*Product broke or was damaged during shipment and the product was 

discarded. 

Unlicensed product was distributed labeled with a license number. 

Licensed establishments: You made a change from what is in your approved 

biologics license application, such as a minor labeling change, and you did 

comply with the requirements of 21 CFR 601.12(f), provided the chan

not affect the safety, purity or potency of the product (e.g., change in 

name of the applicant not reported in accordance with 21 CFR 601.12(f)

A segment was found to be clotted or hemolyzed but the product was 

subsequently evaluated for c

Small residual clots are found in the filter after product was completely 

transfused, unless you did not adequately evaluate the unit for clots prior to 

issuing unit for transfusion. 

No documentation of instrument or reagent QC if there was data from another 

source that showed the instrument or reagent was acceptable, for exam

No documentation of acceptable reagent storage, but reagent QC was 

documented to be acceptable; 

- Temperature was not documented on recording chart, but manual 

temperature readings were documented to be acceptable. 

28 
Contains Nonbinding Recommendations 

* B

manufacturing and are generally tied to an unusual event in shipment. 

For tra u

•

ff transfused the patient with the wrong product or unit; 

- Hospital staff transfused the patient without using the appropriate filter. 

ct was distributed when an autologous product was available. 

G. Miscellaneous 

Other situa oreseeable event that 

may affect 

•

•

r 

f 

or Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and 

photropic Virus Type I (HTLV-I)”, July 19, 1996) 

NO to include all previous donations in the report. The report 

would incl

recommend

DO NOT REPORT

• Recipient identified with transfusion-associated disease, but donor ruled out as 

source of transfusion-associated disease and donor screening, testing, etc., was 

acceptable. 

roken or damaged products are rarely identified as system problems in 

nsf sion services, non-reportable events may also include:

Inappropriate administration practices by the hospital staff in transfusing the 

patient; 

- Hospital staff transfused the wrong patient; 

- Hospital sta

• Allogeneic produ

• Product was distributed using emergency protocol, provided it was labeled 

appropriately. 

tions that would be reportable as an unexpected or unf

the safety, purity, or potency of previously distributed products include: 

Donor was identified as source of transfusion-associated disease, such as, 

hepatitis, HIV, malaria, babesiosis, West Nile Virus. 

Donor tested negative and products were distributed. The donor returned and

tested confirmed positive at your establishment for a viral marker (HIV, HBV

or HCV) for which we require or recommend lookback (21 CFR 610.46 fo

HIV Lookback, and “Recommendations for the Quarantine and Disposition o

Units from Prior Collections from Donors with Repeatedly Reactive 

Screening Tests f

Human T-Lym

TE: You may not need

ude only those products subject to lookback, as identified in the regulation or 

ed in guidance. 

29 
Contains Nonbinding Recommendations 

V. REFERENCES 

1. Biological Products: Reporting of Errors and Accidents in Manufacturing; Proposed Rule 

(62 FR 49642, September 23, 1997). 

2. Biological Products: Reporting of Biological Product Deviations in Manufacturing; Final 

Rule (65 FR 66621, November 7, 2000). 

3. Memorandum to All Registered Blood Establishments: “Responsibilities of Blood 

Establishments Related to Errors & Accidents in the Manufacture of Blood & Blood 

Components,” March 20, 1991. 

4. Memorandum to All Registered Blood and Plasma Establishments: “Guidance Regarding 

Post Donation Information Reports,” December 10, 1993. 

5. Guideline for Quality Assurance in Blood Establishments, July 11, 1995. 

6. Guidance for Industry: Biological Product Deviation Reporting for Licensed 

Manufacturers of Biological Products Other than Blood and Blood Components, October 

2006. 

7. Guidance for Industry: Changes to an Approved Application: Biological Products: 

Human Blood and Blood Components Intended for Transfusion or for Further 

Manufacture, July 2001. 

8. Memorandum to All Registered Blood and Plasma Establishments: “Recommendations 

for the Quarantine and Disposition of Units from Prior Collections from Donors with 

Repeatedly Reactive Screening Tests for Hepatitis B Virus (HBV), Hepatitis C Virus 

(HCV) and Human T-Lymphotropic Virus Type I (HTLV-I),” July 19, 1996. 

30