Guidance for Industry

Notifying FDA of Fatalities Related to 

Blood Collection or Transfusion 

FINAL GUIDANCE

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

Manufacturers Assistance (HFM-40), 1401 Rockville Pike, 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 Lois Simmons at 301-827-6220.

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Biologics Evaluation and Research

September 2003
Contains Nonbinding Recommendations

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Table of Contents

I. PURPOSE.............................................................................................................. 1

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

III. HOW TO NOTIFY FDA................................................................. 2

IV. INITIAL NOTIFICATION.............................................................. 2 

A. Patient/Recipient Fatalities...................................................................... 3

B. Donor Fatalities......................................................................................... 3

C. Fatalities Associated with Therapeutic Apheresis or Certain 

Therapeutic Phlebotomies........................................................................ 3

V. 7-DAY REPORT................................................................................................... 3

A. Patient/Recipient Fatalities...................................................................... 4

B. Donor Fatalities......................................................................................... 4

C. Fatalities Associated with Therapeutic Apheresis or Certain 

Therapeutic Phlebotomies........................................................................ 5

VI. INQUIRIES ........................................................................................................... 5
Contains Nonbinding Recommendations

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Guidance for Industry

Notifying FDA of Fatalities Related to Blood Collection or 

Transfusion 

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. PURPOSE

This document’s goal is to help you, a blood collection or transfusion facility, report fatalities 

related to blood and blood component (blood) collection or transfusion to us, the Food and Drug 

Administration (FDA), Center for Biologics Evaluation and Research (CBER). This guidance 

finalizes the draft guidance of the same title dated June 2002.

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

responsibilities. Instead, guidances describe the FDA’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 FDA’s guidances mean that something is suggested or 

recommended, but not required.

II. BACKGROUND

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

require that you report fatalities related to blood collection or transfusion to CBER (21 CFR

606.170(b)). Section 606.170(b) states:

When a complication of blood collection or transfusion is confirmed to be fatal, 

the Director, Office of Compliance and Biologics Quality, Center for Biologics 

Evaluation and Research, shall be notified by telephone, facsimile, express mail, 

or electronically transmitted mail as soon as possible; a written report of the 

investigation shall be submitted to the Director, Office of Compliance and 

Biologics Quality, Center for Biologics Evaluation and Research, within 7 days 

after the fatality by the collecting facility in the event of a donor reaction, or by 

the facility that performed the compatibility tests in the event of a transfusion 

reaction. (Emphasis added)
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Standard operating procedures for compatibility testing are required in 21 CFR 606.151 

and 606.100(b)(8). Among other things, that regulation requires an establishment to have 

procedures both for collecting and identifying the blood samples of recipients, and for 

demonstrating incompatibility between the donor’s cell type and the recipient’s serum or 

plasma type. CBER is aware that some blood banks and transfusion services may enter 

into contracts with blood centers or other blood banks or clinical laboratories to perform 

testing on blood samples. If this is how your facility operates, the responsibility for 

compatibility testing is shared between the blood bank or transfusion service that collects 

and identifies the blood sample of the recipient, and the blood center or other blood bank 

or clinical laboratory that uses procedures to demonstrate incompatibility between the 

donated blood product and the recipient. If a transfusion-related fatality occurs, both the 

transfusing facility and the blood center or bank that performed the testing under contract 

would be responsible for reporting the death to CBER. Under these circumstances, the 

two facilities may make a joint report under § 606.170(b).

III. HOW TO NOTIFY FDA

Section 606.170(b) states that you may report a fatality by telephone, facsimile, express mail, or 

electronically transmitted mail (e-mail). We recommend that you submit the initial notification 

by e-mail, if possible, and if you do so, you will receive an e-mail confirmation receipt from us. 

If e-mail is not feasible, please notify us by telephone or facsimile. We cannot access 

notification outside of customary working hours unless you use e-mail or telephone. Similarly, 

we recommend that you submit 7-day follow up reports by e-mail, facsimile, or express mail.

• E-mail: fatalities2@cber.fda.gov

• Telephone/voice-mail number: 301-827-6220

• Fax number: 301-827-6748, Attn: CBER Fatality Program Manager 

• Express mail address:

Office of Compliance and Biologics Quality/CBER

Attn: Fatality Program Manager (HFM-650)

1401 Rockville Pike, Suite 200N

Rockville, MD 20852-1448

IV. INITIAL NOTIFICATION

There is no required FDA form or format for notifying us of fatalities related to blood transfusion 

or blood collection. We recommend that you provide at least the following information so we 

can evaluate the potential public health significance of the event.

• Date and time of the notification.

• Your name, title, telephone number with area code, and fax number (if available).

• Your facility's name, mailing address, and FDA registration number (if applicable). 

NOTE: Transfusion services that do not routinely collect or process blood or blood 

components are not required to register with FDA and, therefore, do not usually have a 

registration number.
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• Age and sex of the deceased.

• Date, time, and cause or suspected cause of death (briefly describe what happened).

• If an autopsy was or will be performed.

• Name and address of facility where the fatality occurred if different from your facility.

• Please also include in the initial notification the information listed in A, B, or C below, as 

appropriate:

A. Patient/Recipient Fatality

- Transfusion date(s),

- Blood/blood component(s) and unit number(s) of product(s) that may be 

implicated,

- Name and address of facility(ies) providing the blood, and

- Brief description of events that led to the fatality – include underlying medical 

condition or disease and circumstances necessitating this hospitalization, reason 

for transfusion, how the patient initially responded to the transfusion, any 

medical intervention taken or response to the reaction, and time from initiating 

the transfusion to patient’s death.

B. Donor Fatality

- Collection date,

- What product was collected or attempted to be collected,

- Whether this was a manual or automated collection,

- If automated, the name and model of collection device and device manufacturer, 

and

- Brief description of events that led to the fatality – include an overview of the 

donor’s previous donations/health history, approximate frequency of donation,

any unusual events that occurred during this or any previous donation by the 

donor, any medical intervention taken or response to the reaction, and time from 

initiating the blood collection to donor’s death. 

C. Fatality Associated with Therapeutic Apheresis or Certain Therapeutic 

Phlebotomies

- Date of therapeutic apheresis (e.g., therapeutic plasma exchange) or therapeutic 

phlebotomy,

NOTE: A report is required for a therapeutic apheresis fatality only if blood 

products (e.g., plasma, albumin), rather than products such as crystalloids or 

hydroxyethyl starch, were given as part of the procedure. A report is required 

for a therapeutic phlebotomy fatality only if a blood product was collected for 

manufacture into transfusable biologics. 

- Whether product was collected, and the product’s disposition, 

- Whether this was a manual or automated collection (if automated, include 

manufacturer, name, and model of collection device),

- If any blood product(s) was transfused, identify the product and the unit or lot 

number(s), and

- Brief description of events that led to the fatality – include underlying medical 

condition or disease and circumstances necessitating the therapeutic apheresis or 
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therapeutic phlebotomy, any medical intervention or response to the reaction, 

and time from initiating the procedure to patient’s death.

V. 7-DAY REPORT

You must submit a written report of the fatality investigation to CBER within 7 days after the 

fatality (§ 606.170(b)). We recommend that you identify this report as a follow-up on a fatality 

notification previously reported to CBER and include the initial notification date. We also 

recommend that this 7-day report provide any new findings or information relevant to the fatality 

that have become available since the initial notification, including your follow-up investigation 

and conclusions.

Section 606.170(a) requires that you conduct a “thorough investigation” of adverse reactions 

relating to blood collection or transfusion. Section 606.170(b) requires submission of a written 

report of such investigation within 7 days after an adverse reaction resulting in fatality. We 

recommend that a “thorough investigation,” and an associated written report for a fatality, 

include:

• Discharge summary and/or death certificate,

• Autopsy report (if performed),

• Conclusions and follow-up actions (frequently referred to in the blood community as a 

corrective action plan), if appropriate, and 

• Either A, B, or C listed below, as appropriate.

We understand that, due to the complexity of some fatality investigations, some of this 

information may not be available when you submit your 7-day report. In that event, you may 

amend your 7-day report by filing additional information as it becomes available.

A. Patient/Recipient Fatality

- Complete transfusion reaction report, including the manufacturer and lot number 

of the blood collection system and results of the clerical, serological, and visual 

re-checks performed.

- Additional relevant documents, include hematology reports; clinical chemistry 

reports for cardiac and/or liver enzymes, albumin, and bilirubin; viral marker 

tests; microbiology reports; reports of anti-HLA and/or anti-neutrophil antibody 

testing; tryptase levels; radiology reports; and physicians’ consults/opinions.

- If replacement fluid(s) was given during the transfusion, indicate which fluid(s) 

and the unit or lot number(s), and include any other relevant information, 

manufacturer’s notices, contamination warnings, or replacement fluid recalls.

- If responsibility for the fatality appears to be outside the blood bank, the nurses’ 

and/or physicians’ notes on the patient, radiology reports, and physicians’ 

consults/opinions.

- Results of lookback investigation, including follow-up testing on implicated 

donor(s) when the fatality was the result of transfusion transmitted infectious 

disease such as hepatitis or HIV.
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- Meeting minutes or report from your transfusion committee when the fatality 

was reviewed and discussed. If this incident was reviewed by any other hospital 

oversight group(s) such as risk management or quality practices, include the 

report or summary of their findings.

B. Donor Fatality

- The deceased’s donor record file that includes the donation just before the fatal 

incident and information on all donations during the past 2 years.

- Lot numbers and expiration dates of collection sets or harnesses; if replacement 

fluid(s) was given during the collection, indicate which fluid(s) and the unit or 

lot number(s) and include any other relevant information, such as 

manufacturer’s notices, contamination warnings, or replacement fluid recalls.

- Performance log for the device and any other relevant performance logs, 

maintenance records, manufacturer’s notices, or recalls on significant machine 

part(s) on the device/system during the past 2 years.

- If the donor was hospitalized due to the reaction, provide any relevant 

documents, e.g., reports of laboratory tests, which may help determine the cause 

of the fatality. 

C. Fatality Associated with Therapeutic Apheresis or Certain Therapeutic 

Phlebotomies

- A summary of the deceased’s history of previous therapeutic apheresis or 

therapeutic phlebotomy procedures, including any previous adverse reactions 

related to the procedures. 

- Lot numbers and expiration dates of collection sets or harnesses; if replacement 

fluid(s) was given at any time during the procedure, indicate which fluid(s) and 

the unit or lot number(s) and include any other relevant information, such as 

manufacturer’s notices, contamination warnings, or replacement fluid recalls.

- A summary of the performance log for the device and any other relevant 

performance logs, maintenance records, and manufacturer’s notices or recalls on 

any significant machine part(s) on the device/system during the past 2 years.

- If the fatality followed therapeutic plasma exchange (TPE) and Fresh Frozen 

Plasma (FFP) was the replacement fluid, an abbreviated transfusion reaction 

work-up to rule out ABO incompatibility, bacterial contamination, anaphylactic 

reaction, or WBC antibody reaction may be useful.

VI. INQUIRIES

If you have any questions about reporting fatalities, please contact the CBER Fatality Program 

Manager at 301-827-6220.