Bacterial Risk Control Strategies for 
Blood Collection Establishments and 
Transfusion Services to Enhance the 
Safety and Availability of Platelets for 
Transfusion
 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email ocod@fda.hhs.gov, or 
from the Internet at  
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-
biologics/biologics-guidances.  
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
September 2019 
Updated December 2020 
  Contains Nonbinding Recommendations 
 
Table of Contents 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS .................................................................................................. 3 
A.  General Considerations ........................................................................................ 3 
B.  Strategies for Apheresis Platelets and/or Pre-Storage Pools of WBD Platelets
................................................................................................................................. 4 
1.  Single-step Strategies .............................................................................................. 5 
2.  Two-step Strategies ................................................................................................. 6 
C.  Strategies for Single Units and Post-storage Pools of WBD Platelets .............. 9 
D.  Labeling ............................................................................................................... 10 
1.  Labels on the Container ........................................................................................ 10 
2.  Circular of Information ......................................................................................... 10 
IV.  REPORTING IMPLEMENTATION OF MANUFACTURING AND LABELING 
CHANGES ....................................................................................................................... 10 
A.  Prior Approval Supplement (PAS) .................................................................... 11 
B.  Annual Report ..................................................................................................... 13 
V.  TRANSFUSION SERVICESREGISTRATION AND BLOOD PRODUCT 
LISTING .......................................................................................................................... 13 
VI.  IMPLEMENTATION .................................................................................................... 14 
VII.  REFERENCES ................................................................................................................ 15 
APPENDIX A:  BACTERIAL RISK CONTROL STRATEGIES ASSOCIATED WITH 
SPECIFIC PLATELET STORAGE DURATION AND TYPE OF PLATELET 
UNIT................................................................................................................................. 16 
APPENDIX B:  SUMMARY OF BACTERIAL RISK CONTROL STRATEGIES FOR 
APHERESIS AND PRE-STORAGE POOLS OF WBD DERIVED PLATELETS . 17 
APPENDIX C:  SUMMARY OF BACTERIAL RISK CONTROL STRATEGIES FOR 
SINGLE UNIT WBD PLATELETS AND POST-STORAGE POOLS OF WBD 
PLATELETS ................................................................................................................... 18 
APPENDIX D:  EXAMPLE TIMELINES OF BACTERIAL RISK CONTROL 
STRATEGIES FOR APHERESIS PLATELETS ....................................................... 19 
 
 
i 
  Contains Nonbinding Recommendations 
 
Bacterial Risk Control Strategies for Blood Collection 
Establishments and Transfusion Services to Enhance the Safety and 
Availability of Platelets for Transfusion 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
We, FDA, are issuing this guidance document to provide you, blood collection establishments 
and transfusion services, with recommendations to control the risk of bacterial contamination of 
room temperature stored platelets intended for transfusion.1  The recommendations in this 
guidance apply to all platelet products stored at room temperature in plasma or additive 
solutions, including platelets manufactured by automated methods (apheresis platelets), and 
Whole Blood derived (WBD) single and pooled (pre-storage and post-storage) platelets.   
 
Additionally, this guidance provides licensed blood establishments with recommendations on 
how to report implementation of manufacturing and labeling changes under Title 21 of the Code 
of Federal Regulations (CFR) 601.12.   
 
This guidance updates the final guidance of the same title dated September 2019.  The 
September 2019 guidance finalized the draft guidance of the same title dated December 2018. 
We received numerous comments from blood collection establishments requesting an extension 
of the implementation timeframe because of various unforeseen challenges, including responding 
to the COVID-19 public health emergency.  Consequently, we have extended the recommended 
implementation timeframe in section VI. of the guidance.  In addition, we clarified the 
recommendations for submission of information in a prior approval supplement submission in 
section IV.A.2.f. and g. of the guidance.  We also removed a footnote regarding the lack of 
appropriately labeled devices for implementation of the large volume, delayed sampling no 
sooner than 48 hours strategy for a 7-day dating period in section III.B.1.b. of the guidance 
because of a recent device clearance. 
 
                                                 
1 Cold storage (1 to 6C) of platelet products as a strategy to control bacterial risk is outside the scope of this 
guidance document.  However cold storage of platelets may be found acceptable by FDA as an approach to assure 
that the risk of bacterial contamination is adequately controlled.  Blood establishments should discuss with FDA 
methods of preparation and storage of cold-stored platelets. 
1  Contains Nonbinding Recommendations 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the FDAs 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 FDAs guidances means that something is suggested or 
recommended, but not required. 
 
 
II.  BACKGROUND 
 
Room temperature stored platelets are associated with a higher risk of sepsis and related fatality 
than any other transfusable blood component.  The risk of bacterial contamination of platelets is 
a leading risk of infection from blood transfusion.  Bacterial residual risk per transfused unit on 
the day of transfusion is estimated at about 1/2500 (Ref. 1), and fatal transfusion reactions from 
undetected contaminated platelet collections continue to occur (Refs. 2, 3).  This risk has 
persisted despite the implementation of numerous interventions, including the commonly used 
method of a single culture performed no sooner than 24 hours after collection of the platelets 
(Refs. 1, 3, 4, 5, 6).  
 
The reported rates of septic transfusion reaction from platelets vary from 1/100,000 by passive 
surveillance to 1/10,000 by active surveillance, following testing with single culture performed 
no sooner than 24 hours after collection (Refs. 1, 7).  Surveillance data on platelets stored up to 
5 days have shown that 95 to100% of platelet transfusion-related septic reactions (Refs. 4, 8) and 
100% of associated fatalities (Ref. 8) have occurred with transfusion of day 4 and day 5 stored 
platelets. 
 
FDA has established regulations to address the control of bacterial contamination of platelets.  
Under 21 CFR 606.145(a), blood establishments and transfusion services must assure that the 
risk of bacterial contamination of platelets is adequately controlled using FDA approved or 
cleared devices, or other adequate and appropriate methods found acceptable for this purpose by 
FDA.   
 
Currently, the bacterial contamination risk in room temperature stored platelet products can be 
controlled by bacterial testing or pathogen reduction methods.  Pathogen reduction is typically 
performed shortly after platelet collection.   
 
Bacterial testing is performed using culture-based or rapid detection devices.  Primary testing is 
the initial bacterial detection test, usually by culture methods, performed following collection.  
Primary testing is typically performed using at least an aerobic culture, with sampling of the 
platelets occurring no earlier than 24 hours after collection.  The use of an additional anaerobic 
culture can enhance the detection of obligate anaerobic organisms, which have been associated 
with the occurrence of septic transfusion reactions (Ref. 6), and can shorten time to bacterial 
detection of certain organisms (Ref. 9).  However anaerobic bacterial testing is associated with 
higher false positive rates (Ref. 10) than with aerobic testing alone.  Secondary testing is any 
additional test of a platelet component to detect bacteria in a unit that showed no bacterial 
contamination upon primary testing.  Secondary testing consists of culture-based or rapid testing 
methods. 
2  Contains Nonbinding Recommendations 
 
 
Under 21 CFR 610.53(b), the dating period (expiration date) for platelets with a storage 
temperature between 20 and 24 degrees Celsius is 5 days from the date of collection, unless a 
different dating period is specified in the instructions for use by the blood collection, processing 
and storage system approved or cleared for such use by FDA.  Consistent with this requirement, 
the recommendations in this guidance on extension of platelet dating beyond day 5 may not be 
implemented absent the use of cleared or approved and suitably labeled platelet storage 
containers, bacterial detection, and pathogen reduction devices2.  In the United States (U.S.), the 
current maximum dating period) for platelets with a storage temperature between 20 and 24 
degrees Celsius is up to 7 days in the FDA-cleared or approved storage containers.   
 
Since 2012, FDA has held three Blood Products Advisory Committee (BPAC) meetings to 
address bacterial risk in platelet products.  The most recent BPAC meeting, in July 2018 (Ref. 
11), discussed the scientific evidence and operational considerations of available strategies to 
control the risk of bacterial contamination of platelets with 5-day and 7-day dating, including 
bacterial testing strategies (using culture-based and rapid bacterial detection devices) and 
pathogen reduction technology.  Subsequently, FDA published the December 2018 draft 
guidance.  Comments to the published draft guidance documents, as well as the BPAC 2018 
proceedings, provided the foundation for the recommendations in this guidance. 
 
 
III.  RECOMMENDATIONS 
 
A.  General Considerations 
 
1.  The recommendations in this guidance entail the use of FDA-cleared or approved 
bacterial detection devices, pathogen reduction devices, and platelet storage 
containers.   
 
2.  Bacterial detection testing, pathogen reduction, and storage in platelet containers 
must be conducted consistent with the instructions for use of the device (21 CFR 
606.65(e)).  
 
3.  Blood collection establishments and transfusion services should have in place 
measures to promptly alert the collection establishment or transfusion service if a 
distributed platelet product is subsequently identified as positive for bacterial 
contamination. 
 
4.  Depending on the recommendation, sampling or testing time in this guidance is 
expressed in units of hours or days:  
 
                                                 
2 At the time of finalization of this guidance, storage systems that ensure platelet efficacy past 5 days of storage, and 
up to 7 days of storage, of platelets treated by pathogen reduction technology (PRT) are not available.  Extended 
dating past 5 days based on pathogen reduction of apheresis platelets may not be implemented until such 
technologies are approved for use in this blood component (21 CFR 606.65(e)). 
3  Contains Nonbinding Recommendations 
 
a.  When timing is expressed in units of hours, it is in reference to the actual 
hour of collection or sampling.  For example, if a platelet product is 
collected at 9 am (0:900) on January 1st, sampling performed no earlier 
than 24 hours from time of collection means that sampling should be 
performed no earlier than 9 am (0:900) on January 2nd; sampling 
performed no earlier than 36 hours means sampling no earlier than 9 pm 
(21:00) on January 2nd. 
 
b.  When timing is expressed in units of days, it is in reference to the day of 
collection, which is considered day 0.  A day is defined as beginning at 
midnight (00:00) and ending at 23:59.  Expiry day refers to 23:59 of the 
stated day (i.e., prior to midnight).  For example, if a platelet is collected 
on January 1st (day 0) at 9 am (0:900) with a 5-day storage period, it 
means it will expire at 23:59 on January 6th. 
 
c.  When sampling is recommended to be conducted on a specific day, it 
means that sampling can occur at any time on that day prior to midnight, 
regardless of the time of the initial collection.  For example, if a platelet is 
collected on January 1st at 9 am (day 0), secondary culture performed on 
day 3 should be performed on January 4th, at any time prior to midnight.  
 
5.  Products may be shipped during the recommended culture incubation periods, 
provided the blood collection establishment establishes procedures to maintain 
control of the product during the incubation period. 
 
6.  Blood collection establishments and transfusion services must not release for 
transfusion platelets identified as bacterially contaminated (21 CFR 606.145(b) 
and (c)). 
 
7.  Following secondary testing, it is not expected that blood collection 
establishments or transfusion services retest units to determine platelet yield. 
 
8.  Blood collection establishments and transfusion services should establish 
procedures to assure traceability of the bacterial testing status of platelet products 
in their inventory. 
 
B.  Strategies for Apheresis Platelets and/or Pre-Storage Pools of WBD Platelets 
 
The recommended strategies for apheresis platelets and pre-storage pools of WBD 
platelets are either single-step or two-step.  Each strategy will include the applicable 
platelet component and dating period (up to 5 days, or up to 7 days).  Please see 
Appendices A and B to this guidance for summary tables of the strategies described in 
section III.B. of the guidance.  Example timelines for the strategies for apheresis 
platelets are provided in Appendix D to this guidance. 
 
4  Contains Nonbinding Recommendations 
 
1.  Single-step Strategies 
 
Implementation of a single-step strategy entails the conduct of one step:   
 
a.  Large volume, delayed sampling (LVDS) no sooner than 36 hours 
 
This strategy applies to apheresis platelets and pre-storage pools of WBD platelets, 
and consists of: 
 
1.  A single culture with sampling performed no sooner than 36 hours after 
collection using a sampling volume of at least 16 mL, inoculated evenly 
into aerobic and anaerobic culture media. 
 
2.  Sampling each apheresis unit or each pre-storage pool of WBD platelets 
for culture.  If the apheresis product will be split, each split unit should be 
sampled. 
 
We recommend a minimum incubation period of 12 hours prior to release for 
transfusion.  
 
Dating: 
 
Products should be labeled with a 5-day expiration.  
 
Note:  LVDS conducted no sooner than 36 hours may also constitute Step 1 of a 
2-Step strategy to extend storage beyond 5 days.  See section III.B.2. of this 
guidance for additional detail. 
 
b.  LVDS no sooner than 48 hours 
 
This strategy applies to apheresis platelets and consists of: 
 
1.  A single culture performed no sooner than 48 hours after collection using a 
sampling volume of at least 16 mL, inoculated evenly into aerobic and 
anaerobic culture media. 
 
2.  Sampling each apheresis unit for culture.  If the apheresis product will be 
split, each split unit should be sampled.  
 
We recommend a minimum incubation period of 12 hours prior to release for 
transfusion. 
 
Dating: 
 
Products should be labeled with an expiration of up to 7 days.   
 
5  Contains Nonbinding Recommendations 
 
Note:  Bacterial testing to extend dating beyond day 5 and up to day 7 should be 
performed with devices labeled with LVDS as an acceptable safety measure.3  
Platelet storage containers must be cleared or approved by FDA for 7-day storage. 
 
c.  Pathogen Reduction 
 
Based on current device labeling, this strategy applies to apheresis platelets.  The 
strategy could apply to other platelet products in the future if appropriately 
labeled pathogen reduction devices and storage containers become available.  
Platelets that have been treated by FDA approved pathogen reduction devices 
according to the device instructions for use need no further measures to control 
the risk of bacterial contamination of platelets. 
   
Dating: 
 
Pathogen reduced components should be labeled with expiration dates consistent 
with the instructions for use for the pathogen reduction device, currently 5 days 
(see section III.A.2. of this guidance).  
 
2.  Two-step Strategies 
 
Implementation of a two-step strategy entails the conduct of two successive steps, 
Steps 1 and 2.  
 
a.  Step 1 
 
Step 1 consists of one of the following: 
 
i.  Primary culture performed no sooner than 24 hours 
 
This applies to both apheresis platelets and pre-storage pools of WBD 
platelets, and consists of: 
 
1.  A culture performed no sooner than 24 hours after collection with a 
sampling volume of at least 16 mL, inoculated evenly into aerobic 
and anaerobic culture media  
 
2.  Sampling each apheresis collection or each pre-storage pool of WBD 
platelets.  If the collection will be split into multiple units, either the 
main collection alone (mother bag) or split units may be tested. 
 
We recommend a minimum incubation period of 12 hours. 
                                                 
3 Bacterial testing devices are labeled as a safety measure under one of the following three conditions:  1) when 
clinical studies have shown benefit for detection of bacterial contamination not revealed by previous bacterial 
testing; 2) when the bacterial testing devices have analytical sensitivity at least equivalent to a previously cleared 
safety measure device; or 3) when the bacterial testing devices qualify by other methods found acceptable to FDA.  
6  Contains Nonbinding Recommendations 
 
 
Dating: 
 
Products should be labeled with a 5-day expiration.  To assure that the risk of 
bacterial contamination is adequately controlled for transfusion after day 3 of 
storage, secondary testing should be performed on the product (see Step 2 in 
section III.B.2.b. of this guidance).  
 
ii.  LVDS no sooner than 36 hours 
 
LVDS performed no sooner than 36 hours after collection (see section III.B.1. 
a. of this guidance) can serve as the initial step of a two-step strategy when 
storage is intended to be extended beyond 5 days.  
 
b.  Step 2 
 
Step 2 consists of one of the following: 
 
i.  Secondary culture performed no sooner than Day 3 
 
This applies to apheresis platelets and pre-storage pools of WBD platelets, 
follows Step 1, and consists of:  
 
  Culture performed no sooner than day 3 of storage using at least an 8 
mL sampling volume inoculated into at least an aerobic medium.4  If 
the collection had been split, each split apheresis unit should be 
sampled for culture. 
 
We recommend that you establish a minimum incubation period in your 
Standard Operating Procedures (SOPs) for the secondary culture.  
 
During the incubation period of the secondary culture, products remain in-
date through their labeled storage period, and removal of products from 
inventory is not required during any portion of the labeled storage, provided 
you have developed procedures to 1) identify when secondary testing has 
been completed, and 2) maintain product control during the incubation 
period.  
 
   
                                                 
4 Use of a device labeled as a safety measure is not required when secondary testing is performed to adequately 
control bacterial risk through day 5 of storage (see footnote 3). 
7  Contains Nonbinding Recommendations 
 
Dating: 
 
Products should be labeled with a 5-day expiration. 
 
ii.  Secondary culture performed no sooner than Day 4 
 
This applies to apheresis platelets, follows Step 1, and consists of:  
 
  Culture performed no sooner than day 4 of storage with at least 16 mL 
total sample volume, inoculated evenly between aerobic and 
anaerobic culture media.  If the collection had been split, each split 
apheresis unit, should be sampled for culture. 
 
We recommend a minimum incubation period of 12 hours.  
 
During the incubation period of the secondary culture, products remain in-
date through their labeled storage period, and do not necessitate removal 
from inventory during any portion of the labeled storage, provided you have 
developed procedures to identify when secondary testing has been completed, 
and maintain product control during the recommended incubation period.  
 
Dating: 
 
Products should be labeled with an expiration of up to 7 days.   
 
Note:  Bacterial testing to extend dating beyond day 5 and up to day 7 should 
be performed with devices labeled as safety measure.5  Platelet storage 
containers must be cleared or approved by FDA for 7-day storage. 
 
iii. Secondary rapid testing 
 
This applies to apheresis platelets and pre-storage pools of WBD platelets, 
follows Step 1, and consists of: 
 
  A secondary rapid test performed in accordance with the rapid testing 
device labeling.   
 
Dating: 
 
Products may be labeled with an expiration of up to 7 days.   
 
Note:  Bacterial testing to extend dating beyond day 5 and up to day 7 should 
be performed with devices labeled as safety measure6.  Platelet storage 
containers must be cleared or approved by FDA for 7-day storage. 
                                                 
5 See footnote 3. 
6 See footnote 3. 
8  Contains Nonbinding Recommendations 
 
 
C.  Strategies for Single Units and Post-storage Pools of WBD Platelets 
 
The recommended strategies for single units of WBD platelets and post-storage pools of 
WBD platelets are single-step.  Please see Appendices A and C for summary tables of the 
strategies described in section III.C. of this guidance. 
 
1.  Rapid bacterial testing 
 
This applies to single units of WBD platelets and post-storage pools of previously 
untested WBD platelets and consists of: 
 
  A rapid test performed in accordance with the device labeling.   
 
Dating: 
 
  Single units:  Products should be labeled with a 5-day expiration. 
  Post-storage pools of WBD platelets:  Products expire 4 hours after pooling 
(21 CFR 606.122(l)(2)).  
 
2.  Single culture with sampling performed no sooner than 36 hours after 
collection  
 
This applies to single units of WBD platelets and consists of the following: 
 
  A single culture performed no sooner than 36 hours after collection.  
Testing should include inoculation into aerobic culture media.  A single 
unit of WBD platelets represents a relatively small volume.  Therefore, the 
largest practical volume within the range permitted by the bacterial testing 
device instructions for use should be used for culture.  
 
We recommend a minimum incubation period of 12 hours prior to release for 
transfusion. 
 
Dating: 
 
Products should be labeled with a 5-day expiration.  
 
3.  Single culture with sampling performed no sooner than 24 hours after 
collection  
 
This applies to single units of WBD platelets and consists of the following: 
 
  A single culture performed no sooner than 24 hours after collection.  
Testing should include inoculation into aerobic culture media.  A single 
unit of WBD platelets represents a relatively small volume.  Therefore, the 
9  Contains Nonbinding Recommendations 
 
largest practical volume within the range permitted by the bacterial testing 
device instructions for use should be used for culture.  
 
We recommend a minimum incubation period of 12 hours prior to release for 
transfusion. 
 
Dating: 
 
Products should be labeled with a 5-day expiration.  If the unit is transfused after day 
3 of storage, secondary rapid testing (see section III.C.1. of this guidance) may be 
considered.  
 
D.  Labeling 
 
1.  Labels on the Container 
 
a.  The container labels must comply with 21 CFR 606.121 and 21 CFR 610.60.  
Blood collection establishments and transfusion services, as appropriate, must 
also follow the general requirements for labeling operations described in 21 
CFR 606.120.  
 
b.  The container labels must include the expiration date and time, if applicable, 
of the product based on bacterial detection testing (21 CFR 606.121(c)(4)(i)). 
 
c.  If dating is extended beyond 5 days, the blood establishment or transfusion 
service that performed the secondary testing must update the container label to 
reflect the new expiration date (21 CFR 606.121(c)(4)(i)).  
 
2.  Circular of Information 
 
You must update your Circular of Information to include information about the 
tests performed or pathogen reduction used to control the risk of bacterial 
contamination of platelets (21 CFR 606.122).  
 
 
IV.  REPORTING IMPLEMENTATION OF MANUFACTURING AND LABELING 
CHANGES 
 
An establishment that distributes platelet products in interstate commerce must have an approved 
biologics license application (BLA), in accordance with section 351 of the Public Health Service 
Act. 
 
Licensed establishments must report changes to their approved BLA in accordance with 21 CFR 
601.12.  The information below is intended to assist you in determining which reporting 
mechanism is appropriate for a change to your approved BLA, as it applies to the bacterial testing 
of platelet products and the manufacture of apheresis platelets with a 6-day or 7-day dating 
10  Contains Nonbinding Recommendations 
 
period.7  You should prominently label each submission with the reporting category under which 
you are reporting your change, for example, Prior Approval Supplement, or Annual Report. 
 
A.  Prior Approval Supplement (PAS) 
 
1.  Under 21 CFR 601.12(b), changes that have a substantial potential to have an 
adverse effect on the identity, strength, quality, purity, or potency of the product 
as they may relate to the safety or effectiveness of the product must be reported 
to FDA in a Prior Approval Supplement (PAS).  You must not distribute in 
interstate commerce blood components made using a new or changed 
manufacturing process requiring a PAS until you have received our approval of 
your PAS (21 CFR 601.12(b)(3)). 
 
We believe a PAS submission is appropriate in the following situations: 
 
  You are currently licensed to manufacture apheresis platelets with a 5-day 
expiration date and you choose to extend the storage time to a 6-day or 7-
day expiration date and distribute these products in interstate commerce. 
 
2.  To comply with the requirements in 21 CFR 601.12(b)(3), you must include the 
following minimum information in your PAS submission: 
 
a.  Form FDA 356h, Application to Market a New or Abbreviated New 
Drug or Biologic for Human Use. 
 
b.  List of the platelet products involved. 
 
c.  Address and registration number of the manufacturing facility/facilities. 
 
d.  A detailed description of the manufacturing process.  We recommend 
the submission of written SOPs that include processes for: 
 
i.  Component manufacturing (if these SOPs were previously 
approved by FDA, include the reference number under which 
they were reviewed). 
 
ii.  Bacterial detection testing, including the name of the devices(s) 
used for bacterial detection, when the platelet product is sampled 
and when the product will be released. 
 
                                                 
7 FDAs recommendations for the implementation of pathogen reduction are provided in the guidance document 
titled, Implementation of Pathogen Reduction Technology in the Manufacture of Blood Components in Blood 
Establishments:  Questions and Answers; Draft Guidance for Industry, dated December 2017.  The draft guidance, 
when finalized, will represent FDAs current thinking on this topic. 
 
11  Contains Nonbinding Recommendations 
 
iii. Labeling the platelet product based on the bacterial detection 
testing. 
 
iv. Alerting the consignee that a distributed platelet product has tested 
positive for bacterial contamination. 
 
v.  Quarantine and disposition of unsuitable products. 
 
vi. Investigation of units with positive test results. 
 
vii. Informing consignees of the type of storage container the 
platelets are stored in, for example, whether the storage 
container is approved for 5-day storage or 7-day storage. 
 
e.  The name, address and registration number, if available, of any 
contractors who are performing bacterial detection testing of platelet 
products for you. 
 
f.  Validation plan for the bacterial detection testing method and a 
summary of the validation data if a new testing method is used. 
 
g.  Quality control data for the pH at end of storage (7 days) for a 
minimum of four units prepared from different donors and representing 
all platelet product types (i.e., singles, doubles, triples) at each 
manufacturing facility that will have the expiration date extended to 7 
days. 
 
h.  Labeling  include the following in your supplement: 
 
i.  Container Labels:  A container label for each platelet product, 
unless previously approved by FDA, that includes the 
expiration date, and, if applicable, expiration time, of the 
platelet product.  
 
ii.  Circular of Information.   
 
3.  You may also consider submitting a Comparability Protocol as a PAS under 21 
CFR 601.12(e).  A Comparability Protocol is not required, but an approved 
Comparability Protocol may justify a reduced reporting category for 
manufacturing apheresis platelets with a 6-day or 7-day expiration date in 
multiple locations.  In addition to the content listed in section IV.A. of this 
guidance, Comparability Protocol submissions under 21 CFR 601.12(e) must also 
include the plan for implementing the bacterial detection testing at multiple 
manufacturing sites.  The plan should include a description of how you will 
validate the new procedures.  For additional information about submitting 
Comparability Protocols, please refer to the FDA Guidance for Industry:  Changes 
12  Contains Nonbinding Recommendations 
 
to an Approved Application:  Biological Products: Human Blood and Blood 
Components Intended for Transfusion or for Further Manufacture, dated 
December 2014.  Available at https://www.fda.gov/media/86137/download. 
 
B.  Annual Report 
 
Under 21 CFR 601.12(d), changes in the product, production process, quality controls, 
equipment, facilities, or responsible personnel that have a minimal potential to have an 
adverse effect on the identity, strength, quality, purity, or potency of the product as they 
may relate to the safety or effectiveness of the product must be documented in an annual 
report submitted each year within 60 days of the anniversary date of approval of the 
BLA. 
 
We believe the following changes may be submitted in an Annual Report8 noting the 
date the process was implemented: 
 
1.  Implementation of bacterial detection testing as described in this guidance 
without modification and the expiration date of apheresis, single units of WBD 
platelets, and pre-storage pooled WBD platelets remains at 5 days. 
 
2.  You or your contractor change from one type of FDA cleared bacterial detection 
device to another type of FDA-cleared bacterial detection device.  
 
NOTE:  For assistance in reporting your changes, see FDAs Changes to an Approved 
Application:  Biological Products:  Human Blood and Blood Components Intended for 
Transfusion or for Further Manufacture; Guidance for Industry dated December 2014.  
The December 2014 guidance represents FDAs current thinking on this topic and can 
be found on FDAs website at:  https://www.fda.gov/media/86137/download. 
 
 
V.  TRANSFUSION SERVICESREGISTRATION AND BLOOD PRODUCT 
LISTING 
 
Except as provided in 21 CFR 607.65, all owners and operators of blood establishments that 
engage in the manufacture of blood products must register with FDA and list the blood products 
they manufacture, pursuant to section 510 of the Federal Food, Drug, and Cosmetic Act and the 
implementing regulations under 21 CFR 607.7.  The implementation of a bacterial detection 
device that is used to re-label a platelet product with a 6 or 7-day expiration date, thereby 
extending the dating of the platelet product, is a manufacturing procedure requiring registration 
and blood product listing, as described in 21 CFR 607.3(d).  Transfusion services that 
implement secondary testing on platelets with a 5-day expiration date are not required to register 
and list because they are not extending the dating period of platelets. 
 
If you are a transfusion service that is currently exempt from registration and blood product 
listing under the provisions of 21 CFR 607.65(f), and you implement a bacterial detection test 
                                                 
8 See 21 CFR 601.12(a)(3).  
13  Contains Nonbinding Recommendations 
 
to determine the suitability of platelet products to be released on day 6 or day 7 after collection, 
you are no longer considered exempt because you are engaging in blood product 
manufacturing under 21 CFR 607.3(d).  You must therefore register your blood establishment 
with FDA and list the blood products you manufacture, pursuant to 21 CFR 607.7.  Indicate 
that you are performing bacterial detection testing on platelet products by selecting Bacterial 
Testing as a process for the platelet products. 
 
Instructions on how to register electronically with FDA can be found on FDAs website at: 
https://www.fda.gov/vaccines-blood-biologics/biologics-establishment-registration/blood-
establishment-registration-and-product-listing. 
 
 
VI.  IMPLEMENTATION 
 
We recognize that some of the recommendations contained in this guidance may take time to 
implement.  We recommend prior to October 1, 2021 as a reasonable timeframe for 
implementation.   
 
   
14  Contains Nonbinding Recommendations 
 
VII.  REFERENCES 
 
1.  Hong H, et al., Detection of septic transfusion reactions to platelet transfusions by active and 
passive surveillance, Blood, 2016; 127(4): 496-502. 
 
2.  Fatalities Reported to FDA Following Blood Collection and Transfusion Annual Summary. 
https://www.fda.gov/media/124796/download. 
 
3.  Jacobs MR, et al., Detection of bacterial contamination in prestorage culture-negative 
apheresis platelets on day of issue with the Pan Genera Detection test, Transfusion, 2011; 
51(12): 2573-2582. 
 
4.  Benjamin RJ, Transfusion-related sepsis: a silent epidemic, Blood, 2016; 127(4): 380-381. 
 
5.  Fuller AK, et al., Bacterial culture reduces but does not eliminate the risk of septic 
transfusion reactions to single-donor platelets, Transfusion, 2009; 49(12): 2588-2593. 
 
6.  Horth R, et al; Fatal sepsis associated with bacterial contamination of platelets  Utah and 
California, August 2017, MMWR Morb Mortal Wkly Rep, 2018; 67(25): 718-722. 
https://www.cdc.gov/mmwr/volumes/67/wr/mm6725a4.htm. 
 
7.  Eder AF, et al; Apheresis technology correlates with bacterial contamination of platelets and 
reported septic transfusion reactions, Transfusion, 2017; 57(12): 2969-2976. 
 
8.  Haass, K.A., et al., Transfusion-Transmitted Infections Reported to the National Healthcare 
Safety Network Hemovigilance Module, Transfus Med Rev, 2019; 33(2): 84-91.  
 
9.  Brecher M, Hay SN. Investigation of an isolate of Staphylococcus lugdunensis implicated in 
a platelet fatality: a possible advantage of the use of an anaerobic bottle. Transfusion 2007; 
47: 1390-1394. 
 
10. McDonald C, et al. Bacterial Screening of platelet components by National Health Service 
Blood and Transplant, an effective risk reduction measure. Transfusion 2017; 57: 1122-1131. 
 
11. Blood Product Advisory Committee, July 18, 2018, transcript accessible at 
https://www.fda.gov/advisory-committees/blood-products-advisory-committee/2018-
meeting-materials-blood-products-advisory-committee. 
 
15  Contains Nonbinding Recommendations 
 
APPENDIX A:  BACTERIAL RISK CONTROL STRATEGIES ASSOCIATED WITH SPECIFIC PLATELET 
STORAGE DURATION AND TYPE OF PLATELET UNIT  
 
 
    Types of Units 
Pre-storage pools of  Single units of  Post-storage pools 
    Apheresis 
WBD platelets  WBD platelets   of WBD 
LVDS  36 hours  LVDS  36 hours  Rapid testing  Rapid testing 
Primary culture  24   
hours  Primary culture  
Pathogen reduction 
+ secondary culture   24 hours 
5 days  day 3 
  Primary culture  24   
Primary culture  24 hours  hours  Primary culture  
+ secondary culture  day 3  + secondary rapid  36 hours 
testing 
 
Primary culture  24 hours 
   
+ secondary rapid testing 
Storage duration 
LVDS  48 hours 
LVDS  36 hours 
+ secondary rapid testing 
LVDS  36 hours 
7 days  N/A  N/A  N/A 
+ secondary culture  day 4 
Primary culture  24 hours 
+ secondary culture  day 4 
Primary culture  24 hours 
+ secondary rapid testing 
 
16  Contains Nonbinding Recommendations 
 
APPENDIX B:  SUMMARY OF BACTERIAL RISK CONTROL STRATEGIES FOR APHERESIS AND PRE-STORAGE 
POOLS OF WBD DERIVED PLATELETS 
Volume  Growth  Recommended  
Strategy  Applicable Components1  Time Performed  Product to be Sampled  Expiry 
Sampled2  Conditions  Incubation Period 
Single-step Strategies 
LVDS  Apheresis and   No sooner than 36 hours  Each apheresis split unit or  Aerobic and 
16 mL total  Minimum of 12 hours  Day 53 
36 hours  pre-storage pools  from the time of collection  pre-storage pool  anaerobic 
LVDS  No sooner than 48 hours  Aerobic and 
Apheresis  16 mL total  Each apheresis split unit  Minimum of 12 hours  Day 74 
48 hours  from the time of collection  anaerobic 
Per device instructions   Per device instructions   Per device instructions for  Per device 
Pathogen Reduction  N/A  N/A  N/A 
for use  for use  use   instructions for use 
Two-step Strategies 
Apheresis and   Main collection (mother 
Primary culture  No sooner than 24 hours  Aerobic and 
pre-storage pools   16 mL total  bag), each apheresis split  Minimum of 12 hours  See note5 
24 hours  from time of collection  anaerobic 
  unit, or pre-storage pool 
Step 1   or 
LVDS  Apheresis and   No sooner than 36 hours  Each apheresis split unit or  Aerobic and 
16 mL total  Minimum of 12 hours  Day 56 
36 hours  pre-storage pools  from the time of collection  pre-storage pool  anaerobic 
and 
Apheresis and   Establish a minimum 
No sooner than  Each split unit  At least 
pre-storage pools  8 mL  incubation time period  Day 5 
Secondary  day 3  or pre-storage pool  aerobic 
in SOPs 
culture   or 
No sooner than  Aerobic and 
Step 2  Apheresis  16mL total  Each split unit  Minimum of 12 hours  Day 77 
day 4  anaerobic 
or 
Per device  Per device 
Secondary rapid  Apheresis and   Per device instructions  Each apheresis split unit or 
instructions  N/A  N/A  instructions for use 
testing  pre-storage pools  for use  pre-storage pool 
for use  (up to day 78) 
                                                 
1 This table applies only to apheresis platelets and pre-storage pools of whole blood derived (WBD) platelets.  For post-storage pooled products and single units 
of WBD platelets, see section III.C. and Appendix C of the guidance. 
2 When aerobic and anaerobic cultures are performed, sampled volumes should be split evenly between aerobic and anaerobic culture bottles. 
3 The storage of platelets tested by LVDS no sooner than 36 hours may be extended by secondary testing methods.  See Step 1 of  Two-step strategies, and 
footnote 4 of Appendix B. 
4 Platelets may only be stored beyond day 5 and up to day 7 if each component is tested using a bacterial detection device cleared by FDA and labeled for use as 
a safety measure according to its instructions for use, and if the platelet storage container has been cleared or approved for 7-day storage. 
5 Following primary culture performed no sooner than 24 hours, apheresis and pre-storage pooled platelet components should not be transfused after day 3 unless 
appropriate secondary testing (culture or rapid testing) has been performed to assure that the risk of bacterial contamination has been adequately controlled.  See 
section III.B.2. of the guidance for additional details. 
6 The storage of platelets tested by LVDS no sooner than 36 hours may be extended by secondary testing methods.  See footnote 4 of Appendix B. 
7 See footnote 4 of Appendix B. 
8 See footnote 4 of Appendix B. 
 
17  Contains Nonbinding Recommendations 
 
 
APPENDIX C:  SUMMARY OF BACTERIAL RISK CONTROL STRATEGIES FOR SINGLE UNIT WBD PLATELETS 
AND POST-STORAGE POOLS OF WBD PLATELETS 
 
 
 
 
 
 
 
Recommended 
Applicable  Growth 
Strategy  Time Performed  Volume Sampled  Incubation  Expiry 
Components  Conditions 
Period 
Single-step Strategies 
Per device 
Per device 
Single unit or  Per device instructions  instructions 
Rapid testing  instructions  N/A  N/A 
post-storage pool  for use  for use 
for use 
(up to day 5)1 
No sooner than 
36 hours from 
time of collection  
Largest practical 
 
volume within the range  At least  Minimum of 12 
Single culture  Single unit  or  Day 52 
permitted by the device  aerobic  hours 
 
instructions for use 
No sooner than 
24 hours from 
time of collection 
 
 
 
 
 
                                                 
1 Based on currently available storage systems, storage of these products is limited to 5 days. 
2 Following primary culture performed no sooner than 24 hours, for transfusion after day 3 of storage, secondary rapid testing may be considered. 
18  Contains Nonbinding Recommendations 
 
APPENDIX D:  EXAMPLE TIMELINES OF BACTERIAL RISK CONTROL STRATEGIES FOR APHERESIS PLATELETS 
 
*The storage of platelets tested by LVDS no sooner than 36 hours may be extended by secondary testing methods.  See section III.B.2. of the 
guidance. 
Platelets may only be stored beyond day 5 and up to day 7 if each component is tested using a bacterial detection device cleared by FDA and 
labeled for use as a safety measure according to its instructions for use, and if the platelet storage container has been cleared or approved for 7-
day storage. 
Pathogen reduced platelet components should be treated and labeled consistent with the device instructions for use.  Currently, apheresis platelets 
treated with approved devices should be treated no later than 24 hours after collection and are limited to 5 days of storage. 
Following primary culture performed no sooner than 24 hours, apheresis platelet components should not be transfused after day 3 unless 
appropriate secondary testing (culture or rapid testing) has been performed to assure that the risk of bacterial contamination has been adequately 
controlled.  See section III.B.2. of the guidance for additional detail. 
^Secondary rapid testing should be performed according to the bacterial testing device instructions for use.  Currently, for available cleared or 
approved devices, platelets should be transfused within 24 hours of a non-reactive test.  
19