Guidance for Industry 

Use of Sterile Connecting Devices in
 
Blood Bank Practices
 
Comments and suggestions regarding this document may be submitted at anytime to Dockets 
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.  All comments should be identified with the title of this guidance 
document. 
Additional copies of this guidance document 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 
http://www.fda.gov/cber/guidelines.htm. 
For questions on the content of the document contact Martin Northern at 301-827-3524. 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research (CBER) 
November 2000  Table of Contents 
NOTE: Page numbering may vary for documents distributed electronically. 
I.  INTRODUCTION .................................................................................................................. 1
 
II.  RECOMMENDATIONS....................................................................................................... 1
 
III.  ADDITIONAL COMMENTS ............................................................................................... 5
 
IV.  ADDITIONAL INFOR MATION ........................................................................................... 5
 
V.  APPENDIX ............................................................................................................................ 7
 
i  GUIDANCE FOR INDUSTRY
 
Use of Sterile Connecting Devices in Blood Bank Practices
 
This guidance document represents the agencys current thinking on the use of sterile connecting 
devices in blood banking. It does not create or confer any rights, privileges, or benefits on or for 
any person and does not operate to bind FDA or the public. An alternate approach may be used 
if such approach satisfies the requirements of the applicable statutes and regulations, or both. 
I.  INTRODUCTION 
Sterile connecting devices produce sterile welds between two pieces of compatible tubing. This 
procedure permits sterile connection of a variety of containers and tube diameters. This guidance 
describes recommended practices and procedures for use of these devices. This guidance does 
not address the data or information that a manufacturer of a sterile connecting device must 
submit to FDA in order to obtain approval or clearance for marketing. It is also important to note 
that the use of an approved or cleared sterile connecting device for purposes not authorized in the 
labeling may cause the device to be considered adulterated and misbranded under the Federal 
Food, Drug and Cosmetic Act. 
This document supercedes the August 5, 1994, and August 12, 1994, Food and Drug 
Administration (FDA) memoranda to Blood Establishments regarding Use of an FDA Cleared 
or Approved Sterile Connecting Device (STCD) in Blood Bank Practice.  This guidance is 
essentially unchanged from the previous memorandum, dated August 5, 1994.  The only 
substantive change made in the revised document is the removal of a statement from the previous 
blood guidance that there is only one manufacturer which has FDA clearance for a sterile 
connecting device. There are now are several manufacturers with FDA clearance to market this 
type of device. 
II.  RECOMMENDATIONS 
Manufacturers of blood products who propose to routinely use an FDA-cleared STCD should 
incorporate information regarding such use in standard operating procedure (SOP) manuals for 
each blood product. These entries should include record keeping, product tracking, tube weld 
quality control, lot numbers of software and disposables (including source(s) of elements to be 
added). Quality control procedures should include a test of the integrity of each weld. 
Applications of the STCD 
The user should be aware that use of the device may create a new product or significantly modify 
the configuration of a regulated product for which safety and efficacy have not been 
demonstrated. For those "new products" subject to licensure, applications, or application 
supplements must be submitted to FDA in addition to submission of a SOP. In general, pooling 
or mixing that involves cellular components represents a change in the product that requires  submission and approval of a license application or application supplement.  Such applications 
and application supplements should contain data and descriptions of manufacturing procedures 
that demonstrate that the "new product" is safe and effective for its intended use throughout the 
proposed dating period. 
The following comments are provided as guidance on the more common uses of an FDA cleared 
or approved STCD: 
A. 	 Adding a new or smaller needle to a blood collection set 
1.	  Using the STCD to add a needle prior to the initiation of a procedure (whole 
blood collection, plateletpheresis or source plasma collection) is not considered to 
open a functionally closed system.  If a needle is added during a procedure, only 
an STCD approved to weld liquid-filled tubing should be used.  If the test of weld 
integrity is satisfactory, the use of an STCD is not considered to open a 
functionally closed system. 
Platelets, Pheresis prepared in an open system should be labeled with a 24 hour 
outdate and Platelets, Pheresis products prepared in a functionally closed system 
should be labeled with a five day outdate (See Revised Guideline for Collection 
of Platelets, Pheresis, October 7, 1988). 
2.	  The source and specifications of added tubing and needles should be addressed in 
the blood center's SOP and records.  Using the STCD to add needles does not 
represent a major change in manufacturing for which licensed establishments 
need preapproval. 
B.	  Using the STCD to prepare components 
When the STCD is used to attach additional component preparation bags, records should 
be properly maintained identifying the source of the transfer packs and the appropriate 
verification of blood unit number and ABO/Rh. All blood and blood components must be 
appropriately labeled (21 CFR 606.121). 
Examples: 
	   Adding a fourth bag to a whole blood collection triple-pack for the production of 
Cryoprecipitated AHF from Fresh Frozen Plasma. 
	   Connection of an additive solution to a red blood cell unit. 
	   Addition of an in-line filter that has been FDA cleared for use in manufacturing 
components. 
	   Addition of a third storage container to a plateletpheresis harness. 
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  For the above stated uses, SOPs should be developed and records maintained, but 
licensees need not have FDA approval in order to institute the procedures. 
C. 	 Using the STCD to pool blood products 
Appropriate use of an STCD to pool Platelets prepared from Whole Blood collection may 
obviate potential contamination from the spike and port entries commonly used.  Pooling 
performed immediately before transfusion is an example of such appropriate use. Pooled 
Platelets should be administered not more than 4 hours after pooling (See 21 CFR 
606.122(l)(2)). 
However, pooling and subsequent storage may increase the risk compared to 
administration of random donor units; if one contaminated unit is pooled with others and 
stored before administration, the total bacterial inoculum administered may be increased 
as a result of replication in the additional volume.  Accordingly, the proposed use of an 
STCD to pool and store platelets for more than 4 hours should be supported by data 
which satisfactorily addresses whether such pooling is associated with increased risk. 
Such platelet pooling constitutes manufacture of a new product. 
Pooling or mixing that involves platelets is considered the manufacture of a new product 
that requires submission and approval of a license application or application supplement 
if the storage period is to exceed four hours. 
D.	  Using the STCD to prepare an aliquot for pediatric use and divided units 
Pediatric units and divided units for Whole Blood, Red Blood Cells, and Fresh Frozen 
Plasma prepared using an STCD will not be considered a new product for which a 
biologics license application (BLA) supplement is required providing the following 
conditions are met: 
1.	  The manufacturer should have an approved biologics license or license 
supplement, for the original (i.e., undivided) product, including approval for each 
anticoagulant used. 
2.	  Labels should be submitted for review and approval before distribution.  A 
notation should be made under the comments section of FDA Form 2567, 
Transmittal of Labels and Circulars. 
3.	  Final product containers approved for storage of the component being prepared 
should be used. 
Platelets manufactured under licensure must contain at least 5.5 X (10)10 platelets (21 
CFR 640.24 (c)). Platelets, Pheresis manufactured under licensure should contain at least 
3.0 X (10)11 platelets (See Revised Guideline for the Collection of Platelets, Pheresis, 
October 7, 1988). 
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  SOPs to be followed regarding the use of an STCD to prepare divided products from 
Whole Blood collections and from plasma and platelets prepared by automated 
hemapheresis procedures should include descriptions of: 
	   How the apheresis harness or collection container will be modified with an FDA-
cleared STCD; 
	   the minimum volume of the split plasma or whole blood products; 
	   the volume and platelet concentration of the split plateletpheresis products; 
	   storage time of the product.  The product should be in an approved container and 
should be consistent with the storage time on the label of such container; 
	   method(s) to be used to label and track divided products in the blood center's records. 
NOTE: Procedures for labeling the aliquots should be clearly stated in the SOP. Record 
keeping should be adequate to permit tracking and recall of all components, if necessary. 
E. 	 Using an STCD to connect additional saline or anticoagulant lines during an 
automated plasmapheresis procedure 
SOPs for such procedures should be developed and records maintained consistent with 
the instrument manufacturer's directions for use, but licensees need not have FDA 
approval in order to institute the procedures. 
F. 	 Using the STCD to attach processing solutions 
When using an STCD to attach containers with processing solutions to washed or frozen 
red blood cell products, the dating period for the resulting products is 24 hours, unless 
data are provided in the form of license applications or application supplements to CBER 
to support a longer dating period (21 CFR 610.53(c)). Exemptions or modifications must 
be approved in writing from the Director, CBER (21 CFR 610.53(d)). 
G. 	 Using an STCD to add an FDA-cleared leukocyte reduction filter 
Some leuko-reduction filters are not integrally attached to the Whole Blood collection 
systems. SOPs for use of an STCD for pre-storage filtration should be consistent with 
filter manufacturers' directions for use. 
Leukocyte reduction prior to issue constitutes a major manufacturing change. Therefore, 
for new leukocyte-reduced products prepared using an STCD, manufacturers must submit 
biologics license applications (21 CFR 601.2) or prior approval application supplements 
to FDA (21 CFR 601.12). 
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  H.  Using an STCD to remove samples from blood product containers for testing 
(e.g., using an STCD to obtain a sample of platelets from a container of Platelets 
or Platelets, Pheresis for cross matching). 
If the volume and/or cell count of the product after sample withdrawal differ from what is 
stated on the original label or in the circular of information, the label on the product 
should be modified to reflect the new volume and/or cell count.  For example, samples 
may not be removed that reduce the platelet count of a unit of Platelets to less than 5.5 x 
(10)10 platelets (21 CFR 640.24 (c)). 
III.  ADDITIONAL COMMENTS 
SOPs should include special instructions for product disposition if subsequent inspection of the 
weld reveals signs of leakage or air bubbles. 
The preparation of non-standard blood components using an STCD is limited to research settings 
only, and should be conducted only under an investigational new drug exemption. 
IV.  ADDITIONAL INFOR MATION 
An appendix has been included in this guidance with the currently approved dating periods for 
blood components and source plasma (21 CFR 610.53) and currently recommended dating 
periods for automated plateletpheresis products (See Revised Guideline for Collection of 
Platelets, Pheresis, issued October 7, 1988). 
This guidance presents general guidance as well as specific information and examples 
concerning specifications for submission of applications and application supplements to FDA 
addressing use of an STCD.  If further questions arise concerning appropriate use of an STCD, 
concerns should be directed to the Office of Blood Research and Review, Center for Biologics 
Evaluation and Research. 
Technical questions should be addressed to: 
Division of Hematology, HFM-330 

Office of Blood Research and Review 

Center for Biologics Evaluation and Research 

1401 Rockville Pike, Suite 200N 

Rockville, MD 20852 

Phone: (301) 827-3524 

FAX: (301) 827-3534 

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  Application forms and labeling transmittal forms may be obtained from: 
Division of Blood Applications, HFM-370 

Office of Blood Research and Review 

Center for Biologics Evaluation and Research 

1401 Rockville Pike, Suite 200N 

Rockville, MD 20852 

Phone: (301) 827-3524 

FAX: (301) 827-3534 

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  V.  APPENDIX 
USE OF AN APPROVED STERILE CONNECTING DEVICE (STCD) IN BLOOD BANK 
PRACTICE 
Currently Approved Dating Periods for Blood 
Components and Source Plasma 
PRODUCT  DATING PERIOD 
Cryoprecipitated AHF  12 months from the date of collection of source blood, 
provided labeling recommends storage at -18 C or colder 
Fresh Frozen Plasma  1 year from date of collection of source blood (-18 C or 
colder) 
Liquid Plasma  a) 26 days from date of collection of source blood (between 1 
and 6  C) 
b) 40 days from the date of collection of source blood only 
when CPDA-1 solution is used as the anticoagulant (between 
1 and 6  C). 
Plasma  5 years from the date of collection of source blood (-18  C or 
colder). 
Platelet Rich Plasma  72 hours from time of collection of source blood, provided 
labeling recommends storage between (20-24  C or between 1 
and 6  C).  5 days if certain approved containers are used (20
24  C). 
Platelets, Pheresis  24 hours if collected in an open system. 
Platelets, Pheresis  5 days if collected in a functionally closed system. 
Source Plasma  10 years (at the recommended storage temperature stated on 
the label). 
ACD Red Blood Cells  a) 21 days from the collection of source blood, providing 
labeling recommends  storage between 1 and 6  C and the 
hermetic. seal is not broken during processing. 
b) 24 hours after plasma removal, providing labeling 
recommends storage between 1 and 6  C and the hermetic 
seal is broken during processing. 
CPD Red Blood Cells  a) 21 days from the collection of source blood, providing 
labeling recommends storage between 1 and 6  C and the 
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  hermetic seal is not broken during processing. 
b) 24 hours after plasma removal, providing labeling 
recommends storage between 1 and 6  C and the hermetic 
seal is broken during processing. 
CPDA-1 Red Blood Cells 	 a) 35 days from the collection of source blood, providing 
labeling recommends storage between 1 and 6  C and the 
hermetic seal is not broken during processing. 
b) 24 hours after plasma removal, providing labeling 
recommends storage between 1 and 6  C and the hermetic 
seal is broken during processing. 
Red Blood Cells glycerolized 	 24 hours after removal from storage at -65  C or colder, 
provided labeling recommends storage between 1 and 6  C. 
ACD Whole Blood 	 21 days from date of collection, providing labeling 
recommends storage between 1 and 6  C. 
CPD Whole Blood 	 21 days from date of collection providing labeling 
recommends storage between 1 and 6  C. 
CPDA-1 Whole blood 	 35 days from date of collection providing labeling 
recommends storage between 1 and 6  C. 
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