[Federal Register Volume 77, Number 1 (Tuesday, January 3, 2012)]
[Rules and Regulations]
[Pages 7-18]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-33554]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 606, 610, and 640

[Docket No. FDA-2003-N-0097] (Formerly 2003N-0211)


Revisions to Labeling Requirements for Blood and Blood 
Components, Including Source Plasma

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is revising the 
labeling requirements for blood and blood components intended for use 
in transfusion or for further manufacture by combining, simplifying, 
and updating specific regulations applicable to labeling and circulars 
of information. These requirements will facilitate the use of a 
labeling system using machine-readable information that would be 
acceptable as a replacement for the ``ABC Codabar'' system for the 
labeling of blood and blood components. FDA is taking this action as a 
part of its efforts to comprehensively review and, as necessary, revise 
its regulations, policies, guidances, and procedures related to the 
regulation of blood and blood components. This final rule is intended 
to help ensure the continued safety of the blood supply and facilitate 
consistency in labeling.

DATES: This rule is effective July 2, 2012.

FOR FURTHER INFORMATION CONTACT: Benjamin Chacko, Center for Biologics 
Evaluation and Research (HFM-17), Food and Drug Administration, 1401 
Rockville Pike, Suite 200N, Rockville, MD 20852-1448, (301) 827-6210.

SUPPLEMENTARY INFORMATION: 

I. Introduction

A. Background

    This rule represents FDA's efforts to revise the regulations for 
blood and blood components. The rule consolidates most labeling 
requirements for blood and blood components, including Source Plasma, 
into one section of the Code of Federal

[[Page 8]]

Regulations (CFR). The rule also updates the regulations applicable to 
circulars of information.
    In the Federal Register of July 30, 2003 (68 FR 44678), FDA 
published a proposed rule that proposed revisions to update 
requirements for storage and shipment of blood and blood components. 
FDA received numerous comments in response to these proposals, many of 
which opposed the changes primarily due to economic concerns. FDA has 
reviewed these comments and appreciates the concerns raised, and is 
currently reevaluating these proposals. (See discussion in section II.B 
of this document.)

B. Development of the International Society of Blood Transfusion Code 
(ISBT) 128

    In the Federal Register of August 30, 1985 (50 FR 35472), we 
published a notice of availability entitled ``Guideline for the Uniform 
Labeling of Blood and Blood Components,'' which described the uniform 
container label for blood and blood components and recommended labels 
that incorporated barcode symbology known as ``ABC Codabar.''
    Because the ``ABC Codabar'' system was becoming outdated, we asked 
the Blood Products Advisory Committee (BPAC), on March 23, 1995, 
whether there was persuasive evidence for us to allow conversion from 
``ABC Codabar'' to International Society of Blood Transfusion Code 128 
(ISBT 128), according to the International Council for Commonality in 
Blood Banking Automation (ICCBBA) proposed timetable. The BPAC voted in 
favor of accepting the proposed timetable by ICCBBA. The BPAC meeting 
transcript also indicates the Department of Defense's and the blood 
industry's, including America's Blood Centers' and AABB's (formerly 
known as American Association of Blood Banks), support of the move to 
ISBT 128 for blood and blood components for transfusion.
    After the BPAC meeting, ICCBBA developed and submitted to FDA a 
draft standard entitled ``United States Industry Consensus Standard for 
the Uniform Labeling of Blood and Blood Components Using ISBT 128,'' 
Version 1.2.0 (draft standard), recommending that ISBT 128 replace 
``ABC Codabar.'' In the Federal Register of November 27, 1998 (63 FR 
65600), we announced the availability of the draft standard and 
requested public comment on both the use of ISBT 128 and timeframes for 
implementation.
    The ICCBBA revised the draft standard in response to public comment 
and submitted to FDA a revised draft standard entitled ``United States 
Industry Consensus Standard for the Uniform Labeling of Blood and Blood 
Components Using ISBT 128,'' Version 1.2.0, dated November 1999 (the 
Version 1.2.0 Standard). We reviewed the new draft standard, the 
comments received in response to the Federal Register notice of 
November 27, 1998, and the Version 1.2.0 Standard, and concluded that 
conformance to the Version 1.2.0 Standard, prepared and reviewed by 
ICCBBA, would help facilitate the use of a uniform container label for 
blood and blood components. Thus, in the Federal Register of June 6, 
2000 (65 FR 35944), we announced the availability of a final guidance 
entitled ``Guidance for Industry: Recognition and Use of a Standard for 
the Uniform Labeling of Blood and Blood Components'' dated June 2000, 
which recognized as acceptable, except where inconsistent with the 
regulations, use of the Version 1.2.0 Standard and the implementation 
of the ISBT 128 uniform labeling system. This guidance identified two 
inconsistencies between the Version 1.2.0 Standard and the requirements 
in part 606 (21 CFR part 606) at Sec.  606.121; the first inconsistency 
concerned the requirement that on container labels for Whole Blood the 
name of the applicable anticoagulant must immediately precede the 
proper name of the product (Sec.  606.121(e)(1)(ii)); and the second 
inconsistency concerned the requirement that the proper name of the 
product and any appropriate modifiers must be printed in solid red 
(Sec.  606.121(d)(2)).
    In the Federal Register of August 19, 1999 (64 FR 45366), we 
published a direct final rule entitled ``Revisions to the Requirements 
Applicable to Blood, Blood Components, and Source Plasma,'' which 
amended Sec.  606.121(d)(2) by adding ``or in solid black,'' thereby 
eliminating the inconsistency between the Version 1.2.0 Standard and 
Sec.  606.121(d)(2), which had previously required that any modifier be 
printed in solid red.
    In the ``Guidance for Industry: Recognition and Use of a Standard 
for Uniform Blood and Blood Component Container Labels'' dated 
September 2006 (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm079004.pdf), 
we recognized as acceptable, except where inconsistent with the 
regulations, use of the ``United States Industry Consensus Standard for 
the Uniform Labeling of Blood and Blood Components Using ISBT 128'' 
version 2.0.0, dated November 2005 (the Version 2.0.0 Standard). In the 
guidance, we noted that the Version 2.0.0 Standard revised the Version 
1.2.0 Standard and that there remained an inconsistency between the 
Version 1.2.0 Standard, the Version 2.0.0 Standard and the requirements 
at Sec.  606.121(e)(1)(ii). Since that guidance was issued, we have 
identified another inconsistency between the requirements under Sec.  
606.121(c)(2) and the Version 2.0.0 Standard regarding the requirement 
to include the FDA assigned registration number on blood and blood 
component labels. This final rulemaking addresses these inconsistencies 
by eliminating the existing inconsistencies between the Version 2.0.0 
Standard and the requirements at Sec.  606.121(c)(2) and (e)(1)(ii).
    (FDA has verified the Web site addresses in this document, but FDA 
is not responsible for subsequent changes after this document publishes 
in the Federal Register.)

C. The Proposed Rule

    In the Federal Register of July 30, 2003 (68 FR 44678), we 
published a proposed rule entitled ``Revisions to Labeling and Storage 
Requirements for Blood and Blood Components, Including Source Plasma'' 
(the proposed rule), to combine, simplify and update specific 
regulations applicable to container labeling and instruction circulars 
for all human blood and blood components, including Source Plasma. We 
also proposed to revise the shipping and storage requirements for 
certain human blood and blood components. Furthermore, we proposed the 
use of a labeling system using machine-readable information that would 
be acceptable as a replacement for the ``ABC Codabar'' system for 
labeling blood and blood components, and stated that we would also 
address the existing inconsistencies between the Version 1.2.0 
Standard, and the existing regulations as described in section I.B of 
this document. We also intended to provide more flexibility for 
inventory management, and to update current requirements designed to 
ensure potency of the blood components over time by revising the 
current storage and shipping temperature requirements for frozen 
noncellular blood components, both for transfusion and for further 
manufacture (e.g., Cryoprecipitated Antihemophilic Factor, Fresh Frozen 
Plasma, and Source Plasma).
    We note that the proposed rulemaking inadvertently included 
proposed changes to Sec.  606.121(c)(13) (68 FR 44678 at 44686), which 
were inconsistent with a previously proposed amendment to Sec.  
606.121(c)(13) in an earlier, related proposed rule entitled ``Bar Code 
Label Requirement for

[[Page 9]]

Human Drug Products and Blood'' that published in the Federal Register 
of March 14, 2003 (68 FR 12499). To eliminate any confusion, we 
published a correction to the proposed rule in the Federal Register of 
October 27, 2003 (68 FR 61172), and published the related, final rule 
entitled ``Bar Code Label Requirements for Human Drug Products and 
Blood'' in the Federal Register of February 26, 2004 (69 FR 9120). We 
also note that the proposed rulemaking inadvertently omitted the 
requirement in current 21 CFR 640.70(a)(7) that requires that for 
Source Plasma, in the case of immunized donors, the label must state 
the immunizing antigen. In this final rule, we have corrected this 
omission and have placed this requirement in redesignated Sec.  
606.121(e)(5)(vi).
    Regarding the term ``communicable disease testing,'' used in this 
final rule, we noted in the proposed rule (68 FR 44678 at 44684) that 
the terms ``infectious agent testing'' and ``communicable disease 
testing'' (used interchangeably in the proposed rule and in guidance 
documents) refer to the same testing performed in accordance with Sec.  
610.40 (21 CFR 610.40). We also noted that the term ``infectious 
agent'' is used rather than ``communicable disease agent'' for 
consistency with labeling approved by the Director, Center for 
Biologics and Evaluation Research (CBER), for the Version 1.2.0 
Standard and the ``ABC Codabar'' System. In this final rule, as well as 
in the Version 2.0.0 Standard, the terms ``infectious agent testing'' 
and ``communicable disease testing'' continue to be used 
interchangeably and refer to the same testing performed in accordance 
with Sec.  610.40.

II. Revisions to the Proposed Rule

A. Requirements Finalized in This Rule

    This rule:
     Finalizes, in part, the proposed requirements for labeling 
for blood and blood components intended for use in transfusion or 
further manufacture by all blood establishments, and specific 
regulations applicable to container labeling and circulars of 
information;
     Eliminates the two remaining inconsistencies between the 
Version 2.0.0 Standard and the regulations, described in section I.B of 
this document;
     Facilitates the use of a labeling system using machine-
readable information that would be acceptable as a system for labeling 
blood and blood components, and the use of new labeling systems that 
may be developed in the future;
     Consolidates regulations applicable to labeling standards 
so that most labeling requirements for all blood and blood components, 
including Source Plasma, found previously in Sec. Sec.  606.121 and 
640.70, can now be found in Sec.  606.121;
     Updates some of the consolidated regulations;
     Replaces ``shall'' with ``must'' in all places wherever it 
appears in the regulations;
     Retitles part 606, subpart G; and
     Makes other, necessary conforming changes, and technical 
amendments.

B. Requirements Not Finalized in This Rule

    At this time, we are not finalizing the proposed requirements for 
storage and shipping temperatures of certain human blood and blood 
components, including Source Plasma, because we are continuing to 
reevaluate these proposals, taking into account the adverse comments 
received. Under the proposed rule, we proposed revisions to the 
labeling requirements regarding storage and shipping temperatures for 
frozen noncellular blood components in current part 640 (21 CFR part 
640) at Sec.  640.70(a)(3) and (b). We also proposed revisions to 
storage and shipping temperatures in current Sec. Sec.  600.15 (21 CFR 
600.15), 610.53, 640.34, 640.54, 640.69, and 640.76 to help ensure the 
potency of the frozen noncellular blood components and for consistency 
between the labeling regulations and the regulations concerning 
shipping and storage temperatures of frozen noncellular blood 
components. By updating the storage and shipping temperature 
requirements and addressing as many labeling changes as possible at one 
time, we had believed that the proposed rule would limit the number of 
times establishments would have to revise container labels.
    However, we have concluded, based on comments received, that we 
should reevaluate the proposed revisions to the requirements for 
storage and shipping temperatures. For example, we received comments 
from the plasma fractionation industry stating that the proposed 
freezing/storage temperature of -30 [deg]C was below the temperature 
that would be acceptable to preserve product activity, would be very 
costly to implement, and would pose a safety hazard to employees 
working in that environment. In the Federal Register of August 9, 2004 
(69 FR 48250), we announced a public workshop entitled ``Development of 
Plasma Standards'' that was held August 31 and September 1, 2004. The 
objective of the workshop was to gather information on current industry 
practices that are in place for the manufacture of plasma. We also 
discussed this issue at a March 17, 2005, BPAC meeting and at an April 
2, 2009, BPAC meeting.
    FDA intends to consider revising storage requirements in the 
future, based on our review of scientific literature, data from other 
regulatory authorities and the plasma fractionation industry, and input 
from BPAC. Based on the information received, we intend to develop 
standards for the preparation, labeling, storage, and shipping of 
frozen noncellular blood components for transfusion and for further 
manufacture.

C. Conforming and Clarifying Changes

    This final rule removes Sec.  640.70 from the CFR, and accordingly, 
we have made conforming changes to Sec.  610.40(h)(2)(ii)(B) and Sec.  
640.74(b)(4) both of which currently reference Sec.  640.70. In Sec.  
610.40(h)(2)(ii)(B), we have deleted the reference to Sec.  640.70. In 
Sec.  640.74(b)(4), we have deleted the reference to Sec.  640.70(a) 
and replaced it with Sec.  606.121 and have deleted the reference to 
Sec.  640.70(a)(3) and replaced it with Sec.  606.121(e)(5)(ii).
    We also made a conforming change to Sec.  610.40(i) to cross-
reference another existing requirement for a serological test for 
syphilis under Sec.  640.65(b)(1).
    We also made a conforming change to Sec.  606.121(c)(13)(iii)(D) to 
cross-reference other existing requirements under Sec.  606.121(c)(9) 
and Sec.  606.121(i)(5).
    We are clarifying proposed Sec.  606.121(i)(4) by removing the 
phrase ``unless exempt under'' to ``except as provided in.'' This 
clarifying change will not affect the substantive requirements in this 
regulation.
    Further, we made two clarifying changes to Sec.  606.122(f) by 
changing ``statements'' to ``statement'' and replacing the period after 
``Warning'' with a colon, so that the provision now reads in its 
entirety, ``The statement: `Warning: The risk of transmitting 
infectious agents is present. Careful donor selection and available 
laboratory test do not eliminate the hazard.''

D. Technical Amendment

    We have made a technical amendment to Sec.  606.170 to clarify that 
reports of the investigation of a fatality must be submitted to CBER 
either by mail, facsimile, or electronically transmitted mail; and to 
provide mailing address information for the Director, Office of 
Compliance and Biologics Quality, CBER.
    Further, we have made a technical amendment to Sec.  
606.121(e)(2)(i) to require that with the exception of those

[[Page 10]]

products listed in Sec.  606.121(e)(2), red blood cell product labels 
must include the type of additive solution with which the product was 
prepared.

III. Comments on the Proposed Rule and FDA's Responses

    We received approximately 24 comments on the proposed rule. These 
comments were received from blood establishments, private and public 
interest groups, and the general public. All of the comments expressed 
opinions on the proposed revisions to the storage and shipping 
temperature requirements; about 12 of the comments commented on the 
proposed labeling requirements. Because we are not finalizing the 
proposed storage and shipping temperature requirements at this time, 
this document does not discuss those issues. This document discusses 
information relevant to and comments concerning the proposed revisions 
to the labeling requirements. To make it easier to identify comments 
and our responses, the word ``Comment,'' in parentheses, will appear 
before the description of comments, and the word ``Response,'' in 
parentheses, will appear before our responses.

A. General

    (Comment 1) Numerous comments supported the proposed revisions to 
consolidate, simplify and update the regulations applicable to 
container labeling and the instruction circular; one comment stated 
that the changes were ``long overdue.'' Several comments applauded our 
efforts to develop a proposed rule that will facilitate the 
implementation of ``machine-readable'' bar code standards and strongly 
endorsed the use of ISBT 128 as a unifying bar code standard for blood 
and blood components, which will improve patient safety. In addition, 
one of these comments noted that one bar code standard would lower the 
implementation costs related to the standard and would allow for the 
exchange of inventories so that the needs of patients everywhere could 
be more easily met.
    (Response) We appreciate these supportive comments. We agree that 
this rule facilitates the use of the ISBT 128 machine readable labeling 
system for blood components by eliminating FDA requirements that are 
inconsistent with the use of the ISBT system. We note that once this 
rule is in effect, licensed establishments will no longer need to 
request a variance from the regulations to fully implement the ISBT 
system--thus we anticipate that the new rule will save both industry 
and FDA resources. In addition, the rule updates current labeling 
requirements to ensure appropriate and complete labeling of all blood 
and blood components for infectious disease test results, including 
recovered plasma for further manufacturing. In these ways, the rule 
will support the safety of the nation's blood supply.
    At the same time, we are preserving for industry the option of 
using the older labeling system, ``ABC Codabar.''
    (Comment 2) One comment expressed concern that consolidating the 
labeling requirements for Source Plasma and other blood components into 
the same CFR section may make it more difficult to identify the 
applicable labeling requirements, and suggested as an alternative that 
we consolidate requirements into a single section with a subsection 
dedicated to requirements specific to Source Plasma. Another comment 
noted that consolidating requirements into one section has both 
advantages and disadvantages. This comment noted that the manufacture 
of Source Plasma is significantly different from the manufacture of 
blood components for transfusion. The comment also noted that other 
blood products, which are markedly different from blood components for 
transfusion, have separate labeling requirements in the CFR (e.g., 
Albumin (part 640, subpart H), Plasma Protein Fraction (part 640, 
subpart I), and Immune Globulin (part 640, subpart J)). The comment 
noted that for consistency, we should maintain separate labeling 
requirements for Source Plasma in part 640, subpart G, and instead 
revise Sec.  640.70 to require labeling statements based on 
communicable disease testing.
    Two comments noted that a requirement for all test results to be 
recorded on the product label is not consistent with current industry 
practice for recovered plasma. See response to comment 8 for further 
information.
    (Response) One purpose of the proposed rule was to consolidate the 
labeling regulations that apply to blood and blood components in one 
place in the CFR, including blood components that are used for further 
manufacture. Not all blood components that are used for further 
manufacture currently have additional standards in part 640, e.g., 
recovered plasma. In Sec.  606.121, we have consolidated the labeling 
requirements for blood and blood components intended for use in 
transfusion or further manufacture. To clarify this point, in Sec.  
606.121(a), we have deleted the phrase ``including Source Plasma'' from 
the proposed language and added instead ``intended for use in 
transfusion or further manufacture.'' We have also revised Sec.  
606.121(c)(11) to require that if the product is intended for further 
manufacturing use, a statement listing the results of all the tests for 
communicable disease agents required under Sec.  610.40 for which the 
donation has been tested and found negative must be on the container 
label; except that the container label for Source Plasma is not 
required to list the negative results of serological syphilis testing 
under Sec.  610.40(i) and Sec.  640.65(b).
    In response to comments regarding current industry practice for 
negative labeling of recovered plasma for further manufacture, we 
believe that it is current industry practice to include the 
communicable disease test results for recovered plasma on the container 
label. See the response to comment 8 for full details.
    (Comment 3) One comment requested that in addition to the revisions 
in this final rule, we make changes to further streamline the labeling 
submission process for on-demand ISBT 128 labels.
    (Response) The comment is beyond the scope of this final rule. 
However, we will consider the comments on this issue at a later date.
    (Comment 4) One comment requested more flexibility on tie-tags used 
for autologous donations, suggesting that a computer system-generated 
ABO blood group and Rh type (ABO/Rh) label be applied to the tie-tag as 
opposed to the current practice of hand writing the ABO/Rh result on 
the tag and on the ``For Autologous Use'' label. The comment stated 
that this change would eliminate the need for handwritten information, 
thus reducing the likelihood of human error, thereby improving patient 
safety.
    (Response) The comment regarding the use of a computer system-
generated ABO/Rh label is beyond the scope of this final rule. However, 
we note that in the final rule published in the Federal Register of 
February 26, 2004 (69 FR 9120), entitled ``Bar Code Label Requirements 
for Human Drug Products and Biological Products,'' we revised Sec.  
606.121(c)(13) to require that the ABO blood group and Rh type of the 
donor be present in machine-readable format on the container label of 
all blood and blood components, including autologous units. This 
requirement is consistent with ISBT 128 standards but requires those 
manufacturers using ``ABC Codabar'' to affix an ABO/Rh bar code label 
to the ``For Autologous Use Only'' label on blood and blood components 
bearing the autologous label. In this final rule, we have amended Sec.  
606.121(i)(5) to permit each container label of blood and blood 
components intended for autologous use

[[Page 11]]

and obtained from an unsuitable donor or one who is reactive for 
evidence of infection due to communicable disease agents under Sec.  
610.40 to include the ABO and Rh blood group and type. However, such 
labeling is not required.

B. 21 CFR 606.121(b)

    The proposed rule amended Sec.  606.121(b) by adding the phrase 
``with any appropriate modifiers and attributes'' to clarify that the 
label provided by the collecting facility may be altered under certain 
circumstances and may be altered multiple times to adequately identify 
the contents of a container. Examples of appropriate modifiers include 
``washed,'' ``frozen,'' and ``liquid.'' Examples of appropriate 
attributes include ``irradiated'' and ``divided,'' which would indicate 
a process change. We have finalized these requirements as proposed, 
including the conforming amendments to Sec. Sec.  606.121(c)(1) and 
606.121(d)(2). In addition, we have added the clarifying phrases ``of 
the product'' and ``considered finished products'' to Sec.  606.121(b). 
In this section III.B, we describe two examples of circumstances where 
it is acceptable to alter the label of blood components as finished 
products after they have been prepared. We note that it is appropriate 
to revise the label each time, after the finished product has been 
prepared.
    In the preamble of the final rule entitled ``Current Good 
Manufacturing Practice for Blood and Blood Components; Uniform Blood 
Labeling'' published in the Federal Register of August 30, 1985 (50 FR 
35458), we responded to a comment (comment number 2) that suggested 
that the only instance in which labels are permitted to be altered 
pursuant to Sec.  606.121(b) is when blood components are removed from 
the product. In the response, we noted, that there are certain cases 
when no blood components are removed from a unit, but the unit may 
nonetheless require relabeling. Id. at 35459. For example, such 
relabeling would be appropriate when the product is further processed 
by freezing, pooling, washing, or irradiating, provided that the 
establishments have a validated process for this additional processing. 
The original label would need to be modified to include the additional 
information and then reprinted and the product relabeled, i.e., a new 
label placed over the original label, to accurately identify the 
product.
    Another specific circumstance in which the label of a blood product 
may be altered under Sec.  606.121(b) is when the original label may 
need to be recreated because the original bag is destroyed while the 
product is further processed by, for example, freezing, pooling, 
washing, or irradiation. The recreated label may be placed on the new 
bag under applicable regulations and the establishment's standard 
operating procedures.

C. 21 CFR 606.121(c)(2)

    In the proposed rule, we proposed amending Sec.  606.121(c)(2) by 
replacing ``registration number'' with ``unique facility identifier.'' 
Although, as we discussed in the preamble to the proposed rule (68 FR 
44678 at 44683), the FDA-assigned registration number is acceptable as 
a ``unique facility identifier,'' we wanted to be able to provide for 
the use of other recognized donation facility identification numbers, 
such as the ISBT facility code (which includes machine-readable 
information). In addition, we proposed removing the requirements of 
current Sec.  640.70(a)(10) for ``name, address, and license number'' 
on the Source Plasma label because they are included in proposed Sec.  
606.121(c)(2).
    (Comment 5) One comment suggested that this change imposes an 
additional requirement on collectors of Source Plasma operating 
multiple sites under a single license.
    (Response) FDA believes that the final rule addresses this concern. 
In consideration of this comment, we are not requiring the container 
label for blood components for further manufacture to contain a unique 
facility identifier at this time, because we believe that the blood 
establishment's FDA approved product label contains sufficient 
information to permit identification of the collection facility. 
Regarding Source Plasma, we have learned that most collection 
facilities include a unique facility identifier on the container label. 
We agree that this is useful information for identifying the location 
where the Source Plasma was collected.
    The final rule requires a unique facility identifier for the 
container label of blood and blood components intended for transfusion, 
to aid in identifying the location where the blood or blood component 
was collected or processed. We note that the final rule provides 
flexibility by using the term ``unique facility identifier,'' which may 
be satisfied by using an establishment's registration number, the FDA 
establishment identifier, an ISBT facility code, or other designation 
that will allow identification of the specific location where the blood 
or blood component was collected or processed. For example, a blood 
establishment may incorporate its unique facility identifier into the 
blood component donor, lot, or pool number and use a validated computer 
or other recordkeeping system that will enable identification of the 
facility that collected that blood or blood component.
    (Comment 6) One comment expressed concern that their current 
approved labels do not contain a unique site specific identifier that 
was assigned by FDA, other than the license number, and that the 
effective date for the final rule should provide adequate time for 
implementation to allow for label design, acquisition, procedural 
changes, and depletion of available stock to minimize transition costs.
    (Response) Anticipating the need to deplete existing label stock, 
the effective date for the final rule (refer to section VIII of the 
proposed rule) (68 FR 44678 at 44685) provides reasonable time for use 
of the existing label stock. The final rule becomes effective 180 days 
after the date of publication in the Federal Register.

D. 21 CFR 606.121(c)(10)

    The proposed rule combined current Sec.  606.121(c)(11) and part of 
current Sec.  640.70(a)(2) and redesignated the combined regulations as 
proposed Sec.  606.121(c)(10). In addition, FDA proposed to revise 
Sec.  606.121(c)(10) by adding a phrase to the first sentence to 
clarify that blood and blood components intended for further 
manufacture are subject to these requirements. Furthermore, FDA 
proposed to revise Sec.  606.121(c)(10) by adding an alternative 
warning statement and provided for the use of ``other cautionary 
statements as approved by CBER.'' FDA now is finalizing the above 
amendments as proposed (including deleting current Sec.  
606.121(e)(5)(ii)), because it is now redundant in light of new Sec.  
606.121(c)(10)).
    (Comment 7) Two comments suggested that it is difficult to select 
the proper cautionary statement to use because information regarding 
cautionary statements can be found in other sections of the CFR, as 
well as in certain FDA guidance documents.
    (Response) We acknowledge that the circumstances surrounding which 
cautionary statement to use may vary. We believe that the consolidation 
of the labeling requirements in this rulemaking for blood and blood 
components for further manufacture, including Source Plasma, should 
enhance industry's ability to select the appropriate cautionary 
language. We also note that reference 1 and reference 2 to this 
rulemaking provide general guidelines about the uniform labeling of 
blood and blood components. Further,

[[Page 12]]

we suggest that the commenters may want to pose any specific questions 
to CBER to obtain further guidance.

E. 21 CFR 606.121(c)(11)

    We had proposed to redesignate and combine current Sec. Sec.  
640.70(a)(8) and (a)(11) as Sec.  606.121(c)(11) and to revise 
redesignated Sec.  606.121(c)(11) to require labeling statements 
indicating the results of communicable disease tests performed. The 
proposed change provided that the labeling requirements apply to all 
blood and blood components for further manufacture, including Source 
Plasma, and would require establishments to label products for further 
manufacture with the results of communicable disease testing for which 
the donation has been tested and found negative.
    (Comment 8) Some comments expressed concern regarding the resulting 
burdens from consolidating previously referenced requirements into 
Sec.  606.121. One comment requested that Sec.  606.121(c)(11) be re-
worded to indicate that communicable disease tests performed on a 
sample from the donor of the unit are listed in the current circular of 
information, thus providing a much simpler and more flexible method of 
meeting labeling requirements without the expense of constantly 
changing labels. Additionally, the comment stated that use of the 
circular of information would also address concerns regarding the 
shipment of positive units for further manufacture, by labeling only 
the positive units or alternatively recommended continuing the current 
method of noting ``positives'' on the shipping form.
    In addition, as discussed previously, regarding recovered plasma, 
two comments stated that a requirement for all test results to be 
recorded on the product label is not consistent with current industry 
practice. The comments indicated that to require constant updating of 
labels to report all negative test results is counterproductive to the 
positive labeling aspects of the proposed rule, and requested that this 
requirement be deleted from the final rule.
    (Response) FDA disagrees with the comments related to the use of 
the circular of information to list communicable disease test results. 
We believe that it is not appropriate to re-word proposed Sec.  
606.121(c)(11) to require that information on communicable disease 
testing performed on components intended for further manufacture be 
included in the circular of information because the circular of 
information applies only to transfusable products and not to products 
intended for further manufacture.
    We note that we have periodically addressed the uniformity of 
labeling. For example, we announced the availability of the final 
guideline entitled ``Guideline for Uniform Labeling of Blood and Blood 
Components'' dated August 1985, which described acceptable criteria for 
labels consistent with current good manufacturing practice regulations 
for blood and blood components (part 606) (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM080974.pdf 
). The guideline included illustrated labels for certain blood 
components used for further manufacture (e.g., Source Plasma, recovered 
plasma, and Source Leukocytes), that had been reviewed and approved by 
FDA. We also issued ``Guidance for Industry: Recognition and Use of a 
Standard for Uniform Blood and Blood Component Container Labels'' dated 
September 2006, which recognizes the ``United States Industry Consensus 
Standard for the Uniform Labeling of Blood and Blood Components Using 
ISBT 128,'' dated November 2005, as an acceptable standard for blood 
and blood component container labels, except where inconsistent with 
the regulations. (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM079159.pdf 
). As discussed in section I.B of this document, we further note that 
this final rulemaking addresses the inconsistencies that existed.
    FDA also disagrees with the comments concerning the labeling of 
recovered plasma because we believe they are incorrect. We believe it 
is the usual and customary practice of the blood industry to label the 
container label of blood and blood components for further manufacture 
with the negative communicable disease test results of all the tests 
for communicable disease agents required under Sec.  610.40, except for 
Source Plasma with respect to serological syphilis testing. We are 
therefore finalizing the requirement in this rulemaking that the label 
of blood and blood components for further manufacture must include a 
statement listing the results of all the tests for communicable disease 
agents required under Sec.  610.40 for which the donation has been 
tested and found negative except that the label for Source Plasma is 
not required to list the negative results of serological syphilis 
testing under Sec. Sec.  610.40(i) and 640.65(b).
    (Comment 9) One comment noted that consistent with Sec. Sec.  
610.40(i) and 640.65(b)(1), Source Plasma is unique because a 
serological test for syphilis is performed at intervals of no more than 
4 months, rather than at each individual donation. The comment 
requested clarification on whether syphilis is considered a 
``communicable disease agent'' and if the labeling of serological 
syphilis testing results is required on units of Source Plasma. This 
comment also expressed the concern that requiring syphilis test results 
on each Source Plasma unit would be burdensome for industry because it 
is current industry practice to pre-label Source Plasma with required 
communicable disease testing results.
    (Response) As noted previously in the response to comment 8, we are 
not finalizing Sec.  606.121(c)(11) as proposed. We will therefore 
answer this comment in light of the revised provisions of Sec.  
606.121(c)(11). Syphilis is deemed to be a communicable disease agent; 
the testing requirements for which are included in part 610, subpart E 
(Testing Requirements for Communicable Disease Agents), specifically 
Sec.  610.40(i). Section 610.40(i) incorporates the requirement in 
Sec.  640.65(b) to test a Source Plasma donor using a serological test 
for syphilis at the donor's initial examination and at least once every 
four months thereafter. (More limited testing for Source Plasma 
reflects the reduced risk presented by syphilis infected collections of 
Source Plasma. In an FDA Compliance Policy Guide revised in 1995, FDA 
observed that ``the disease-causing spirochetes are destroyed during 
the storage and/or fractionation of the [source] plasma.'') \1\
---------------------------------------------------------------------------

    \1\ http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm073876.htm.
---------------------------------------------------------------------------

    Under Sec.  606.121(c)(11) as finalized, the label for blood and 
blood components intended for further manufacture must list the results 
of all the tests for communicable disease agents required under Sec.  
610.40 for which the donation has been tested and found negative; 
except that the container label for Source Plasma is not required to 
list the negative results of serological syphilis testing under Sec.  
610.40(i) and Sec.  640.65(b). This is because the regulations do not 
require that each Source Plasma donation be tested for syphilis. In the 
absence of test results for each donation (e.g., in connection with 
donations made in month three) or where testing for syphilis was 
performed and the test was negative, the label is silent. When testing 
is performed and is reactive for

[[Page 13]]

syphilis, the label for the unit associated with the positive test and 
the label for the unit of any donation(s) made after obtaining the test 
results must appropriately disclose that the Source Plasma tested 
reactive by a serologic test for syphilis as described in Sec.  
606.121(e)(5)(iv).
    More generally, concerning the pre-labeling of Source Plasma, it is 
FDA's expectation that tests for required infectious disease tests are 
completed prior to shipment of the Source Plasma for further 
manufacture to the fractionator or for distribution. However, we also 
recognize that in certain circumstances, nucleic acid test (NAT) 
testing of Source Plasma may take an extended period to resolve 
positive NAT pools to identify an individual positive unit. 
Additionally, we recognize the difficulty of placing a ``label'' on a 
frozen product. We note that Source Plasma may be labeled and then may 
be shipped for pre-release storage at another facility while still 
under the manufacturer's control due to the manufacturer's storage 
limitations. This raises the question of whether it is acceptable for a 
manufacturer to pre-label (at the time of collection) Source Plasma as 
``tested and found negative'' while performing NAT testing and shipping 
such products under quarantine (i.e., while still under the 
manufacturer's control) and delaying release and distribution until all 
the test results are obtained.
    Under the revised regulation, if the product is intended for 
further manufacturing use, a statement listing the results of all the 
tests for communicable disease agents required under Sec.  610.40 for 
which the donation has been tested and found negative must be listed on 
the container label; except that the container label for Source Plasma 
is not required to list the negative results of serological syphilis 
testing under Sec.  610.40(i) and Sec.  640.65(b). In addition, blood 
and blood components intended for further manufacture must be labeled 
in accordance with Sec.  610.40, when the donation has been tested and 
demonstrates evidence of infection due to a communicable disease 
agent(s).
    Under Sec.  606.121(c)(11) as finalized, it is acceptable for 
Source Plasma manufacturers to place the label indicating negative 
communicable disease test results on the product prior to completion of 
communicable disease testing (pre-label) as long as either (1) The unit 
is shipped to a storage facility and remains under quarantine control 
by the collection establishment until all testing is completed and 
accurately reflected on the label or (2) the unit is not released and 
distributed into interstate commerce until the results from all 
communicable disease tests are obtained and accurately reflected on the 
label. Thus, the requirements under Sec. Sec.  606.121(c)(11) and 
610.40 are not fulfilled until the container label accurately lists the 
results obtained from all communicable disease testing required under 
Sec.  610.40. At that time, the product is ready for distribution and 
release into interstate commerce.
    In the event that a shipped unit is pre-labeled with a negative 
test result but is later found positive upon completed testing, that 
unit must be relabeled in accordance with Sec.  610.40, including 
obliteration of the negative result.

F. 21 CFR 606.121(e)(2)(i) and 21 CFR 606.121(e)(5)(vi)

    In finalizing this rulemaking, we have amended Sec.  
606.121(e)(2)(i) to require that with the exception of those products 
listed in Sec.  606.121(e)(2), red blood cell product labels must 
include the type of additive solution with which the product was 
prepared as this information is useful when making determinations in 
connection with the shelf life of the product. For example, red cell 
additive solutions (e.g., AS-1, AS-3, AS-5) provide nutrients to the 
blood components which in turn allows for an extended shelf life. We 
note that the labeling of the container with the additive solution is 
also industry practice.
    We proposed to redesignate current Sec.  640.70(a)(7) as Sec.  
606.121(e)(5)(vi). We also proposed to update redesignated Sec.  
640.70(a)(7) to broaden the labeling requirements to include 
collections from donors who are not immunized but are in specific 
collection programs. The proposal replaced the term ``normal donor'' 
with the term ``nonimmunized donor.'' After consideration, we have 
determined that ``nonimmunized donor'' is not a recognized term, and we 
will continue to use the term ``normal donor.''

G. 21 CFR 606.122

    We proposed to amend Sec.  606.122 by revising the introductory 
paragraph and paragraphs (e), (f), and (m). We received comments only 
on the heading of this regulation, ``Instruction circular,'' which we 
did not propose to change, and paragraphs (e) and (m).
1. Title for Sec.  606.122
    (Comment 10) A few comments desired consistency between Sec.  
606.121(c)(8)(ii), which refers to the ``Circular of Information,'' and 
Sec.  606.122, which refers to the ``Instruction circular.'' One 
comment suggested revising Sec.  606.121(c)(8)(ii) to use the same 
language in the AABB ``Standards for Blood Banks and Transfusion 
Services'': ``See Circular of Information for the Use of Human Blood 
and Blood Components.''
    (Response) We agree that there should be consistency between 
Sec. Sec.  606.121(c)(8)(ii) and 606.122. We are therefore revising the 
title of Sec.  606.122 and the corresponding language in Sec. Sec.  
606.122(k), (l), (m), and (n) by replacing ``Instruction circular'' 
with ``Circular of Information'' to be consistent with the wording 
required on labels of blood and blood components for transfusion, as 
illustrated in the ``Guideline for the Uniform Labeling of Blood and 
Blood Components'' and the ``United States Industry Consensus Standard 
for the Uniform Labeling of Blood and Blood Components Using ISBT 
128,'' dated November 2005, (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM079159.pdf). However, although it is a common 
industry practice for blood establishments to refer to the ``Circular 
of Information for the Use of Human Blood and Blood Components,'' we 
decline to change Sec.  606.121(c)(8)(ii) as suggested because existing 
regulations do not preclude blood establishments from creating their 
own circulars of information to address the labeling standards required 
in Sec.  606.122. Moreover, Sec.  606.121(c)(8)(ii) is consistent with 
labeling approved by the Director, CBER, i.e., ISBT 128 and ``ABC 
Codabar.''
2. 21 CFR 606.122(e) and 21 CFR 606.122(f)
    We proposed that the instruction circular contain statements 
regarding the results of each infectious agent for which the blood was 
tested, including all FDA required tests, and found negative. We have 
decided to clarify that under Sec.  606.122(e), a product intended for 
transfusion must include a statement that the product was prepared from 
blood that was found negative when tested for communicable disease 
agents as required under Sec.  610.40 (include each test that was 
performed). We also proposed to amend Sec.  606.122(f) by updating the 
warning statement to reflect the risk associated with the communicable 
disease agents for which testing is currently performed. We have 
decided to keep the currently required statement but note that we have 
made two clarifying changes to this statement by changing 
``statements'' to ``statement'' and replacing the period after 
``Warning'' with a colon, so that

[[Page 14]]

the provision now reads in its entirety, ``The statement: `Warning: The 
risk of transmitting infectious agents is present. Careful donor 
selection and available laboratory tests do not eliminate the 
hazard.''' to be consistent with the warning statements reflected in 
the current Circular of Information.
    (Comment 11) One comment supported the change if they correctly 
interpreted ``name each infectious agent'' as requiring a list of 
infectious agents, and opined that it is not necessary to ``name'' each 
type of test that is performed for each infectious agent. For example, 
according to the comment, it is not necessary to list both antibody 
tests and nucleic acid tests. Another comment recommended that either 
Sec.  606.121(c)(11) or Sec.  606.121(c)(8)(ii) should be revised to 
require the label to bear a statement ``See Circular of Information * * 
* results of infectious agent testing.''
    (Response) We do not agree that the infectious agent need only be 
listed once on the labeling for both transfusable products and products 
for further manufacturing if the blood or blood component was tested by 
different tests for the same infectious agent. We have revised Sec.  
606.122(e) to clarify that the circular of information must list the 
results of all donor screening tests for communicable disease agents 
required under Sec.  610.40 for which the blood or blood component was 
tested and found negative (e.g., negative for antibodies to HIV and 
Non-reactive for HIV-1 RNA). We interpret ``negative'' to include 
``Non-reactive.'' In response to the suggestion to revise Sec.  
606.121(c)(11), we refer to our response to comment 8. As noted in that 
response, we are not finalizing Sec.  606.121(c)(11) as proposed. We 
also believe that it is not practical to revise Sec.  606.121(c)(8)(ii) 
to require a statement of all negative test results on the container 
label of blood and blood components for transfusion, due to space 
limitations on the container label. We believe that the circular of 
information is the best place to list this type of information.
3. 21 CFR 606.122(m)(3)
    The proposed rule proposed to clarify that the instruction circular 
must contain, when applicable, instructions to begin administration of 
plasma within ``a specified time'' after thawing.
    (Comment 12) One comment requested clarification of Sec.  
606.122(m)(3) and suggested that the current statement in the Circular 
of Information for the Use of Human Blood and Blood Components, 
``Transfusion should be completed within four hours and prior to 
component expiration,'' could be used.
    (Response) We do not want to establish in regulation a specified 
time to begin or complete the transfusion of a plasma component. 
Instead, we believe that it is appropriate to provide industry with 
increased flexibility for developing and specifying timeframes for 
which thawed plasma components can still be used for transfusions if 
stored at appropriate temperatures per industry standards. We are 
therefore finalizing the amendment to Sec.  606.122(m)(3) as proposed.

H. Concerns About Labeling for Transfusable Products

    (Comment 13) One comment asked if manufacturers of licensed 
products will have to resubmit labels for approval, citing that such a 
requirement would add to the cost of compliance and impact the ability 
of some centers to support out-of-state regions in need of blood during 
FDA label review/approval process time.
    (Response) This rulemaking, in part, updates existing regulations 
to be consistent with current practice. Under the final rule, licensed 
manufacturers who have FDA approved container labels that meet the 
requirements of the final rule do not have to resubmit their labels for 
approval. If a manufacturer wishes to make labeling changes, a 
supplement submission must be submitted to FDA consistent with the 
requirements under Sec.  601.12(f)(1) (21 CFR 601.12(f)(1)).
    (Comment 14) One comment expressed concern that the proposed 
revision to Sec.  606.121(c)(2) will change the commenter's current FDA 
approved labels and will cost blood establishments approximately 
$40,000 annually in registration and licensing fees if ISBT or a 
similar system is utilized. A substantial additional cost will be 
involved in the purchase of printers, scanners, bar code readers, 
validation, and training.
    (Response) We are not requiring blood establishments to utilize the 
ISBT labeling system. Blood establishments may continue to use the 
``ABC Codabar'' system. Both of these systems are acceptable labeling 
under the bar code requirements.

IV. Legal Authority

    FDA is issuing this rulemaking under the biological products 
provisions and the communicable diseases provisions of the Public 
Health Service Act (PHS Act) (42 U.S.C. 216, 262, 263, 263a, 264, 
300aa-25), and the drugs, devices, and general administrative 
provisions of the Federal Food, Drug, and Cosmetic Act) (21 U.S.C. 321, 
331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360j, 371, 372, 374 and 
381). Under these provisions of the PHS Act and the Federal Food, Drug, 
and Cosmetic Act, we have the authority to issue and enforce 
regulations designed to ensure that biological products are safe, pure, 
potent, and properly labeled, and to prevent the introduction, 
transmission, and spread of communicable disease.

V. Analysis of Economic Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all 
costs and benefits of available regulatory alternatives and, when 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety, and other advantages; distributive impacts; and 
equity). The Agency believes that this final rule is not a significant 
regulatory action under Executive Order 12866.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because the requirements of the final rule are 
either consistent with industry practice or would be industry practice 
absent existing prohibitions, the Agency certifies that the final rule 
will not have a significant economic impact on a substantial number of 
small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that Agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $136 million, using the most current (2010) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.
    A purpose of the final rule is to simplify and unify the existing 
labeling standards. Labeling standards are currently found in multiple 
sections of the regulations and these amendments would move these 
standards to one section of the regulations. Through our

[[Page 15]]

revising, consolidating, and redesignating these regulations, parties 
wishing to understand the labeling requirements will be able to refer 
to a single source. This final rule also includes provisions that add 
flexibility to the regulations that should lower the cost of 
compliance.
    In the proposed rule, we asserted that the new labeling 
requirements were consistent with current industry practice and did not 
impose an additional burden. We received comments stating that the 
proposed labeling requirements for including all communicable disease 
test results and a unique facility identifier on the product label did 
not conform to current industry practice for certain blood and blood 
components intended for further manufacture. In the final rule, as a 
result of these comments, we revised these requirements. We have also 
amended Sec.  606.121(e)(2)(i) to require that certain red blood cell 
product labels must include the type of additive solution with which 
the product was prepared. We believe that the labeling requirements of 
the final rule conform to current industry practice.
    The final rule requires a change in the circular of information to 
reflect current testing practices. Existing labeling regulations do not 
allow the circular to reflect current required testing or to adjust to 
future changes in required testing or plasma thawing procedures. We 
believe the circular of information would already be in compliance with 
the final rule amendments and reflect current requirements and 
practices if compliance were permitted by existing regulations. As the 
circular is updated regularly, we believe any required changes can be 
made in the ordinary revision cycle at a cost too small to reliably 
quantify.
    Overall, because the requirements of this final rule are either 
industry practice or would be industry practice absent existing 
prohibitions, estimated costs are negligible. We believe this action to 
be beneficial as it increases flexibility and lowers compliance costs. 
Because we believe costs to any entity will be too small to reliably 
quantify, we certify that this final rule will not have a significant 
impact on a substantial number of small entities.

VI. Environmental Impact

    The Agency has determined under 21 CFR 25.30(h) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VII. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the final 
rule does not contain policies that have substantial direct effect on 
the States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, FDA has concluded that the 
final rule does not contain policies that have federalism implications 
as defined in the Executive order and, consequently, a federalism 
summary impact statement is not required.

VIII. The Paperwork Reduction Act of 1995

    This final rule contains information collection provisions that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The title, 
description, and respondent description of the information collection 
provisions are shown in this section VIII with a discussion of the 
information collection burden.
    Title: Revisions to Labeling Requirements for Blood and Blood 
Components, Including Source Plasma.
    Description: FDA is consolidating the regulations related to 
labeling blood and blood components. Regulations for labeling of all 
blood and blood components would be consolidated in Sec. Sec.  606.121 
(Container label) and 606.122 (Circular of information).
    Description of Respondents: Manufacturers of blood and blood 
components, and blood derivatives.
    Burden Estimate: Section 606.121(c)(11) requires that if the 
product is intended for further manufacturing use, a statement listing 
the results of all the tests for communicable disease agents required 
under Sec.  610.40 for which the donation has been tested and found 
negative must be on the container label; except that the label for 
Source Plasma is not required to list the negative results of 
serological syphilis testing under Sec. Sec.  610.40(i) and 640.65(b). 
The Agency believes that as a part of industry's usual and customary 
labeling business practices, industry currently labels blood and blood 
components for further manufacture with the results of required testing 
found in Sec.  610.40. In addition, Sec.  606.121(e)(2)(i) requires 
that certain red blood cell product labels must include the type of 
additive solution with which the product was prepared. The Agency 
believes that this labeling requirement of the final rule also is part 
of usual and customary industry practice.
    Because the Agency believes the rule amendments and the information 
collection provisions under Sec.  606.121(c)(11) and (e)(2)(i) in the 
final rule are part of usual and customary business practice and do not 
create any new burden for respondents, FDA is not estimating the burden 
associated with the information collection provisions in this final 
rule.
    The collection of information requirements under Sec. Sec.  606.121 
and 606.122 are approved under OMB control number 0910-0116; in Sec.  
640.70 have been approved under OMB control number 0910-0338.
    To comply with section 3506(c)(2)(A) of the PRA (44 U.S.C. 
3506(c)(2)(A)), elsewhere in this Federal Register, FDA is publishing a 
notice of the proposed collection of information set forth in this 
document. The collection of information provisions of this final rule 
have been submitted to OMB for review. Prior to the effective date of 
this final rule, FDA will publish a notice in the Federal Register 
announcing OMB's decision to approve, modify, or disapprove the new 
collection of information provisions in this final rule. An Agency may 
not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB 
control number.

IX. References

    The following references have been placed on display in the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday. 
FDA has verified the Web site addresses in this document, but FDA is 
not responsible for subsequent changes after this document publishes in 
the Federal Register.

1. ``Guideline for the Uniform Labeling of Blood and Blood 
Components,'' August 1985, http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM080974.pdf.
2. ``United States Industry Consensus Standard for the Uniform 
Labeling of Blood and Blood Components Using ISBT 128,'' November 
2005, http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM079159.pdf.
3. ``Guidance for Industry: Recognition and Use of a Standard for 
Uniform Blood and

[[Page 16]]

Blood Component Container Labels,'' September 2006, http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm079004.pdf.

List of Subjects

21 CFR Part 606

    Blood, Labeling, Laboratories, Reporting and recordkeeping 
requirements.

21 CFR Part 610

    Biologics, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 640

    Blood, Labeling, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, and the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, 21 CFR parts 606, 610, and 640 are 
amended as follows:

PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD 
COMPONENTS

0
1. The authority citation for 21 CFR part 606 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371, 
374; 42 U.S.C. 216, 262, 263a, 264.

0
2. Revise the heading for subpart G to read as follows:

Subpart G--Additional Labeling Standards for Blood and Blood 
Components

0
3. Section 606.121 is revised to read as follows:


Sec.  606.121  Container label.

    (a) The container label requirements are designed to facilitate the 
use of a uniform container label for blood and blood components 
intended for use in transfusion or further manufacture by all blood 
establishments.
    (b) The label provided by the collecting facility and the initial 
processing facility must not be removed, altered, or obscured, except 
that the label may be altered to indicate the proper name of the 
product, with any appropriate modifiers and attributes, and other 
information required to identify accurately the contents of a container 
after blood components considered finished products have been prepared.
    (c) The container label must include the following information, as 
well as other specialized information as required in this section for 
specific products:
    (1) The proper name of the product in a prominent position, with 
any appropriate modifiers and attributes.
    (2) The name, address, unique facility identifier, and, if a 
licensed product, the license number of each manufacturer; except the 
container label for blood and blood components for further manufacture 
is not required to include a unique facility identifier.
    (3) The donor or lot number relating the unit to the donor. If 
pooled, all donor numbers, all donation numbers, or a pool number that 
is traceable to each individual unit comprising the pool.
    (4)(i) The expiration date, including the day, month, and year, 
and, if the dating period for the product is 72 hours or less, 
including any product prepared in a system that might compromise 
sterility, the hour of expiration.
    (ii) If Source Plasma intended for manufacturing into noninjectable 
products is pooled, the expiration date for the pool is determined from 
the collection date of the oldest unit in the pool, and the pooling 
records must show the collection date for each unit in the pool.
    (5) For Whole Blood, Plasma, Platelets, and partial units of Red 
Blood Cells, the volume of the product, accurate to within 10 percent; or optionally for Platelets, the volume or volume 
range within reasonable limits.
    (6) Where applicable, the name and volume of source material.
    (7) The recommended storage temperature (in degrees Celsius).
    (8) If the product is intended for transfusion, the statements:
    (i) ``Rx only.''
    (ii) ``See circular of information for indications, 
contraindications, cautions, and methods of infusion.''
    (iii) ``Properly identify intended recipient.''
    (iv) ``This product may transmit infectious agents.''
    (v) The appropriate donor classification statement, i.e., ``paid 
donor'' or ``volunteer donor,'' in no less prominence than the proper 
name of the product.
    (A) A paid donor is a person who receives monetary payment for a 
blood donation.
    (B) A volunteer donor is a person who does not receive monetary 
payment for a blood donation.
    (C) Benefits, such as time off from work, membership in blood 
assurance programs, and cancellation of nonreplacement fees that are 
not readily convertible to cash, do not constitute monetary payment 
within the meaning of this paragraph.
    (9) If the product is intended for transfusion or as is otherwise 
appropriate, the ABO group and Rh type of the donor must be designated 
conspicuously. For Cryoprecipitated Antihemophiliac Factor (AHF), the 
Rh type may be omitted. The Rh type must be designated as follows:
    (i) If the test using Anti-D Blood Grouping Reagent is positive, 
the product must be labeled: ``Rh positive.''
    (ii) If the test using Anti-D Blood Grouping Reagent is negative, 
but the test for weak D (formerly Du) is positive, the 
product must be labeled: ``Rh positive.''
    (iii) If the test using Anti-D Blood Grouping Reagent is negative 
and the test for weak D (formerly Du) is negative, the 
product must be labeled: ``Rh negative.''
    (10) If the product is not intended for transfusion, a statement as 
applicable: ``Caution: For Manufacturing Use Only,'' or ``Caution: For 
Use in Manufacturing Noninjectable Products Only,'' or other cautionary 
statement as approved by the Director, Center for Biologics Evaluation 
and Research (CBER).
    (11) If the product is intended for further manufacturing use, a 
statement listing the results of all the tests for communicable disease 
agents required under Sec.  610.40 of this chapter for which the 
donation has been tested and found negative; except that the container 
label for Source Plasma is not required to list the negative results of 
serological syphilis testing under Sec. Sec.  610.40(i) and 640.65(b) 
of this chapter.
    (12) The blood and blood components must be labeled in accordance 
with Sec.  610.40 of this chapter, when the donation is tested and 
demonstrates evidence of infection due to a communicable disease 
agent(s).
    (13) The container label of blood or blood components intended for 
transfusion must bear encoded information in a format that is machine-
readable and approved for use by the Director, CBER.
    (i) Who is subject to this machine-readable requirement? All blood 
establishments that manufacture, process, repack, or relabel blood or 
blood components intended for transfusion and regulated under the 
Federal Food, Drug, and Cosmetic Act or the Public Health Service Act.
    (ii) What blood products are subject to this machine-readable 
requirement? All blood and blood components intended for transfusion 
are subject to the machine-readable information label requirement in 
this section.
    (iii) What information must be machine-readable? Each label must 
have machine-readable information that contains, at a minimum:

[[Page 17]]

    (A) A unique facility identifier;
    (B) Lot number relating to the donor;
    (C) Product code; and
    (D) ABO and Rh of the donor, except as described in paragraphs 
(c)(9) and (i)(5) of this section.
    (iv) How must the machine-readable information appear? The machine-
readable information must:
    (A) Be unique to the blood or blood component;
    (B) Be surrounded by sufficient blank space so that the machine-
readable information can be scanned correctly; and
    (C) Remain intact under normal conditions of use.
    (v) Where does the machine-readable information go? The machine-
readable information must appear on the label of any blood or blood 
component which is or can be transfused to a patient or from which the 
blood or blood component can be taken and transfused to a patient.
    (d) Unless otherwise approved by the Director, CBER, the container 
label for blood and blood components intended for transfusion must be 
white and print must be solid black, with the following additional 
exceptions:
    (1) The ABO and Rh blood groups must be printed as follows:
    (i) Rh positive: Use black print on white background and use solid 
black or other solid color for ABO.
    (ii) Rh negative: Use white print on black background for Rh and 
use black outline on a white background for ABO.
    (2) The proper name of the product, with any appropriate modifiers 
and attributes, the donor classification statement, and the statement 
``properly identify intended recipient'' may be printed in solid red or 
in solid black.
    (3) The following color scheme may be used for differentiating ABO 
Blood groups:

------------------------------------------------------------------------
                 Blood group                        Color of label
------------------------------------------------------------------------
O...........................................  Blue
A...........................................  Yellow
B...........................................  Pink
AB..........................................  White
------------------------------------------------------------------------

    (4) Special labels, such as those described in paragraphs (h) and 
(i) of this section, may be color-coded.
    (e) Container label requirements for particular products or groups 
of products.
    (1) Whole Blood labels must include:
    (i) The name of the applicable anticoagulant approved for use by 
the Director, CBER.
    (ii) The volume of anticoagulant.
    (iii) If tests for unexpected antibodies are positive, blood 
intended for transfusion must be labeled: ``Contains (name of 
antibody).''
    (2) Except for frozen, deglycerolized, or washed Red Blood Cell 
products, Red Blood Cell labels must include:
    (i) The type of anticoagulant, and if applicable, the volume of 
Whole Blood and type of additive solution, with which the product was 
prepared.
    (ii) If tests for unexpected antibodies are positive and the 
product is intended for transfusion, the statement: ``Contains (name of 
antibody).''
    (3) If tests for unexpected antibodies are positive, Plasma 
intended for transfusion must be labeled: ``Contains (name of 
antibody).''
    (4) Recovered plasma labels must include:
    (i) In lieu of an expiration date, the date of collection of the 
oldest material in the container.
    (ii) For recovered plasma not meeting the requirements for 
manufacture into licensable products, the statement: ``Not for Use in 
Products Subject to License Under Section 351 of the Public Health 
Service Act.''
    (iii) The type of anticoagulant with which the product was 
prepared.
    (5) Source Plasma labels must include the following information:
    (i) The cautionary statement, as specified in paragraph (c)(10) of 
this section, must follow the proper name with any appropriate 
modifiers and attributes and be of similar prominence as the proper 
name.
    (ii) The statement ``Store at -20 [deg]C or colder,'' provided, 
that where plasma is intended for manufacturing into noninjectable 
products, this statement may be replaced by a statement of the 
temperature appropriate for manufacture of the final product to be 
prepared from the plasma.
    (iii) The total volume or weight of plasma and total quantity and 
type of anticoagulant used.
    (iv) When plasma collected from a donor is reactive for a serologic 
test for syphilis, a statement that the plasma is reactive and must be 
used only for the manufacturing of positive control reagents for the 
serologic test for syphilis.
    (v) Source Plasma diverted for Source Plasma Salvaged must be 
relabeled ``Source Plasma Salvaged'' as prescribed in Sec.  640.76 of 
this chapter. Immediately following the proper name of the product, 
with any appropriate modifiers and attributes, the labeling must 
prominently state as applicable, ``STORAGE TEMPERATURE EXCEEDED -20 
[deg]C'' or ``SHIPPING TEMPERATURE EXCEEDED -5 [deg]C.''
    (vi) A statement as to whether the plasma was collected from normal 
donors, or from donors in specific collection programs approved by the 
Director, CBER. In the case of specific collection programs, the label 
must state the defining characteristics of the plasma. In the case of 
immunized donors, the label must state the immunizing antigen.
    (f) Blood and blood components determined to be unsuitable for 
transfusion must be prominently labeled ``NOT FOR TRANSFUSION,'' and 
the label must state the reason the unit is considered unsuitable. The 
provision does not apply to blood and blood components intended solely 
for further manufacture.
    (g) [Reserved]
    (h) The following additional information must appear on the label 
for blood and blood components shipped in an emergency prior to 
completion of required tests, in accordance with Sec.  610.40(g) of 
this chapter:
    (1) The statement: ``FOR EMERGENCY USE ONLY BY ---- .''
    (2) Results of any tests prescribed under Sec. Sec.  610.40 and 
640.5(a), (b), or (c) of this chapter completed before shipment.
    (3) Indication of any tests prescribed under Sec. Sec.  610.40 and 
640.5(a), (b), or (c) of this chapter not completed before shipment.
    (i) The following additional information must appear on the label 
for blood and blood components intended for autologous transfusion:
    (1) Information adequately identifying the patient, e.g., name, 
date of birth, hospital, and identification number.
    (2) Date of donation.
    (3) The statement: ``AUTOLOGOUS DONOR.''
    (4) The ABO and Rh blood group and type, except as provided in 
paragraph (c)(9) of this section.
    (5) Each container of blood and blood component intended for 
autologous use and obtained from a donor who fails to meet any of the 
donor suitability requirements under Sec.  640.3 of this chapter or who 
is reactive to or positive for one or more tests for evidence of 
infection due to communicable disease agents under Sec.  610.40 of this 
chapter must be prominently and permanently labeled ``FOR AUTOLOGOUS 
USE ONLY'' and as otherwise required under Sec.  610.40 of this 
chapter. Such units also may have the ABO and Rh blood group and type 
on the label.
    (6) Units of blood and blood components originally intended for 
autologous use, except those labeled as prescribed under paragraph 
(i)(5) of this section, may be issued for allogeneic transfusion 
provided the container label complies with all applicable provisions of 
paragraphs (b) through (e) of this section. In such case, the special 
label

[[Page 18]]

required under paragraphs (i)(1), (i)(2), and (i)(3) of this section 
must be removed or otherwise obscured.
    (j) A tie-tag attached to the container may be used for providing 
the information required by paragraphs (e)(1)(iii), (e)(2)(ii), and 
(e)(3), (h), or (i)(1), (i)(2), and (i)(3) of this section.

0
4. Section 606.122 is amended by:
0
a. Revising the section heading;
0
b. Revising the introductory text;
0
c. Revising paragraphs (e), (f), (m)(2), (m)(3), and (m)(5); and
0
d. Revising the introductory text in paragraphs (k), (l), (m), and (n).
    The revisions read as follows:


Sec.  606.122  Circular of information.

    A circular of information must be available for distribution if the 
product is intended for transfusion. The circular of information must 
provide adequate directions for use, including the following 
information:
* * * * *
    (e) A statement that the product was prepared from blood that was 
found negative when tested for communicable disease agents, as required 
under Sec.  610.40 of this chapter (include each test that was 
performed).
    (f) The statement: ``Warning: The risk of transmitting infectious 
agents is present. Careful donor selection and available laboratory 
tests do not eliminate the hazard.''
* * * * *
    (k) For Red Blood Cells, the circular of information must contain:
* * * * *
    (l) For Platelets, the circular of information must contain:
* * * * *
    (m) For Plasma, the circular of information must contain:
    (1) * * *
    (2) Instructions to thaw the frozen product at a temperature 
appropriate for the product.
    (3) When applicable, instructions to begin administration of the 
product within a specified time after thawing.
* * * * *
    (5) A statement that this product has the same risk of transmitting 
infectious agents as Whole Blood; other plasma volume expanders without 
this risk are available for treating hypovolemia.
    (n) For Cryoprecipitated AHF, the circular of information must 
contain:
* * * * *

0
6. Section 606.170 is amended by revising paragraph (b) to read as 
follows:


Sec.  606.170  Adverse reaction file.

* * * * *
    (b) When a complication of blood collection or transfusion is 
confirmed to be fatal, the Director, Office of Compliance and Biologics 
Quality, CBER, must be notified by telephone, facsimile, express mail, 
or electronically transmitted mail as soon as possible. A written 
report of the investigation must be submitted to the Director, Office 
of Compliance and Biologics Quality, CBER, by mail, facsimile, or 
electronically transmitted mail (for mailing addresses, see Sec.  600.2 
of this chapter), 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.

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

0
7. The authority citation for 21 CFR part 610 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 
264.

0
8. Section 610.40 is amended by revising paragraphs (h)(2)(ii)(B) and 
(i) to read as follows:


Sec.  610.40  Test requirements.

* * * * *
    (h) * * *
    (2) * * *
    (ii) * * *
    (B) You must appropriately label such blood or blood components as 
required under Sec.  606.121 of this chapter, and with the 
``BIOHAZARD'' legend;
* * * * *
    (i) Syphilis testing. In addition to the testing otherwise required 
under this section, you must test by a serological test for syphilis 
under Sec. Sec.  640.5(a), 640.14, 640.23(a), 640.33(a), 640.53(a), and 
640.65(b)(1) and (b)(2) of this chapter.

PART 640--ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS

0
9. The authority citation for 21 CFR part 640 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371; 42 
U.S.C. 216, 262, 263, 263a, 264.


Sec.  640.70  [Removed]

0
10. Section 640.70 is removed.
0
11. Section 640.74 is amended by revising paragraph (b)(4) to read as 
follows:


Sec.  640.74  Modification of Source Plasma.

* * * * *
    (b) * * *
    (4) The label affixed to each container of Source Plasma Liquid 
shall contain, in addition to the information required by Sec.  606.121 
of this chapter, but excluding Sec.  606.121(e)(5)(ii) of this chapter, 
the name of the manufacturer of the final blood derivative product for 
whom it was prepared.
* * * * *

    Dated: December 22, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-33554 Filed 12-30-11; 8:45 am]
BILLING CODE 4160-01-P