[Federal Register Volume 77, Number 1 (Tuesday, January 3, 2012)]
[Rules and Regulations]
[Pages 7-18]
[FR Doc No: 2011-33554]

=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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,<PHONE_NUMBER>.

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

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

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

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

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,

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

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

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

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

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:

    (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

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


[Federal Register: July 13, 2009 (Volume 74, Number 132)]
[Notices]
[Page 33508-33509]
[DOCID:fr13jy09-144]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF TRANSPORTATION

National Highway Traffic Safety Administration

Reports, Forms and Record Keeping Requirements; Agency
Information Collection Activity Under OMB Review

AGENCY: National Highway Traffic Safety Administration, DOT.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: In compliance with the Paperwork Reduction Act of 1995 (44
U.S.C. 3501 et seq.), this notice announces that the Information
Collection Request (ICR) abstracted below has been forwarded to the
Office of Management and Budget (OMB) for review and comment. The ICR
describes the nature of the information collections and their expected
burden. The Federal Register Notice with a 60-day comment period was
published on February 19, 2009 [FR Doc. 2009-0037, Vol. 74, No. 32,
Pages 7737-7738].

DATES: Comments must be submitted on or before August 12, 2009.

FOR FURTHER INFORMATION CONTACT: Charlene Doyle, Contracting Officer's
Technical Representative, Office of Regulatory Analysis and Evaluation,
National Highway Traffic Safety Administration, 1200 New Jersey Ave.,
SE., NVS-431, Washington, DC 20590. Ms. Doyle's phone number is 202-
366-1276 and her e-mail address is<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

National Highway Traffic Safety Administration

    Title: An In-Depth Examination of Pedestrian Involved Hit and Run
Traffic Crashes.
    OMB Number: 2127-New.
    Type of Request: Request for public comment on proposed collection
of information.
    Abstract: The National Highway Traffic Safety Administration
(NHTSA) was established to reduce the mounting number of deaths,
injuries and economic losses resulting from motor vehicle crashes on
the Nation's highways. As part of this statutory mandate, NHTSA is
authorized to conduct research as a foundation for the development of
motor vehicle standards and traffic safety programs. Between 1998 and
2007, of the more than 48,000 pedestrian deaths recorded within the
United States, over 9,000 (19 percent) were caused by hit-and-run
drivers. The data collected in this survey of drivers, along with
police crash and court data from 10 counties, will be used to identify
areas for targeting improvements, identify scenarios in which hit-and-
run collisions are more likely to occur, and assist in the selection of
cost-effective countermeasures to reduce the incidence of pedestrian
hit-and-run crashes.
    Affected Public: Individuals.
    Estimated Total Annual Burden: 855 hours.

ADDRESSES: Send comments, within 30 days, to the Office of Information
and Regulatory Affairs, Office of Management and Budget, 725-17th
Street, NW., Washington, DC 20503, Attention NHTSA Desk Officer.
    Comments are invited on: Whether the proposed collection of
information is necessary for the proper performance of the functions of
the Department, including whether the information will have practical
utility; the accuracy of the Department's estimate of the burden of the
proposed information collection; ways to enhance the quality, utility
and clarity of the information to be collected; and ways to minimize
the burden of the collection of information on respondents, including
the use of automated collection techniques or other forms of
information technology. A comment to OMB is most effective if OMB
receives it within 30 days of publication.

    Authority: 44 U.S.C. 3506(c)(2)(A).

James F. Simons,
Director, Office of Regulatory Analysis and Evaluation.
 [FR Doc. E9-16585 Filed 7-10-09; 8:45 am]

BILLING CODE 4910-59-P