further manufacturing; and notify a donor who is deferred from donating
because the donor did not satisfy the eligibility criteria described in
part 630 or because the donor's test results revealed a relevant
transfusion-transmitted infection as described under Sec.  610.40. This
section is consistent with the proposed rule, with one change. Since we
are not defining the term ``you'' in Sec.  630.3, we have finalized
Sec.  630.1(b) to describe the scope as ``Blood establishments that
manufacture blood and blood components, as defined in Sec.  630.3(a)
and (b) of this chapter, must comply with subparts A, B, and C of this
part.'' Accordingly, the requirements in part 630 apply to any
establishment or facility that collects, or performs other
manufacturing steps for, blood or blood components for transfusion,
including components for autologous use, for further manufacturing use,
or for use as a component of a medical device.

I. Medical Supervision (Sec. Sec.  630.5, 640.130)

    Final Sec.  630.5(a) requires a responsible physician, as defined
in Sec.  630.3(i), to determine the eligibility of a donor of blood or
blood components, including Source Plasma, in accordance with the
regulations in 21 CFR Chapter I, subchapter F. This section describes
the activities related to the collection of blood and blood components
that the responsible physician may delegate to a physician substitute
or other trained person, taking into account the training and medical
expertise needed to assess whether the donor's health permits the
collection, and to mitigate the risks related to donation. Recognizing
that conditions may change, final Sec.  630.5(a)(1)(i)(C) provides that
the Director, CBER, may authorize the delegation of additional
activities, after determining that delegating the activity would
present no undue medical risk to the donor or to the transfusion
recipient. The requirements in this section are not intended to preempt
State or local laws when those laws require a higher level of medical
oversight for certain blood collection activities This section combines
the existing requirements related to eligibility for donors of Whole
Blood (Sec.  640.3) and Source Plasma (Sec.  640.63) into a single
section.
    For the collection of blood and blood components other than Source
Plasma and plasma collected by plasmapheresis, Sec.  630.5(b)
authorizes the responsible physician to delegate the following
activities to a physician substitute or other trained person:
Determining the eligibility of a donor and documenting assessments
related to that determination; collecting blood and blood components;
returning red blood cells to a donor during apheresis procedures; and
obtaining the informed consent of a plateletpheresis donor as described
in Sec.  640.21(g). Under

Sec.  630.5(b)(2), the responsible physician is not required to be
present at the collection site when any of these activities are
performed, provided that the responsible physician has delegated
oversight of these activities to a trained person who is not only
adequately trained and experienced in the performance of these
activities but also adequately trained and experienced in the
recognition of and response to the known adverse responses associated
with blood collection procedures.
    However, under Sec.  630.5(b)(1)(i)(A), the responsible physician
must not delegate the examination and determination that the health of
a donor would not be adversely affected by donating, when the donor's
systolic blood pressure falls outside the range of 90 to 180
millimeters (mm) of mercury, or when the diastolic blood pressure falls
outside the range of 50 to 100 mm of mercury. Additionally, the
responsible physician must not delegate the examination and
determination that the health of a donor would not be adversely
affected by donating Whole Blood or Red Blood Cells more frequently
than specified under Sec.  630.15(a)(1).
    Under Sec.  630.5(b)(1)(i)(B), the responsible physician must not
delegate the following determinations: That the health of a donor whose
pulse measurement falls outside the range of 50 to 100 beats per
minute, or is irregular, would not be adversely affected by donating;
that the health of an ineligible autologous donor permits the
collection procedure; and that a dedicated plateletpheresis donor is in
good health. The responsible physician may make the determinations
addressed in Sec.  630.5(b)(1)(i)(B) by telephonic or other offsite
consultation.
    Under Sec.  630.5(b)(1)(i)(C), the responsible physician must not
delegate the determination of the health of the donor or the
determination that the blood or blood component collected would present
no undue medical risk to the transfusion recipient, as required for
dedicated donations by an ineligible donor for a specific transfusion
recipient based on documented exceptional medical need. The responsible
physician may make this determination by telephonic or other offsite
consultation. In recognition that conditions may evolve in the future,
we have added Sec.  630.5(b)(1)(v) to permit the responsible physician
to delegate other activities when authorized by the Director, CBER,
based on a determination that delegating the activities would present
no undue medical risk to the donor or to the transfusion recipient. We
anticipate that the Director, CBER, would authorize such delegations
under 21 CFR 640.120, or in response to submissions from individual
establishments, as appropriate. In addition, such authorizations may be
discussed in guidance issued under good guidance practices.
    For the collection of Source Plasma and plasma collected by
plasmapheresis, Sec.  630.5(c)(1)(i) authorizes the responsible
physician to delegate to a physician substitute or other trained person
the following activities related to donor eligibility and blood
component collection, provided that the responsible physician or a
physician substitute is on the premises at the collection site: (1)
Determining and documenting donor eligibility, (2) collecting blood and
blood components, (3) returning red blood cells to the donor during
apheresis, (4) other activities authorized by the CBER Director, (5)
the collection of Source Plasma in an approved collection program from
a donor who is otherwise determined to be ineligible, and (6) the
collection of a blood sample for testing required under Sec.
640.65(b)(1)(i). Similar to collections of blood and blood components
subject to delegations under Sec.  630.5(b), Sec.  630.5(c)(1)(i)(A)(1)
through (c)(1)(i)(A)(3) provide that the responsible physician must not
delegate specific responsibilities related to the assessment of donor
blood pressure, donation frequency after red blood cell loss, donor
pulse, and certain plasmapheresis collections from an ineligible donor.
Section 630.5(c)(1)(i)(A)(4) and (c)(1)(i)(A)(5) provide that the
responsible physician must not delegate the responsible physician's
determination related to a donor's false-positive reaction to a
serologic test for syphilis, or the responsible physician's
determination to permit plasmapheresis of a donor with syphilis. In
addition, Sec.  630.5(c)(1)(ii) authorizes the responsible physician,
who may or may not be present when these activities are performed, to
delegate to a trained physician substitute the approval and signature
for a plasmapheresis procedure and review and signature for accumulated
laboratory data, the calculated values of each component, and the
collection records. However, the responsible physician must not
delegate the decision to reinstate a donor in accordance with Sec.
640.65(b)(2)(i). These provisions in Sec.  630.5(c)(1)(ii) were not
expressly included in proposed Sec.  630.5. We have included them here
in order to state more clearly how the new delegation provisions in
Sec.  630.5 affect the existing responsibilities of the responsible
physician.
    With respect to donor immunization, consistent with the proposed
rule, Sec.  630.5(c)(2)(i) authorizes the responsible physician to
delegate to a physician substitute or other trained person the
administration of an immunizing agent other than red cells to a donor
in an approved immunization program, provided that the responsible
physician or physician substitute is on the premises. Section
630.5(c)(2)(ii) authorizes the responsible physician to delegate to a
physician substitute the function of donor immunization with red blood
cells, provided that the responsible physician has approved the
procedure and is on the premises when the procedure is performed.
Section 630.5(c)(3) authorizes the responsible physician to delegate to
a physician substitute the administration of the medical history,
physical examination (including examination before immunization), and
informed consent required in Sec.  630.15(b)(1), (b)(2), and (b)(5).
The responsible physician is not required to be present at the
collection site when the physician substitute performs these
activities.
    Section 630.5(c)(4) addresses delegations for collections from
infrequent plasma donors, as defined in Sec.  630.3(e). This section
authorizes the responsible physician to delegate to a trained person
the following activities related to collections from infrequent plasma
donors: the activities listed in Sec.  630.15(b)(1)(i) through
(b)(1)(iii) and (b)(1)(v), and the administration of the informed
consent under Sec.  630.15(b)(2). The responsible physician or a
physician substitute is not required to be present at the collection
site provided that the responsible physician has delegated these
activities to a trained person who is also adequately trained and
experienced in the recognition of and response to the known adverse
responses associated with blood collection procedures. However, if
Source Plasma is collected from an infrequent plasma donor and the
donor is otherwise ineligible or is participating in an approved
immunization program, the responsible physician may only delegate
activities as described in Sec.  630.5(c)(1) through (c)(3), as
appropriate to that collection.
    Section 630.5(d) requires that, for all collections, establishments
must establish, maintain, and follow standard operating procedures for
obtaining rapid emergency medical services for donors when medically
necessary. In addition, establishments must assure that an individual
(responsible physician, physician substitute, or trained person,

as defined in Sec.  630.3) who is currently certified in
cardiopulmonary resuscitation is located on the premises whenever the
establishment is performing collections of blood or blood components.
    Finally, we have added Sec.  640.130 to new subpart M of 21 CFR
part 640, entitled ``Definitions and Medical Supervision.'' Section
640.130 clarifies that the requirements for medical supervision
established in Sec.  630.5 supplement the regulations in part 640. We
are adding this provision to aid the reader in identifying applicable
requirements for medical supervision related to the collection of blood
and blood components in accordance with part 640.
    (Comment 36) One comment agreed that the responsible physician
should direct and control the physician substitutes and trained
personnel, and supported proposed provisions under which the
responsible physician could authorize trained personnel, including
physician substitutes, to determine the donor's eligibility and collect
blood and blood components in the absence of a responsible physician.
    (Response) We have finalized the proposed rule to permit delegation
of blood collection activities to trained persons, including physician
substitutes, who are adequately instructed and qualified to perform the
delegated functions. This delegation provision is not intended to
preempt more restrictive requirements under State or local law. We do
not require the responsible physician to be on the premises, except for
red blood cell immunizations, although State or local law may provide
otherwise. We have also clarified the activities that the responsible
physician may not delegate. Delegation is not permitted in these
circumstances because the medical expertise of the responsible
physician is necessary to assess whether the donor's health permits the
collection.
    (Comment 37) One comment requested clarification that designated
physician substitutes and trained persons may perform the collection of
platelets, Red Blood Cells and plasma (as distinct from Source Plasma)
and may return red blood cells during an apheresis collection in the
absence of the responsible physician. Another comment criticized a
requirement for the presence of a physician substitute in the
collection of Source Plasma, noting that red blood cells are now
routinely returned by automated equipment during apheresis collections
of plasma, Red Blood Cells, and platelets. The comment stated that,
since modern apheresis devices return red blood cells to the donor
through automated processes, the return of red blood cells does not
pose a heightened risk relative to other procedures, and therefore
there is no need for a responsible physician or physician substitute to
be present during the return of red blood cells to apheresis donors.
The comment suggested that the presence of a physician substitute or
the responsible physician should only be required in the unlikely event
that a Source Plasma establishment was returning red blood cells
manually.
    (Response) Section 630.5(b)(1)(iii) and (c)(1)(i)(A) of the final
rule authorize the responsible physician to delegate to a physician
substitute or other trained person the return of red blood cells to the
donor during apheresis. Subject to an exception for certain
plasmapheresis collections, the regulation does not require the
responsible physician to be present at the collection site when red
blood cells are returned to the donor during apheresis, provided that
the responsible physician has delegated oversight of these activities
to a trained person who is also adequately trained and experienced in
the recognition of and response to the known adverse responses
associated with blood collection procedures. However, when this
activity is performed in relation to the collection of plasma by
plasmapheresis (other than a collection from an infrequent plasma
donor), the regulation requires the responsible physician or physician
substitute to be present at the collection site. We have determined
that the presence of the responsible physician or of a physician
substitute under the supervision of the responsible physician is
necessary to help ensure the continued safety of plasmapheresis donors
who are not infrequent donors, as defined in Sec.  630.3(e). This is
because such donors are permitted to donate up to two times every week,
and larger volumes of fluid may be collected at each donation than from
other donors. These factors may increase risks for the donor, and
warrant the on-site presence of a physician substitute or the
responsible physician.
    (Comment 38) One comment noted that Sec.  630.5(c) would permit a
collecting establishment to authorize a physician substitute to perform
the functions of a responsible physician in the collection of Source
Plasma, except the responsible physician would be required to be
present for red blood cell immunizations. The comment stated that they
assume that FDA is requiring the presence of the responsible physician
for the red blood cell immunization to assist the recipient of red
blood cells if a life-threatening situation arises during the
immunization process. The comment asserted that this is most likely
based on the fact that potential life-threatening reactions most
commonly occur within 10 to 15 minutes of the start of the transfusion
with as little as 10 milliliters (mL) transfused.
    The comment said that they understand the potential risks
associated with red blood cell immunization. However, the comment
stated that having a physician present during the immunization process
does not protect against the single greatest risk to recipients of red
blood cells, which is human error when identifying the blood product
for administration to the recipient of red blood cells. Therefore, in
protecting against this risk, the comment stated that it is imperative
that plasma establishments have processes and procedures in place to
assure that the correct red blood cell product is infused to the
intended recipient. The comment reports that this is currently achieved
by adherence to current good manufacturing practices. The comment
recommended that FDA remove the requirement of having a physician
present during immunization with red blood cells as long as current
good manufacturing practices are followed.
    (Response) We agree with the description of the risks of red blood
cell immunizations. We also agree that Source Plasma establishments
must adhere to Current Good Manufacturing Practice for Blood and Blood
Components (21 CFR part 606), including Sec.  606.100(b), which require
establishments to establish, maintain, and follow written standard
operating procedures for all steps in the collection, processing,
compatibility testing, storage, and distribution of blood and blood
components for allogeneic transfusion, and further manufacturing
purposes. However, adherence to current good manufacturing practices
does not replace the medical oversight provided by the responsible
physician, or the clinical expertise that a responsible physician can
provide in the case of an emergency at the establishment. Accordingly,
we require that the responsible physician must be present when a donor
is immunized with red blood cells. Section 630.5(c)(2)(ii) authorizes
the responsible physician to delegate to a physician substitute the
function of donor immunization with red blood cells, provided that the
responsible physician has approved the procedure and is on the premises
at the collection site when the procedure is performed.

    (Comment 39) A comment to proposed Sec.  630.5(e) asserted that
blood collection personnel should be trained in cardiopulmonary
resuscitation and the use of automated external defibrillators, and
should call 911 to transport donors to a medical facility for emergency
care as soon as possible. Another comment noted that the final rule
could require that collection staff be trained in cardiopulmonary
resuscitation.
    (Response) Final Sec.  630.5(d) requires blood collection
establishments to establish, maintain, and follow standard operating
procedures for obtaining rapid emergency medical services for donors
when necessary. In addition, blood collection establishments must
assure that an individual (responsible physician, physician substitute,
or trained person) who is currently certified in cardiopulmonary
resuscitation is located on the premises whenever collections of blood
or blood components are performed. We agree that the availability of
such a person on the premises will provide important donor protections
in the event they are needed. We are not including in the codified
language a requirement for a person also to be trained in the use of
automated external defibrillators because such devices are not always
available at collection sites. However, we believe that the presence of
automated external defibrillators may be helpful, and establishments
may choose to provide training on available automated external
defibrillators, in addition to assuring that a person currently
certified in cardiopulmonary resuscitation is located on the premises
during collections. As noted in our response to comment 40, we believe
that establishments will incorporate the use of 911 services into their
procedures for obtaining rapid emergency medical services for donors
when necessary.
    (Comment 40) One comment noted that proposed Sec.  630.5(e) would
have required establishments to establish, maintain, and follow
standard operating procedure for providing emergency medical services
for donors within 15 minutes. The comment agreed that SOPs should be
established, maintained, and followed for the provision of emergency
medical services but stated that ensuring a 15 minute response time
would not be feasible in some communities and in any event is beyond
the control of the blood establishment. Other comments also noted that
local emergency medical service response time is community dependent.
Blood centers cannot control how quickly emergency medical services
respond and cannot guarantee a 15 minute response time.
    (Response) After considering the comments, we have finalized this
provision without referencing a 15 minute timeframe. We recognize that
in many instances blood collection facilities must rely on the response
time of emergency medical services available through local 911
services. Instead, we are requiring in Sec.  630.5(d) that that
establishments establish, maintain, and follow standard operating
procedures for obtaining rapid emergency medical services for donors
when necessary. In addition, the final rule requires that at least one
person (responsible physician, physician substitute, or trained person)
on the premises during the collection of blood and blood components be
currently certified in cardiopulmonary resuscitation. FDA expects that
procedures established by blood collection establishments for obtaining
rapid emergency medical services will generally result in the provision
of emergency medical services within 15 minutes. However, by not
specifying a 15 minute response time (and instead calling only for a
``rapid'' response), we are recognizing that unanticipated
circumstances that are outside the control of the blood establishment
may delay such care. Establishments should consider the availability of
emergency medical services and local response times, particularly when
determining locations for mobile collections.
    (Comment 41) One comment responded that proposed Sec.  630.5(e)
should be reworded to include public emergency medical services. The
comment agreed that the establishment of standard procedures for
providing emergency medical services within 15 minutes, if necessary,
for donors seems appropriate.
    (Response) We decline to include the term ``public'' prior to
emergency medical services in Sec.  630.5(d). We interpret emergency
medical services to include an onsite responsible physician or access
to emergency medical services available through 911. If an
establishment determines that emergency medical services accessible
through 911 may not be available rapidly, due to the location of the
collection facility or mobile unit, the establishment should provide
for a responsible physician to be present at the collection site.

J. General Donor Eligibility Requirements (Sec.  630.10)

    This section includes requirements to ensure that blood and blood
components are safe, pure and potent. It also includes requirements to
determine that the donor is in good health and the donor's health will
not be adversely affected by the donation. We require the establishment
to provide the donor with certain educational material related to
infectious disease risk so that the donor can self-defer, to check
donor deferral records, to perform a limited physical assessment of the
donor, to assess the donor for risk factors for relevant transfusion-
transmitted infections and other factors that might adversely affect
the donation or the donor's health, to obtain a donor acknowledgement
that is signed or otherwise recorded, to defer ineligible donors, and
to obtain proof of the donor's identity and a postal address where the
donor may be contacted for 8 weeks after donation for purposes of donor
notification under Sec.  630.40.
    We received comments on this section from individuals, blood
establishments and trade organizations. We are finalizing this section
largely as proposed, except that we have clarified the language in some
sections and combined or revised other sections. We have combined
proposed Sec.  630.10(e), (f), and (g) covering various aspects of
donor eligibility into one section, Sec.  630.10(e). We have renumbered
proposed Sec.  630.10(h) into final Sec.  630.10(f). Final Sec.
630.10(f)(3) provides a modified standard for donor hemoglobin or
hematocrit. Proposed Sec.  630.10(i) is final Sec.  630.10(g), and we
have clarified proposed Sec.  630.10(i)(2) Donor's written statement of
understanding, now titled ``Donor's acknowledgement'' in Sec.
630.10(g)(2). We also added Sec.  630.10(h) to state more explicitly
what an establishment must do when a donor is ineligible.
1. Section 630.10(a)
    Consistent with FDA's long standing requirement that a donor be in
good health at the time of donation to assure that blood, blood
components and blood products manufactured from their donations will be
safe, pure and potent, this section states that an establishment must
not collect blood or blood components before determining that the donor
is eligible to donate. We received no comments on this provision. We
added language to explain that, to be eligible, a donor must be in good
health and free from transfusion-transmitted infections as can be
determined by the processes in this subchapter. The phrase ``as can be
determined by the processes in this subchapter'' clarifies that blood
establishments must assess a donor's eligibility in accordance with
these regulations. Like the proposed rule, this section states that a
donor is ineligible if the donor is not in good health or if the blood
establishment identifies

factors that may adversely affect the health of the donor or the
safety, purity, or potency of the blood or blood components collected
from the donor.
2. Section 630.10(b)
    Section 630.10(b) requires that, before determining eligibility, an
establishment must provide the donor with educational material in an
appropriate format regarding certain relevant transfusion-transmitted
infections when providing that information is necessary to assure the
safety, purity, and potency of blood and blood components, such as for
HIV risk factors. Currently, the only relevant transfusion-transmitted
infection for which FDA has determined that providing such information
is necessary to assure blood safety, purity, and potency is HIV. FDA
first made this recommendation in 1983 (Ref. 30). The donor history
questionnaires and accompanying materials found acceptable by FDA
include blood donor educational material addressing HIV risk behaviors
and signs and symptoms of HIV (Refs. 6, 7, 8). Providing this
educational information in written or electronic format would meet the
requirements of this section. In addition, the provision permits
establishments to provide, in the educational material, information
concerning the risks and hazards of donation. This provision differs
from proposed Sec.  630.10(b) in two significant ways: (1) In response
to comments, we have clarified that blood collection establishments
must provide information concerning certain, and not all, relevant
transfusion-transmitted infections and (2) to provide greater
flexibility and to accommodate existing practices, we have revised this
section to expressly permit establishments to provide, in this
educational material, information regarding the risks and hazards of
the donation procedure to meet the requirements under Sec.
630.10(g)(2)(ii)(E).
    (Comment 42) Two comments raised concern that the proposal would
require establishments to provide the donor with too much information
about too many relevant transfusion-transmitted infections. Several
comments suggested that the rule should not require the educational
material to include signs and symptoms of a relevant transfusion-
transmitted infection. Several comments suggested that providing the
donor history questionnaire should be sufficient to meet this
requirement, while several comments suggested that the donor history
questionnaire should not include signs and symptoms of HIV.
    (Response) FDA believes that providing educational material to
donors protects the safety of the blood supply and donor health. FDA
believes that self-deferral by at risk donors because of information
provided in the educational materials has helped ensure blood safety
(Refs. 6, 7, 8, 31, 32, 33). Blood establishments have voluntarily
developed donor educational material in response to potential threats
(Refs. 6, 7, 8, 31, 32, 33).
    FDA agrees with the comments that educational materials should not
describe all relevant transfusion-transmitted infections. Instead, this
section requires establishments to provide donor information about a
relevant transfusion-transmitted infection when necessary to assure the
safety, purity, and potency of blood and blood components. As noted
previously, currently HIV is the only relevant transfusion-transmitted
infection for which providing such information is necessary. The
longstanding practice of providing educational material about HIV,
including information about signs and symptoms, would continue as a
requirement under this provision.
    FDA believes that establishments may choose to include in the donor
educational material information to explain the collection procedure
and the risks and hazards of the procedure, as required under Sec.
630.10(g)(2)(ii)(E). This section expressly permits the incorporation
of that information into the donor educational material, but does not
require it.
3. Section 630.10(c)
    Section 630.10(c) requires establishments to determine the donor's
eligibility on the day of donation and prior to collection. Under Sec.
630.10(c)(1), which is applicable to products that cannot be stored for
more than 24 hours, an establishment may determine the donor's
eligibility and collect a sample for testing required under Sec.
610.40 no earlier than 2 calendar days before the day of donation. In
Sec.  630.10(c)(2), the final rule authorizes blood establishments to
clarify a donor's response to a donor history question under Sec.
630.10(e) or (g) in accordance with standard operating procedures and
within 24 hours of the time of collection.
    (Comment 43) Several comments stated that for components having a
shelf life of 24 hours, collecting a sample for testing for infectious
diseases one day before donation may not provide enough time to obtain
the results. They requested that FDA allow the donor to be tested 3
days prior to collection of the donation or alternatively allowing the
donation to be released under emergency provisions in Sec.  610.40(g)
or where appropriately labeled as from a donor who has been previously
tested.
    (Response) FDA agrees with that there is a need for some
flexibility on the timing for collecting a sample for testing and
making a donor eligibility determination for donors of blood components
that cannot be stored for more than 24 hours. We have decided to
finalize the proposed provision, now Sec.  630.10(c)(1), and provide
that ``when a donor is donating blood components that cannot be stored
for more than 24 hours, you may determine the donor's eligibility and
collect a sample for testing required under Sec.  610.40 of this
chapter, no earlier than 2 calendar days before the day of donation,
provided that your standard operating procedures address these
activities.'' We believe that this 2 calendar day timeframe will be
adequate to accommodate donor testing before collection. We also note
that current Sec.  610.40(g) allows release of untested components in
appropriately documented medical emergency situations.
    (Comment 44) FDA received several comments requesting that FDA
permit blood establishments to obtain answers to missing donor
information for 24 hours after the collection occurred.
    (Response) FDA realizes that sometimes blood establishments become
aware that there are missing answers to donor history questions, or
they need clarification of answers to certain donor history questions.
In response to comments, and consistent with current FDA policy (Ref.
34), we are adding new Sec.  630.10(c)(2) to the final rule. Section
630.10(c)(2) expressly authorizes establishments to clarify donor
records after collection under these circumstances, ``In the event
that, upon review, you find that a donor's responses to the donor
questions before collection were incomplete, within 24 hours of the
time of collection, you may clarify a donor's response or obtain
omitted information required under paragraph (e) of this section,
provided that your standard operating procedures (required under 21 CFR
606.100) address these activities.'' This applies only to responses to
donor questions, and not to information that establishments are
required to obtain as part of the physical assessment of the donor
addressed in Sec.  630.10(f).
4. Section 630.10(d)
    Section 630.10(d) requires a blood establishment to determine the
donor's eligibility before collection by performing four tasks: (1)
Consulting the records of deferred donors maintained under Sec.
606.160(e)(1) and (2). Because it

may not be feasible to review the cumulative record described in Sec.
606.160(e)(2) prior to collection at all collection sites, the
regulation provides that if pre-collection review is not feasible, the
establishment must consult the cumulative record prior to release of
any blood or blood component prepared from the collection; (2) assuring
that the interval since the donor's last donation is appropriate; (3)
assessing the donor's medical history; and (4) performing a physical
assessment of the donor. We have finalized the description of the last
two steps as proposed, and we have clarified the language used to
describe the second step by omitting unnecessary language.
    The first factor has been changed to reference the ``records of
deferred donors maintained under Sec.  606.160(e)(1) and (2) of this
chapter'' instead of the proposed ``list of ineligible donors required
under Sec.  606.160(e)(2) of this chapter'', and to provide flexibility
for consulting the cumulative record before release of blood or blood
components when the record cannot be available at the collection site.
We discuss final Sec.  606.160(e) at comment 25. The review of the
records of deferred donors may be accomplished by making an electronic
query of a centralized database.
    (Comment 45) One comment questioned the validity of donor deferral
registries in ensuring the safety of the blood supply. For example, the
comment asserted that requiring collection facilities to consult the
donor deferral registry prior to donation would negatively affect
mobile operations and impact other facilities when computer outages
occur that would have a significant negative impact on blood
availability.
    (Response) The requirements in Sec. Sec.  606.160(e) and
630.10(d)(1) will help assure that blood and blood components that are
not suitable for use are not collected or distributed. These provisions
protect donors from making donations that should not be collected,
protect recipients from the release and use of unsuitable donations,
and help establishments to conserve resources used in collecting,
testing, and manufacturing blood and blood components. Moreover, since
Sec.  630.10(d)(1) helps to prevent the collection of unsuitable units,
we believe that it will be feasible for establishments to comply with
these requirements while at the same time maintaining adequate supplies
of suitable blood and blood components. We believe that the
requirements, as finalized, are similar to existing practices within
blood establishments. Moreover, Sec.  630.10(d)(1) of the final rule
now provides additional flexibility so that if unusual circumstances
prevail (for example, at a distant mobile collection, or when an
establishment is having temporary technical difficulties), and pre-
collection review is not feasible because the establishment cannot
consult the cumulative record at the collection site, the establishment
may collect from the donor, but must consult the cumulative record
before release of any blood or blood component prepared from the
collection.
5. Section 630.10(e)
    The requirements of proposed Sec.  630.10(e), (f), and (g) are
interrelated. We have combined proposed Sec.  630.10(e), (f), and (g)
into one section, final Sec.  630.10(e). This section requires
establishments to conduct a medical history interview as described in
this section to determine if the donor is in good health, to identify
risk factors closely associated with exposure to, or clinical evidence
of, a relevant transfusion-transmitted infection, and to determine if
there are other conditions that may adversely affect the health of the
donor or the safety, purity, or potency of the blood or blood
components or any product produced from the blood or blood components.
Blood establishments must take a medical history as described in this
section.
    Section 630.10(e) also contains specific requirements for
determining that the donor is in good health and free from risk factors
for a relevant transfusion-transmitted infection. This assessment must
include the following factors: (1) Factors that make the donor
ineligible to donate because of an increased risk for, or evidence of,
a relevant transfusion-transmitted infection, including the factors
described in Sec.  630.10(e)(1)(i) through (vi) and (2) other factors
described in Sec.  630.10(e)(2)(i) through (vii) that may make the
donor ineligible, including factors related to donor health or travel
history.
    Section 630.10(e) is intended to provide explicitly in our
regulations for our current donor deferral recommendations and blood
establishment practices. We discuss the comments received on that
provision. We received no comments on our proposal in Sec.
630.10(g)(7), under which a donor would be ineligible because she was
pregnant at the time of, or within 6 weeks of, donation, and have
finalized that proposal in Sec.  630.10(e)(2)(v).
    (Comment 46) Several organizations requested FDA not to finalize
the provision in proposed Sec.  630.10(e) that would have required an
establishment to determine whether a health care practitioner ever told
the donor not to donate blood.
    (Response) We agree. We included this provision, in part, as a
result of the anthrax exposures in 2001, where individuals may have
been advised not to donate. However, prior advice not to donate blood
may be based on a number of factors, including a transient infection,
now cured, or blood loss due to an accident, from which the donor has
long recovered. We have not included this provision in the final rule.
Instead we require establishments to take a medical history, as
described in Sec.  630.10(e). Such a medical history would be focused
on eliciting information related to potential and current risks, either
to the donor, or to the safety of the donated blood product.
    (Comment 47) We received comments stating that FDA has recognized
uniform donor history questionnaires and should not add the criteria
for deferral in proposed Sec.  630.10(f).
    (Response) FDA believes that use of a current and acceptable donor
history questionnaire, such as the donor history questionnaires and
accompanying materials found acceptable by FDA in guidance (Refs. 6, 7,
8), would meet these requirements. If the need arises, FDA will
describe how to comply with these provisions in guidance documents
issued in accordance with good guidance practices.
    (Comment 48) One comment suggested that we abandon the term
``social'' in proposed Sec.  630.10(f)(1), ``social behaviors
associated with relevant transfusion-transmitted infections.''
    (Response) We agree and have dropped the term ``social.'' Section
630.10(e)(1)(i) now refers simply to ``behaviors.''
    (Comment 49) Other comments stated that FDA should not consider the
behavior of men who have had sex with another man even one time since
1977 to be ``behaviors associated with relevant transfusion-transmitted
infections'' under proposed Sec.  630.10(f)(1).
    (Response) This rule does not specify the circumstances under which
FDA would consider men who have sex with another man to be a behavior
associated with relevant transfusion-transmitted infections. Instead,
that is an issue FDA has addressed in previous guidance related to the
issue (Ref. 10). We are currently reviewing this policy. If we
determine that modifications of any behavior-based donor deferral
recommendations are warranted, we will issue new guidance to blood

establishments in accordance with good guidance practices.
    (Comment 50) We received several comments suggesting that FDA
change the following phrase in proposed Sec.  630.10(f)(2), ``Medical
treatments and procedures associated with exposure to relevant
transfusion-transmitted infections.'' The comments stated that this
criterion was too vague and suggested that the donor history
questionnaire would provide a sufficient basis for determining whether
the donor had risk exposures from medical procedures.
    (Response) We agree with the comment in part and have made this
criterion, now contained in Sec.  630.10(e)(1)(ii), more specific. FDA
recognizes that many medical procedures present some risk, which cannot
be specifically quantified. Consequently, final Sec.  630.10(e)(1)(ii)
states, ``Receipt of blood or blood components or other medical
treatments and procedures associated with possible exposure to a
relevant transfusion-transmitted infection.'' In any event, we agree
with comments that an acceptable donor history questionnaire, such as
the donor history materials that are currently recognized in FDA
guidances (Refs. 6, 7, 8), may be used to elicit information adequate
to satisfy these provisions.
    (Comment 51) One comment asked FDA to clarify how establishments
would gather information related to signs and symptoms of relevant
transfusion-transmitted infections under proposed Sec.  630.10(f)(3).
    (Response) In final Sec.  630.10(e)(1)(iii), we require
establishments to assess ``Signs and/or symptoms of a relevant
transfusion-transmitted infection.'' For example, FDA has issued
guidance on signs and symptoms of HIV (Refs. 10, 30). If a donor
exhibits signs or symptoms of HIV, they would be deferred under this
provision. We believe that an establishment would meet this requirement
by determining that the donor is in good health, and using a currently
acceptable donor history questionnaire. FDA has periodically issued new
guidance recommending assessment for signs and symptoms of a new
infectious agent or disease (Refs. 35, 36). FDA will issue guidance in
accordance with good guidance practices in the event that different
information is needed to satisfy the requirements of this section.
    (Comment 52) Several comments asked FDA to reconsider the
longstanding requirement for deferral of donors with a ``history of
viral hepatitis.''
    (Response) Neither the proposed nor the final rule refers to a
``history of viral hepatitis'' as a factor in determining donor
eligibility. We are finalizing the donor eligibility requirements
without reference to a requirement to defer donors with a history of
viral hepatitis after the age of 11. Instead, under new Sec.
630.3(h)(1)(ii) and (iii), HBV and HCV are relevant transfusion-
transmitted infections. Under Sec.  630.10(e)(1)(iii), an establishment
must defer a donor exhibiting signs and/or symptoms of relevant
transfusion-transmitted infections, including HBV and HCV. Reactive
test results for these relevant transfusion-transmitted infections
would result in donor deferral as described in Sec.  610.41(a).
    (Comment 53) One comment requested that that we not finalize the
requirement in proposed Sec.  630.10(f)(4) to determine whether a donor
has been institutionalized in a correctional institution, preferring
that this be addressed in guidance, not regulation. Another comment
recommended that FDA clarify that deferral would be for
institutionalization in a correctional institute for 3 days or more.
    (Response) We have finalized a requirement in Sec.
630.10(e)(1)(iv) that establishments determine whether a donor has been
institutionalized in a correctional institution. We have rejected the
suggestion that we leave this deferral to guidance because we concluded
that this deferral is readily described and unlikely to change due to
technological developments. We agree with the second comment and have
further clarified that the deferral applies to donors who were
institutionalized in a correctional institution for 72 consecutive
hours or more in the 12 months before donation.
    (Comment 54) We received comments asking us to revise the
definition for ``intimate contact'' provided in proposed Sec.
630.3(e), which was applicable to proposed Sec.  630.10(f)(5), and to
clarify that the deferral for ``intimate contact'' would only apply to
those relevant transfusion-transmitted infections where such
transmission occurs through intimate contact.
    (Response) We agree in part with the comment. We have modified the
defined term in Sec.  630.3(f) so that it is now ``intimate contact
with risk for a relevant transfusion-transmitted infection'' and
clarified that this term refers to conduct that could result in the
transfer of potentially infectious body fluids from one person to
another. The provision that is now finalized in Sec.  630.10(e)(1)(v)
incorporates this clarified definition, and requires inquiry concerning
such intimate contact with risk for a relevant transfusion-transmitted
infection, which is defined in Sec.  630.3(f) as having engaged in an
activity that could result in the transfer of potentially infectious
body fluids from one person to another. We have issued guidance when we
believed that deferral for intimate contact with an individual infected
with a relevant transfusion-transmitted infection or exposed to a
relevant transfusion-transmitted infection was appropriate (Refs. 11,
37). FDA will issue a future guidance document as necessary for
deferral of donors because of specific intimate contact with risk for a
relevant transfusion-transmitted infection.
    (Comment 55) One comment requested that we state that nonsterile
percutaneous inoculation, as proposed in Sec.  630.10(f)(6), be
considered a basis for deferral only when the inoculation took place
within 4 months of the donation.
    (Response) We did not specify in the proposed regulation a
timeframe for this deferral, stating that the blood establishment
should defer the donor if the factor was ``still applicable'' at the
time of donation, and we have not specified a timeframe in the final
rule codifying this factor at Sec.  630.10(e)(1)(vi). FDA's 1992
guidance entitled, ``Revised Recommendations for the Prevention of
Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood
Products,'' recommends a 1 year deferral for nonsterile percutaneous
exposure, and this recommendation is still current (Ref. 10).
    (Comment 56) We received several comments asking FDA to modify
proposed Sec.  630.10(g)(1), which identified ``Medical or dental
treatment, or symptoms of a recent or current illness'' as a basis for
ineligibility. These comments asked FDA to delete the reference to
dental treatment.
    (Response) We agree with these comments in part. In finalizing
proposed Sec.  630.10(g)(1), we have revised this provision and
separated it into two sections. Section 630.10(e)(2)(i) now requires
establishments to assess donors for symptoms of a recent or current
illness. Section 630.10(e)(2)(ii) now requires establishments to assess
donors for certain medical treatments or medications, such as a major
surgical procedure, that indicates that the donor should not donate. We
have omitted the requirement to defer donors for recent dental
treatment.
    (Comment 57) We received several comments asking FDA to delete the
provision in proposed Sec.  630.10(g)(1) through (g)(3) which refer to
ineligibility because of medical treatment, medication, or major
surgical procedure.

One comment suggested that the deferral be limited to the criteria and
medications enumerated in current FDA guidance documents. Several
comments asked FDA to identify major medical procedures.
    (Response) We have finalized Sec.  630.10(e)(2)(ii) to require
blood establishments to assess donors for certain medical treatments or
medications, such as a major surgical procedure, that indicate that the
donor should not donate. This provision is intended to protect the
health of the donor and ensure the safety and purity of the blood
product. We note that we have issued guidance on donor deferral
criteria for certain medications (Ref. 38). We believe that
establishments can meet the requirements of this section by using
current donor history questionnaire materials recognized as acceptable
by FDA, or other approved donor history questionnaire. If our
recommendations for deferral for medical procedures or specific
medications change, we would issue guidance in accordance with good
guidance practices.
    (Comment 58) We received several comments asking FDA not to
finalize proposed Sec.  630.10(g)(4), under which a donor would be
ineligible on the basis of travel to, or residence in, an area endemic
for a transfusion-transmitted infection. The comments criticized the
provision as vague and more appropriately dealt with in FDA guidance
documents.
    (Response) In finalizing this provision in Sec.  630.10(e)(2)(iii),
we have provided additional clarity by stating that a donor would be
ineligible on the basis of such travel or residence only when such
screening is necessary to assure the safety, purity, and potency of
blood and blood components due to the risks presented by donor travel
and the risk of transmission of that transfusion-transmitted infection
by such donors. For example, in the future we may determine that
screening donors under this provision for the Chickungunya virus, a
transfusion-transmitted infection that is transmitted by mosquitoes, is
necessary to assure the safety, purity, and potency of blood and blood
components. If so, we would address deferral of donors with a travel
history to an area endemic for Chickungunya in accordance with good
guidance practices.
    (Comment 59) Several comments suggested that we delete the
provision in proposed Sec.  630.10(g)(6), which would have required a
determination of ineligibility due to exposure or possible exposure to
a released disease or disease agent relating to a transfusion-
transmitted infection, if it was known or suspected that such a release
has occurred. The comments suggested that this provision was vague and
better addressed in guidance when an event occurs.
    (Response) In Sec.  630.10(e)(2)(iv), we have finalized this
provision as proposed. This factor only becomes relevant when a disease
or disease agent for a transfusion-transmitted infection has been
released. We expect this to apply in rare circumstances, such as after
a serious accident or bioterrorism attack involving the release of such
agents. FDA intends to issue guidance, as practicable, when a released
disease or disease agent is identified and is of a nature or type that
donor deferral would be warranted. We note that we previously issued
guidance on the deferral of donors with possible exposure to anthrax
due to a possible bioterrorism event (Ref. 39).
    (Comment 60) We received several comments on proposed Sec.
630.10(g)(8), which would have required blood establishments to
determine to be ineligible donors who gave answers to medical history
questions that appeared unreliable due to the apparent influence of
drugs or alcohol, or due to another reason affecting the reliability of
the donor's answers. The comments agreed with the deferral, but stated
that blood establishment procedures were adequate to address this
issue.
    (Response) We combined donor suitability requirements from existing
regulations for Whole Blood donations (Sec.  640.3) and Source Plasma
donations (Sec.  640.63) in the final rule. Source Plasma regulations
have had a longstanding requirement (Sec.  640.63(d)) that ``any donor
who, in the opinion of the interviewer, appears to be under the
influence of any drug, alcohol, or for any reason does not appear to be
providing reliable answers to medical history questions, shall not be
considered a suitable donor.'' Until now, there has not been a
corresponding provision in the requirements for Whole Blood donors,
even though a donor who does not provide reliable answers presents
similar risks in that venue. We are finalizing this requirement for all
donations in Sec.  630.10(e)(2)(vi).
    In the preamble to the proposed rule we gave, as an example of an
unreliable answer, a donor who states that he or she is donating in
order to be tested for infectious agents. This is because of our
concern that the donor may be aware of some additional, undisclosed,
risk factor that leads him or her to seek information on their
infection status by presenting at a blood donation center. Such
undisclosed risk factors endanger blood safety, particularly when the
donor is in the ``window period'' when the donor is infected and
infectious, but the infection cannot yet be detected by donor screening
tests. We did not receive comments on this example. We have decided to
expressly require the deferral of a donor who states they are seeking
testing for a relevant transfusion-transmitted infection. We expect
that blood establishments may then refer the donors to public health
testing clinics and other venues providing testing.
    (Comment 61) We received comments requesting that we not finalize
the proposed requirement to determine a donor to be ineligible due to
receipt of a xenotransplantation product, or intimate contact with such
a recipient (proposed Sec.  630.10(g)(5)).
    (Response) In final Sec.  630.10(e)(2)(vii), we require
establishments to assess the eligibility of a donor on the basis of
receipt of a xenotransplantation product. We finalized this provision
to protect the health of the donor who received the xenotransplantation
product and to address the risk of transmission of animal infectious
agents by blood and blood products collected from such a donor. In
2002, we discussed those risks in a draft guidance entitled ``Guidance
for Industry: Precautionary Measures to Reduce the Possible Risk of
Transmission of Zoonoses by Blood and Blood Products from
Xenotransplantation Product Recipients and Their Intimate Contacts''
(Ref. 37). We have not finalized the proposed requirement to require
screening for intimate contact with a xenotransplantation recipient.
If, in the future, we determine that donation by an individual who has
had intimate contact with a recipient of a xenotransplantation product
may affect that donor's health, or the safety, purity, or potency of
the blood or blood component, or product produced from the blood or
blood component collected from that donor, we will issue guidance to
address these risks.
6. Section 630.10(f)
    As we described earlier, we combined proposed Sec.  630.10(e)
through (g) into Sec.  630.10(e) in the final rule. We have finalized
proposed Sec.  630.10(h) as final Sec.  630.10(f).
    The physical assessment criteria set forth in Sec.  630.10(f)(1)
through(6) in this final rule requires establishments to determine that
a donor is in good health which helps to assure that blood and blood
components collected are safe, pure, and potent. This section requires
establishments to determine on the day of donation and prior to
collection of blood or blood components that the

donor is in good health, indicated in part by a normal temperature, a
blood pressure within acceptable limits, an acceptable hemoglobin or
hematocrit level, a regular pulse, and a minimum weight requirement.
Blood establishments are also required to perform an examination of the
donor's phlebotomy site and the donor's arms and forearms.
    a. Temperature (Sec.  630.10(f)(1)).
    (Comment 62) We received no comments objecting to the requirement
for measuring a donor's temperature. We received one comment asking
whether we would specify a subnormal temperature.
    (Response) We are finalizing the proposed requirement to determine
that the donor's oral body temperature does not exceed 37.5 [deg]C
(99.5[emsp14][deg]F), or the equivalent if measured at another body
site, since an elevated temperature indicates that the donor is not in
good health and may be a symptom of infection or other adverse
condition. On the other hand, a temperature that is a few degrees lower
than 37.5 [deg]C (99.5[emsp14][deg]F), is not necessarily indicative of
poor health. We decline to specify a subnormal temperature at this
time. Instead, we leave assessment of an apparently healthy donor who
presents for donation with an unusually low temperature for blood
establishments to address in their standard operating procedures.
    b. Blood Pressure (Sec.  630.10(f)(2)).
    (Comment 63) Several comments recommended that FDA should not
finalize a requirement for determining the donor's blood pressure,
while others recommended not specifying limits for systolic and/or
diastolic blood pressure measurements, or addressing such bounds only
in guidance. One comment stated that a baseline blood pressure for all
donors at each donation is needed in the event of a reaction.
    (Response) Current Sec.  640.3(b)(2) requires that donors be in
good health, as demonstrated by systolic and diastolic blood pressure
within normal limits, unless the examining physician is satisfied that
an individual with blood pressure outside these limits is an otherwise
qualified donor. In the preamble to the proposed rule we had solicited
comments requesting supporting scientific data regarding the necessity,
or lack of necessity of requiring specific upper and lower blood
pressure limits for a donor (72 FR 63416 at 63426 and 63427). We did
not receive significant data. In November 2009, we asked the Blood
Products Advisory Committee whether available data support the utility
of obtaining pre-donation blood pressure measurements as predictors of
risk of an adverse response to donation, and the majority responded
that data did not establish pre-donation blood pressure as a predictor
of risk of an adverse response. However, even though the vote did not
support blood pressure measurement as a predictor of risk, many members
of the committee stated that blood pressure measurement should be
retained as part of the donor assessment. The committee members noted
that studies examining adverse events and blood pressure have been
restricted to donors with currently acceptable blood pressure levels.
Several committee members were concerned that it was not safe for
donors with blood pressures above 180 mm of mercury to donate. They
noted the lack of data on the safety of blood donations in hypertensive
donors and the potential for severe adverse events in such donors.
Other committee members noted that low blood pressure could be
predictive of adverse events in young female donors who have low blood
volume.
    We are finalizing a requirement to measure the donor's blood
pressure before donation. If a donor's systolic blood pressure is
outside the range of 90 to 180 mm of mercury, or if the donor's
diastolic blood pressure is outside the range of 50 to 100 mm of
mercury, establishments may permit the donor to donate only when the
responsible physician has examined the donor and determined that the
health of the donor would not be adversely affected by donating. Note
that under Sec.  630.5(b)(1)(i)(A) and (c)(1)(i)(A)(1), the responsible
physician is not authorized to delegate this examination and
determination of the health of the donor, and must personally perform
this examination and determination. Final Sec.  630.10(f)(2) is
consistent with the proposed rule and largely consistent with the
current requirement in Sec.  640.3(b)(2), and will assure that donors
who present with either unusually high, or unusually low, blood
pressure will be examined by the responsible physician before they are
permitted to donate. We are establishing these criteria in the
regulation, rather than providing a flexible standard, because we have
determined that establishing clear criteria will be more protective of
donor health. We note that, under the limits provided in Sec.
630.10(f)(2), donors with blood pressure readings above 140/90 would be
eligible to donate, even though such donors may be hypertensive (Ref.
40). However, experience to date indicates that donors with blood
pressures in the range provided in this rule may safely donate (Refs.
41, 42).
    (Comment 64) In response to our request for comments on the
accuracy of blood pressure measurements, one comment stated that ``Many
factors can influence blood pressure along with pulse such as stress,
exercise, and caffeine intake. In addition, interobserver differences
are found with measurements that rely on sphygmomanometers and
stethoscopes. Therefore, a general preference for automated devices is
found not only among donor centers but also among clinics, hospitals,
and for use at home. These devices are commercially available and
approved for sale. We recommend that FDA acknowledge the acceptance of
automated devices in either the preamble to the final rule or in
guidance. FDA also notes that an isolated measurement of blood pressure
may not reliably assess acceptability for donation.''
    (Response) We are not requiring that a specific type of device to
be used to measure blood pressure. Establishments may use manual or
automated devices as long as such use is consistent with the applicable
standards or current good manufacturing practices, and their own
standard operating procedures.
    (Comment 65) The comment recommended that FDA provide the
following, or similar, guidance: ``Firms should have a procedure for
re-measuring the vital signs if there is reason to believe stress or
other factors have affected the initial measurement.''
    (Response) We are not issuing guidance on this issue at this time.
We recognize that stress and other factors may affect initial
measurements of the donor's blood pressure and pulse, required under
Sec.  630.10(f)(2) and (f)(4). In accordance with Sec.  606.100(b)(2),
establishments must have standard operating procedures for taking a
donor's blood pressure and pulse before collection. However, these
requirements do not prevent a blood collection establishment from
providing in those standard operating procedures for taking and relying
upon a second measurement of blood pressure if there is reason to
believe stress or another factor affected the initial measurement and
taking a second measurement is consistent with medical practice.
    c. Hemoglobin or hematocrit determination (Sec.  630.10(f)(3)).
    We proposed to require that a donor's hemoglobin level or
hematocrit value be determined using a sample of blood obtained by
fingerstick, venipuncture or by a method that provides equivalent
results. Blood obtained from the earlobe is not acceptable. We received
no

comments on this provision and are finalizing this provision as
proposed. This section was proposed as Sec.  630.10(h)(3)(i); we now
finalize it as the first paragraph of Sec.  630.10(f)(3). We further
proposed to retain the existing requirement for autologous donations
that a donor's hemoglobin level be no less than 11 grams of hemoglobin
per deciliter of blood or a hematocrit value of 33 percent. We received
no comments on this provision and are finalizing this provision as
proposed. In addition, for allogeneic donations, we proposed to retain
existing requirements that a donor's hemoglobin level be no less than
12.5 grams of hemoglobin per deciliter of blood or a hematocrit value
of no less than 38 percent. We also solicited comments (72 FR 63416 at
63427) on:
     Changing the minimum acceptable hemoglobin level to 12.0
grams per deciliter of blood or hematocrit of 36 percent for female
allogeneic donors, or whether a decision to collect from donors with
such levels should be left to the discretion of the medical director of
the collecting establishment on a case-by-case basis;
     The possibility of adverse effects caused by the
collection of blood and blood components from female allogeneic donors
with a minimum level of 12.0 grams of hemoglobin per deciliter of blood
or a hematocrit value of 36 percent;
     The possibility of adverse effects caused by the
collection of blood and blood components from allogeneic donors with a
minimum level of 12.5 grams of hemoglobin per deciliter of blood or a
hematocrit value of 38 percent;
     Establishing a more stringent interdonation interval; and
     The use of copper sulfate solution based methods as an
appropriate method to determine acceptable hemoglobin levels.
    Since the proposed rule was published, FDA has brought up issues
related to blood donation, hemoglobin levels, and iron depletion in
donors for discussion at two Blood Products Advisory Committee meetings
on September 10, 2008 and July 27, 2010 (Refs. 43, 44). In addition,
the Department of Health and Human Services, Public Health Service,
Advisory Committee on Blood Safety and Availability discussed iron
depletion and donor informed consent at its December 17, 2008 meeting
(Ref. 45). In co-sponsorship with the Department of Health and Human
Services, National Heart, Lung and Blood Institute, AABB, America's
Blood Centers and Plasma Protein Therapeutics Association, FDA held a
workshop entitled ``Public Workshop: Hemoglobin Standards and
Maintaining Adequate Iron Stores in Blood Donors'' on November 8-9,
2011 (November 2011 Workshop) (Ref. 46).
    At the July 2010 Blood Products Advisory Committee meeting,
following the discussion of hemoglobin qualification standards and iron
depletion in donors, the committee voted unanimously (10 yes votes, 0
no votes, 1 abstention) in support of raising the hemoglobin level for
men, but did not support a change in the hemoglobin level for women (10
no votes and 1 abstention) (Ref. 44). The shortcomings of relying
solely on hemoglobin measurement and the need to study measures to
mitigate iron deficiency in blood donors were discussed at both
meetings of the Blood Products Advisory Committee (Refs. 43, 44) and at
the November 2011 Workshop (Ref. 46). After reviewing those discussions
and the data presented at those meetings, we have decided to promulgate
different standards for male and female donors, but not to alter the
current 8 week interval between donations of Whole Blood and single
donations of apheresis Red Blood Cells. Recognizing that research in
this area continues and that data may be developed to support a change
in donor hemoglobin standards, we have provided for greater flexibility
in donor hemoglobin standards.
    Section 630.10(f)(3)(i) now requires that allogeneic donors must
have a hemoglobin level or hematocrit value that is adequate to assure
donor safety. In addition, we establish minimum standards. The minimum
standard established for female allogeneic donors in Sec.
630.10(f)(3)(i)(A) is consistent with the current standard: A
hemoglobin level that is equal to or greater than 12.5 grams per
deciliter of blood, or a hematocrit value that is equal to or greater
than 38 percent. However, we recognize that a lower hemoglobin/
hematocrit level is also within the normal range for female donors.
Since hemoglobin levels are influenced by the male hormone
testosterone, female donors typically have lower hemoglobin levels than
male donors. The fact that a female donor's hemoglobin/hematocrit level
is lower than that of a male of similar age does not necessarily mean
that the female donor has low iron stores, which the body uses to
replace hemoglobin lost to blood donation (Refs. 47, 48). For this
reason, in the preamble to the proposed rule we specifically requested
comment on whether to permit collections from female allogeneic donors
with a hemoglobin level of 12.0 grams per deciliter of blood or a
hematocrit value of 36 percent. We are not establishing that minimum
level at this time. However, Sec.  630.10(f)(3)(i)(A) provides that an
establishment may collect blood from female allogeneic donors who have
a hemoglobin between 12.0 and 12.5 grams per deciliter of blood, or
hematocrit value between 36 and 38 percent, provided that the
establishment takes additional steps to assure that the lower value is
adequate with respect to donor safety, in accordance with a procedure
that has been found acceptable for this purpose by FDA. FDA has not yet
recognized any such procedures, and awaits the development of data
related to these issues. Conceivably, these steps might include a pre-
donation measure of iron stores by means of a ferritin test, or iron
replacement therapy and monitoring of iron stores. We have determined
that standard collections from a donor with a hemoglobin level as low
as 12.0 grams per deciliter of blood or hematocrit value of 36 percent
would meet minimum potency levels based on calculated hemoglobin
content.
    Section 630.10(f)(3)(i)(B) of the final rule establishes a minimum
standard for male allogeneic donors of 13.0 grams of hemoglobin per
deciliter of blood, or a hematocrit value that is equal to or greater
than 39 percent. This standard aligns more closely with the low range
of normal levels for men, and is higher than the current regulation's
minimum standard of 12.5 grams of hemoglobin per deciliter of blood, or
a hematocrit value that is equal to or greater than 38 percent (Ref.
48). We requested comment in the preamble to the proposed rule on the
possibility of adverse effects on male donors with a minimum hemoglobin
level of 12.5 grams per deciliter of blood or a hematocrit value of 38
percent. We solicited these comments, in part, because of our concern
about possible adverse effects of collecting blood from male donors
with below normal hemoglobin or hematocrit levels, and reports about
iron depletion resulting from blood donation (Refs. 46, 49, 50). Males
with below normal hemoglobin or hematocrit levels may have a higher
incidence of iron deficiency due to frequent blood donations or
undiagnosed conditions such as gastrointestinal bleeding due to colon
cancer. Since the proposed rule published, the results of a study
sponsored by the Department of Health and Human Services, National
Heart, Lung and Blood Institute, the Retrovirus Epidemiology Donor
Study-II (REDS-II)

Donor Iron Status Evaluation Study (REDS-II-RISE study) on hemoglobin
levels in donors have become available (Refs. 49, 50). The results of
the REDS-II-RISE study amplified existing concern about frequent
donation and iron depletion. In this rule, we are establishing higher
minimum hemoglobin/hematocrit levels for male donors after reviewing
that study and considering the comments submitted.
    (Comment 66) We received numerous comments asking FDA not to make
changes in acceptable hemoglobin and hematocrit levels for male and
female donors until the REDS-II-RISE study on hemoglobin levels in
donors was completed.
    (Response) We are finalizing this rule after reviewing the results
of the REDS-II-RISE study. Preliminary results of the REDS-II-RISE
study were presented at the July 2010 Blood Products Advisory Committee
meeting. At the conclusion of that discussion, the advisory committee
voted unanimously that the available scientific evidence supported
raising the minimum hemoglobin/hematocrit levels for male donors. The
committee did not support lowering minimum standards for female donors
(Ref. 44). The REDS-II-RISE study published on October 10 and 24, 2011,
and the results were discussed at a November 2011 Workshop (Ref. 46).
Results from the REDS-II-RISE study were published in an article
entitled, ``Iron deficiency in blood donors: The REDS-II Donor Iron
Status Evaluation (RISE) Study,'' (Ref. 50). The authors reported a
high prevalence of iron depletion in frequent blood donors. As
recommended by the comments, FDA has considered the results of the
REDS-II-RISE study in determining appropriate hemoglobin standards for
this rule. We agree that the study provides important new information
on hemoglobin levels in donors, and supports increasing the minimum
hemoglobin/hematocrit requirements for male donors. We recognize that
this is an important donor safety issue, and we will continue to review
the scientific data as we consider these issues in the future.
    (Comment 67) We received one comment supporting lowering the
hemoglobin level for women and one opposing lowering the hemoglobin
level for women. The comment supporting a lower minimum hemoglobin
level stated that a hemoglobin level of 12.0 grams per deciliter of
blood was normal for women, and allowing such donors to donate would
improve blood availability. The comment opposing lowering the minimum
hemoglobin level stated that this practice would make more women
susceptible to anemia and iron deficiency.
    (Response) For female allogeneic donors, the current minimum
hemoglobin/hematocrit levels remain the default minimum levels under
this rule. In the event that an establishment takes additional steps
that are adequate to assure donor safety an establishment may collect
from female donors with normal, but lower, hemoglobin levels, between
12.0 and 12.5 grams per deciliter of blood, or a hematocrit value
between 36 and 38 percent, provided the establishment has taken
additional steps to assure that this alternative standard is adequate
to ensure that the health of the donor will not be adversely affected
due to the donation, in accordance with a procedure that has been found
acceptable for this purpose by FDA. We have not yet found such a
procedure adequate for this purpose. However, we recognize that, in the
future, new data may support revised hemoglobin/hematocrit standards
for female allogeneic donors, particularly if it becomes possible to
measure other values, including iron stores, before donation. In
determining or recognizing an alternative measure, FDA intends to
consider other evidence related to donor health, including iron stores.
Until then, establishments must follow the current standard for female
allogeneic donors: A hemoglobin level of 12.5 grams per deciliter of
blood or a hematocrit value of 38 percent.
    (Comment 68) One comment stated that changing the hemoglobin level
could affect cleared devices as some are cleared based on a specified
hemoglobin/hematocrit lower limit.
    (Response) We recognize that some operator's manuals for apheresis
devices describe the minimum hemoglobin level of 12.5 grams per
deciliter of blood, or a hematocrit value of 38 percent, and that these
references would need to be updated to reflect the new minimum standard
for male donors. In addition, related changes to apheresis device
software may be needed.
    d. Pulse (Sec.  630.10(f)(4)).
    Current regulations require that a donor of Source Plasma have a
normal pulse, but do not specify a related requirement for donors of
Whole Blood or other blood components. We proposed in Sec.
630.10(h)(4) to require that all donors have a regular pulse that
measures between 50 and 100 beats per minute. A donor with an irregular
pulse or measurements outside these limits would be permitted to donate
only when the responsible physician has examined the donor and
determines and documents that the health of the donor would not be
adversely affected by donating. We have finalized this provision in
Sec.  630.10(f)(4) with one change. The final rule provides that a
donor with an irregular pulse or measurements outside these limits may
be permitted to donate only when the responsible physician determines
and documents that the health of the donor would not be adversely
affected by donating. This determination may be made by the responsible
physician on the basis of an assessment of the donor's information (for
example, the responsible physician may conclude that the donor's low
pulse rate is due to regular marathon running). This provision thus
does not require that the responsible physician personally examine the
donor. Note that under final Sec.  630.5(b)(1)(i)(B) and
(c)(1)(i)(A)(2), the responsible physician cannot delegate this
determination that the donor's health would not be adversely affected
by donating.
    (Comment 69) Several comments opposed adding a requirement for
determining that the donor has a regular pulse between 50 and 100 beats
per minute. One comment indicated that the physician should examine the
donor for any irregularity in their pulse, not just a pulse outside the
proposed limits.
    (Response) To assure that donors are in good health and will not be
adversely affected by donating, we are finalizing the requirement to
measure the donor's pulse and assess eligibility based on pulse rate
and regularity. In November 2009, FDA asked the Blood Products Advisory
Committee if available data support the utility of obtaining pre-
donation pulse measurements as predictors of risk of adverse response
to donation. The majority of the committee agreed (10 yes votes, 8 no
votes) that pulse measurement was a predictor of risk of adverse
response to donation. In particular, high pulse rates may be associated
with higher rates of vasovagal reactions. We also agree with the
comment that an irregular pulse can indicate that a donor is not in
good health (Ref. 51). Therefore, final Sec.  630.10(f)(4) requires
that the donor's pulse must be regular and between 50 and 100 beats per
minute--no less than 50 beats per minute, and no more than 100 beats
per minute. A donor with an irregular pulse or measurements outside
these limits is ineligible unless the responsible physician determines
and documents that the health of the donor would not be adversely
affected by donating.
    (Comment 70) One comment asserted that a phone consultation between
the blood collection center and the responsible physician should be
sufficient to determine whether a donor

with an irregular pulse can donate, rather than the proposed
requirement that responsible physician actually ``examine'' the donor.
For example, the comment stated that their blood collection center
routinely permits the responsible physician on-call to give phone
authorization for donors with pulse rates between 40 and 50 beats per
minute to donate, when it is ascertained by the donor's history that
the donor is an athlete.
    (Response) We agree with the comment. A donor with an irregular
pulse or measurements outside the limits provided in final Sec.
630.10(f)(4) may be permitted to donate when the responsible physician
has determined that the health of the donor would not be adversely
affected by donating. We have not finalized a requirement that the
responsible physician must examine the donor, and we provide that in
appropriate circumstances the responsible physician may make a
determination of whether a donor's health would be adversely affected
by donating blood or blood components. Such a determination may be
reached by a phone consultation between the establishment and the
responsible physician, though under Sec.  630.5(b)(1)(i)(B) and
(c)(1)(i)(A)(2), the responsible physician cannot delegate the
determination that the donor's health would not be adversely affected
by donating.
    e. Weight (Sec.  630.10(f)(5)).
    We proposed in Sec.  630.10(h)(5) that a donor weigh a minimum of
50 kilograms (110 pounds) and not have any unexplained loss of greater
than 10 percent of body weight within the past 6 months. We are
finalizing the requirement that donors weigh at least 110 pounds, but
have not finalized the requirement related to unexplained weight loss.
    (Comments 71) Several comments suggested deleting the requirement
to assess the donor's weight because most blood establishments do not
currently weigh donors. Several comments said there was no
justification for the 110 pounds lower weight limit and that deferrals
based on the overall health of the donor were better addressed through
the donor history questionnaire.
    (Response) Section 630.10(f)(5) does not require blood
establishments to weigh Whole Blood donors. Blood establishments may
make this determination by asking a donor whether the donor weighs at
least 110 pounds.
    f. Skin examination (Sec.  630.10(f)(6)).
    In proposed Sec.  630.10(h)(6) we proposed requirements that: (1)
The donor's phlebotomy site be free of evidence of infection,
inflammation, lesions, and pitted skin and (2) the donor's arms and
forearms be free of punctures and scars indicative of injected drugs of
abuse. We have finalized these provisions, except that we have deleted
the reference to ``pitted skin''.
    (Comment 72) One comment recommended that FDA not include the term
``pitted skin'' from the final rule. The comment stated frequent
plasmapheresis donors would be expected to have pitted areas of their
skin due to the needle punctures for their donations as frequently as
twice per week. The comments asserted that a close examination for
pitted skin could lead to deferral of committed donors.
    (Response) We agree with the comment that frequent donors often
have pitted areas of their skin due to needle punctures. Therefore, we
do not include the term pitted skin in Sec.  630.10(f)(6) of the final
rule, and require only that the donor's arms must be free of infection,
inflammation, and lesions. We note that pitted skin may be more
difficult to decontaminate, which may affect the choice of the
phlebotomy site.
7. Section 630.10(g)
    a. Proof of identity and postal address (Sec.  630.10(g)(1)).
    We proposed in Sec.  630.10(i)(1) that collection establishments
obtain, before donation, proof of the donor's identity and a mailing
address where the donor may be contacted for 8 weeks following
donation. Establishments are currently required to maintain a record of
this address in the donor record as required under Sec.
606.160(b)(1)(x) (redesignated in this rule as Sec.
606.160(b)(1)(ix)). Establishments may use this information to contact
the donor to communicate regarding test results for evidence of
infection, as required under Sec.  630.40. We are finalizing this
provision as proposed, except that the final rule specifies that the
donor's mailing address must be a postal address.
    (Comment 73) One comment suggested that the donor's name and last
four digits of their Social Security Number (United States) or Social
Insurance Number (Canada), with proof of an address, would be adequate
proof of a donor's identification. Another comment stated that it is
not always possible to obtain photographic identification, stating that
members of certain groups are reluctant to have their photographs
taken. The comment stated that FDA should allow for other means of
identifying the donor.
    (Response) We have finalized the rule to require that blood
establishments obtain proof of identity of the donor prior to donation.
However, we have not specified the means of establishing proof. We
believe that photographic identification, a valid driver's license,
validated biometric means, or other means can be useful in establishing
the donor's identity. Establishments must include procedures for
establishing donor identity in their standard operating procedures
under Sec.  606.100(b). We also note that, while this provision
establishes a requirement for Whole Blood donors, Sec.  640.65(b)(3)
has long required Source Plasma establishment to have a donor
identification system in place. For Source Plasma establishments, Sec.
630.10(g)(1) does not add new requirements.
    (Comment 74) We received several comments objecting to the
requirement to obtain an address where the donor may be contacted for 8
weeks after donation. One comment stated that this provision would have
an impact on blood collection on college campuses due to the movement
of college students to other addresses for the summer. One comment
referenced information from the United States Postal Service,
indicating that most individuals who move do leave a forwarding
address. The comment suggested that donors can be contacted through
this mechanism. The comment further suggested that newer communication
technologies such as email and cell phones can be used for notification
purposes when necessary.
    (Response) We have finalized the rule to require that blood
establishments obtain a postal address where the donor may be contacted
for 8 weeks after donation. This provision supports effective
communication on issues that may be important to the donor and his or
her contacts. We recognize that, when the donors are found ineligible
prior to collection, they are deferred and notified of the reasons for
their deferral at the blood center. However, communication with the
donor becomes necessary after donation due to reactive or positive test
results obtained on the donation. We believe that most establishments
invite the donor back to the donor center to inform the donor of
reactive or positive infectious disease test results on the donation.
We do not believe that the provision improperly burdens blood
establishments because of college students and other mobile
populations. Student donors would provide the postal address where they
expect to be in residence if they plan to leave school during the 8
weeks

following donation. We recognize that other means of contact, such as
email or telephone, may permit more rapid communication. Establishments
may also request an email address or telephone number, although the
rule does not require establishments to collect this information. If
the donor has been successfully contacted by other means, then we do
not require that contact be made using the postal service.
    b. Donor acknowledgement (Sec.  630.10(g)(2)).
    In proposed Sec.  630.10(i)(2), we proposed to require
establishments to provide the donor with a written statement of
understanding to be read and signed by the donor. The establishment
would be required to use procedures to assure that the donor
understands the material provided in the statement, which must not
include language that would waive any of the donor's legal rights and
must address seven elements: (1) The donor statement that he or she has
reviewed the educational material required by Sec.  630.10(b); (2) the
donor's agreement not to donate if the donation could put the blood
supply at risk; (3) testing of the donor's blood; (4) additional
testing of the donor's blood if initial tests are reactive; (5) the
consequences if the donation is determined not to be suitable, or if
the donor is ineligible; (6) the risks and hazards of the specific
donation procedure or of immunization, if applicable; and (7) the
donor's opportunity to ask questions and withdraw consent at any time.
    We have modified the provision after considering comments received
to the proposed rule and the recommendations made from the Blood
Products Advisory Committee at the April 28-29, 2011, meeting (Ref.
52). For clarity, we now call this ``Donor's acknowledgement,'' instead
of the proposed ``Donor's written statement of understanding.'' The
statement does not have to be in a written form only, although it must
provide for a signature or other documented acknowledgement.
    In proposed Sec.  630.10(i)(2)(iv), we proposed to require that the
donor be informed that a blood sample will be tested for specified
relevant transfusion-transmitted infections and that the further
testing might be required for reactive donations. Although we are
finalizing the requirement that the donor be informed of infectious
disease testing, following the recommendation of the Blood Products
Advisory Committee at the April 2011 meeting (Ref. 52), we are not
finalizing a requirement that the donor acknowledge that infectious
disease testing may include additional testing of reactive samples
(proposed Sec.  630.10(i)(2)(iv)). We are not including this detailed
requirement in the final rule, and are finalizing 6 out of the 7
proposed requirements.
    We have also clarified the requirement that the donor be informed
of the risks and hazards of the donation procedure. We now require in
Sec.  630.10(g)(2)(ii)(E) that the donor acknowledgement include
acknowledgment that the donor has been provided and reviewed
information regarding the risks and hazards of the specific donation
procedure that the donor will undergo. This is required for every
donation of blood and blood components, including Source Plasma and
other donations by apheresis. We are finalizing this section with the
additional modifications discussed in our responses to comments.
    (Comment 75) One comment questioned the use of the term
``understanding'' as used in ``written statement of understanding'' in
proposed Sec.  630.10(i)(2).
    (Response) We have revised the provision to require that the donor
acknowledge that the donor has read the material provided. Accordingly,
we now designate this as ``Donor's acknowledgement''.
    (Comment 76) We were also asked how this section relates to other
sections of the existing Source Plasma regulations on informed consent.
    (Response) For collections of plasma and platelets for apheresis,
Sec. Sec.  630.15(b) and 640.21(g) require establishments to engage the
donor at least annually in an informed consent dialogue. See discussion
in comments 86 and 117. The requirement to obtain a donor
acknowledgement applies to every collection of blood and blood
components, including apheresis collections of plasma and platelets.
The donor's acknowledgement must be obtained at each donation.
    (Comment 77) Several comments objected to a requirement that the
donor ``sign'' a statement and urged FDA to allow an electronic
signature.
    (Response) We agree that this requirement can be satisfied by an
electronic signature. Final Sec.  630.10(g)(2)(i) requires that the
donor's acknowledgement be provided by signature or other documented
acknowledgement.
8. Section 630.10(h)
    We have added Sec.  630.10(h) to make explicit a requirement in the
proposed regulation. Section 630.10(h) provides that a blood
establishment must not collect from a donor found, before collection,
to be ineligible, unless an exception exists. In addition, we
incorporated existing requirements to defer donors found to be
ineligible and to notify the donors of their deferral as required in
Sec.  630.40(a).

K. Donor Eligibility Requirements Specific to Whole Blood, Red Blood
Cells and Plasma Collected by Apheresis (Sec.  630.15)

    Section 630.15(a) establishes donor eligibility requirements for
the collection of Whole Blood and Red Blood Cells collected by
apheresis, and Sec.  630.15(b) establishes donor eligibility
requirements for collections of Source Plasma and plasma collected by
plasmapheresis. These requirements are in addition to those in Sec.
630.10.
    For donors of Whole Blood and Red Blood Cells collected by
apheresis, this rule requires that donation frequency be consistent
with protecting the donor's health, describes minimum intervals between
donations, and addresses donations by donors undergoing therapeutic
phlebotomy. We have added references to Red Blood Cells collected by
apheresis to the heading and at several points in this section to
clarify the applicability of Sec.  630.15(a) to Red Blood Cells
collected by apheresis.
    For donors of Source Plasma and plasma collected by plasmapheresis,
the rule requires the responsible physician, subject to Sec.  630.5(c),
to conduct an appropriate medical history and physical examination of
the donor. Additionally, blood establishments are required to weigh the
donor before each plasmapheresis procedure and to assess the donor's
total protein level prior to each donation. This provision includes a
requirement in Sec.  630.15(b)(1)(ii) to defer a plasmapheresis donor
found to have a medical condition that would place the donor at risk
from plasmapheresis, and to defer a donor because of red blood cell
loss as described in the rule. This section also contains informed
consent requirements for donors of Source Plasma and plasma collected
by plasmapheresis. These provisions complement other requirements for
the collection of plasma by plasmapheresis in part 640 and part 630,
including restrictions on frequency of collection as specified in
Sec. Sec.  640.32 and 640.65. In addition Sec.  630.15(b)(1) cross-
references certain exceptions provided for plasmapheresis collections
from infrequent plasma donors in Sec.  630.25.
1. Section 630.15(a)
    Consistent with the proposed rule, final Sec.  630.15(a)(1)
requires that for a

collection resulting in a single unit of Whole Blood or Red Blood Cells
collected by apheresis, the donation frequency must be no more than
once in 8 weeks. For an apheresis collection resulting in two units of
Red Blood Cells, the donor must not donate more than once in 16 weeks.
These limitations on donation frequency reflect long standing donation
interval practices established to protect the donor from potential
health risks associated with frequent donations of Whole Blood or Red
Blood Cells. The purpose of these provisions is to protect the health
of the donor and allow time for red blood cell recovery. In Sec.
630.15(a)(1)(ii), we provide two exceptions to the donation interval:
(1) The donation is for autologous use as prescribed by the donor's
physician and the responsible physician determines and documents that
the donation may proceed or (2) the donation is a dedicated donation
based on the intended recipient's documented exceptional medical need
and the responsible physician determines and documents that the health
of the donor would not be adversely affected by donating. In the final
rule, we added the term ``exceptional'' to clarify that this exception
to donation frequency should apply only in those rare situations where
the recipient's need for a component from a donor with particular
characteristics is exceptional. For example, it may be appropriate to
rely on this exception in the event that a recipient needs a blood
component that is negative for a rare blood cell antigen. Under this
exceptional medical need provision, the responsible physician must
examine the donor and determine and document that the health of the
donor would not be adversely affected by donating. Under Sec.
630.5(b)(1)(i), the responsible physician is not authorized to delegate
the examination of the donor or the determination that the health of
the donor would not be adversely affected by donating.
    For clarity, the requirements regarding therapeutic phlebotomy have
been consolidated in the final rule in Sec.  630.15(a)(2).
    (Comment 78) One comment stated that the applicability of proposed
Sec.  630.15 to Red Blood Cells collected by apheresis was unclear. The
comment stated that ``double unit collection programs,'' often have
additional and different donor eligibility requirements, as described
in proposed Sec.  630.15(a)(1).
    (Response) Final Sec.  630.15(a) now more expressly includes Red
Blood Cells collected by apheresis. Final Sec.  630.15(a)(1)
establishes minimum time intervals between collections of Whole Blood,
and single and double units of Red Blood Cells by apheresis. These time
intervals are consistent with existing regulations and guidance. This
addition makes explicit what was less directly stated in the proposed
rule. Proposed Sec.  630.15(a)(1) referred to ``double unit collection
programs,'' which are double Red Blood Cell collections by apheresis.
Moreover, proposed Sec.  640.12 required establishments to determine
the eligibility of donors of Red Blood Cells in accordance with
Sec. Sec.  630.10 and 630.15.
    (Comment 79) One comment stated that FDA should not specify 8 and
16 week donation intervals. Instead, the comment recommended that a
blood establishment determine donation frequency without reference to a
specific donation interval, taking into account the donor history, the
results of a limited physical examination, the participation of a
medical director or his or her designee, and the blood center's
procedures. Another comment recommended that a physician be allowed to
authorize more frequent collection by certifying that the prospective
donor has recovered from the prior donation without evidence of
residual effects or to allow the physician to simply certify that the
prospective donor meets his/her requirements for a repeat donation on
the day of the examination.
    (Response) FDA regulations have long specified a minimum interval
of 8 weeks between Whole Blood donations, unless a physician examines
the donor and certifies the donor to be in good health. FDA is
finalizing minimum donation intervals in this rule to protect the
health of donors of Whole Blood and Red Blood Cells collected by
apheresis because too frequent donation may adversely affect a donor's
health (Refs. 47, 48). In the final rule at Sec.  630.15(a)(1), we are
retaining a minimum requirement for an 8 week interval between the
donation of a unit of Whole Blood or donation of a single unit of Red
Blood Cells by apheresis, and requiring a 16 week interval after a
double collection of Red Blood Cells. A 16 week interval following a
double collection of Red Blood Cells is recommended in current FDA
guidance (Ref. 53). Blood establishments are free to establish longer
donation intervals.
    We have provided a limited exception to these donation intervals to
allow for more frequent collections for: (1) An autologous donation as
prescribed by the donor's physician only when the donor has been
examined by the responsible physician who determines and documents that
the donation may proceed and (2) a dedicated donation based on the
intended recipient's documented exceptional medical need, only when the
responsible physician examines the donor and determines and documents
that the health of the donor would not be adversely affected by
donating.
    (Comment 80) Several comments requested that we clarify in the
final rule that donors with hereditary hemochromatosis can donate more
frequently than the 8 week interval set forth in proposed Sec.
630.15(a)(1) and also to clarify that more frequent donations from such
donors may be collected more frequently without an exception or
alternative under Sec.  640.120.
    (Response) Final Sec.  630.15(a)(2) states clearly that a donation
may be collected from a donor more frequently than once in 8 weeks for
collections resulting in a single unit of Whole Blood or Red Blood
Cells, or 16 weeks for apheresis collections resulting in a double
collection of Red Blood Cells, when the donor is determined to be
eligible under Sec.  630.10 and the collection is a physician-ordered
therapeutic phlebotomy of a donor, including a donor with hereditary
hemochromatosis. Establishments do not need an exception or alternative
under Sec.  640.120 to make a collection under this provision if the
requirements set forth in Sec.  630.15(a)(2) are met.
    (Comment 81) One comment recommended that the term ``iron
overload'' should be substituted for the term ``hereditary
hemochromatosis'' in the provision providing an exception to the
requirement to label a collection with the disease state of a donor
undergoing therapeutic phlebotomy.
    (Response) We decline to substitute the term ``iron overload'' for
the term ``hereditary hemochromatosis'' in final Sec.  630.15(a)(2).
The term, ``iron overload'' describes imprecisely the donors for whom
establishments would perform phlebotomies without charge. However, we
agree with the comment that this provision may, at some time in the
future, appropriately be applied to collections from donors whose
therapeutic phlebotomy is necessitated by a disease or condition other
than hereditary hemochromatosis. Accordingly, final Sec.  630.15(a)(2)
provides that no labeling for the disease or condition is required if:
(i) The donor meets all eligibility criteria; (ii) the donor undergoes
a therapeutic phlebotomy as prescribed by a licensed health care
provider treating the donor for (A) hereditary hemochromatosis; or (B)
another disease or condition, when the health of a donor with that
disease or condition will not be adversely

affected by donating, the donor's disease or condition will not
adversely affect the safety, purity, and potency of the blood and blood
components collected, or any products manufactured from them, and the
collection is in accordance with a procedure that has been found
acceptable for this purpose by FDA; and (iii) the establishment
performs without charge therapeutic phlebotomies for all individuals
with that disease or condition. Labeling to identify the disease state
or condition that necessitated the therapeutic phlebotomy is still
required when these criteria are not met.
    (Comment 82) Another comment suggested that the final rule should
not require a physical examination by a responsible physician at the
time of donation for individuals presenting a prescription for
therapeutic phlebotomy for medical reasons. The comment observed that
the 2001 guidance document entitled, ``Guidance for Industry: Variances
for Blood Collection from Individuals with Hereditary
Hemochromatosis,'' (Ref. 54) did not provide for such a physical
examination for exceptions or alternatives granted in accordance with
that guidance document.
    (Response) We agree with this suggestion. The final rule does not
require that an individual undergoing a prescribed therapeutic
phlebotomy to promote the donor's health be examined by a responsible
physician at the time of donation. The physical assessment required for
all donors under Sec.  630.10(f) still applies, however.
    (Comment 83) One comment supported the proposal that disease
labeling would not be required for blood and blood components donated
by an individual with hereditary hemochromatosis if the donor meets all
eligibility criteria and the collecting establishment performs
therapeutic phlebotomies without charge for all individuals with
hereditary hemochromatosis, including those who need therapeutic
phlebotomy but do not wish or are not eligible to donate. However, the
comment recommended that the final rule authorize blood establishments
to accept grants and gifts from third parties, including partial
insurance coverage, related to the costs of phlebotomy.
    (Response) The final rule provides that blood establishments do not
have to label donations from a donor with hereditary hemochromatosis
with the donor's disease state if the donor is eligible and the
establishment does not charge anyone with hereditary hemochromatosis
(or another disease or condition, if the conditions in the regulation
are met) for therapeutic phlebotomy. This provision is intended to
remove the incentive for an individual with hereditary hemochromatosis
to provide untruthful answers to donor eligibility questions for a
blood donation in order to receive the benefit of a phlebotomy without
charge. If a blood establishment charged a fee for an ineligible donor
to undergo a therapeutic phlebotomy, but not for an eligible donor with
hereditary hemochromatosis, the ineligible hereditary hemochromatosis
donor would have an incentive to deny risk conditions that might
preclude cost-free donation (Ref. 55). This policy is in part based on
recommendations of the Advisory Committee on Blood Safety and
Availability (Ref. 56). We decline to modify this provision to address
the acceptance of grants, gifts, or insurance payments. We note that we
did not propose such a provision, and we believe that a reference to
grants, gifts, or insurance payments could confuse patients seeking a
therapeutic phlebotomy.
    (Comment 84) One comment suggested that hospitals that transfuse
suitable blood and blood components labeled with the donor's iron
overload disease state should include a statement to that effect in
their informed consent for transfusion.
    (Response) This rule does not address the content of hospital
discussions related to informed consent for transfusion. Final Sec.
630.15(a)(2) authorizes blood establishments to collect blood and blood
components only from donors, including donors with hereditary
hemochromatosis, determined to be eligible. Blood from hereditary
hemochromatosis donors has been used for transfusion in other countries
without reports of adverse events in recipients (Refs. 57, 58, 59).
1. Section 630.15(b)
    We revised proposed Sec.  630.15(b)(1), formerly entitled
``Physical examination and informed consent,'' by dividing it into two
sections. This clarifies that separate requirements apply for the
medical history and physical examination (final Sec.  630.15(b)(1)) and
for obtaining informed consent (final Sec.  630.15(b)(2)). As a result,
proposed Sec.  630.15(b)(2) through (b)(7) are finalized as Sec.
630.15(b)(3) through (b)(8).
    a. Medical history and physical examination (Sec.  630.15(b)(1)).
    This section, titled ``Physical examination and informed consent''
in the proposed rule, is now titled ``Medical history and physical
examination.'' Informed consent requirements are now addressed in Sec.
630.15(b)(2). The new heading more accurately describes the assessment
required under this section. As proposed, we would have required the
responsible physician to examine the donor for medical conditions that
would place the donor at risk during plasmapheresis. We intended for
this physical examination to include conducting an appropriate medical
history and physical examination to identify medical conditions that
may place the donor at risk from plasmapheresis.
    (Comment 85) One comment stated that FDA should not require a
responsible physician to examine the donor before the initial donation
and at least annually thereafter. The comment asserted that
plasmapheresis collection has been in place for years without risk to
donors. The comment also stated that an annual and initial exam is
unnecessary for infrequent plasma donors and donors not participating
in immunization programs.
    (Response) Examination by a qualified licensed physician is already
required under current Sec.  640.63(b) for all Source Plasma donors,
and we believe that the requirement to conduct a medical history and
physical examination before the first donation, and at least annually
thereafter, contributes to the safety record of these collections. We
have modified this requirement by authorizing the responsible physician
in Sec.  630.5(c)(3) to delegate this activity to a physician
substitute, as defined in Sec.  630.3(g). During the annual physical,
donors may be examined for a variety of conditions, such as heart
disease, seizures, trouble breathing, allergies, recent medical
operations, or medications, in order to ensure that donating will not
adversely affect the health of the donor. Such evaluations would
include a physical examination and medical history which might identify
medications or underlying medical conditions that would lead to donor
deferral. Because frequent donation by plasmapheresis of plasma for
transfusion raises similar donor safety concerns, this requirement now
applies to collections from frequent plasmapheresis donors, and not
only to Source Plasma donors.
    However, we agree with the comment that an annual and initial
examination is unnecessary for an infrequent plasma donor, as defined
in Sec.  630.3(e). Final Sec.  630.25 provides certain exceptions from
donor eligibility requirements for infrequent plasma donors, including
the requirement for an enhanced medical history and physical
examination under Sec.  630.15. These donors remain subject to

the requirements for medical history and physical assessment under
Sec.  630.10.
    b. What requirements apply to obtaining informed consent? (Sec.
630.15(b)(2)).
    (Comment 86) Several comments stated that for plasmapheresis
donors, the distinction between the written statement of understanding
and informed consent should be clarified.
    (Response) We have clarified that the written statement of
understanding, renamed and revised as the donor's acknowledgement in
final Sec.  630.10(g)(2), applies to the collection of all blood and
blood components, including Source Plasma and plasmapheresis
collections. Informed consent for Source Plasma donation has long been
required under current Sec.  640.61, and this rule continues those
requirements for Source Plasma and plasmapheresis collections. In
recognition that the donation of Source Plasma and plasma by
plasmapheresis may present additional and potentially greater risks to
the donors, Sec.  630.15(b)(2) requires the responsible physician to
obtain the informed consent of such a donor on the first day of
donation or no more than 1 week before the first donation. Section
630.5 addresses the authority of the responsible physician to delegate
this task. The responsible physician must explain the risks and hazards
of the procedure to the donor. The explanation must be made in such a
manner that the donor may ask questions of the responsible physician.
The explanation must also give the donor a clear opportunity to refuse
the procedure. This informed consent process involves a dialogue
between the donor and the responsible physician. The establishment must
obtain informed consent from these donors at least once every year. If
a donor does not return for 6 months, the establishment must obtain
informed consent again. If new risks and hazards are identified, or if
the donor is enrolled in a new program such as an immunization or
special collection program, then a new informed consent, addressing the
specific risks and hazards of that program, must be obtained. The
informed consent requirements in Sec.  630.15(b)(2) are in addition to
the donor acknowledgement, which under Sec.  630.10(g)(2), must be
obtained from the donor at each donation.
    c. Weight (Sec.  630.15(b)(3)).
    Section 630.15(b)(2) of the proposed rule would have required that
establishments determine a donor's weight at each donation of plasma by
plasmapheresis. We received several comments regarding this provision,
which we address in this rule, and are finalizing this provision in
Sec.  630.15(b)(3) as proposed.
    (Comment 87) Two comments asserted that weighing a donor at each
donation is not useful. One comment further stated that donors are not
weighed prior to plateletpheresis procedures, and there is no evidence
that asking the donor to state their weight, as opposed to weighing
donors, has been unsafe. The comment further asserted that it would not
make sense to require a donor to be weighed prior to a co-collection of
plasma and platelets by apheresis as donors are currently not weighed
prior to triple plateletpheresis procedures, and there have been no
adverse events.
    (Response) We are finalizing this provision as proposed, and
require establishments to weigh a donor before collecting plasma by
plasmapheresis. A current weight measurement permits the collecting
establishment to calculate accurately the plasma volumes to be
collected based on a weight specific nomogram. The need for accurate
measurement applies to all collections by plasmapheresis, whether
Source Plasma, or frequent or infrequent plasmapheresis collection. We
have not included a requirement to weigh plateletpheresis donors. The
instructions for use for the apheresis devices used for such
collections vary concerning whether they require the user to weigh the
donor. Instead, establishments would address donor weight in their
standard operating procedures for plateletpheresis collection in a
manner that is consistent with the instructions for use (operator's
manual) for the apheresis devices used by the establishment to collect
platelets.
    When there is a co-collection including plasma by apheresis, this
provision requires the establishment to weigh the donor because the
collection of plasma by apheresis will be based on the donor's weight.
In addition, the instruction for use, including the operator's manual
of the device used to collect platelets by apheresis, may include an
instruction to determine the donor's weight for co-collections with
plasma.
    (Comment 88) One comment also recommended that in addition to
weighing donors at Source Plasma establishments, the donor's height be
taken once a year. The comment suggested that conversion of the
measurement of height and weight to lean body mass should be the basis
for the quantity of plasma removed.
    (Response) Measuring the donor's height combined with measuring a
donor's weight may be useful in identifying and using a more accurate
nomogram to determine the maximum quantity of plasma that should be
collected from the donor by plasmapheresis. However, we believe donors
are able to accurately report their height, which is less likely to
fluctuate over time than their weight. Therefore, Sec.  630.15(b)(3)
requires establishments to weigh each donor prior to each donation,
while permitting reliance on a donor's self-reported height when needed
to determine an accurate nomogram for the maximum quantity of plasma
that should be collected. We note that under current Sec.  606.65(e)
establishments must follow the device instructions for use and
operators manual of the apheresis collection device.
    d. Total protein level (Sec.  630.15(b)(4)).
    We are finalizing the requirement for collection establishments to
test the donor's blood sample for total plasma protein, and that the
donor have a value of no less than 6.0 grams per deciliter and no more
than 9.0 grams per deciliter. Consistent with current Sec.
640.63(c)(5) and proposed Sec.  630.15(b)(4), this section requires
establishments to continue the practice of assessing protein levels
before each plasmapheresis procedure. In addition, we are maintaining
the existing requirement in current Sec.  640.65(b)(1)(i), which
requires establishments to assess a Source Plasma donor's total protein
levels, and to perform a plasma or serum protein electrophoresis or
quantitative immuno-diffusion test or an equivalent test to determine
immunoglobulin composition of the plasma or serum, on the day of the
first medical examination or plasmapheresis, and at least every 4
months thereafter. Final Sec.  640.65(b)(2)(i) requires the responsible
physician to review the accumulated laboratory data, including any
tracings of the plasma or serum protein electrophoresis pattern, the
calculated values of the protein composition of each component, and the
collection records within 14 calendar days after the sample is drawn to
determine whether or not the donor should be deferred from further
donation. Comments on Sec.  640.65(b)(2)(i) are discussed at comment
118.
    (Comment 89) Several comments questioned the validity of the
proposal to require 9.0 grams protein per deciliter value for the upper
limit for total plasma protein. One comment stated the requirement for
total protein should specify that the donor's total plasma or serum
protein must have a value of no less than 6.0 grams per deciliter and
that the acceptable upper limit may be established based on applicable

statistical analysis of test results on their donors.
    (Response) After further consideration, we are finalizing these
limits largely as proposed. We consider the lower limit, no less than
6.0 grams protein per deciliter, and the total upper limit of 9.0 grams
protein per deciliter in a plasma or serum sample, as appropriate
measurement parameters to ensure the donor's health. We have determined
that the reference ranges for testing protein in serum and plasma are
comparable (Ref. 60); the final rule now applies these lower and upper
limits whether testing is performed on either a plasma or serum sample.
Although the comments questioned the value of an upper limit, we
consider an upper limit to be necessary to ensure donor health, because
high protein levels can be associated with adverse health conditions,
such as plasma cell dyscrasias (Ref. 61).
    (Comment 90) Another comment suggested FDA should consider a
flexible regulation to allow for the development of an acceptable
alternative to the current procedures.
    (Response) We have not identified a need to provide for a variable
standard in this rule. An establishment that proposes to use a
different standard may submit a request for an exception or alternative
under Sec.  640.120.
    e. Examination before immunization (Sec.  630.15(b)(5)).
    We have finalized Sec.  630.15(b)(5) to be consistent with proposed
Sec.  630.15(b)(4), but we have revised the language for clarity. This
section requires the responsible physician, subject to Sec.  630.5, to
conduct an appropriate medical history and physical examination of the
donor no more than 1 week before the first immunization injection of a
donor for the production of high-titer antibody plasma. This requires
that the responsible physician conducts an appropriate medical history
and physical examination, as described in Sec.  630.15(b)(1), before
the first immunization. It further provides an opportunity to obtain an
informed consent specific for participation in an immunization program,
as required in Sec.  630.15(b)(2)(iv) (Ref. 62). However, it is not
necessary to repeat the medical history and physical examination
required in Sec.  630.15(b)(1) if the immunized donor's plasma is
collected within 3 weeks of the first immunization injection. Under
Sec.  630.15(b)(5)(ii), establishments are not required to re-examine a
donor before immunizing the donor for the production of high-titer
antibody plasma if the donor is currently participating in a
plasmapheresis collection program and is eligible under Sec.  630.10.
    f. Deferral of donors due to red blood cell loss (Sec.
630.15(b)(6)).
    For the safety of the donor, we are requiring establishments to
defer donors from donating Source Plasma and plasma collected by
plasmapheresis following red blood cell loss due to a donation of Whole
Blood or Red Blood Cells collected by apheresis. Establishments must
also ensure that the cumulative red blood cell loss resulting from
previous donations does not adversely affect the health of the donor.
    Under final Sec.  630.15(b)(6)(i), establishments must defer a
donor from donating plasma by plasmapheresis for 8 weeks following a
donation of Whole Blood or a single unit of Red Blood Cells by
apheresis. However, establishments may collect Plasma by plasmapheresis
48 hours after a donation of Whole Blood or a single unit of Red Blood
Cells, provided the extracorporeal volume of the apheresis collection
device is less than 100 mL (Sec.  630.15(b)(6)(i)). We authorize
collection under these circumstances because the risk of red blood cell
loss in the donor is lower. The limited volume of the extracorporeal
circuit limits the donor's potential red blood cell loss in routine
apheresis collection. In addition, under Sec.  630.15(b)(6)(ii), plasma
donors must be deferred for 16 weeks if the donor donates two units of
Red Blood Cells during a single apheresis procedure. Final Sec.
630.15(b)(6)(iii) requires deferral for 8 weeks or more if the
cumulative red blood cell loss in any 8 week period could adversely
affect donor health.
    We have not finalized the provisions in the proposed rule that
would have required deferral after red blood cell loss of equal to or
greater than 200 mL (proposed Sec.  630.15(b)(5)(i) and (b)(5)(iii)).
We recognize that it is difficult to measure the amount of blood lost
in order to determine whether the volume is equal to or greater than
200 mL. Instead, we are finalizing the requirement in Sec.
630.15(b)(6)(iii) to defer the donor if the donor's cumulative red
blood cell loss in any 8 week period could adversely affect donor
health. We have addressed deferral due to red blood cell loss in
guidance (Ref. 63) and intend to issue future guidance on the impact of
the cumulative red blood cell loss following frequent apheresis
procedures.
    (Comment 91) One comment noted that FDA's guidance, ``Guidance for
Industry and FDA Review Staff: Collection of Platelets by Automated
Methods,'' which published in December 2007 during the comment period
for the proposed rule, contained recommendations for 16 week deferral
of platelet donors who experienced losses of red blood cells of 300 mL
or more. The comment recommended that 16 week deferrals for larger red
blood cell loss should be included for plasma donors in this final
rule.
    (Response) We agree with this comment about the relevance of FDA's
recommendations in ``Guidance for Industry and FDA Review Staff:
Collection of Platelets by Automated Methods,'' hereafter, referred to
as the ``2007 Guidance'' (Ref. 64). Because the risks associated with
red blood cell loss are comparable for donors of plasma and platelets
by apheresis, Sec.  630.15(b)(6)(iii) requires establishments to defer
for 16 weeks plasma donors who donate two units of Red Blood Cells
during a single apheresis procedure.
    (Comment 92) Another comment stated that specific deferral periods
are unnecessarily restrictive, and that there should be a provision
similar to that in the proposed rule at Sec.  640.21(e), to the effect
that collection of plasma by apheresis should be permitted following a
donation of Whole Blood or other red cell loss, if the extracorporeal
red blood cell volume for the apheresis device is less than or equal to
100 mL. The comment noted that most of the plasma collected by
apheresis from volunteer blood donors is plasma collected concurrently
with apheresis platelets. The comment stated that since FDA recognizes
that plateletpheresis collection is safe in this circumstance, it does
not make sense to have more restrictive criteria for the collection of
plasma by apheresis during plateletpheresis, as the red blood cell loss
would be the same for these procedures.
    (Response) We recognize that a co-collection of Plasma and
Platelets may occur and we agree that the risks associated with red
blood cell loss for collections of Source Plasma and Plasma by
apheresis are similar to those for collections of Platelets by
apheresis. The requirements for deferral of Plasma donors due to red
blood cell loss following Whole Blood or Red Blood Cell donation or
inadvertent red blood cell loss are addressed in this section.
Separately, we are finalizing a corresponding provision for the
deferral of Platelet donors due to Whole Blood or Red Blood Cell
donation or red blood cell loss in Sec.  640.21. We intend for the
deferrals for red blood cell loss to be the same for all collections of
Plasma and Platelets by apheresis, including co-collections, because we
consider the

risks of red blood cell loss to be the same.
    In the final rule, we require the deferral of plasmapheresis donors
following the donation of Whole Blood and Red Blood Cells, and because
of cumulative red blood cell loss over time. Consistent with the final
requirements for Platelets in Sec.  640.21, Sec.  630.15(b)(6)(i)
permits the collection of Source Plasma and Plasma by plasmapheresis 2
days after a donation of Whole Blood or a single unit of Red Blood
Cells, provided the extracorporeal volume of the apheresis collection
device is less than 100 mL.
    g. Exceptions to deferral due to red blood cell loss (Sec.
630.15(b)(7)).
    Final Sec.  630.15(b)(7) provides an exception to deferral due to
red blood cell loss for certain Source Plasma donors. While the
introductory paragraph of proposed Sec.  630.15(b)(6) referred to
participation in a plasmapheresis program instead of to Source Plasma
collections, we finalized this exception using the more explicit term
``Source Plasma.'' In proposed Sec.  630.15(b)(6)(i), the responsible
physician would have been required to conduct an examination and
``certify'' the donor's good health; final Sec.  630.15(b)(7)(i)
requires that the responsible physician examine the donor at the time
of the current donation and determine and document that the donor is in
good health and the donor's health permits the plasmapheresis. Under
Sec.  630.5(c)(1)(i)(A), the responsible physician is not authorized to
delegate this examination and determination. In proposed Sec.
630.15(b)(6)(ii), this exception would apply when the ``donor possesses
an antibody that is transitory, of a highly unusual or infrequent
specificity, or of an unusually high titer.'' In final Sec.
630.15(b)(7)(ii), the exception is reserved for donors whose plasma
possesses a property such as an antibody, antigen, or protein
deficiency, that is transitory, of a highly unusual or infrequent
specificity, or of an unusually high titer. This reference to the
donor's plasma, instead of the narrower reference to an ``antibody'' in
the plasma is repeated in final Sec.  630.15(b)(7)(iii), which requires
the establishment to document the special characteristics of the
donor's plasma and the need for plasmapheresis of that donor. We
altered this provision to refer more generally to the unusual
characteristics of the plasma, rather than to a specific antibody,
because we recognized that this exception should be available under
appropriate circumstances where the donor's plasma has other unusual
characteristics, such as a rare antigen. As additional protection
against additional red blood cell loss in a collection under this
provision, final Sec.  630.15(b)(7)(iv) provides that the
extracorporeal volume of the apheresis device used to collect plasma
under this provision must be less than 100 mL. We note that donors who
donate subject to this exception must be advised of the risks and
hazards related to this donation under Sec. Sec.  630.10(g)(2) and
630.15(b)(2), or under Sec.  630.15(b)(2)(iv), if the donor is newly
enrolled in the program.
    (Comment 93) One comment asserted that the statement in the
proposed rule at Sec.  630.15(b)(6)(ii), ``the donor possesses an
antibody that is transitory. . .'' requires modification. The comment